1.1.1.1 alcohol dehydrogenase medicine isozyme ADH2 is a target for anti-amoebic agents 1.1.1.1 alcohol dehydrogenase medicine organ simulations indicate that higher therapeutic acetaminophen (0.5 mM) inhibits 16% of allotype ADH1B*1/*1 hepatic ADH activity at 2-20 mM ethanol and that therapeutic salicylate (1.5 mM) inhibits 30-31% of the allotype ADH1B*2/*2 activity, suggesting potential significant inhibitions of ethanol first-pass metabolism in these allelotypes 1.1.1.2 alcohol dehydrogenase (NADP+) medicine - 1.1.1.2 alcohol dehydrogenase (NADP+) medicine brain aldehyde reductase activity is closely associated with pharmalogical actions of drugs affecting the central nervous system, anti-convulsant drugs have inhibitory effects, more work is needed for the mechanism of action of psychoactive drugs and interactions of barbiturates with aldehyde reductase 1.1.1.2 alcohol dehydrogenase (NADP+) medicine inhibitors alrestatin and sorbinil, possible method of preventing neuropathy and cataractogenesis associated with diabetes 1.1.1.2 alcohol dehydrogenase (NADP+) medicine enzyme as a target for anti-tuberculosis and other drugs 1.1.1.2 alcohol dehydrogenase (NADP+) medicine enzyme may be an interesting target for development of new anti-mycobacterial agents 1.1.1.2 alcohol dehydrogenase (NADP+) medicine drugs for testing function of liver and kidney 1.1.1.2 alcohol dehydrogenase (NADP+) medicine daunorubicin, a cancer chemotherapeutic agent can be reduced by aldehyde reductase 1.1.1.2 alcohol dehydrogenase (NADP+) medicine ability of aldehyde reductase from liver to reduce certain cancer chemotherapeutic antibiotics suggested a role for this enzyme in drug metabolism 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) medicine the hyperthyroid status leads to a significant decrease and the hypothyroid status to a significant increase of both enzyme amount and activity in both female and male animals. The euthyroid and hyperthyroid females show a higher activity and the hyperthyroid females also show a higher enzyme amount in comparison with male animals, while the hypothyroid animals show low levels in both sexes. The enzyme-dependent oxygen consumption of freshly isolated liver mitochondria from hyperthyroid animals is higher compared with euthyroid animals, and is activated bycoenzyme Q analogue idebenone, in both euthyroid and hyperthyroid rats. Determination of enzyme amount and activity can serve as an additional criterion for the evaluation of the thyroid hormone status 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) medicine pomolic acid suppresses the increase in GPDH activity in adipocytes when 3T3-L1 cells are treated with pomolic acid during culture in an insulin-containing medium after induction of differentiation. Pomolic acid promotes an increase in GPDH activity in differentiated 3T3-L1 adipocytes when these cells are treated with pomolic acid during culture in the differentiation medium 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) medicine the mRNA expression level of glycerol-3-phosphate dehydrogenase (GPD1) is significantly downregulated in human breast cancer patients. Patients with reduced GPD1 expression exhibit poorer overall metastatic relapse-free survival. The reduced expression of GPD1 is an independent predictor of overall survival in oestrogen receptor-positive and nodal-negative breast cancer patients. GPD1 is a direct target of miR-370, which is significantly upregulated in human breast cancer. Exogenous expression of GPD1 in MCF-7 and MDA-MB-231 breast cancer cells significantly inhibits cell proliferation, migration, and invasion 1.1.1.14 L-iditol 2-dehydrogenase medicine target for inhibitor design 1.1.1.14 L-iditol 2-dehydrogenase medicine target for inhibitor design in hyperglycaemia and diabetes mellitus treatment 1.1.1.21 aldose reductase medicine enzyme protein levels and activity decrease progressively during heart failure upon rapid left ventricular pacing, such as myocardial capacity to detoxify lipid-peroxidation derived aldehydes 1.1.1.21 aldose reductase medicine inhibition of enzyme by tolrestat or sorbinil prevents apotosis and activation of calpase-3, attenuation of TNF-alpha and hyperglykemia-induced activation of protein kinase C, but does not prevent the activation of transkription factor NK-kappaB and protein kinase C by phorbol ester, enzyme is an obligatory mediator of the apoptotic events upstream of protein kinase C 1.1.1.21 aldose reductase medicine inhibition of enzyme by zolrestat attenuates apoptosis in sorbitol-treated cells. Hyperosmolarity-induced cell death requires induction of enzyme as well as a decrease in intracellular glutathione levels 1.1.1.21 aldose reductase medicine inhibition of enzyme inhibits vascular smooth muscle cell growth upon injuries via a decrease in activity of transcription factor NF-kappaB 1.1.1.21 aldose reductase medicine inhibition of enzyme prevents TNF-alpha-induced increase in Bax and Bak and the downregulation of Bcl-2, inhibition abrogates Ap-1 DNA binding activity and prevents the activation of caspase-3, JNK, and p38 MAPK in cells stimulated by TNFalpha 1.1.1.21 aldose reductase medicine myocardial enzyme activity is increased during ischemia, partially due to activation by nitric oxide, enzyme inhibition increases glycolysis and glucose oxidation 1.1.1.21 aldose reductase medicine pharmacological inhibition of enzyme significantly reduces ischemic injury and improves functional recovery in enzyme transgenic mice 1.1.1.21 aldose reductase medicine inhibition of AR may assist in the chemotherapy of malignant tumors by suppressing the rapid growth of cancer cells 1.1.1.21 aldose reductase medicine inhibition of AR may be a significant therapeutic approach in preventing bacterial endotoxin-induced sepsis and tissue damage 1.1.1.21 aldose reductase medicine in streptozotocin-diabetic mice, aldose reductase inhibitor treatment or genetic deficiency of aldose reductase result in significant dephosphorylation of both peroxisome proliferator-activated receptor alpha and ERK1/2 1.1.1.21 aldose reductase medicine inhibition of enzyme in neural stem cells exposed to high glucose concentration results in decrease of oxidative stress, restoration of cell viability and proliferation, and reduction of apoptotic cell death. Inhibition attenuates the down-regulation of glucose transporter 1 expression 1.1.1.21 aldose reductase medicine inhibition/antisense abolition of aldose reductase inhibits the tumor necrosis factor alpha-induced synthesis of prostaglandin E2 and the activity of cyclooxygenase. Inhibition of aldose reductase prevents tumor necrosis factor alpha-induced activation of protein kinase C and NF-kappaB which results in the abrogation of Cox-2 mRNA and protein expression 1.1.1.21 aldose reductase medicine treatment with the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester prevented ischemia-induced aldose reductase activation and myocardial sorbitol accumulation in rat hearts subjected to global ischemia ex vivo or coronary ligation in situ, whereas inhibition of inducible nitric oxide synthase and neuronal nitric oxide synthase have no effect. Activation of aldose reductase in the ischemic heart is abolished by pretreatment with peroxynitrite scavengers hesperetin or 5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron [III] 1.1.1.21 aldose reductase medicine ALR2 is a critical target to prevent and control diabetic complications through the inhibition of its activity 1.1.1.21 aldose reductase medicine inhibition of aldose reductase may represent a useful strategy for treating vascular inflammation associated with diabetes 1.1.1.21 aldose reductase medicine levels of ALR2 activity as well as sorbitol in erythrocytes may have value as a quantitative trait to establish a risk profile for development of diabetic retinopathy, type 2 diabetic patients with diabetic retinopathy show significantly higher specific activity of ALR2 as compared to type 2 diabetic patients without diabetic retinopathy 1.1.1.21 aldose reductase medicine aldose reductase ALR2 is a target enzyme for the treatment of diabetic complications 1.1.1.21 aldose reductase medicine the enzyme may be a potential drug target or vaccine candidate for schistosomes 1.1.1.21 aldose reductase medicine fidarestat decreases doxorubicin-induced upregulation of CD11b in THP-1 monocytes. Fidarestat attenuates doxorubicin-induced upregulation of IL-6, IL-1bta, and Nos2 in murine bone-marrow derived macrophages. Fidarestat also attenuates doxorubicin-induced activation and infiltration of multiple subsets of inflammatory immune cells identified by expression of markers CD11b+, CD11b+F4/80+, Ly6C+CCR2high, and Ly6C+CD11b+ in the mouse spleen and liver. Upregulation of markers of mitochondrial biogenesis PGC-1alpha, COX IV, TFAM, and phosphorylation of AMPKalpha1 (Ser485) is observed in THP-1 cells and livers of mice treated with doxorubicin in combination with fidarestat 1.1.1.21 aldose reductase medicine mice devoid of AKR1B3 and exposed to acute occlusion of the left anterior descending coronary artery display reduced infarct size and improved functional recovery at 48 hours compared to wild-type mice. The cardioprotection observed in AKR1B3 null mice is linked to acute activation of the beta-catenin pathway and consequent activation of mesenchymal markers and genes linked to fibrotic remodeling. The increased activity of the beta-catenin pathway at 48 hours of recovery is not observed at 28 days post-infarction. In ex vivo studies, inhibition of beta-catenin blocks the cardioprotection observed in AKR1B3 null mice hearts 1.1.1.22 UDP-glucose 6-dehydrogenase medicine possibility that gallic acid and quercetin may modulate human breast cancer cell proliferation by inhibiting UGDH 1.1.1.22 UDP-glucose 6-dehydrogenase medicine UGDH content in prostatic acini is a novel candidate biomarker that may complement the development of a multi-biomarker panel for detecting prostate cancer within the tumor adjacent field on a histologically normal biopsy specimen 1.1.1.22 UDP-glucose 6-dehydrogenase medicine manipulation of UGDH activity by hexamer stabilization may offer therapeutic options in cancer and other pathologies 1.1.1.22 UDP-glucose 6-dehydrogenase medicine biallelic mutations in UGDH cause developmental epileptic encephalopathy. In 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia, mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors 1.1.1.22 UDP-glucose 6-dehydrogenase medicine epirubicin accumulation increases and apoptosis decreases during UGDH knockdown. Hyaluronan-coated matrix increases and a positive modulation of autophagy is detected. Higher levels of UGDH are correlated with worse prognosis in triple-negative breast cancer patients that receive chemotherapy. High expression of UGDH is found in tumoral tissue from HER2--patients. UGDH knockdown contributes to epirubicin resistance 1.1.1.22 UDP-glucose 6-dehydrogenase medicine expression of UDP-glucose dehydrogenase is up-regulated in highly metastatic ovarian cancer TOV-21G cells, but not in normal adjacent tissue. RNAi-mediated silencing results in a significant decrease in metastatic ability in transwell migration, transwell invasion and wound healing assays. The knockdown of UGDH causes cell cycle arrest in the G0/G1 phase and induces a massive decrease of tumour formation rate in vivo. UGDH-depletion leads to the down-regulation of epithelial-mesenchymal transition-related markers as well as MMP2, and inactivation of the ERK/MAPK pathway 1.1.1.22 UDP-glucose 6-dehydrogenase medicine high UGDH expression is associated with decreased patient survival in poor-prognosis breast cancer subsets 1.1.1.22 UDP-glucose 6-dehydrogenase medicine knocking out UGDH in highly metastatic 6DT-1 breast cancer cells impairs migration ability without affecting in vitro proliferation. UGDH-KO results in significantly decreased metastatic capacity in vivo when the cells are orthotopically injected in syngeneic mice 1.1.1.22 UDP-glucose 6-dehydrogenase medicine shRNA-mediated knockdown of UGDH inhibits breast cancer invasion, colony formation, and tumor growth 1.1.1.26 glyoxylate reductase medicine identification of point mutations and minor deletions resulting in primary hyperoxaluria type 2 1.1.1.27 L-lactate dehydrogenase medicine potential drug target for new antimalarials 1.1.1.27 L-lactate dehydrogenase medicine structural characterization of the enzyme and active-site differences from the human lactate dehydrogenase may be useful for structural-based design of new treatments for toxoplasmic infections 1.1.1.27 L-lactate dehydrogenase medicine suitable drug target for design of novel babesial chemotherapeutics 1.1.1.27 L-lactate dehydrogenase medicine serum LDH zymograms of patients can be used as prognostic marker, since they tend to reach the normal level during recovery signifying the effect of chemotherapy in hospitalized patients. Elevation along with the rise in total LDH activity may be used in the diagnosis and monitoring of tubercular pyothorax 1.1.1.27 L-lactate dehydrogenase medicine the enzyme is a target for treatment of cancer 1.1.1.27 L-lactate dehydrogenase medicine LDH-5 is considered a highly promising target in cancer therapy, LDH-5 significance in the treatment and prognosis of neoplastic diseases 1.1.1.27 L-lactate dehydrogenase medicine LDHB is a therapeutic target in cancer 1.1.1.27 L-lactate dehydrogenase medicine alpha-HBDH is an independent risk factor for systemic lupus erythematosus-related liver injury. alpha-HBDH level is significantly higher in the systemic lupus erythematosus-related liver injury patients than in the non-systemic lupus erythematosus-related liver injury patients. alpha-HBDH is positively correlated with levels of aspartate aminotransferase and lactate dehydrogenase, the aspartate aminotransferase/alanine aminotransferase ratio, and the systemic lupus erythematosus disease activity index 2000, and it is negatively correlated with albumin and C3. The optimal cutoff value of alpha-HBDH for distinguishing systemic lupus erythematosus patients with and without liver injury is 258.50 U/l, which provides a 60.94% sensitivity and a 94.67% specificity 1.1.1.27 L-lactate dehydrogenase medicine alpha-hydroxybutyrate dehydrogenase as an independent prognostic factor for mortality in hospitalized patients with COVID-19. Among 1751 patients with confirmed COVID-19, 15 patients (0.87%) died. The mortality during hospitalization was 0.26% for patients with normal alpha-HBDH levels and 5.73% for those with elevated alpha-HBDH levels 1.1.1.27 L-lactate dehydrogenase medicine HBDH is associated with atherothrombotic events in 83 stable patients undergoing infrainguinal angioplasty and stenting. HBDH levels at baseline are significantly higher in patients who subsequently developed the primary endpoint. HBDH can distinguish between patients without and with future atherothrombotic events. A HBDH concentration at/above 115 U/l is the best threshold to predict the composite endpoint, providing a sensitivity of 83.3% and a specificity of 71.4%, and is therefore defined as high HBDH. Ischemic events occur significantly more often in patients with high HBDH than in patients with lower HBDH levels 1.1.1.29 glycerate dehydrogenase medicine glyoxylate reductase/hydroxypyruvate reductase is a prognostic marker for hepatocellular carcinoma patients after curative resection 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) medicine the enzyme is a target for intervention in the treatment of hypercholesterolaemia, clinical utility of inhibitors to decrease the levels of atherogenic lipiproteins in patients 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) medicine dual therapy with the HMG-CoA reductase inhibitor pravastatin and the angiotensin receptor antagonist olmesartan, which produce an additive reduction in cardiomyocyte hypertrophy and cardiac fibrosis after myocardial infarction through different mechanisms, decreases the propensity of the heart to arrhythmogenesis 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) medicine genistein, eicosapentaenoic acid and docosahexaenoic acid down-regulate reductase activity, primarily through posttranscriptional effects. Diets rich in soy isoflavones and fish oils, therefore, may exert anti-cancer effects through the inhibition of mevalonate synthesis in the breast. Genistein and docosahexaenoic acid, in particular, may augment the efficacy of statins, increasing the potential for use of these drugs in adjuvant therapy for breast cancer 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) medicine the cholesterol absorption inhibitor ezetimibe profoundly lowers serum cholesterol levels in animals expressing very low rates of hepatic cholesterol synthesis and produces large compensatory increases in hepatic HMG-CoA reductase expression without signifucantly affecting expression of hepatic low density lipoprotein receptors. This indicates that ezitimibe should be most effective in lowering serum cholesterol levels in peaple with low rates of cholesterol synthesis/High rates of cholesterol absorption 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) medicine treatment with the inhibitor atorvastatin exerts early nephroprotective effects in a rat model of chronic inhibition of nitric axide synthesis 1.1.1.35 3-hydroxyacyl-CoA dehydrogenase medicine HADH protects against excess amino acid-induced insulin secretion 1.1.1.35 3-hydroxyacyl-CoA dehydrogenase medicine lack of Hadh2 activity may impart early developmental problems, leading to embryo lethality. In addition to the 3-hydroxyacyl-CoA dehydrogenase activity, the HSD10 (formerly Hadh2) activity is also relevant to the metabolism and meiotic maturation of oocytes 1.1.1.35 3-hydroxyacyl-CoA dehydrogenase medicine the leptospiral enzyme is an early urinary biomarker of leptospirosis 1.1.1.37 malate dehydrogenase medicine therapy development for sexually transmitted disease of humans 1.1.1.39 malate dehydrogenase (decarboxylating) medicine ME2 as a potentially novel metabolic target for leukemia therapy 1.1.1.40 malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) medicine enzyme ME2 is a potential target for cancer therapy 1.1.1.40 malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) medicine isoform ME2 is a potential anticancer target 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) medicine exposure of fetus to high levels of synthetic glucocorticoid may have long-lasting effects on the hippocampal expression of hypothalamic-pituitary-adrenal-related genes into adulthood 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) medicine squirrel monkeys protect the mineralocorticoid receptor from activation by high cortisol levels in the kidney via upregulation of 11beta-HSD2 activity through increased production of the enzyme 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) medicine treatment of rats with dehydroepiandrosterone induces a shift from isoform 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) medicine high-fat fed animals overexpress 11beta-hydroxysteroid dehydrogenase type 2 in subcutaneous but not in retroperitoneal fat. Enzyme mRNA levels strongly correlate in both tissues with different parameters related to obesity, such as body weight, adiposity, and insulin resistance 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) medicine 11beta-HSD1 is a drug target for treatment of insulin resistance, diabetes and cardiovascular disease 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) medicine age-related reduced 11beta-HSD2 activity contributes to the rising prevalence of arterial hypertension in elderly 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) medicine at baseline, mRNA levels are similar in skeletal muscle of diabetic and control sugjects for 11beta-HSD1, 11beta-HSD2, and hexose-6-phosphate dehydrogenase. 11beta-HSD1 activity is reduced in diabetic subjects, while 11beta-HSD2 activity is increased. After application of dexamethasone, 11beta-HSD1 mRNA increases in both groups, whereas 11beta-HSD2 mRNA decreases. 11beta-HSD1 activity increases in diabetic subjects, but not in controls, whereas 11beta-HSD2 activity does not change in either group; mRNA levels are similar in diabetic and control subjects for 11beta-hydroxysteroid dehydrogenase 1 and 11beta-hydroxysteroid dehydrogenase 2. 11beta-Hydroxysteroid dehydrogenase 2-activity is higher in diabetic patients. After treatment with dexamethasone, 11beta-hydroxysteroid dehydrogenase 1-mRNA increases in both groups, whereas 11beta-hydroxysteroid dehydrogenase 2-mRNA decreases. 11beta-Hydroxysteroid dehydrogenase 1-activity increases in diabetic patients, but not in control, whereas 11beta-hydroxysteroid dehydrogenase 2-activity does not change in either group 1.1.1.42 isocitrate dehydrogenase (NADP+) medicine sensitizing effect of NADP+-dependent isocitrate dehydrogenase siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer therapy 1.1.1.42 isocitrate dehydrogenase (NADP+) medicine the sensitizing effect of NADP+-dependent isocitrate dehydrogenase siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy 1.1.1.42 isocitrate dehydrogenase (NADP+) medicine transfection of HeLa cells with an NADP+-dependent isocitrate dehydrogenase small interfering RNA decreased the activity of IDPm, enhancing the susceptibility of radiation-induced apoptosis. The effect of NADP+-dependent isocitrate dehydrogenaseIDPm small interfering RNA on HeLa cells offers the possibility of developing a modifier of radiation therapy 1.1.1.42 isocitrate dehydrogenase (NADP+) medicine the sensitizing effect of IDPm siRNA and autophagy inhibitor on the ionizing radiation induced apoptotic cell death of glioma cells offers a novel redox-active therapeutic strategy for the treatment of cancer 1.1.1.42 isocitrate dehydrogenase (NADP+) medicine the enzyme is a vaccine candidate against the fish pathogen Edwardsiella tarda infection. The serum of enzyme-vaccinated flounder exhibit the highest bactericidal activity compared with other groups. The recombinant enzyme can enhance the expressions of interferon-gamma, natural killer enhancing factor, interleukin-6, major histocompatibility complex Ialpha, CD4-1 and CD8alpha 1.1.1.44 phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating) medicine - 1.1.1.44 phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating) medicine with a deficiency of 6-phosphogluconate dehydrogenase some reticulocytosis occurs 1.1.1.44 phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating) medicine 6PGDH might be a target for chemotherapy against parasitic infections as trypanosomiasis 1.1.1.44 phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating) medicine 6-phosphogluconate dehydrogenase is a potential target for new drugs against African trypanosomiasis 1.1.1.45 L-gulonate 3-dehydrogenase medicine role in an alternative pathway of the production of xylitol in the lens that causes cataracts in mammalian organisms 1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) medicine G6PD deficiency due to its polymorphism causes neonatal jaundice, acute hemolysis in malaria, favism, severe chronic non-spherocytic hemolytic anemia, and lipid dysregulation. G6PD deficiency may be responsible for the high incidence of coronary artery disease among African-Americans and reduces mortality due to ischemic heart disease and cerebrovascular disease in Sardinian males. In Mediterranean and Sardinian G6PD-deficient individuals, G6PD deficiency may confer a partial protection against atherosclerosis, leading to a reduced risk of cardiovascular diseases in G6PD-deficient individuals. G6PD appears to be an attractive therapeutic target for diabetes-induced cardiomyopathy, ischemic cardiomyopathy, pulmonary hypertension, angiotensin II-induced hypertension, vascular smooth muscle hypertrophy and coronary disease in humans 1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) medicine G6PD deficiency is the commonest clinically significant enzymopathy in humans. More than 400 million people worldwide are affected by this condition which may determine favism, drug-induced acute hemolytic anemia, severe chronic nonspherocytic haemolytic anemia, neonatal jaundice and hemolytic anemia associated with viral or microbiological infections. The highest prevalence of G6PD deficiency mainly regards tropical Africa, the Middle East, tropical and subtropical Asia, Papua New Guinea, and various Mediterranean regions, for example Sardinia island. G6PD deficiency may represent a selective advantage due to the increased resistance to severe Plasmodium falciparum infection of the affected individuals. G6PD/pyruvate kinase ratio is more reliable than the G6PD activity alone, for the identification of G6PD heterozygotes, especially in patients with microcytic anemia. G6PD/6PDG ratio is an absolute measure of G6PD deficiency of female carriers 1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) medicine in Vietnam the blackwater fever syndrome is associated with malaria infection, quinine ingestion and G6PD deficiency. G6PD deficiency is a major risk factor for haemoglobinuria in ethnic Vietnamese Kinh and within the G6PD deficient population G6PD Viangchan is significantly associated with haemoglobinuria 1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) medicine refolding protocol can be applied to produce high recovery yield of folded protein with unaltered properties, paving the way for future studies on clinical G6PD mutants with folding defects and providing a useful model system to study the folding process of oligomeric proteins 1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) medicine fluoride-containing bioactive glasses as used in tissue engineering as well as bone repair, inhibit the pentose phosphate oxidative pathway and the glucose 6-phosphate dehydrogenase activity. The effects are ascribable to the fluoride content/release of glass powders, they are mimicked by NaF solutions and are prevented by radical scavengers dimethyl sulfoxide and tempol, by superoxide dismutase, and by glutathione, but not by apocynin 1.1.1.50 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) medicine enzyme as part of commercial enzyme test kit for bile acid content in serum as an index for hepatic diseases 1.1.1.50 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) medicine enzyme is a potential drug target 1.1.1.51 3(or 17)beta-hydroxysteroid dehydrogenase medicine inhibitor Strogen forte extract can be used for treatment of benign prostatic hyperplasia 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine binding of equilin at the active site of the enzyme is the basis for inhibition of reduction of estrone to estradiol. One possible outcome of estrogen replacement therapy in vivo can be the reduction of estradiol levels in breast tissues and hence the reduced risk of estrogen-dependent breast cancer 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine attractive drug target in hormone-sensitive breast cancer 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine target for suppression of estrogen synthesis in breast cancer 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine as estradiol stimulates the growth and development of hormone-dependent breast cancer, inhibition of the final step of its synthesis is an attractive target for the treatment of this disease 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine estrogenic response for estrone is enhanced by the local action of HSD17B1 in vivo. Thus the enzyme is a potential target for pharmacological inhibition of estrogen activation. Targeted inhibition of HSD17B1 is a promising therapeutic approach to modulate estrogen response in the target tissue with less severe side effects as compared with antiestrogens 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine type 1 17beta-hydroxysteroid dehydrogenase is an interesting biological target for designing drugs for the treatment of estrogen-sensitive diseases such as breast cancer 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine 17beta-HSD1 inhibitors such as STX1040 may provide a treatment for hormone-dependent breast cancer 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine 17beta-HSD1 is an attractive target for the treatment of mammary tumours 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine 17beta-HSD1 is overexpressed in many breast tumors. Thus, it is an attractive target for the treatment of these diseases 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine disease iondications for HSD17B1 inhibitors in disorders in the female reproductive organs associated with enhanced androgen action, such as ovarian serous cystadenomas 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine inhibitors of the enzyme have potential as treatments for hormone dependent breast cancer 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine 17beta-hydroxysteroid dehydrogenase type 2 is mainly involved in the conversion of estradiol into estrone. Their ratio is decreased from 9/1 to 7/3 after over-expression of 17beta-hydroxysteroid dehydrogenase type 2 in MCF-7 cells already over-expressing 17beta-hydroxysteroid dehydrogenase type 1. The ratio is further decreased by the addition of the oxidative cofactor, NAD, to the cell culture to facilitate the estradiol to estrone conversion catalyzed by 17beta-hydroxysteroid dehydrogenase type 2 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine application of medroxyprogestrone acetate, dydrogesterone and dienogest significantly decreases isoforms HSD17B1 and CYP19A1 expression and significantly increases isoform HSD17B2 expression. Dydrogesterone and dienogest also significantly suppress estrogen receptors ESR1 and ESR2 transcription, whereas medroxyprogestrone acetate and dydrogesterone significantly reduce mRNA levels of G protein-coupled estrogen receptor 1. Results thus suggest that in peritoneal endometriosis the beneficial effects of these progestins can be explained by lower HSD17B1 and higher HSD17B2 mRNA and protein levels, which lead to reduced local estradiol biosynthesis 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine isoform 17betaHSD6 is expressed in estrogen receptor beta-positive epithelial cells of the human prostate. In prostate cancers of Gleason grade higher than 3, both estrogen receptor beta and isoform 17betaHSD6 are undetectable 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine Patients with oestrogen positive tumours with high isoform 17betaHSD14 expression have fewer local recurrences when treated with tamoxifen compared to patients with lower tumoural 17betaHSD14 expression, for whom tamoxifen does not reduce the number of local recurrences. No prognostic importance of 17betaHSD14 is seen for systemically untreated patients 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine twenty four hours after addition of different concentrations of estrone and estradiol, the ratio stabilizes to around 9/1 in breast cancer cell lines with high expression of 17beta-hydroxysteroid dehydrogenase type 1, such as T47D, BT 20, and JEG 3 cells, whereas it approaches 1/5 in cells with low expression of 17beta-hydroxysteroid dehydrogenase type 1, such as MCF-7 cells. The estradiol/estrone concentration ratio is modified to 9/1 in MCF-7 and HEK-293 cells over-expressing 17beta-hydroxysteroid dehydrogenase type 1. In T47D and BT 20 cells , this ratio is decreased from 9/1 to nearly 1/5 after 17beta-hydroxysteroid dehydrogenase type 1 knockdown by specific siRNAs 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine 17betaHSD1 is an important prognostic factor in non-small cell lung carcinoma, NSCLC, patients and targeting 17betaHSD1 activity may further improve the clinical response in estrogen responsive NSCLC patients 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine enzyme inhibition can lead to desired increase of estradiol and testosterone levels in the bone tissue and may be used for the treatment of osteoporosis 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine enzyme inhibition is considered as a treatment option for osteoporosis to ameliorate estrogen deficiency 1.1.1.62 17beta-estradiol 17-dehydrogenase medicine inhibition of 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) can help maintaining the appropriate bone mass density in osteoporosis by increasing the level of estradiol and testosterone in bone 1.1.1.64 testosterone 17beta-dehydrogenase (NADP+) medicine exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression. The resistance lowers the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigates the cytotoxicity of the aldehydes and cisplatin. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the aldo-keto reductases increases the sensitivity to ciplatin toxicity. Pretreatment of the resistant cells with proteasome inhibitor Z-Leu-Leu-Leu-al augments the cisplatin sensitization elicited by aldo-keto reductase inhibitors 1.1.1.64 testosterone 17beta-dehydrogenase (NADP+) medicine positive isoform AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. Isoform AKR1C3 immunoreactivity is absent in small cell carcinoma of the lung 1.1.1.64 testosterone 17beta-dehydrogenase (NADP+) medicine uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium 1.1.1.72 glycerol dehydrogenase (NADP+) medicine NADP(+)-dependent glycerol dehydrogenase homologous protein is a major allergen. Glycerol dehydrogenase shows IgE reactivity amongst the selected atopic patient cohort. All together, 10 cross-reactive IgE-binding proteins are detected 1.1.1.87 homoisocitrate dehydrogenase medicine detection of unique gene LYS1 for rapid identification of pathogenic fungi, LYS1 gene is a possible target for selective inhibition of growth of pathogenic fungi in vivo 1.1.1.88 hydroxymethylglutaryl-CoA reductase medicine target enzyme for chemotherapy of hypercholesterolemias 1.1.1.88 hydroxymethylglutaryl-CoA reductase medicine in endotoxemic mice, leukocyte infiltration in the liver is significantly elevated. Simvastatin significantly reduces endotoxin-induced hepatocellular damage and apoptosis. Hepatic accumulation of leukocytes is attenuated by simvastatin. Co-administration of mevalonate abolishes the protective effects of simvastatin on endotoxin-provoked increases in serum alanine transferase and serum alanine transferase as well as leukocyte recruitment 1.1.1.88 hydroxymethylglutaryl-CoA reductase medicine pterygium has an altered metabolism of cholesterol, namely increased LDL-R and HMG-CoA-R mRNAs. Both genes may play important roles in the pathogenesis of pterygium 1.1.1.105 all-trans-retinol dehydrogenase (NAD+) medicine mutations in RDH12 are associated with Leber congenital amaurosis 1.1.1.135 GDP-6-deoxy-D-talose 4-dehydrogenase medicine L122C and R130C are missence mutations found in patients with inborn error of isoleucine degradation, almost complete loss of enzyme activity 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine 15-hydroxyprostaglandin dehydrogenase hypomorphic mice show a decreased level of enzyme mRNA and activity in all tissues examined. Mice show spontaneous preterm labor in the absence of progesterone withdrawal, and the onset of labor is preceded by prematurely increased concentrations of prostaglandin E2 and F2alpha. The fetal genotype plays a role in birth timing 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine A140P is a naturally occuring mutation in patients with pulmonary hypertrophic osteoarthropathy. Homozygous individuals develop pulmonary hypertrophic osteoarthropathy secondary to chronically elevated prostaglandin E2 levels. Heterozygous relatives also show milder biochemical and clinical manifestations. Identification of an insertion-deletion mutation in 15-hydroxyprostaglandin dehydrogenase exon 3, this alters the open reading frame from codon 78, truncating the protein after ten altered amino acids, and of a homozygous 2-bp deletion within the duplicated dinucleotide CTCT at nucleotides 175 and 176. This alters the reading frame from residue 59 and truncates the HPGD protein at residue 65 after seven altered amino acids. Both of these predicted truncated proteins lack the entire PGE2-binding domain and cause primary hypertrophic osteoarthropathy 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine expression in nontumorigenic IEC-18 cells, with and without K-RasV12 and analysis of the ability of cells to form tumors in nu/nu mice. Transformed cells show increased 15-hydroxyprostaglandin dehydrogenase activity with decreased prostaglandin E2 and prostaglandin I2 levels, cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and proliferation rates. Xenografts of cells expressing both the enzyme and K-RasV12 exhibit delayed tumor formation with negligible cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and significantly decreased prostaglandin E2 levels. Tumors have decreased staining of the proliferative marker, Ki-67, and a significant increase in apoptosis in the central region of the tumor 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine in non-small-cell lung cancer cells, i.e. NSCLC cells, much lower expression of 15-hydroxyprostaglandin dehydrogenase in all histologic groups compared with healthy lung cell. Treatment with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib increases the expression of the enzyme in a subset of NSCLC lines 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine loss of 15-hydroxyprostaglandin expression in 65% of lung cancers. Enzyme acts as a tumor suppressor in lung cancer and is a direct downstream effector of hepatocyte nuclear factor 3beta 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine thiazolidinediones rosiglitazone and pioglitazone upregulate expression of 15-hydroxyprostaglandin dehydrogenase, involving peroxisome proliferator-activated receptor gamma. Upregulation results in reduced production of prostaglandin E2 and finally inhibition of lung cancer growth 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine up-regulation of cyclooxygenase-2 expression by pro-inflammatory cytokines is accompanied by down-regluation of 15-hydroxyprostaglandin dehydrogenase expression. Over-expression of cyclooxygenase-2 but not -1 also attenuates 15-hydroxyprostaglandin dehydrogenase expression. Similarly, overexpression of 15-hydroxyprostaglandin dehydrogenase inhibits interleukin 1beta-induced cyclooxygenase-2 expression and results in apoptosis. The levels of 15-hydroxyprostaglandin dehydrogenase expression in transfected cells correlate positively with those of mesenchymal markers, and negatively with those of epithelial markers 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) medicine PGDH expression suppresses K-RasV12-mediated tumorigenesis in intestinal epithelial cells 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine 3beta-hydroxysteroid dehydrogenase protein is present in the glandular epithelia and endothelia of blood vessels without difference in distribution pattern between normal and hyperplastic prostate 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine identification of 17 single nucleotide polymorphisms in isoforms Hsd3B1 and Hsd3B2. Analysis of polymorphism locations, alterations in nucleotide and amino acid sequences and frequencies of the polymorphisms. None of the polymorphisms alters cellular localization of the enzyme 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine identification of mutations L341P, W355stop, and R355stop, in HSD3B2 gene in neonates with classical 3beta-hydroxysteroid dehydrogenase type II deficiency and under-virilization 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine twenty-four hours after bilateral contusion of the medial prefrontal cortex, similar levels of 3beta-hydroxysteroid dehydrogenase mRNA expression are observed in males and pseudopregnant females in the non-injured group, with a significant decrease in the 3beta-hydroxysteroid dehydrogenase mRNA expression in the contusion site within the frontal cortex in both males and pseudopregnant females. In all other regions analyzed, 3beta-hydroxysteroid dehydrogenase mRNA expression is not affected by traumatic brain injury and there is no difference between males and pseudopregnant females 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine patient with inborn error of bile acid metabolism, that is, 3beta-hydroxy-DELTA5-C27-steroid dehydrogenase/isomerase deficienc, receives as treatment chenodeoxycholic acid and cholic acid, orally administered for 10 years. After the oral bile acid therapy, the biochemical liver function values and serum alanine aminotransferase and total bilirubin levels are maintained at normal levels, while the 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholenoic acid levels significantly decrease. The patient gave birth to a healthy boy and a girl during the 10-year follow-up period 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine in a female patient with pseudo-hermaphrodism caused by an androgen-producing adrenocortical tumor. The activities of 3beta-hydroxysteroid dehydrogenase 2 and CYP17 in the tumor tissue are higher than those in the normal tissue, whereas the activity of 17beta?hydroxysteroid dehydrogenase 3 is lower. The mRNA levels of 3beta-hydroxysteroid dehydrogenase 2 and CYP17 are higher and the levels of 17beta-hydroxysteroid dehydrogenase 3 and LH/hCG receptor are lower in the tumor tissue compared with those of the normal tissue 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine in aldosterone-producing adenoma, isoform HSD3B2 mRNA is significantly more abundant than HSD3B1 mRNA, but only HSD3B1 mRNA significantly correlates with CYP11B2 (aldosterone synthase) mRNA and plasma aldosterone concentration of the patients. A significant correlation is also detected between isoform HSD3B1 and CYP11B2. In KCNJ5 mutated aldosterone-producing adenoma, CYP11B2 mRNA and HSD3B1 mRNA are significantly higher than those of wild-type aldosterone-producing adenoma 1.1.1.145 3beta-hydroxy-DELTA5-steroid dehydrogenase medicine in aldosterone-producing adenoma, isoform HSD3B2 mRNA is significantly more abundant than HSD3B1 mRNA, but only HSD3B1 mRNA significantly correlates with CYP11B2 (aldosterone synthase) mRNA and plasma aldosterone concentration of the patients. Isoform HSD3B2 immunoreactivity is detected in the great majority of aldosterone-producing adenoma 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine exposure of fetus to high levels of synthetic glucocorticoid may have long-lasting effects on the hippocampal expression of hypothalamic-pituitary-adrenal-related genes into adulthood 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine high-fat diet-induced obesity is accompanied by increased visceral fat preadipocyte differentiation in wild-type but not 11beta-HSD1 -/- mice 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine methionine restriction disrupts the lipogenic/lipolytic balance, contributing importantly to adiposity resistance in Fischer 344 rats 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine treatment of rats with dehydroepiandrosterone induces a shift from isoform 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine activation of cortisol by 11beta-hydroxysteroid dehydrogenase in granulosa cells increases with follicle development but is significantly decreased in ovarion cysts 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine changes in ovarian cortisol metabolism are accompanied by corresponding changes in the levels of paracrine inhibitors of 11beta-hydroxysteroid dehydrogenase within growing ovarian follicles and cysts 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine differentiation of cells causes a strong increase in 11beta-hydroxysteroid dehydrogenase protein levels, occuring late in the differentiation protocol. Reduction of 11beta-hydroxysteroid dehydrogenase activity in 3T3-L1 fibroblasts, achieved by pharmacological inhibition or adenovirally mediated delivery of short hairpin RNA constructs, specifically blocks the ability of inactive glucocorticoids to drive 3T3-L1 differentiation. Even modest increases in exogenous 11beta-hydroxysteroid dehydrogenase expression in 3T3-L1 fibroblasts, to levels comparable with endogenous 1 11beta-hydroxysteroid dehydrogenase in differentiated 3T3-L1 adipocytes, are sufficient to block adipogenesis 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine in morbidly obese patients, 11beta-hydroxysteroid dehydrogenase 1 mRNA levlels are higher in subcutaneous adipose tissue than in visceral adipose tissue. Subcutaneous adipose tissue 11beta-hydroxysteroid dehydrogenase 1 levels increase parallel according to body mass index category. No correlation between subcutaneous adipose tissue or visceral adipose tissue with fasting glucose, total cholesterol, triglycerides, and high-density lipoprotein 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine inhibition of 11beta-hydroxysteroid dehydrogenase type 1 activity reduces the availability of cortisol to activate the glucocorticoid receptor, down regulates gluconeogenesis and thus reduces plasma glucose levels in cortisone-induced diabetic KK mice. In mice treated with 11beta-hydroxysteroid dehydrogenase type 1-antisense oligonucleotide, plasma blood glucose levels are significantly reduced by up to 54% upon induction of diabetes. Cortisol and other diabetes end products are also reduced, and hepatic 11beta-hydroxysteroid dehydrogenase type 1 mRNA is suppressed by up to 84% 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine significant decrease in 11beta-hydroxysteroid dehydrogenase reductase activity in mice with glycogen storage disease type 1b, whereas mice with glycogen storage disease type 1a show a marked increase in enzyme activity 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine significant decrease in 11beta-hydroxysteroid dehydrogenase reductase activity in patients with glycogen storage disease type 1b, whereas patients with glycogen storage disease type 1a show a marked increase in enzyme activity 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine significant induction of 11beta-hydroxysteroid dehydrogenase type 1 gene expression and activity in patients with alcoholic liver disease during long-term and short-term abstinence from alcohol 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine sucrose can promote increased 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase message in mesenteric fat while concomitantly decreasing 11beta-dehydroxysteroid dehydrogenase message and increasing hexose-6-phosphate dehydrogenase message in liver 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine 11beta-HSD1 inhibition may be a valid target for the treatment of diabetes 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine 11beta-HSD1 is a drug target for treatment of insulin resistance, diabetes and cardiovascular disease 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine inhibiting 11beta-HSD1 activity signifies a promising therapeutic strategy in the treatment of type 2 diabetes and related diseases 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine measures of 11beta-HSD1 enzyme activity can predict the response of bone formation markers to therapeutic glucocorticoids 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine at baseline, mRNA levels are similar in skeletal muscle of diabetic and control sugjects for 11beta-HSD1, 11beta-HSD2, and hexose-6-phosphate dehydrogenase. 11beta-HSD1 activity is reduced in diabetic subjects, while 11beta-HSD2 activity is increased. After application of dexamethasone, 11beta-HSD1 mRNA increases in both groups, whereas 11beta-HSD2 mRNA decreases. 11beta-HSD1 activity increases in diabetic subjects, but not in controls, whereas 11beta-HSD2 activity does not change in either group; mRNA levels are similar in diabetic and control subjects for 11beta-hydroxysteroid dehydrogenase 1 and 11beta-hydroxysteroid dehydrogenase 2. 11beta-Hydroxysteroid dehydrogenase 2-activity is higher in diabetic patients. After treatment with dexamethasone, 11beta-hydroxysteroid dehydrogenase 1-mRNA increases in both groups, whereas 11beta-hydroxysteroid dehydrogenase 2-mRNA decreases. 11beta-Hydroxysteroid dehydrogenase 1-activity increases in diabetic patients, but not in control, whereas 11beta-hydroxysteroid dehydrogenase 2-activity does not change in either group 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine curcumin is inhibitory to isoform 11beta-HSD1 in intact cells with IC50 value of 5.79 microM, competitive. Treatment with curcumin reduces serum glucose, cholesterol, triglyceride, low density lipoprotein levels in high-fat-diet-induced obese rats 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine the enzyme activity is inversely associated with urinary cortisol/cortisone levels and it is not associated with the subclinical hypercortisolism complications 1.1.1.146 11beta-hydroxysteroid dehydrogenase medicine in breast cancer tissue, cholesterol epoxide hydrolase ChEH metabolizes cholesterol-5,6-epoxide into cholestane-3beta,5alpha,6beta-triol, which is transformed into the oncometabolite 6-oxo-cholestan-3beta,5alpha-diol by 11beta-hydroxysteroid-dehydrogenase 11betaHSD2. ChEH inhibition and 11betaHSD2 silencing inhibit 6-oxo-cholestan-3beta,5alpha-diol production and tumor growth. Patient breast cancer samples show significantly increased 6-oxocholestan-3beta,5alpha-diol levels and greater ChEH and 11betaHSD2 protein expression compared with normal tissues, and 11betaHSD2 and ChEH overexpression correlate with a higher risk of patient death 1.1.1.149 20alpha-hydroxysteroid dehydrogenase medicine enzyme activity is 8-14fold higher in nontumorgenic strain MCF-10A than in tumorgenic strains MCF-7, MDA-MB-231, T-47D 1.1.1.149 20alpha-hydroxysteroid dehydrogenase medicine diesel exhaust components are inhibitory on 20alpha-hydroxysteroid dehydrogenase in liver and lung cytosol, with little inhibition in kidney cytosol 1.1.1.149 20alpha-hydroxysteroid dehydrogenase medicine targeted disruption of 20alpha-hydroxysteroid dehydrogenase gene results in complete loss of catalytic activity and lack of increase in serum concentrations of 20alpha-dihydroprogesterone during pseudopregnancy or pregnancy. The durations of the estrious cycle, pseudopregnancy, and pregnancy are significantly prolonged in the mutant mice, and the number of pups, espcially live pups, is markedly decreased 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming) medicine polymorphisms of sepiapterin reductase gene alter promoter activity and may influence risk of bipolar disorder 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming) medicine high sepiapterin reductase expression is significantly correlated to unfavorable neuroblastoma characteristics like high age at diagnosis, MYCN amplification, and high INSS stage. Sulfasalazine inhibits the growth of neuroblastoma cells in vitro, presumably due to the inhibition of sepiapterin reductase. The combination of sulfasalazine with alpha-difluoromethylornitine produces synergistic antiproliferative effects in vitro 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming) medicine siRNA-mediated knock-down of sepiapterin reductase expression significantly reduces endogenous ornithine decarboxylase enzyme activity in neuroblastoma cells. In a cohort of 88 human neuroblastoma tumors, high SPR mRNA expression correlates significantly with poor survival prognosis 1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming) medicine the enzyme can regulate chronic pain and is a target for the development of analgesics 1.1.1.178 3-hydroxy-2-methylbutyryl-CoA dehydrogenase medicine used for coupled enzyme assay to detect 3-oxothiolase deficiency in L-isoleucine degrading pathway 1.1.1.178 3-hydroxy-2-methylbutyryl-CoA dehydrogenase medicine important in brain development and aging, SCHAD deficiency is an inherited defect in mitochondrial fatty acid oxidation, reported cases of SCHAD deficiency are actually due to a deficiency of HAD, abnormal levels may contribute to the pathogenesis of some neural disorders, potential target for intervention in Alzheimer's disease, Parkinson's disease, and an X-linked mental retardation 1.1.1.178 3-hydroxy-2-methylbutyryl-CoA dehydrogenase medicine MHBD deficiency is a X-linked inborn error in the metabolism of isoleucine. Impairment of energy metabolism seems to play a role in the pathogenesis of MHBD deficiency. Males are more severely affected than females by MHBD deficiency. Male patients with MHBD deficiency before 10 months of age show neurodegeneration, while female carriers show a variety of symptoms (borderline learning difficulties to psychomotor and speech delay) 1.1.1.178 3-hydroxy-2-methylbutyryl-CoA dehydrogenase medicine mutation p.D86G c.257A>G in exon 3 was diagnosed in one child with a very severe neonatal presentation, absent neurological development and death from progressive hypertrophic cardiomyopathy at the age of 7 months. MHBD activity in fibroblasts was only partially reduced to approximately 30% of normal. Mutation p.Q165H c.495A>C in exon 5 was diagnosed in a boy who presented with pre- and postnatal failure to thrive but normal cognitive and motor development. Neurological examination in this boy and two affected relatives has been entirely normal up to the present age of 8 years. There is no measurable MHBD activity in fibroblasts, molecular studies identified hemizygosity for the mutation. There is no correlation between enzyme activity and clinical presentation. HSD10 is essential for structural and functional integrity of mitochondria independently of its enzymatic activity. Impairment of this function in neural cells causes apoptotic cell death whilst the enzymatic activity of HSD10 is not required for cell survival 1.1.1.178 3-hydroxy-2-methylbutyryl-CoA dehydrogenase medicine mutant loses most or all catalytic functions, and the males with this mutation have a severe clinical phenotype. The mutation eliminates several hydrogen bonds and reduces the van der Waals interaction between HSD10 subunits. The resulting disruption of protein structure impairs some if not all of the catalytic and non-enzymatic functions of HSD10. Eight patients with the R130C mutation show an average 2-methyl-3-hydroxybutyryl-CoA dehydrogenase activity of only 6% of the normal control level 1.1.1.181 cholest-5-ene-3beta,7alpha-diol 3beta-dehydrogenase medicine molecular analysis of 15 patients with neonatal cholestasis reveals 12 different mutations in HSD3B7 gene, 10 of them leading to complete inactivation of enzyme 1.1.1.184 carbonyl reductase (NADPH) medicine the single nucleotide polymorphisms in the human CBR1 gene generating the V88I and P131S mutations may prove to be clinically useful genetic biomarkers for guiding anthracycline therapy in cancer patients to minimize adverse effects 1.1.1.184 carbonyl reductase (NADPH) medicine antidepressant bupropion is reduced to erythrohydrobupropion and threohydrobupropion in liver. Menadione and 18beta-glycyrrhetinic acid are inhibitory 1.1.1.188 prostaglandin-F synthase medicine peri- and postimplantation conceptus. Prostaglandin H synthase and prostaglandin E synthase are down-regulated, and prostaglandin G synthase, prostaglandin F synthase and carbonyl reductase/prostaglandin 9-reductase are down-regulated in conceptuses during trophoblasic elongation. After initiation of implantation, expression of prostaglandin G synthase, prostaglandin F synthase and carbonyl reductase/prostaglandin 9-reductase in conceptuses increases and remains higher until days 24-25 of pregnancy 1.1.1.188 prostaglandin-F synthase medicine AKR1C3 likely plays important roles in the development of hormone-dependent, and possibly hormone-independent, breast cancer. It is highly expressed in normal breast and upregulated in breast cancer, where its expression is associated with a worse prognosis 1.1.1.188 prostaglandin-F synthase medicine lentiviral vector-mediated delivery of the prostaglandin F synthase (PGFS) gene resultes in long-term reduction of intraocular pressure and may eliminate off-target tissue effects and the need for daily topical PGF2alpha self-administration 1.1.1.188 prostaglandin-F synthase medicine estradiol causes a short-term increase in cyclooxygenase COX-2, which stimulates PGE2 and PGF2alpha secretion, and a subsequent decrease in COX-2 and an increase in cyclooxygenase COX-1 produce a high PGE2 : PGF2alpha ratio 1.1.1.188 prostaglandin-F synthase medicine mice infected with PGFS overexpressing parasites show an early parasitemia peak and higher heart muscle parasitic load 1.1.1.188 prostaglandin-F synthase medicine significantly higher expression of the prostaglandin-endoperoxide synthase PTGS 2 gene is detected in repeat-breeding cows with subclinical endometritis, whereas there is no significant difference in the expression of prostaglandin F2alpha synthase PTGFS and prostaglandin E2 microsomal synthase mPTGES 1 mRNAs between repeat-breeding cows with subclinical endometritis and those without it 1.1.1.189 prostaglandin-E2 9-reductase medicine peri- and postimplantation conceptus. Prostaglandin H synthase and prostaglandin E synthase are down-regulated, and prostaglandin G synthase, prostaglandin F synthase and carbonyl reductase/prostaglandin 9-reductase are down-regulated in conceptuses during trophoblasic elongation. After initiation of implantation, expression of prostaglandin G synthase, prostaglandin F synthase and carbonyl reductase/prostaglandin 9-reductase in conceptuses increases and remains higher until days 24-25 of pregnancy 1.1.1.205 IMP dehydrogenase medicine the enzyme is a major therapeutic target 1.1.1.205 IMP dehydrogenase medicine the enzyme is a target for immunosuppression therapy suing mycophenolic acid, prodrug is mycophenolate mofetil 1.1.1.205 IMP dehydrogenase medicine changes in expression of IMPDH1 and IMPDH2 in patient samples after initiation of an immunosuppressive regimen that includes calcineurin inhibitors, mycophenolate mofetil, and stroids 1.1.1.205 IMP dehydrogenase medicine in patients with kidney transplantation, type I IMPDH activity and gene expression increases during the first three months following transplantation and reaches its maximal level during acute rejection episodes, whereas type II mRNA is stable. Patients with a prolonged mycophenolate mofetil treatment exhibit an increase in the induction potency of both IMPDH activity and gene expression. Measurement of IMPDH mRNAs may provide reliable information to predict acute rejection 1.1.1.205 IMP dehydrogenase medicine in renal transplant patients, transplantation and initiation of immunosuppressive therapy is associated with increased isoform IMPDH1 and decreased IMPDH2 expression. In CD4+ cells, however, IMPDH2 expression increases. Two weeks posttransplant, mycophenolic acid-treated patients display elevated IMPDH1 and IMPDH2 expression in reticulocyte. Patients with acute rejection during follow-up demonstrate higher IMPDH2 expression in Cd4+ cells pretransplant than nonrejecting patients 1.1.1.205 IMP dehydrogenase medicine in stable kidney transplant recipients, inosine 5'-phosphate dehydrogenase activity is 17.5 versus 46.6 nmol XMP/h/microgramm protein in diabetic and nondiabetic patients, respectively. Activity in diabetic patients is significantly lower irrespective of concomitant therapy with cyclosporine or tacrolimus and independent of the bound or unbound mycophenolic acid 1.1.1.205 IMP dehydrogenase medicine study on inosine 5'-phosphate activity in thiopurine-treated patients with inflammatory bowel disease. Negative correlation between inosine 5'-phosphate dehydrogenase activity and dose-normalized 6-methylthioinosine concentrations, no evident correlation to 6-thioguanine nucleotide or the 6-methylthioinosine/6-thioguanine nucleotide ratio 1.1.1.205 IMP dehydrogenase medicine a poorer response to mycophenolic acid therapy in some individuals may be due to the presence of the rs11706052 polymorphism 1.1.1.205 IMP dehydrogenase medicine IMPDH activity in erythrocytes may be useful indicator of short-term immunosuppression and long-term exposure of the immunosuppressant mycophenolic acid 1.1.1.205 IMP dehydrogenase medicine inhibition of IMPDH may represent a novel strategy to reduce adipose tissue mass 1.1.1.205 IMP dehydrogenase medicine modified method for the measurement of IMPDH activity, that is less labor-intensive, more robust in general, and capable of yielding a better reproducibility, which can be used reliably in multicenter trials and in longitudinal studies to evaluate the additional value of any pharmacodynamic monitoring among a diversity of patients treated with mycophenolic acid 1.1.1.205 IMP dehydrogenase medicine study on a target range for inosine 5'-monophosphate dehydrogenase activity in maintenance therapy with tacrolimus, on patients with renal transplants and healthy volunteers. Inosine 5'-monophosphate dehydrogenase activity in cell lysates can be reliably determined indirectly by measuring xanthosine 5'-monophophate in cell lysates supplemented with IMP and beta-nicotine adenine dinucleotide using an HPLC method. Cell lysates show a 5-6 nmol /l IC50 mycophenolic acid concentration. Tacrolimus, cyclosporine and prednisolone do not affect IMPDH activity. The peak mycophenolic acid concentration is achieved at 1 h after dosing. IMPDH activity decreases to 75% and 67% at 1 and 2 h after dosing respectively 1.1.1.205 IMP dehydrogenase medicine MPDH inhibitors are used as immunosuppressive, antiviral, and anticancer agents 1.1.1.211 long-chain-3-hydroxyacyl-CoA dehydrogenase medicine inverse correlation between enzyme activity and gestational age during second and third trimester of pregnancy, involvement of enzyme defects in a subset of pregnancy complications 1.1.1.211 long-chain-3-hydroxyacyl-CoA dehydrogenase medicine treatment of patients with defects in enzymic activity, provision of odd-chain species of medium fatty acids decreases the build-up of long-chain fatty acid oxidation intermediates in an in vitro skin fibroblast model 1.1.1.211 long-chain-3-hydroxyacyl-CoA dehydrogenase medicine case study on a Korean male newborn who presented with severe lactic acidosis, seizures, and heart failure and an increase of 3-hydroxy species: 3-OH-palmitoylcarnitine, at 0.44 nmol/ml, 3-hydroxylinoleylcarnitine, at 0.31 nmol/ml, and 3-hydroxyoleylcarnitine, at 0.51 nmol/ml. The findings suggest either long-chain 3-hydroxyacyl-coA dehydrogenase deficiency or complete MTP deficiency. The patient was a compound heterozygote for c.358dupT and c.1364T>G mutations. Although the patient was treated by reduction of glucose administration and supplementation of a medium-chain triglyceride-based diet with L-carnitine, he died 2 months after birth due to advanced cardiac failure 1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific) medicine exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression. The resistance lowers the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigates the cytotoxicity of the aldehydes and cisplatin. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the aldo-keto reductases increases the sensitivity to ciplatin toxicity. Pretreatment of the resistant cells with proteasome inhibitor Z-Leu-Leu-Leu-al augments the cisplatin sensitization elicited by aldo-keto reductase inhibitors 1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific) medicine positive isoform AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. Isoform AKR1C3 immunoreactivity is absent in small cell carcinoma of the lung 1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific) medicine uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium 1.1.1.215 gluconate 2-dehydrogenase medicine ability of Campylobacter jejuni to use gluconate as an electron donor via GADH activity is an important metabolic characteristic that is required for full colonization of avian but not mammalian hosts 1.1.1.239 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) medicine distribution of human and rat AKR1C3 is comparable but not identical between the two species. These features warrant future studies of AKR1C3 in both hormone- and non-hormone-associated tissues and identification of the rodent homolog for establishing animal models 1.1.1.239 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) medicine enzyme is involved in activation of prodrug PR-104A designed to exploit tumor hypoxia. AKR1C3 protein is detected by Western blot in 7 of 23 cell lines and correlates with oxic PR-104A metabolism. AKR1C3 is unable to sensitize cells to 10 other bioreductive prodrugs and is associated with single-agent PR-104 activity across a panel of 9 human tumor xenograft models. Overexpression in two AKR1C3-negative tumor xenograft models strongly enhances PR-104 antitumor activity. Marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma 1.1.1.239 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) medicine establishment of MCF-7 cells that stably express AKR1C3 to model its over-expression in breast cancer. AKR1C3 expression increases steroid conversion by MCF-7 cells, leading to a pro-estrogenic state. Estrone is reduced fastest by MCF-7 cells expressing AKR1C3 when compared to other substrates at 0.1M. MCF-7 cells expressing AKR1C3 cells proliferate three times faster than parental cells in response to estrone and 17-estradiol. MCF-7 cells expressing AKR1C3 cells also reduce PGD2, limiting its dehydration to form PGJ2 products 1.1.1.239 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) medicine in patients with cryptorchid testis, AKR1C3 expression occurs in a Tanner stage dependent-fashion. Pre- and peri-pubertal changes appear to promote expression of the enzyme in Leydig cells. In contrast to the normal adult testis, the pediatric cryptorchid testis reveals AKR1C3 expression in Sertoli cells 1.1.1.239 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) medicine exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression. The resistance lowers the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigates the cytotoxicity of the aldehydes and cisplatin. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the aldo-keto reductases increases the sensitivity to ciplatin toxicity. Pretreatment of the resistant cells with proteasome inhibitor Z-Leu-Leu-Leu-al augments the cisplatin sensitization elicited by aldo-keto reductase inhibitors 1.1.1.239 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) medicine positive isoform AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. Isoform AKR1C3 immunoreactivity is absent in small cell carcinoma of the lung 1.1.1.239 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) medicine uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium 1.1.1.252 tetrahydroxynaphthalene reductase medicine development of a monoclonal antibody to be used in combination with a semiselective isolation procedure in order to track the opportunistic pathogen Scedosporium apiospermum in environmental samples containing mixed populations of human pathogenic fungi 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase medicine 50% inhibition of growth of parasite in cultured infected erythrocytes is 2-3 times lower with fetal bovine serum in the culture liquide than with human serum 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase medicine study on inhibitory effect of antimalarial drugs in clinical isolates of Plasmodium falciparum. No correlation between chloroquine or pyrimethamine and fosmidomycin. Fosmidomycin is moderately active against both chloroquine-susceptible and chloroquine-resistant isolates 1.1.1.270 3beta-hydroxysteroid 3-dehydrogenase medicine the selective inhibition of human 3beta-HSD1 in breast tumors represents a potential treatment for hormone-sensitive breast cancer 1.1.1.282 quinate/shikimate dehydrogenase [NAD(P)+] medicine development of novel antimicrobial agents 1.1.1.284 S-(hydroxymethyl)glutathione dehydrogenase medicine under asthmatic conditions, including lung epithelial cell damage, ADH3, GSH and NAD+ are likely to be present in the airway lining fluid, where inhalation of formaldehyde can then lead to rapid depletion of S-nitrosoglutathione, resulting in bronchoconstriction and enhanced airway hyperresponsivity 1.1.1.300 NADP-retinol dehydrogenase medicine enzyme is associated with retinal dystrophy and encodes an enzyme with unique, nonredundant role in the photoreceptor cells 1.1.1.300 NADP-retinol dehydrogenase medicine transfection with retinol dehydrogenase 12 protects cells against nonanal-induced toxicity but is ineffective against 4-hydroxynonenal. 4-Hydroxynonenal strongly inhibits the activities of lecithin:retinol acyl transferase and aldehyde dehydrogenase, resulting in decreased levels of retinyl esters and retinoic acid and accumulation of unesterified retinol 1.1.1.305 UDP-glucuronic acid dehydrogenase (UDP-4-keto-hexauronic acid decarboxylating) medicine modification of the lipid A moiety of lipopolysaccharide by the addition of the sugar 4-amino-4-deoxy-L-arabinose is a strategy adopted by pathogenic Gram-negative bacteria to evade cationic antimicrobial peptides produced by the innate immune system. L-Ara4N biosynthesis is therefore a potential anti-infective target 1.1.1.315 11-cis-retinol dehydrogenase medicine evaluation of patients with hereditary retinal diseases featuring subretinal spots, i.e. retinitis punctata albescens and fundus albipunctatus, and patients with typical dominant or recessive retinitis pigmentosa for mutations in RDH5. Mutations are found only in two unrelated patients, both with fundus albipunctatus. Mutations segregate with disease in the respective families. Recombinant mutant 11-cis retinol dehydrogenases have reduced activity compared with recombinant enzyme with wild-type sequence 1.1.1.315 11-cis-retinol dehydrogenase medicine examination of two unrelated families, each family with two affected members with typical fundus albipunctatus. RDH5 mutations were found in the affected siblings in both families. The proband in one has a homozygotic Gly238Trp missense mutation (GGG to TGG) involving exon 4 and in the other carries compound heterozygotic changes Arg280His (CGC to CAC) and Ala294Pro (GCC to CCC) in exon 5. The disease phenotype is only manifested in family members with two abnormal RDH5 alleles consistent with autosomal recessive inheritance in both pedigrees 1.1.1.315 11-cis-retinol dehydrogenase medicine mutations in gene RDH5 are associated with fundus albipunctatus, an autosomal recessive eye disease. Characterization of 11 mutants shows that all RDH5 mutants show decreased protein stability and subcellular mislocalization and, in most cases, loss of enzymatic activity in vitro and in vivo. The mutated enzymes, in a transdominant-negative manner, influence the in vivo enzymatic properties of functional variants of the enzyme. Under certain conditions, nonfunctional alleles act in a dominant-negative way on functional but relatively unstable mutated alleles. In heterozygous individuals carrying one wild-type allele, the disease is recessive, probably due to the stability of the wild-type enzyme 1.1.1.341 CDP-abequose synthase medicine insertion of the gene rfbJ encoding abequose synthase into a suicide vector and integration into the rfb clusters of wild-type Salmonella typhi Vi-positive strain ISP 1820, Salmonella typhi Vi-negative strain H400, and a double aro mutant of Salmonella typhi ISP 1820, strain CVD 906. Strains carrying the vector express the O4 antigen in place of the O9 antigen in the lipopolysaccharide molecule. Results support the hypothesis that the chemical composition of the Salmonella 0-antigen influences the interaction of individual serotypes with complement 1.1.2.3 L-lactate dehydrogenase (cytochrome) medicine both LldD and LldA are important for growth of Pseudomonas aeruginosa PAO1 in synthetic cystic fibrosis sputum medium 1.1.3.2 L-lactate oxidase medicine L-lactate oxidase based lactate sensors are widely used for clinical diagnostics, sports medicine, and food quality control. Rational engineering of Aerococcus viridans L-lactate oxidase for the mediator modification to achieve quasi-direct electron transfer type lactate sensor 1.1.3.4 glucose oxidase medicine analysis of the chronic inflammatory skin disorder Atopic eczema (AE) 1.1.3.6 cholesterol oxidase medicine determination of cholesterol in various sample types, determination of cholesterol in gall stones, determination of cholesterol on the cell membrane of erythrocytes, other cells and cellular compartments 1.1.3.8 L-gulonolactone oxidase medicine a gene therapy approach can be successfully employed in the treatment and further study of vitamin C deficiency in scurvy-prone mammals 1.1.3.15 (S)-2-hydroxy-acid oxidase medicine enzyme is used in clinical chemistry for the determination of (S)-lactate in blood in some pathological diseases such as diabetes, heart diseases and shock syndrome 1.1.3.15 (S)-2-hydroxy-acid oxidase medicine decrease of enzyme activity upon oxidative stress induced by glutathione depletion or postischemic perfusion, down-regulation of enzyme as mechanism to prevent excessive H2O2 formation in liver peroxisome 1.1.3.15 (S)-2-hydroxy-acid oxidase medicine the ability of such siRNAs to reduce urinary oxalate in the mouse model suggests that this approach is promising for the treatment of primary hyperoxalurias, PH, particularly PH type I, in humans, genes HYPDH and GO appear to be the best targets for reducing the production of glyoxylate and oxalate in PH patients 1.1.3.15 (S)-2-hydroxy-acid oxidase medicine application of oan in vivo CRISPR/Cas9-mediated substrate reduction therapy to treat primary hyperoxaluria type I that results in excessive hepatic oxalate production causing end-stage renal disease. A single systemic administration of an AAV8-CRISPR/Cas9 vector targeting glycolate oxidase, prevents oxalate overproduction and kidney damage, with no signs of toxicity in Agxt1-/- mice 1.1.3.21 glycerol-3-phosphate oxidase medicine isolation of mutants with decreased or increased production of H2O2 from children and teens with bronchitis and pneumonia diagnoses. Mutant D55H displays 250% increase in H2O2 production and shows increased cytotoxicity to respiratory epithelium cells, mutant H51L displays 50% reduction in H2O2 production and shows decreased cytotoxicity to respiratory epithelium cells 1.1.3.41 alditol oxidase medicine - 1.1.3.41 alditol oxidase medicine monitoring xylitol using immobilized xylitol oxidase 1.1.3.41 alditol oxidase medicine quantitative analysis of xylitol 1.1.5.2 glucose 1-dehydrogenase (PQQ, quinone) medicine insertion of a calmodulin domain into enzyme results in a selective Ca2+ biosensor that could be used to rapidly measure Ca2+ concentrations in human biological fluids 1.1.5.9 glucose 1-dehydrogenase (FAD, quinone) medicine use of the enzyme as an indicator of cellular immune response activation 1.1.5.13 (S)-2-hydroxyglutarate dehydrogenase medicine lower enzyme expression is associated with tumor progression and/or worsened prognosis in patients with renal cell carcinoma 1.1.98.2 glucose-6-phosphate dehydrogenase (coenzyme-F420) medicine PA-824 is a compound for the treatment of tuberculosis (undergoing human trials). PA-824 is a prodrug of the nitroimidazole class, requiring bioreductive activation of an aromatic nitro group to exert an antitubercular effect. Resistance to PA-824 (a nitroimidazo-oxazine) and CGI-17341 (a nitroimidazo-oxazole) is most commonly mediated by loss of a specific glucose-6-phosphate dehydrogenase or its deazaflavin cofactor F420, which together provide electrons for the reductive activation of this class of molecules. Although glucose-6-phosphate dehydrogenase and F420 are necessary for sensitivity to these compounds, they are not sufficient and require additional accessory proteins that directly interact with the nitroimidazole. The sensitivity of Mtb to PA-824 and related compounds is mediated by a protein that is highly specific for subtle structural variations in these bicyclic nitroimidazoles 1.1.98.6 ribonucleoside-triphosphate reductase (formate) medicine ribonucleotide reductase class III is a virulence determinant in the pathogenesis of staphylococcal arthritis. Mice inoculated with the wild-type strain display significantly more severe arthritis, with significantly more synovitis and destruction of the bone and cartilage versus mice inoculated with a NrdDG mutant strain. The persistence of bacteria in the kidneys is significantly more pronounced in the group inoculated with the wild-type strain 1.1.99.1 choline dehydrogenase medicine population-based study, relation of plasma choline and betaine to smoking, physical activity, BMI, percent body fat, waist circumference, blood pressure, serum lipids and glucose 1.1.99.2 L-2-hydroxyglutarate dehydrogenase medicine L-2-hydroxyglutaric aciduria is a neurometabolic disorder that produces a variety of clinical neurological deficits, mutations within the gene L2HGDH encoding L-2-hydroxyglutaric acid dehydrogenase causes the disease, the canine model shares many of the clinical features of the disease in humans and represents a valuable resource as a spontaneous model of L-2-hydroxyglutaric aciduria 1.1.99.2 L-2-hydroxyglutarate dehydrogenase medicine L-2-hydroxyglutaric aciduria is a rare autosomal recessive neurometabolic organic aciduria, case report, mutation analysis and measurement of L-2-hydroxyglutaric acid in the amniotic fluid is used for prenatal diagnosis of the disease 1.1.99.2 L-2-hydroxyglutarate dehydrogenase medicine an enzyme assay for the determination of L-2-hydroxyglutarate dehydrogenase activity in cells derived from L-2-hydroxyglutaric aciduria patients is developed and implemented 1.1.99.18 cellobiose dehydrogenase (acceptor) medicine application in biomedicine as an antimicrobial and antibiofilm agent 1.1.99.18 cellobiose dehydrogenase (acceptor) medicine biomedical applications 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine glyceryl trinitrate is used in the treatment of angina pectoris and cardiac failure, but the rapid onset of glyceryl trinitrate tolerance limits its clinical utility.The majority of the vascular ALDH2 is present in the cytoplasm, suggesting that mitochondrial biotransformation of glyceryl trinitrate by ALDH2 plays a minor role in the overall vascular biotransformation 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine the ALDH2 genotype is associated with essential hypertension 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine ALDH activity is observed in esophageal cancer tissues 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine ALDH activties are significantly higher in liver cancer cells than in normal tissue and might, therefore, be a factor of metabolic changes in low-maturity cancer cells 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine breast cancers with ALDH1+ cancer stem cells possess biologically aggressive phenotypes with a tendency leading to poor prognosis 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine findings are useful for basic studies about normal erythropoietic differentiation as well as for enabling the employment of ALDH as a red cell marker in polychromatic flow cytometry characterization of bone marrow from patients with aplastic anemia and myelodysplasia 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine in human capacitance vessels ALDH2 is s a key enzyme for the biotransformation of the frequently used antianginal drug nitroglycerin 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine serum levels of aldehyde dehydrogenase are not significantly higher in patients with gastric cancer in comparison with the healthy group 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine white blood cell ALDH activity is a reliable marker for organic nitrate tachyphylaxis and may be a useful marker for clinical tolerance as well 1.2.1.3 aldehyde dehydrogenase (NAD+) medicine ALDH isoenzymes play a major role in the biology and drug resistance of various malignant cells 1.2.1.4 aldehyde dehydrogenase (NADP+) medicine ALDH3A1 contributes to the detoxification of various aldehydes produced in response to oxidative stress 1.2.1.5 aldehyde dehydrogenase [NAD(P)+] medicine 19 ALDH genes are identified in the human genome and mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjögren-Larsson syndrome, type II hyperprolinemia, gamma-hydroxybutyric aciduria and pyridoxine-dependent seizures. ALDH enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer. ALDH enzymes display multiple catalytic and non-catalytic functions including ester hydrolysis, antioxidant properties, xenobiotic bioactivation and UV light absorption 1.2.1.5 aldehyde dehydrogenase [NAD(P)+] medicine high ALDH1 activity and ALDH1A1 overexpression are associated with poor cancer prognosis 1.2.1.8 betaine-aldehyde dehydrogenase medicine betaine aldehyde dehydrogenase is a potential target for antimicrobial agents against Pseudomonas aeruginosa 1.2.1.8 betaine-aldehyde dehydrogenase medicine Pseudomonas aeruginosa is an important pathogen, glycine betaine could play an important physiological role under the conditions present in the infection sites 1.2.1.8 betaine-aldehyde dehydrogenase medicine PaBADH could be an antimicrobial target 1.2.1.8 betaine-aldehyde dehydrogenase medicine the enzyme could be a target for antibiotic design 1.2.1.11 aspartate-semialdehyde dehydrogenase medicine enzyme is a validated drug target 1.2.1.11 aspartate-semialdehyde dehydrogenase medicine enzyme is potential target for antimicrobial drugs 1.2.1.11 aspartate-semialdehyde dehydrogenase medicine target for antibiotic development 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine crystallography may provide structural detail for the development of lead compounds and drug design of novel antimalarials 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine functions are of chemotherapeutic interest, structure is a necessity for structure-based drug design 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine pathogenesis of Porphyromonas gingivalis involves interaction with oral mucosal epithelial cells, mediated by binding glyceraldehyde-3-phosphate dehydrogenase 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine potential antimalarial target 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine target for the design of antitrypanosomatid and anti-apoptosis drugs 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine the pathogenic fungus causes paracoccidioidomycosis, GAPDH is reported as an adhesin, which can be related to fungus adhesion and invasion 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine the Plr-SDH-GAPDH complex participates in invasive streptococcal infections 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine action as a selective insulin receptor modulator 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine G3PDH is a potential target for antimalarial drug development 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine among 256 ovarian and fallopian tube cancer specimens, GAPDH is regulated, with almost 50% of specimens having no GAPDH staining.Low GAPDH staining is associated with a low macrophage colony stimulating factor CSF-1 score 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine glyceraldehyde 3-phosphate dehydrogenase from malignant sources shows altered properties compared with enzyme from healthy subjects 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine glyceraldehyde 3-phosphate dehydrogenase may be involved in the postranscriptional regulation of hepatitis B virus. Recombinant glyceraldehyde 3-phosphate dehydrogenase binds to hepatitis B virus regulatory element RNA in vitro and inhibits hepatitis B virus regulatory element function. Overexpression of glyceraldehyde 3-phosphate dehydrogenase depresses the expression of hepatitis B virus antigen 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine in diabetic rats, modification of GAPDH by S-(2-succinyl)cysteine is increased in muscle, and the extent of succination correlates strongly with the decrease in specific activity of the enzyme 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine in experimental autoimmune encephalomyelitis, the proportion of S-nitrosylated neurofilament proteins, NMDA receptors, alpha/beta-tubulin, beta-actin, and GAPDH is increased. Neuronal specific enolase is the major S-nitrosylated protein in acute experimental autoimmune encephalomyelitis 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine non-native forms of GAPDH may be involved in the formation of amyloid structures during Alzheimer's disease, binding to soluble amyloid-beta peptide 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine the Porphyromonas gingivalis client proteins tonB-dependent receptor protein RagA4, 4-hydroxybutyryl-coenzyme A dehydratase AbfD, GAPDH, NAD-dependent glutamate dehydrogenase GDH, and malate dehydrogenase MDH function as regulators in Porphyromonas gingivalis biofilm formation with oral streptococci 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) medicine GAPDHS, which is regulated by SOX10, controls glycolysis and contributes to uveal melanoma tumorigenesis, is a therapeutic target in cancer therapy 1.2.1.13 glyceraldehyde-3-phosphate dehydrogenase (NADP+) (phosphorylating) medicine Onchocerca volvulus antigens possibly involved in protection against human onchocerciasis, GAPDH as a therapeutic target in helminth infections 1.2.1.13 glyceraldehyde-3-phosphate dehydrogenase (NADP+) (phosphorylating) medicine results suggest that GAPDH may have a common role in modulating the pathophysiology of polyQ diseases like the Huntington desease 1.2.1.13 glyceraldehyde-3-phosphate dehydrogenase (NADP+) (phosphorylating) medicine the results suggest that GAPDH is an active regulator in the phosphoinositide-mediated signaling pathway and a potential new target for insulin resistance treatment, diabetes, obesity and aging research 1.2.1.24 succinate-semialdehyde dehydrogenase (NAD+) medicine SSADH (Aldh5a1) deficiency is a rare autosomal recessive disease. Hippocampal and cortical dysfunction in Aldh5a1-/- brain, but no evidence that accumulating key metabolites of SSADH deficiency directly induce impairment of energy metabolism 1.2.1.24 succinate-semialdehyde dehydrogenase (NAD+) medicine succinic semialdehyde dehydrogenase deficient patients show widespread reduction in benzodiazepine receptor binding on [(11)C]-flumazenil-positron emission tomography 1.2.1.24 succinate-semialdehyde dehydrogenase (NAD+) medicine GABA oxidation and SSADH activity might be additional therapeutic targets in gliomas/glioblastomas 1.2.1.31 L-aminoadipate-semialdehyde dehydrogenase medicine alpha-AASA dehydrogenase deficiency results in pyridoxine dependent epilepsy. Patients show pathogenic mutations in the ALDH7A1 gene. Increase of alpha-AASA in urine of patients with alpha-AASA dehydrogenase deficiency makes this biomarker preferable towards the measurement of pipecolic acid, which shows non-specificity 1.2.1.36 retinal dehydrogenase medicine retinoic acid down-regulates aldehyde dehydrogenase and increases cytotoxicity of 4-hydroperoxycyclophosphamide and acetaldehyde in lung cancer cell lines 1.2.1.36 retinal dehydrogenase medicine activity of any one isoform is not rate limiting in the visual response 1.2.1.36 retinal dehydrogenase medicine RALDH1 is a negative regulator of allergic inflammation 1.2.1.36 retinal dehydrogenase medicine low retinal dehydrogenase 5 expression is associated with metastasis and poor patient prognosis 1.2.1.41 glutamate-5-semialdehyde dehydrogenase medicine in humans a natural S352L mutation gives rise to type II hyperprolinemia, mental retardation 1.2.1.48 long-chain-aldehyde dehydrogenase medicine diagnosis and therapeutic approaches of Sjögren-Larsson syndrome 1.2.1.48 long-chain-aldehyde dehydrogenase medicine FALDH activity is induced 1.4fold after a 3-day treatment with 0.8 mM bezafibrate in fibroblasts of control subjects. In fibroblasts of two Sjögren-Larsson patients homozygous for the p.R228C substitution, FALDH activity could by induced to 37% of control values by bezafibrate treatment. mRNA analysis in fibroblasts of these patients also reveals a mean 1.8fold induction of FALDH mRNA after bezafibrate treatment. No induction is observed in fibroblasts of patients with mutations that cause instability of FALDH mRNA or that result in a protein without any residual activity 1.2.1.48 long-chain-aldehyde dehydrogenase medicine direct link between FALDH inactivation and disease pathology of Sjögren-Larsson syndrome caused by accumulation of alcohols 1.2.1.79 succinate-semialdehyde dehydrogenase (NADP+) medicine analysis of Escherichia coli SSADH structure with respect to human disease-linked mutations 1.2.1.88 L-glutamate gamma-semialdehyde dehydrogenase medicine investigation of regulation of antibiotic production, i.e. undecylprodigiosin and related compounds, in secondary metabolism from proline as amino acid precursor 1.2.1.104 pyruvate dehydrogenase system medicine enzyme/pyruvate dehydrogenase kinase dependent pathway is repressed in 73% of non-small cell lung carcinomas, which may be a key reason for hypoxia-inducible factor 1alpha stabilization and aerobic glycolysis. About half of enzyme-deficient carcinomas are not able to switch on the hypoxia-inducible factor 1alpha pathway, patients with these tumours have an excellent postoperative outcome. In contrast to cancer cells, fibroblasts in the tumour-supporting stroma exhibit an intense enzyme but reduced pyruvate dehydrogenase kinase 1 expression favoring maximum enzyme activity 1.2.1.104 pyruvate dehydrogenase system medicine in a patient with primary lactic acidaemia, about 30% residual pyruvate dehydrogenase activity is observed, while the Km value is similiar to control. The enzyme deficiency is likely to be quantitative rather than qualitative. The patient developed severe metabolic acidosis at 8 months, accompanied by elevation of serum lactate and pyruvate. The lactate and pyruvate concentrations are also increased in cerevbrospinal fluid 1.2.1.104 pyruvate dehydrogenase system medicine the acute promyelocytic leukemia is greatly alleviated in the PDT-PAO-F16 treated group in an acute promyelocytic leukemia mice model 1.2.1.104 pyruvate dehydrogenase system medicine high salt intake downregulates sirtuin SIRT3 level in brown adipose tissue, accompanied by decreased oxygen consumption rate, and causes a severe loss of brown adipose tissue characteristics. SIRT3 interacts with pyruvate dehydrogenase E1alpha (PDHA1) and deacetylates residue Lys83 both in vitro and in vivo under high salt intake. In parallel, high salt intake suppresses salt-induced kinase (Sik) 2 phosphorylation. Silencing Sik2 further diminishes SIRT3 activity and enhances acetylation of PDHA1 K83. Reconstruction of SIRT3 restores PDH activity and thermogenic markers expression in differentiated brown adipocytes from SIRT3 knockout mice 1.2.1.104 pyruvate dehydrogenase system medicine nitric oxide produced by murine macrophages is responsible for TCA cycle alterations and citrate accumulation associated with polarization. Inflammatory macrophages reroute pyruvate away from pyruvate dehydrogenase in an NO-dependent and hypoxia-inducible factor Hif1alpha-independent manner, thereby promoting glutamine-based anaplerosis 1.2.1.105 2-oxoglutarate dehydrogenase system medicine altered in the post-mortem substantia nigra samples from patients suffering from Parkinson's disease, decreased activity in the brain of Alzheimer's disease patients, involving regions affected by the disease as well as regions that remain normal, reduced activity or increased vulnerability to oxidative stress in fibroblasts from patients with presenlilin-1 mutation 1.2.1.105 2-oxoglutarate dehydrogenase system medicine hypochlorous acid and chloramines have the potential to inactivate KGDHC, a major target in neurodegeneration 1.2.1.105 2-oxoglutarate dehydrogenase system medicine hypochlorous acid and chloramines have the potential to inactivate KGDHC, a major target in neurodegeneration, without significant loss of cellular viability 1.2.1.105 2-oxoglutarate dehydrogenase system medicine key regulatory branch points of mitochondrial metabolism are targets of a cellular derivative of phytanic acid, decreased activity of the complexes may contribute to neurological symptoms upon accumulation of phytanic acid in Refsum disease 1.2.1.105 2-oxoglutarate dehydrogenase system medicine KGDHC is diminished in brains from patients with Alzheimers's disease, Parkinson's disease, Huntington's disease, Wernicke-Korskoff disease, and progressive supranuclear palsy, not diminished in brains of patients that died with schizophrenia, reduced KDGDHC may be a better indicator of the primary reactive oxygen species action than commonly used measures of oxidative stress 1.2.1.105 2-oxoglutarate dehydrogenase system medicine loss of KGDHC activity resulting from the lack of thiamine diphosphate coenzyme may lead to oxidative stress and to neuronal death both directly and by predisposing to other insults 1.2.1.105 2-oxoglutarate dehydrogenase system medicine plays a role in neurodegenerative diseases 1.2.1.105 2-oxoglutarate dehydrogenase system medicine potential of succinyl phosphonate esters for modeling the biochemical and pathophysiological consequences of reduced KGDHC activity in brain diseases 1.2.1.105 2-oxoglutarate dehydrogenase system medicine succinyl phosphonate and its esters may be useful in studying the effects of reduced KGDHC activity on neuronal and brain function 1.2.1.105 2-oxoglutarate dehydrogenase system medicine susceptibility of KGDHC to inactivation in kidney cells exposed to cisplatin metabolites my be due to the proximity of mitochondrial aspartate aminotransferase to KGDHC in mitochondria, mitochondrial aspartate aminotransferase may catalyze a beta-lyase reaction with the cisplatin-cysteine S-conjugate, converting cisplatin to a toxicant 1.2.3.1 aldehyde oxidase medicine surgical stress model of oxidative stress in retinoid metabolism, prevention of alterations in enzyme activity and alkaline phosphatase activity by inhibition of superoxide generation using allopurinol 1.2.3.1 aldehyde oxidase medicine adiponectin and fenobibric acid reduce enzyme isoform AOX1 by activating peroxisome proliferator-activated receptor alpha whereas fatty liver disease is associated with elevated hepatic AOX1 level 1.2.3.1 aldehyde oxidase medicine measurements of NMN and its pyridones usually excreted in the urine can be used to predict the in vivo activity of enzyme 1.2.3.1 aldehyde oxidase medicine aldehyde oxidase activity in rats estimated on the basis of benzaldehyde, N1-methylnicotinamide and methotrexate oxidase activities rapidly increases from birth, reaching a plateau within 4 weeks, and is regulated by expression of the protein. Aldehyde oxidase plays an important role in metabolizing many drugs that may be administered to pediatric patients. Developmental changes are important for the clinical application in infants of methotrexate and other drugs that are detoxified by aldehyde oxidase 1.2.3.1 aldehyde oxidase medicine aldehyde oxidase can be an important basal source of superoxide that will be enhanced in disease settings where cellular aldehyde levels are increased 1.2.3.1 aldehyde oxidase medicine aldehyde oxidase plays an important role in metabolizing many drugs, so aldehyde oxidase activity in individual patients may be a useful parameter for dose adjustment to avoid severe toxicity. Aldehyde oxidase activity is immature in children below 1 year of age, dose adjustment based on individual aldehyde oxidase activity shall be made for such patients 1.2.3.1 aldehyde oxidase medicine aldehyde oxidases represent an important drug-metabolizing system in the cytosol of the hepatic cell. AOX1 is potentially useful in the bioactivation of pro-drugs in human liver and lung, given that the two tissues are the only ones reported to express significant amounts of this enzymatic activity. Variability in the levels of liver aldehyde oxidase in the human population 1.2.3.1 aldehyde oxidase medicine AOX1 may affect plasma HDL levels by altering ATP-binding cassette transporter A1 activity 1.2.3.1 aldehyde oxidase medicine significant correlations between reduced AOX1 expression and tumor stage, or metastatic or regional lymph node states. Reduced expression of AOX1 in malignant transformed hepatocytes supports the differentiation dependent upregulation of AOX1 1.2.3.1 aldehyde oxidase medicine combined computational and experimental investigation of drug-like molecules that are potential aldehyde oxidase substrates and identification of multiple sites of metabolism mediated by AOX 1.2.3.1 aldehyde oxidase medicine 3-substituted quinoline triazolopyridine compounds used as c-Met kinase inhibitors are subject to aldehyde oxidase-mediated metabolism. Several compouinds are unstable in monkey liver cytosolic incubations. Small electron-donating groups at the 3-quinoline moiety make the analogs more susceptible to metabolism, whereas large 3-substituents may reverse the trend 1.2.3.3 pyruvate oxidase medicine Lactobacillus delbrueckii commercia l yogurt strains STYM1 and GVKM1 inhibit Pseudomonas gingivalis growth in vitro, while raw milk isolates SYB7 and SYB13 have little impaxct. Purified, catalytically active, recombinant pyruvate oxidase is sufficient to inhibit P. gingivalis growth in vitro without the addition of cofactors 1.2.3.4 oxalate oxidase medicine immobilized oxalate oxidase to determine oxalate concentration in urine for diagnosis of various forms of hyperoxaluria 1.2.3.4 oxalate oxidase medicine colorimetric or UV-determination of oxalic acid in biological fluids and beverages 1.2.3.4 oxalate oxidase medicine oxalate oxidase is immobilized onto arylamine glass beads affixed on the surface of a plastic strip and employed for oxalate determination in urine and serum samples 1.2.3.4 oxalate oxidase medicine delivery strategy whereby therapeutic enzymes are encapsulated within a thin zwitterionic polymer shell to form enzyme nanocapsules. The strategy is applicated by the encapsulation of oxalate oxidase OxO for the treatment of hyperoxaluria, as-synthesized OxO nanocapsules have a prolonged blood circulation half-life and elicit reduced immunogenicity 1.2.4.1 pyruvate dehydrogenase (acetyl-transferring) medicine both subunits PDHA and PDHB are surface-exposed immunogenic proteins of Mycoplasma gallisepticum. The mouse anti-PDHA and anti-PDHB sera kill 48.0% and 75.1% of mycoplasmas, respectively. A combination of PDHA and PDHB antisera has a mean bactericidal rate of 65.2%. Both PDHA and PDHB adhere to DF-1 chicken embryo fibroblast cells and adherence is significantly inhibited by antisera against PDHA and PDHB. Both PDHA and PDHB are plasminogen-binding proteins 1.2.4.1 pyruvate dehydrogenase (acetyl-transferring) medicine high salt intake downregulates sirtuin SIRT3 level in brown adipose tissue, accompanied by decreased oxygen consumption rate, and causes a severe loss of brown adipose tissue characteristics. SIRT3 interacts with pyruvate dehydrogenase E1alpha (PDHA1) and deacetylates residue Lys83 both in vitro and in vivo under high salt intake. In parallel, high salt intake suppresses salt-induced kinase (Sik) 2 phosphorylation. Silencing Sik2 further diminishes SIRT3 activity and enhances acetylation of PDHA1 K83. Reconstruction of SIRT3 restores PDH activity and thermogenic markers expression in differentiated brown adipocytes from SIRT3 knockout mice 1.2.4.1 pyruvate dehydrogenase (acetyl-transferring) medicine nitric oxide produced by murine macrophages is responsible for TCA cycle alterations and citrate accumulation associated with polarization. Inflammatory macrophages reroute pyruvate away from pyruvate dehydrogenase in an NO-dependent and hypoxia-inducible factor Hif1alpha-independent manner, thereby promoting glutamine-based anaplerosis 1.2.4.1 pyruvate dehydrogenase (acetyl-transferring) medicine recombinant subunits PdhA and PdhB show binding activity with chicken plasminogen and human fibronectin. Rabbit anti-PdhA and anti-PdhB sera have distinct mycoplasmacidal efficacy in the presence of guinea pig complement, and the adherence of Mycoplasma synoviae to DF-1 cells pretreated with plasminogen is effectively inhibited by treatment with anti-rPdhA or anti-PdhB sera 1.2.4.4 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) medicine activation of the BCKDH complex appears responsible for the increase in branched-chain amino acid catabolism caused by exercise and liver cirrhosis, branched-chain amino acid administration improves protein turnover in humans with liver cirrhosis, suggesting that branched-chain amino acid supplements are appropriate for patients with liver cirrhosis, branched-chain amino acid administration in patients with acute liver failure, especially those with high serum branched-chain amino acid concentrations, may not be appropriate because of the likelihood of branched-chain amino acid overload 1.2.4.4 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) medicine activation of the BCKDH complex appears responsible for the increase in branched-chain amino acid catabolism caused by exercise and liver cirrhosis, branched-chain amino acid administration improves protein turnover in rats with liver cirrhosis, suggesting that branched-chain amino acid supplements are appropriate for patients with liver cirrhosis 1.2.4.4 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) medicine variations in the gene of branched-chain alpha-keto acid dehydrogenase are associated with the occurrence of premature ovarian failure 1.2.4.4 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) medicine in male rats administered with 4 doses of 5-FU, 150 mg/kg b.wt. each, 5-FU treatment causes an increase in branched-chain alpha-keto acid dehydrogenase complex BCKDH activity that results mainly from increased dephosphorylation of the complex and is associated with an increase of phosphatase PPM1K mRNA level and reduction of BDK and dehydrogenase E1 mRNA levels 1.3.1.1 dihydropyrimidine dehydrogenase (NAD+) medicine target for inhibitor design to enhance the cytotoxical effect of 5-fluorouracil in tumor cells by inhibiting the DPD activity with 5-fluorouracil as substrate 1.3.1.1 dihydropyrimidine dehydrogenase (NAD+) medicine dihydropyrimidine dehydrogenase deficiency is known to be a major cause of severe 5-fluorouracil-related toxicity 1.3.1.1 dihydropyrimidine dehydrogenase (NAD+) medicine DPD is a molecular marker for identifying tumor cells sensitivity in breast cancer patients receiving 5-fluorouracil-based chemotherapy 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) medicine target for inhibitor design to enhance the cytotoxical effect of 5-fluorouracil in tumor cells by inhibiting the DPD activity with 5-fluorouracil as substrate 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) medicine rate limiting enzyme for detoxification of exogenous fluoropyrimidines, antitumor drug design 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) medicine rate limiting enzyme in catabolic degradation of pyrimidine derivatives, selective inhibition is strategy for design of antitumor, antimicrobial and potentially antiparasitic agents 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) medicine development of a HPLC method, sufficient, accurate, fast and sensitive to be applied to the analysis of 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in plasma and cytoplasmic samples, allowing accurate pharmacokinetic analyses and measurements of dihydropyrimidine dehydrogenase in patients who are candidates for fluoropyrimidine-based chemotherapy without the need of a labeled substrate for enzyme studies 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) medicine identification of mutants G366A and T768K in healthy Japanese volunteers. G366A results in marked decrease in enzyme affinity to NADPH, reduction of Vmax for 5-fluorouracil degrading activity, T768K leads to rapid loss of enzyme activity 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) medicine identification of mutations E244V and A551T and splice site mutation IVS11+1G to T in patients with complete loss of enzymic activity 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) medicine uracil breath test breath 13CO2 pharmacokinetics parallel plasma [2-13C]uracil and [2-13C]dihydrouracil pharmacokinetics and are an accurate measure of interindividual variation in enzyme activity. Data support the use of uracil breath test to identify enzyme deficiency before 5-fluorouracil-based therapy 1.3.1.3 DELTA4-3-oxosteroid 5beta-reductase medicine role for bile acids in inhibiting hepatic glucocorticoid clearance, of sufficient magnitude to suppress hypothalamic-pituitary-adrenal axis activity. Elevated hepatic bile acids may account for adrenal insufficiency in liver disease 1.3.1.6 fumarate reductase (NADH) medicine might serve as target for anti-Leishmania drugs 1.3.1.6 fumarate reductase (NADH) medicine aurones and auronols can be used as antiprotozoal compounds because the kill intracellularly persisting amastigozyte of Leishmania major by inhibiting respiratory function of parasite mitochondria 1.3.1.6 fumarate reductase (NADH) medicine the enzyme is a target in anticancer therapy 1.3.1.6 fumarate reductase (NADH) medicine pyrvinium pamoate has an anti-cancer effect within tumour-mimicking microenvironments. Pyrvinium pamoate inhibits NADH-fumarate reductase activities in both parasites and mammalian mitochondria and increases the activity of complex II, succinate-ubiquinone reductase, which is part of fumarate reductase, in mitochondria from human cancer cells cultured under normoxia-normoglycemic conditions but not under hypoxia-hypoglycemic conditions 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine anti-malarial target 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine antibacterial target 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine antimalarial target 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine tuberculosis, TB, target of anti-tubercular agents 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine enoyl-acyl carrier protein reductase from Plasmodium falciparum is an important target for anti-malarial agents 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine enoyl-acyl carrier protein reductase inhibitors turn out to be clinically useful antimicrobials 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine enoyl-acyl carrier protein reductase is a target for anti-malarial drugs 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine epigallocatechin gallate is a promising candidate for the development of tea catechin based antimalarial drugs 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine FabI is a target for antibacterial therapy 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine Mycobacterium tuberculosis enoyl acyl carrier protein reductase represents a prospective drug target against tuberculosis, identified MtENR binders can be characterized as potential therapeutic targets laying a foundation for future lead identification and optimization studies 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine targeting bacterial fatty acid biosynthesis is a viable approach to new antimicrobial agents 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine targeting enoyl-ACP reductase is a viable approach to new antimicrobial agents 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine targeting enoyl-ACP reductase is an attractive approach for the development of novel antibacterials 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine the results can be of primary importance in to elucidate the mechanism of action of isoniazid and to better understand the isoniazid-dependent resistances, and they can also prove useful in the design of a new generation of antitubercular drugs 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine WYW is a potential lead compound for the development of new anti-tuberculosis drugs 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine de novo fatty acid biosynthetic components encoded in Francisella tularensis are transcriptionally active during infection in the mouse model of tularemia 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) medicine the enzyme is a target for development of anti-tuberculosis drugs 1.3.1.14 dihydroorotate dehydrogenase (NAD+) medicine - 1.3.1.14 dihydroorotate dehydrogenase (NAD+) medicine enzyme is a part of the pyrimidine biosynthesis pathway and plays a role as target for the chemotherapy of parasitic and neoplastic diseases 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine enzyme can be used for screening of antiinflammatory potency of drugs 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine enzyme may play an important role in benz[a]pyrene carcinogenesis via oxidative DNA damage 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine enzyme overexpression is detected in 66.9% of pathological sections and in 41.6% of metastatic lymph nodes in patients with esophageal squamous cell carcinoma, the major isoform is DDH2. Enzyme overexpression is positively correlated with smoking habit, tumor stage, number of metastatic lymph nodes, lymphovascular invasion and COX-2 expression, and inversely correlated with glutathione-S-transferase and nm23-HI expression. Patients with low enzyme expression have significantly lower incidence of tumor recurrences and better survival 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine expression of enzyme isoforms 1 and 2 is detected in 59.6% of pathologicla sections, enzyme expression is significantly higher in patients with tumor size over 2 cm, an in those who had early local recurrence. enzyme expression correlates with those of COX-2, interleukin-6, microsomal epoxide hydrolase and soluble epoxide hydrolase in patients. It is inversely correlated with expression of glutathione S-transferase and NADPH p450 reductase 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine enzyme is expressed in a high percentage of primary ovarian tumors and may be associated with cisplatin-based chemotherapy resistance 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine high expression level of enzyme in A431 squamous cell carcinoma, which is barely detectable in other normal or malignant cutaneous cells, including keratinocytes 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine reduction of enzyme expression in lung tumors may contribute to an increase in DNA adduct levels and may partly be responsible for the higher susceptibility of female lung cancer patients to DNA damage. Detection of DNA adducts correlates with CYP1A1-positive tumors, but not with isoform DDH1-positive tumors 1.3.1.20 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase medicine resistance to doxorubicin and cisplatin in lung adenocarcinoma cell lines is closely associated with enzyme isoforms DDH1 and DDH2 activity 1.3.1.21 7-dehydrocholesterol reductase medicine mutation apoB38.9 in apolipoprotein B results in a hypobetalipoproteinemia-like phenotype and leads to downregulation of enzyme and several other cholesterogenic enzymes 1.3.1.21 7-dehydrocholesterol reductase medicine mutational analysis of the DHCR7 gene in individuals from five families with Smith-Lemli-Opitz syndrome. No single mutation is responsible for the photosensitivity which characterizes Smith-Lemli-Opitz syndrome 1.3.1.21 7-dehydrocholesterol reductase medicine Smith-Lemli-Opitz syndrome is caused not only by disruption of the enzymatic role of 7-dehydrocholesterol reductase as a reductase in cholesterol biosynthesis, but may also involve defects in enzyme resulting in derepression of Sonic Hedgehog signaling 1.3.1.21 7-dehydrocholesterol reductase medicine a 7-dehydrosterol reductase deficiency is known as Smith-Lemli-Opitz syndrome 1.3.1.21 7-dehydrocholesterol reductase medicine although cholesterol synthesis is impaired in both Dhcr7-deficient and lathosterol 5-desaturase-deficient embryonic brain tissues, the synthesis of nonsterol isoprenoids may be increased and thus contribute to Smith-Lemli-Opitz syndrome and lathosterolosis pathology 1.3.1.21 7-dehydrocholesterol reductase medicine construction of an adeno-associated virus vector containing the DHCR7 gene and infusion of this vector into mice deficient for the enzyme leads to identification of the introduced DHCR7 gene in liver, expression of mRNA production of a functional enzyme. Evidence of functionality comes from the ability to partially normalize the serum ratio of 7-dehydrocholesterol/cholesterol in treated animals, apparently by increasing cholesterol production with concomitant decrease in the 7-dehydrocholesterol precursor. By five weeks after treatment the mean ratio for 7 animals has fallen to 0.05 while the ratio for untreated littermate controls has risen to 0.14 1.3.1.21 7-dehydrocholesterol reductase medicine screening of patients diagnosed for elevated 7-dehydrocholesterol levels identified three individuals affected with Smith-Lemli-Opitz Syndrome, and 22 with elevated 7-dehydrocholesterol levels in the absence of Smith-Lemli-Opitz Syndrome. Seven of these individuals showed no mutation in the gene encoding 7-dehydrocholesterol reductase. The medication history of these individuals revealed aripiprazole and trazodone as common medications to all the false positive results 1.3.1.21 7-dehydrocholesterol reductase medicine in a time-pregnant mouse model where wild-type and Dhcr7+/- embryos are maternally exposed to aripiprazole or vehicle, aripiprazole and its metabolites are transported across the placenta and reach the brain of offspring. Maternal aripiprazole exposure leads to decreased viability of embryos and increased 7-DHC levels, regardless of maternal or offspring Dhcr7 genotype. Dhcr7+/- pups are more vulnerable to maternal aripiprazole exposure than their wild-type littermates, and maternal Dhcr7+/- genotype also exacerbates offspring response to aripiprazole treatment. Both 7-DHC levels and 7-DHC/cholesterol ratio is the highest in Dhcr7+/- pups from Dhcr7+/- mothers exposed to aripiprazole 1.3.1.21 7-dehydrocholesterol reductase medicine interaction with endothelial cells for 48 h down-regulates expression of genes in vascular smooth muscle cells controlling rate-limiting steps of the cholesterol biosynthesis such as HMG-CoA reductase, HMG-CoA-synthase-1, 24-dehydrocholesterol reductase and DHCR7. A decrease in the abundance of 24-dehydrocholesterol reductase and lower cholesterol levels in vascular smooth muscle cells cocultured with endothelial cells is observed 1.3.1.21 7-dehydrocholesterol reductase medicine upon DNA and RNA viral infection, macrophages reduce 7-dehydrocholesterol reductase (DHCR7) expression. DHCR7 deficiency or treatment with 7-dehydrocholesterol (7-DHC) can specifically promote phosphorylation of IRF3 and enhance type I interferon production in macrophages. Viral infection or 7-DHC treatment enhances AKT3 expression and activation. Deletion of DHCR7 and the DHCR7 inhibitors including AY9944 and the chemotherapy drug tamoxifen promote clearance of Zika virus and multiple viruses in vitro or in vivo 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine analysis of single-type nucleotide polymorphisms in isoforms SRD5A1 and SRD5A2. Haplotypes within both genes are associated with homocystic ovary syndrome risk. V89L variant of isoform SRD5A2 is associated with protection against homocystic ovary syndrome. Haplotypes in SRD5A1 are also associated with the degree of hirsutism in affected women 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine 30 min incubation with dutasteride results in the lowest apparent Ki values overall and the lowest variation, significant for designing protocols for treatment and/or chemoprevention of prostatic diseases 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine 5alphaR1 is increased and 5alphaR2 is decreased during development of prostate cancer, increased expression of both isozymes in recurrent and metastatic cancer, both isozymes may be important in the development and progression of prostate cancer 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine higher expression of 5alpha-R2, which is considered a masculinizing enzyme, in the female versus male central nervous system, sexual dimorphism in the regulation of 5alpha isozymes by dihydrotestosterone 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine 5alpha reductase inhibitors decrease prostate volume and induce atrophy and apoptosis in benign prostatic epithelium 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine assay for evaluating 5alpha-reductase activity in large-scale clinical studies using the S9 fraction obtained by centrifugation of the homogenate supernatant at 9000 g for 30 min and gas chromatography-mass spectrometry 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine functional variation within isoform SRD5A2 influences, in a sex-specific way, the severity of post-traumatic stress symptoms and risk for diagnosis of post-traumatic stress disorder. There is a significant sex-dependent effect of genotype for the V89L variant in male but not female subjects on symptoms 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine morphine significantly reduces the testosterone concentration after acute and chronic exposure in the spinal cord. In contrast, the 5alpha-reductase 1 expression and of course dihydrotestosterone levels increase the following chronic morphine administration 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine testosterone concentrations during postnatal sexual differentiation of the rat Ccentral nervous system, among other sex-dependent factors, influence brain levels of 5alpha-reductase isozymes in adulthood and the pattern of their regulation by androgen hormones 1.3.1.22 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) medicine transcription and expression levels of both 5alpha-reductase isozymes were significantly higher in environmentally stressed rats than in unstressed rats. Increased 5alpha-reductase isozyme levels may play a role in the development or maintenance of prostate disease 1.3.1.24 biliverdin reductase medicine BVR may represent a novel strategy for the treatment of multiple sclerosis and other oxidative stress-mediated diseases, treatment with BVR ameliorates both clinical and pathological signs of autoimmune encephalomyelitis more efficiently than treatments with traditional antioxidant enzymes 1.3.1.24 biliverdin reductase medicine data gathered to date have identified the potential utility of hBVR in modulating cell signaling and the wide range of functions that are regulated by protein kinases that include growth, differentiation, gene transcription and metabolism, regulation of glucose uptake, induction of HO-1, and cytokine and Toll-like receptor signaling are potential target candidates for hBVR-based therapeutic strategies 1.3.1.24 biliverdin reductase medicine hyperbiliverdinaemia, green jaundice, with green plasma and urine may be caused by a genetic defect in the BVR-A gene in conjunction with decompensated liver cirrosis 1.3.1.24 biliverdin reductase medicine finding that BVR and HO-2 levels, myocyte apoptosis, and contractile function of the heart can be modulated by small human BVR-based peptides offers a promising therapeutic approach for treatment of cardiac dysfunctions 1.3.1.24 biliverdin reductase medicine therapeutic potential of human BVR and human HVR-based peptides by affecting the MAPK signaling pathways, overview 1.3.1.24 biliverdin reductase medicine biliverdin reductase B is a prostate cancer marker 1.3.1.24 biliverdin reductase medicine Tat-mediated transduction of biliverdin reductase A may provide a potential tool to ameliorate beta-cell deficit in pancreas with type 2 diabetes mellitus 1.3.1.44 trans-2-enoyl-CoA reductase (NAD+) medicine enzyme is a target for drugs in treatment of tuberculosis 1.3.1.72 DELTA24-sterol reductase medicine DHCR24 plays crucial role for skin development and its proper function 1.3.1.72 DELTA24-sterol reductase medicine DHCR24 gene therapy might be useful for treatment of Alzheimer's disease 1.3.1.72 DELTA24-sterol reductase medicine surface DHCR24 can be a valuable target for hepatitis C virus-related hepatocellular carcinoma therapy, and 2-152a MAb appears to be useful for this targeted therapy 1.3.1.91 tRNA-dihydrouridine20 synthase [NAD(P)+] medicine upregulation of hDUS2 is a relatively common feature of pulmonary carcinogenesis. Selective suppression of hDUS2 enzyme activity and/or inhibition of formation of the hDUS2-tRNA synthetase complex could be a promising therapeutic strategy for treatment of many lung cancers. Significant association between higher levels of hDUS2 in tumors and poorer prognosis of lung cancer patients 1.3.1.91 tRNA-dihydrouridine20 synthase [NAD(P)+] medicine the enzyme may serve as a valuable target for therapeutic intervention in pulmonary carcinogenesis 1.3.1.92 artemisinic aldehyde DELTA11(13)-reductase medicine artemisinin is the main ingredient for malaria prevention. The World Health Organization recommends artemisinin combination therapies (ACT) as the first-line therapy for malaria worldwide 1.3.1.94 polyprenol reductase medicine loss of function mutations of the SRD5A3 gene cause a multisystemic syndrome with eye malformations, cerebellar vermis hypoplasia, and psychomotor delay. Plasma from patients shows increased level of polyprenoids 1.3.1.98 UDP-N-acetylmuramate dehydrogenase medicine computional design of 3-D structures of MurB enzymes and docking studies will provide highly useful information towards rational design of new tuberculosis drugs through experimental research design for further formulations as per pharmaceutical norms 1.3.1.124 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing] medicine mitochondrial 2,4-dienoyl-CoA reductase is a clinically relevant biomarker for castration-resistant prostate cancer. DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitizes castration-resistant prostate cancer cells to ferroptosis. In vivo, DECR1 deletion impairs lipid metabolism and reduces castration-resistant prostate cancer tumor growth 1.3.3.3 coproporphyrinogen oxidase medicine abnormal route for heme biosynthesis in humans suffering from porphyria cutanea tarda or related syndromes such as hexachlorobenzene poisoning 1.3.3.3 coproporphyrinogen oxidase medicine COPX4 polymorphism is associated with the atypical keto-isocoproporphyrin, utility of urinary porphyrin changes as a biomarker of exposure and potential toxicity in subjects with mercury exposure 1.3.3.3 coproporphyrinogen oxidase medicine CPOX4 polymorphism may affect susceptibility for specific neurobehavioral functions associated with mercury exposure in human subjects 1.3.3.3 coproporphyrinogen oxidase medicine first patient with porphyria where both CPO and delta-aminolaevulinic acid dehydratase are deficient at the molecular level 1.3.3.3 coproporphyrinogen oxidase medicine function of CPO in heme biosynthesis is apparently conserved between zebrafish and human, suggesting that CPO-MO-injected zebrafish embryos might be a useful in vivo assay system to measure the biological activity of human CPO mutations 1.3.3.3 coproporphyrinogen oxidase medicine His158 may have a role in the active site of CPO, none of the conserved histidine residues of the enzyme are essential for catalytic activity although changes in histidines are implicated in the disease state hereditary coproporphyria 1.3.3.3 coproporphyrinogen oxidase medicine increase of severity of porphyrias with monovinyl accumulation, ability of the increased levels of C-IV to compete with the authentic substrate has important implications for clinical porphyrias 1.3.3.3 coproporphyrinogen oxidase medicine new combination photodynamic therapy approach for certain cancers 1.3.3.3 coproporphyrinogen oxidase medicine patients with the specific mutation K404E have a unifying syndrome in which hematological disorders predominate, the so called ‘harderoporphyria’, harderoporphyric patients exhibit iron overload secondary to dyserythropoiesis 1.3.3.3 coproporphyrinogen oxidase medicine chronic exposure of rats to hexachlorobenzene produces an experimental model for human porphyria cutanea tarda. In digitonin-treated hexachlorobenzene mitochondria, coproporphyrinogen oxidase is free in the mitochondrial intermembrane space, whereas in normal mitochondria, 30%-50% remain anchored to the inner membrane 1.3.3.3 coproporphyrinogen oxidase medicine natural polymorphism A814C leading to mutation N272H results in twofold decrease in affinity for coproporphyrinogen-III. Specific activity in liver samples is 40-50% lower than in wild-type, mutation may predispose to impaired heme biosynthesis 1.3.3.3 coproporphyrinogen oxidase medicine the regulation of the enzyme is important in differentiation therapy for cancer treatment 1.3.3.4 protoporphyrinogen oxidase medicine conserved structural features in relation to a number of South African variegate porphyria-causing mutations in the human enzyme 1.3.3.4 protoporphyrinogen oxidase medicine tobacco PPO2 represents a useful model system for the understanding of the structure–function relationship underlying detrimental human enzyme defects, Arg98, Phe392, Leu356 and Leu372 are functionally involved in substrate co-ordination within the active site 1.3.3.4 protoporphyrinogen oxidase medicine variegate porphyria resulting from a deficiency in protoporphyrinogen oxidase 1.3.3.5 bilirubin oxidase medicine - 1.3.3.5 bilirubin oxidase medicine immobilized bilirubin oxidase reactor could be used for the degradation of bilirubin in neonatal jaundice 1.3.3.5 bilirubin oxidase medicine great potential for use as a diagnostic reagent, can be used for accurate determination of serum bilirubin levels in patients with hepatobiliary disease 1.3.3.5 bilirubin oxidase medicine mutants I402G and C457S are not appropriate for diagnostic purpose due to their much lower enzyme activities compared to the recombinant enzyme 1.3.3.6 acyl-CoA oxidase medicine AOX activity is negatively correlated with postprandial triacylglycerol levels 1.3.3.6 acyl-CoA oxidase medicine ACOX1 is a rate-limiting enzyme in peroxisomal fatty acids beta-oxidation and its deficiency is associated with a lethal, autosomal recessive disease, called pseudoneonatal-adrenoleukodystrophy 1.3.3.6 acyl-CoA oxidase medicine inhibition of ACOX1 is an effective approach for the treatment of high fat diet or obesity-induced metabolic diseases by improving mitochondrial lipid and reactive oxygen species metabolism 1.3.5.1 succinate dehydrogenase medicine the succinate dehydrogenase iron-sulfur protein is a promising candidate for a partially protective vaccination against Schistosoma, SjSDISP vaccine may primarily play a role in anti-embryonation or anti-fecundity immunity 1.3.5.1 succinate dehydrogenase medicine an SDHB-related pheochromocytoma/paragangliomas patient is presented bearing a SDHB gene mutation with extensive tumor burden, numerous organ lesions, and rapidly growing tumors, which responded extremely well to cyclophosphamide, vincristine, and dacarbazine combination chemotherapy 1.3.5.1 succinate dehydrogenase medicine mutations in the genes encoding succinate dehydrogenase are associated with hereditary predisposition to pheochromocytoma and paraganglioma. The results support the notion that loss of mitochondrial function alters epigenetic processes and might provide a signature methylation mark for paraganglioma 1.3.5.1 succinate dehydrogenase medicine no DNA methylation is identified in the promoter regions of the succinate dehydrogenase A, B, C, D and fumarate hydratase genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation sensitive high resolution melting which detects both homogeneous and heterogeneous methylation, implying that that inactivation via DNA methylation of the promoter CpG islands of SDH and fumarate hydratase is unlikely to play a major role in sporadic breast carcinomas 1.3.5.1 succinate dehydrogenase medicine species-selective inhibition by siccanin is unique among succinate dehydrogenase inhibitors, and thus siccanin is a potential lead compound for new chemotherapeutics 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine - 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine enzyme inhibition is a mechanism of action that may be relevant for the therapeutic effects of leflunomide 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine great interest in inhibitors as potential therapeutic agents for the treatment of diseases involving aberrant cell proliferation 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine inhibition of pyrimidine biosynthesis by targeting enzyme activity, mechanism for antimicrobial intervention 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine molecular target of the antiproliferative, immunosuppressive compound brequinar sodium 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine background for the development of antipyrimidines with high efficacy for decreasing in situ pyrimidine nucleotide pools in Candida albicans 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine development of small molecule inhibitors against DHODH 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine PfDHODH is a promising target for chemotherapeutic intervention in prevention of malaria 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine promising new target for chemotherapeutic intervention in prevention of malaria, synthesized inhibitors prevent growth of cultured parasites at low micromolar concentrations, interaction of inhibitors with amino acid residues F188, H185, and R265 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine promising new target for chemotherapeutic intervention in prevention of malaria, synthesized inhibitors show considerable lower affinity for the human DHODH enzyme relative to the Plasmodium DHODH enzyme 1.3.5.2 dihydroorotate dehydrogenase (quinone) medicine DHODH represents a potential target for anti-malarial therapy 1.3.8.1 short-chain acyl-CoA dehydrogenase medicine newborn screening assays for short-chain acyl-CoA dehydrogenase deficiency are based on the detection of elevated butyrylcarnitine (C4) levels 1.3.8.1 short-chain acyl-CoA dehydrogenase medicine short-chain-acyl-CoA-dehydrogenase deficiency is an inborn error of mitochondrial fatty acid metabolism caused by rare mutations as well as common susceptibility variations in the SCAD gene 1.3.8.1 short-chain acyl-CoA dehydrogenase medicine short-chain acyl-coenzyme A dehydrogenase deficiency is attributed to alterations in the SCAD gene 1.3.8.2 4,4'-diapophytoene desaturase (4,4'-diapolycopene-forming) medicine the enzyme CrtN is an attractive and druggable target for fighting pigmented Staphylococcus aureus infections 1.3.8.4 isovaleryl-CoA dehydrogenase medicine isovaleric acidemia is caused by isovaleryl-CoA dehydrogenase deficiency 1.3.8.4 isovaleryl-CoA dehydrogenase medicine isovaleric acidaemia, caused by isovaleryl coenzyme A dehydrogenase deficiency, is an autosomal-recessive disorder of L-leucine catabolism 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) medicine altered expression levels in colorectal cancer, which is mainly associated with fatty acid metabolic pathways, speculated to have an important role linked to carcinogenesis 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) medicine glutaric acid, 3-hydroxyglutric acid, and glutarylcarnithine accumulate in patients with GCDH deficiency 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) medicine glutaryl-CoA dehydrogenase deficiency (glutaric acidaemia or aciduria type I) is an autosomal recessive disease which is characterized by an accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid (less frequently), and glutarylcarnitine in body fluids and tissues 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) medicine glutaryl-CoA dehydrogenase deficiency (glutaric acidemia type 1, GA1) is a disorder of lysine and tryptophan degradation that results in accumulation of glutaric acid and 3-hydroxyglutaric acid in the brain and other tissues 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) medicine glutaryl-CoA dehydrogenase deficiency is an autosomal recessive disease characterized by the accumulation of glutaric and 3-hydroxyglutaric acids in tissues and body fluids causing uncompetitive inhibition of alpha-ketoglutarate dehydrogenase complex 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) medicine glutaryl-CoA dehydrogenase deficiency leads to strong glutaric acid and 3-hydroxyglutaric acid accumulation in the central nervous system 1.3.8.6 glutaryl-CoA dehydrogenase (ETF) medicine studies of 18 missense mutations identified in glutaric aciduria type 1 patients affecting surface amino acids. The stability of half of the GCDH mutants is significantly reduced. None of the mutations impairs the 3D structure of GCDH. All GCDH mutants are correctly translocated into mitochondria 1.3.8.7 medium-chain acyl-CoA dehydrogenase medicine inhibitor may become a lead for further development for treating non-insulin-dependent diabetes mellitus 1.3.8.7 medium-chain acyl-CoA dehydrogenase medicine among 11 Japanese patients with medium-chain acyl-CoA dehydrogenase deficiency, mutation c.449-452delCTGA accounts for 45%. Seven of 10 independent patients carried at least one copy of the mutation. Phenotypes of homozygous patients with the c.449-452delCTGA mutation varied from asymtomatic to life-threatening metabolic decompensations 1.3.8.7 medium-chain acyl-CoA dehydrogenase medicine in medium-chain acyl-CoA dehydrogenase deficiency, the affected patients predominantly present high levels of octanoic and decanoic acids and their glycine and carnitine by-products in tissues and body fluids. Treatment of healthy brain mitochondrial preparations with octanoic and decanoic acid markedly increases state 4 respiration and diminishes state 3 respiration as well as the respiratory control ratio, the mitochondrial membrane potential and the matrix NAD(P)H levels. Decanoic acid-elicited increase in oxygen consumption in state 4 respiration is partially prevented by atractyloside. Octanoic and decanoic acid also reduce ADP/O ratio, CCCP-stimulated respiration and the activities of respiratory chain complexes.The major accumulating fatty acids in MCADD may act as uncouplers of oxidative phosphorylation and as metabolic inhibitors. Decanoic acid, but not octanoic acid, provokes a marked mitochondrial swelling and cytochrome c release from mitochondria, reflecting a permeabilization of the inner mitochondrial membrane 1.3.8.7 medium-chain acyl-CoA dehydrogenase medicine in the Brazilian population, about 0.41% of individuals are heterozygous for the A985G mutation. The mutant homozygous genotype was not found 1.3.8.7 medium-chain acyl-CoA dehydrogenase medicine analysis of variant enzymes identified in newborns. Enzyme analyses with hexanoyl-CoA, hexanoyl-CoA + butanoyl-CoA, and phenylpropionyl-CoA show significantly higher residual medium-chain acyl-CoA dehydrogenase activities in subjects with variant ACADM genotypes when compared to patients with classical ACADM genotypes. After prolonged fasting no hypoglycaemia is observed. Increasing concentrations of free fatty acids indicate lipolysis, and ketone body concentrations are sufficient for blood glucose concentrations in 5 out of 6 subjects. Phenylpropionic acid loading demonstrates in vivo residual enzyme activity in all studied subjects 1.3.8.7 medium-chain acyl-CoA dehydrogenase medicine cloning and functional characterization of mutations with unknown clinical relevance identified in asymptomatic newborns. Eighteen of these mutations were separately cloned into the human ACADM and functionally characterized 1.3.8.7 medium-chain acyl-CoA dehydrogenase medicine mutations in the ACADM gene identified in newborn lower the temperature threshold at which loss-of-function occurs. Increased temperature as it occurs during intercurrent infections, significantly increases the risk of further conformational derangement and loss of function of the enzyme, explaining the life-threatening clinical courses observed during fever episodes 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine BACH is expressed in a cell-specific manner and plays a role in spermatogenesis 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine development of a durable gene therapy for VLCAD deficiency 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine presence of a novel long-chain ACAD, i.e., ACAD9 in human embryonic and fetal brain 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine VLCAD represents a likely site for the modulation of substrate utilization during myocardial ischemia 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine VLCAD deficiency is characterized by elevated tissue levels of C14-C18 acyl-carnitines 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine consensus guidelines for clinicians for the diagnosis and management of infants who are screen-positive for VLCAD deficiency 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine LCAD gene replacement to the tibialis anterior muscle and livers of partially deficient LCAD mice is described, a surrogate model for human VLCAD deficiency 1.3.8.8 long-chain acyl-CoA dehydrogenase medicine the developed LC-MS/MS method is able to provide ample sensitivity to correctly and rapidly determine MCAD and VLCAD residual activity in human lymphocytes 1.3.98.1 dihydroorotate dehydrogenase (fumarate) medicine enzyme is inhibited by 59% and 58% by methanol extracts of the brown algae Fucus evanescens and Pelvetia babingtonii, resp., the extracts decrease significantly the infection rate of HeLa host cells and the average parasite number per infected cell 1.3.98.1 dihydroorotate dehydrogenase (fumarate) medicine despite their genetic variations, kinetic properties of the three DHODs are conserved, these findings facilitate further exploitation of Trypanosoma cruzi DHOD inhibitors, as chemotherapeutic agents against Chagas' disease 1.3.98.1 dihydroorotate dehydrogenase (fumarate) medicine in patients with rheumatoid arthritis treated with leflunomide, the frequency of remission is increased in patients carrying the C allele of single nucleotide polymorphism 19C>A compared with patients carrying the A allele 1.3.98.1 dihydroorotate dehydrogenase (fumarate) medicine integration of a single copy of the yeast fumarate-dependent dihydroorotate dehydrogenase gene yDHODH into the genomes of strains D10attB, 3D7attB, Dd2attB, and HB3attB of Plasmodium falciparum. The yeast gene is equally expressed in all of the transgenic lines. All four yeast dihydroorotate dehydrogenase transgenic lines show strong resistance to atovaquone in standard short-term growth inhibition assays. During longer term growth with atovaquone, D10attB-yDHODH and 3D7attB-yDHODH parasites remain fully resistant, but Dd2attB-yDHODH and HB3attB-yDHODH parasites lose their tolerance to the drug after 3 to 4 days of exposure. No differences are found in growth responses among all of these strains to the Plasmodium-specific DHODH inhibitor DSM1 in either short- or long-term exposures. The ubiquinone analog decylubiquinone substantially reverses the atovaquone inhibition of Dd2attB-yDHODH and HB3attByDHODH transgenic parasites during extended growth 1.3.98.1 dihydroorotate dehydrogenase (fumarate) medicine use of yeast enzyme as a positive selectable marker for transfections of Plasmodium falciparum, including its use in gene disruption strategies. A transfection vector designed for gene disruption, containing the yeast DHODH gene as the positive selection marker in combination with a previously described fused yeast cytosine deaminase-uracil phosphoribosyl transferase gene as a negative selection marker, yields positively selected parasites containing the plasmid after transfection of the Plasmodium falciparum D10 strain followed by selection with atovaquone. Yeast DHODH transgenic parasites can be selected in strains D10 and Dd2 by Plasmodium DHODH-specific triazolopyrimidine-based inhibitors 1.3.98.3 coproporphyrinogen dehydrogenase medicine EPR spectrum of a potential substrate radical for HemN 1.3.99.5 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) medicine enzyme isoform 2 gene variants are associated with sperm concentration and motility, but not with epidymal and accessory sex gland markers 1.3.99.5 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) medicine in patients with hirsutism, positive correlation of enzyme isoforms 1 and 2 mRNA and concentration of free serum testosterone in dermal papillae from lower abdominal region 1.3.99.5 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) medicine in recurrent prostate cancer, expression levels and isozyme activity shifts from isoform II towards isoform I. Immunostaining shows higher expression of isoform I than isoform II in recurrent prostate cancer, androgen-stimulated benign prostate, and in androgen-stimulated prostate cancers. Activity of isoform I is 3.7fold higher than isoform II in recurrent prostate cancers 1.3.99.5 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) medicine therapeutic potential of enzyme inhibitors MK386 and MK906 to reduce growth and progression of prostatic cancer 1.3.99.5 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) medicine treatment of patients with clinically localized prostate cancer with enzyme inhibitor dutasteride before radical prostatectomy. Treatment with dutasteride is associated with reductions in serum and intraprostatic dihydrotestosterone of more than 90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride is noted on Gleason grade 1.3.99.5 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) medicine two Korean sisters with male pseudohermaphroditism, showing a homozygous deletion of the thymine at nucleotide position c.655, leading to a frameshift mutation predicted to result in abnormally long protein with an extended termination signal 1.3.99.5 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) medicine inhibitor Strogen forte extract can be used for treatment of benign prostatic hyperplasia 1.3.99.23 all-trans-retinol 13,14-reductase medicine RetSat plays an important role in the biology of adipocytes, where it favors normal differentiation, yet is reduced in the obese state, RetSat is thus a novel target for therapeutic intervention in metabolic disease 1.3.99.23 all-trans-retinol 13,14-reductase medicine enzyme RetSat is a critical regulator of liver metabolism functioning upstream of ChREBP. Pharmacological inhibition of liver RetSat may represent a therapeutic approach for steatosis 1.4.1.1 alanine dehydrogenase medicine L-alanine catabolism can be conferred on Mycobacterium bovis BCG by introduction of the gene encoding Ald of Mycobacterium tuberculosis, restoration of Ald activity does not change the in vivo growth of BCG in macrophages or mice, and protection against aerosol Mycobacterium tuberculosis infection is not altered by addition of the gene encoding Ald to the BCG vaccine 1.4.1.1 alanine dehydrogenase medicine an Ald-specific inhibitor and respiration inhibitory antitubercular drugs, such as Q203 and BDQ, are likely to enable more efficient therapies for tuberculosis 1.4.1.1 alanine dehydrogenase medicine plausible application of Ald inhibitors for treatment of tuberculosis. An Ald-specific inhibitor and respiration inhibitory antitubercular drugs, such as Q203 and BDQ, are likely to enable more efficient therapies for tuberculosis 1.4.1.2 glutamate dehydrogenase medicine prolonged exposure to Corydalis ternata may be one of the ways to regulate glutamate concentration in brain through the activation of GDH 1.4.1.2 glutamate dehydrogenase medicine the findings emphasize the integration of glucose metabolism, glutamine metabolism, and oncogenic signaling in glioblastoma cells and suggest that exploiting compensatory pathways of glutamine metabolism can improve the efficacy of cancer treatments that impair glucose utilization 1.4.1.2 glutamate dehydrogenase medicine evaluation of comercially available rapid membrane enzyme immunoassays that use either glutamate dehydrogenase antigen or toxin A and B detection or a combination of both. Sensitivity, specificity, positive predictive values, and negative predictive values are 63.6%, 98.0%, 76.1%, and 96.4%, respectively, for the CD COMPLETE-toxin assay and 75.5%, 97.4%, 72.5%, and 97.8%, respectively, for the VIDAS CDAB assay. In comparison to the enriched Clostridium difficile cultures, the sensitivity, specificity, positive predictive values, and negative predictive values for the CD COMPLETE-GDH assay are 91.0%, 92.4%, 70.5%, and 98.1%, respectively. The CD COMPLETE assay is a reliable method for the diagnosis of Costridium difficile infection and provides greater sensitivity than toxin enzyme immunoassay alone 1.4.1.2 glutamate dehydrogenase medicine gluD gene encoding glutamate dehydrogenase is highly conserved and glutamate dehydrogenase, which is used as marker for the presence of Clostridium difficile in fecal specimens, is readily expressed in vitro by all 77 Clostridium difficile ribotypes assayed. All ribotypes, including ARL 002, ARL 027, and ARL 106, are reactive in assays that detect Clostridium difficile glutamate dehydrogenase 1.4.1.2 glutamate dehydrogenase medicine the latex test-reactive protein is a glutamate dehydrogenase present in all isolates of Peptoclostridium difficile analyzed, suggesting that it is not related to pathogenicity 1.4.1.3 glutamate dehydrogenase [NAD(P)+] medicine serum GLDH activity is an ideal marker of alcoholism since it is elevated in alcohol abuse but its activity declines promptly after the last alcohol intake 1.4.1.3 glutamate dehydrogenase [NAD(P)+] medicine by regulating bioenergetics and redox homeostasis human GDH1/2 have emerged as key players in the pathogenesis of human neoplasias and as therapeutic targets for halting tumor development and expansion 1.4.1.4 glutamate dehydrogenase (NADP+) medicine in the parasite protein, several salt-bridges mediate contacts between the subunits, possesses a unique N-terminal extension that does not occur in any other GDH sequence so far studied, design of peptidomimetics capable of disrupting the oligomeric organisation of the parasite enzyme 1.4.1.20 phenylalanine dehydrogenase medicine plays an important role in detection and screening of phenylketonuria diseases 1.4.1.27 glycine cleavage system medicine in 14 patients from 13 families with clinical and biochemical features suggestive of glycine encephalopathy, mutations of the glycine cleavage system are identified. Seven patients (50%) have biallelic mutations in GldC gene, six patients (43%) have biallelic mutations in Amt gene and one patient (7%) has mutation identified in only one allele in GldC gene. Majority of the mutations in GldC and AMT are missense mutations and family-specific. No mutation is found in GcsH gene 1.4.1.27 glycine cleavage system medicine in a patient with nonketotic hyperglycinemia, the H-protein purified from the liver is devoid of functional lipoic acid. H-protein from the patient is able to stimulate the P-protein-catalyzed exchange of the carboxyl carbon of glycine and CO2, although to a limited extent. P-Protein is inactivated when incubated with glycine in the presence of H-protein, and the inactivation is completely prevented when bicarbonate is further added. The inactivation is accompanied by a spectral change of P-protein. The inactivation of P-protein seems to reflect the formation of a ternary complex of P-protein, H-protein and aminomethyl moiety of glycine through a Schiff base linkage of the H-protein-bound aminomethyl moiety with the pyridoxal phosphate of P-protein 1.4.3.1 D-aspartate oxidase medicine the additional N-terminal peptide present in the DASPO_369 splicing isoform only has been identified in hippocampus of Alzheimer's disease female patients, while peptides corresponding to the remaining part of the protein are present in samples from male and female healthy controls and Alzheimer's disease patients. Upon expression in U87 human glioblastoma cells, the DASPO_369 protein shows a lower expression compared with the canonical isoform. Both protein isoforms are active, localize to the peroxisomes, are very stable, and are primarily degraded through the ubiquitin-proteasome system 1.4.3.2 L-amino-acid oxidase medicine enzyme displays dosedependent inhibition on HIV-1 infection and replication 1.4.3.2 L-amino-acid oxidase medicine antiviral (Dengue virus) and antiprotozoal (trypanocidal and leishmanicide) activities 1.4.3.2 L-amino-acid oxidase medicine induces apoptosis in Hela cervical cancer cells in a concentration- and time-dependent manner. Caspase activation and PARP cleavage are involved in ACTX-8-induced apoptosis. ACTX-8 activates a mitochondrial pathway of apoptosis, which is regulated by Bcl-2 family members. Reactive oxygen species generated by ACTX-8 are involved in apoptosis. Translocation of Bax and Bad from the cytosol into mitochondria in ACTX-8-treated cells 1.4.3.2 L-amino-acid oxidase medicine LAAO does not induce platelet aggregation, but it has potent inhibitory activity on platelet aggregation induced by ADP and U46619. It shows no effect on platelet aggregation induced by thrombin, mucetin, ristocetin and stejnulxin 1.4.3.2 L-amino-acid oxidase medicine LAAO-I exhibited bactericidal, antitumoral, trypanocidal, edematogenic, and platelet-aggregating activities. It induces typical apoptotic DNA fragmentation in HL-60 cells. Potential use of LAAO-I as a therapeutic agent for treatment of diseases in which induction of H2O2 production can be beneficial 1.4.3.2 L-amino-acid oxidase medicine LAO decreases perfusion pressure, renal vascular resistance, glomerular filtration rate, sodium, potassium and chloride tubular reabsortion. Causes acute tubular necrosis foci 1.4.3.2 L-amino-acid oxidase medicine LAO potently induces lesions in lungs and livers. LAO causes severe pneumorrhagia, pulmonary interstitial edema, fusion of pulmonary alveoli, cardiac interstitial edema and bleeding when being intravenously injected into BALB/c mice. Also induces liver cell necrosis and release of cytokines including IL-6, IL-12 and IL-2 from highly purified human peripheral blood monocytes and T cells, respectively. The ability of LAO will contribute to the understanding of the pathogenesis of snakebite wound 1.4.3.2 L-amino-acid oxidase medicine significantly inhibits Ehrlich ascites tumour growth and induces an influx of polymorphonuclear cells, as well as spontaneous liberation of H2O2 from peritoneal macrophages. Later, LAAO-I induces mononuclear influx and peritoneal macrophage spreading. Animals treated with LAAO-I show higher survival time 1.4.3.2 L-amino-acid oxidase medicine a high level of enzyme expression seems associated with absence of bone marrow involvement and better outcome in follicular lymphoma cases, enzyme levels could serve as prognosis factor 1.4.3.2 L-amino-acid oxidase medicine the antibacterial activity of the enzyme is similar to that of kanamycin 1.4.3.2 L-amino-acid oxidase medicine the enzyme does not exhibit cytotoxic activities against erythrocytes and peripheral blood mononuclear cells but causes cytotoxicity on several cancer cell lines and induces platelet aggregation in dose-dependent manner. Furthermore, the enzyme shows remarkable effect against Gram-positive and Gram-negative bacteria 1.4.3.2 L-amino-acid oxidase medicine the enzyme has a strong selective cytotoxic activity on tumor cell lines (JURKAT, SK-BR-3 and B16F10) 1.4.3.2 L-amino-acid oxidase medicine the enzyme is a potential tool to instigate antiapoptotic protein regulation that contributes to drive chronic myeloid leukemia therapy 1.4.3.2 L-amino-acid oxidase medicine after infection with Cryptocaryon irritans, the LAAO mRNA is upregulated early post infection (from 6 to 24 h) in both gill and spleen, but then returns to normal levels 1.4.3.2 L-amino-acid oxidase medicine apotxin can selectively kill tumor cells, with less cytotoxicity to the normal cells. Its anti-tumor activity is mainly due to the hydrogen peroxide produced from LAAO oxidation, but catalase does not reverse its anti-tumor effect completely. Deglycosylation can significantly reduce the LAAO activity and anti-tumor activity of apotxin 1.4.3.2 L-amino-acid oxidase medicine coadministering adipose-derived mesenchymal stromal cells and Ophiophagus hannah L-amino acid oxidase in a mouse model of methicillin-resistant Staphylococcus aureus-infected wounds results in reduction of MRSA load by one order of magnitude to the approximate range of 6 log10 colony-forming units compared to untreated controls (7.3 log10 CFU). Similar wound healing and improvements in histological parameters are observed between the two groups. Coadministration of adipose-derived mesenchymal stromal cells and L-amino acid oxidase reduces bacterial burden by approximately two orders of magnitude to 5.1 log10 CFU and leads to a significant enhancement in the wound healing process 1.4.3.2 L-amino-acid oxidase medicine enzyme displays fibrinogen polymerizing procoagulation and PMSF-associated anticoagulation. The LAAO must be polymerizing fibrinogen independent of endogenous thrombin generation and FXIII crosslinking. The direct deaminating action of LAAO, not the coincident generation of H2O2, is responsible for the coagulation procoagulant profile 1.4.3.2 L-amino-acid oxidase medicine LAAO exhibits a considerable cytotoxic activity against breast cancer cell line MCF-7 with IC50 value of 2.75 microg/ml. LAAO triggers antiproliferative activity via extensive H2O2 generation. LAAO exhibits a significant bactericidal activity against gram-positive and gram-negative bacteria, particularly Staphylococcus aureus and Escherichia coli with MIC values of 20 microg/ml 1.4.3.2 L-amino-acid oxidase medicine LAAO is involved in dermonecrosis in mice and shows cytotoxic effects in normal human keratinocytes, the major cell type in the epidermis, which undergoes extensive necrosis at the snakebite site. Pharmacological inhibition by N-acetyl cysteine prevents Bothrops atrox venom-induced necrosis. Treatment with purified LAAO decreases keratinocyte viability with an effective Concentration (EC50) of 5.1 microg/ml. Cytotoxicity caused by LAAO is mediated by H2O2 and treated cells undergo autophagy, followed by apoptosis and necrosis. LAAO induces morphological alterations that precede cell death 1.4.3.2 L-amino-acid oxidase medicine the enzyme exhibits cytotoxicity against fibroblast cell line and kills Leishmania amazonensis promastigotes, intensified by substrate addition 1.4.3.3 D-amino-acid oxidase medicine human gene therapy 1.4.3.3 D-amino-acid oxidase medicine D-serine availability in the nervous system may be altered in schizophrenia because of increased D-amino acid degradation by DAAO 1.4.3.3 D-amino-acid oxidase medicine involvement of DAO (and the interacting gene DAO activator) with a cluster of symptoms involving guilt, anxiety and depression in schizophrenia patients 1.4.3.3 D-amino-acid oxidase medicine polyethylene glycol-conjugated D-amino acid oxidase exhibits potent antitumor activity by generating toxic reactive oxygen species, namely oxidation therapy, subsequently shows remarkable antitumor effect on murine sarcoma 180 solid tumor 1.4.3.3 D-amino-acid oxidase medicine potential in vivo applicability of this evolved mutant DAAO, with increased activity at low O2 and D-Ala concentrations and a 10fold lower Km for O2, for tumor therapy 1.4.3.3 D-amino-acid oxidase medicine the enzyme inhibition might have an therapeutic effect in schizophrenia treatment 1.4.3.3 D-amino-acid oxidase medicine the purified recombinant or native enzyme is used in therapeutic treatment of cancer combined with injection of D-proline. The enzyme is a target in the development of medical treatment for neurodegeneration and cancer 1.4.3.3 D-amino-acid oxidase medicine the enzyme is a potential valuable tool for cancer treatments that exploit the production of H2O2 1.4.3.3 D-amino-acid oxidase medicine comprehensive analysis of catalogued DAAO rare variants triggering amyotrophic lateral sclerosis. Certain rare variants disrupt key interactions with the active site and decrease the conformational flexibility of active site loop comprising residues 216-228, which is essential for substrate binding and product release. These variants lost crucial interactions with the cofactor flavin-adenine-dinucleotide, resulting in weaker binding affinity 1.4.3.3 D-amino-acid oxidase medicine in blood serum of individuals with amnestic mild cognitive impairment, mild Alzheimer's disease, moderate to severe Alzheimer's disease, and healthy elderly, the DAO levels increase with the severity of the cognitive deficits. DAO levels are significantly associated with D-glutamate and D-serine levels 1.4.3.3 D-amino-acid oxidase medicine molecular dynamics simulations of wild-type, and all reported amyotrophic lateral sclerosis-associated DAO mutants. The mutations disrupt several key interactions with the active site residues and decrease the conformational flexibility of active site loop comprising 216 to 228 residues, necessary for substrate binding and product release, mainly due to the distortion of critical salt bridge and hydrogen bond interactions compared with wild-type. DAO mutants have a lower binding affinity toward cofactor flavin adenine dinucleotide and substrate iminoserine than the wildtype 1.4.3.3 D-amino-acid oxidase medicine transgenic mice overexpressing mutant R199W show marked abnormal motor features, e.g. kyphosis, associated with a significant loss (19%) of lumbar spinal cord motor neurons, analyzed at 14 months. This effect is greater in females. In transgenic mice expressing mutant R199W and superoxide dismutase SOD1 G93A mutant, overall survival is not affected, but the onset of neurological signs is significantly earlier in female double transgenic animals than their female SOD1 G93A littermates 1.4.3.4 monoamine oxidase medicine ethiology of schizophrenia and affective disorders e.g. Parkinson's disease and epilepsy 1.4.3.4 monoamine oxidase medicine target for antidepressant and neuroprotective drugs 1.4.3.4 monoamine oxidase medicine the enzyme is a target for anti-depression drug design 1.4.3.4 monoamine oxidase medicine the enzyme is a valuable target for many neurological disorders 1.4.3.4 monoamine oxidase medicine the enzyme is a possible target for therapeutic aproaches for obesity and insulin-resistant states 1.4.3.4 monoamine oxidase medicine the enzyme is a target for antidepressant and neuroprotective drugs 1.4.3.4 monoamine oxidase medicine a significant association is found between the G-allele of 941G/T in MAO-A and attention deficit hyperactivity disorder (ADHD) 1.4.3.4 monoamine oxidase medicine aminoguanidine may be useful for treating obesity via its SSAO blocking properties 1.4.3.4 monoamine oxidase medicine an atypical case of Norrie disease, consisting of a patient harboring a large submicroscopic deletion affecting not only the NDP gene but also the MAOA, MAOB, and EFHC2 genes, is described 1.4.3.4 monoamine oxidase medicine association study of MAO-A and frontotemporal dementia which does not support the notion that this gene has a major role in the predisposition to this form of dementia 1.4.3.4 monoamine oxidase medicine boys with the short (three-repeat) variant of the MAO-A gene, who had been maltreated/abused or came from families with poor relations, show significantly higher scores of alcohol-related problems. Both maltreatment and MAO-A genotype may be useful for the understanding of male adolescent alcohol-related problem behaviour 1.4.3.4 monoamine oxidase medicine brain MAO A correlates inversely with the multidimensional personality questionnaire trait measure of aggression (but not with other personality traits) 1.4.3.4 monoamine oxidase medicine DRD4 and MAO-A genes may be involved in aggressive schizophrenic patients 1.4.3.4 monoamine oxidase medicine female patients homozygous for the A-allele of monoamine oxidase B have a significantly faster and more pronounced antidepressant treatment response than AG/GG-carriers. In paroxetine-treated females these differences remain statistically significant. In mirtazapine-treated females homozygous for the A-allele compared to AG/GG-carriers, HAMD-17 scores during the study period are constantly and markedly lower, but not statistically different. In males, no association between the MAOB A644G intron 13 SNP and antidepressant treatment response is detected. The MAOB A644G single nucleotide polymorphism is involved in the outcome of treatment with mirtazapine or paroxetine in females with major depression. If replicated, the MAOB A644G polymorphism could be considered useful for prospective confirmatory pharmacogenetic trials in patients with major depression 1.4.3.4 monoamine oxidase medicine females with low platelet MAO-B activity show an increased risk of alcohol-related problem behaviour in an unfavourable environment 1.4.3.4 monoamine oxidase medicine gender-specific contribution of the more active MAO-A variable number tandem repeat (VNTR) variant to an increased vulnerability for complicated grief as a potential intermediate phenotype of major depression 1.4.3.4 monoamine oxidase medicine high-activity MAO-A genotypes possibly by consecutively decreased serotonin and/or norepinephrine availability negatively influence antidepressant treatment response during the first six weeks of pharmacological treatment in female patients with Major Depression 1.4.3.4 monoamine oxidase medicine individuals with less active MAOA-uVNTR alleles who are under chronic stress may be at increased risk for exhaustion of the hypothalamic-pituitary-adrenal response to such stress 1.4.3.4 monoamine oxidase medicine interaction between the norepinephrine transporter and monoamine oxidase A polymorphisms, and novelty-seeking personality traits in Korean females 1.4.3.4 monoamine oxidase medicine MAO B is a stable trait marker for alcoholism. The associations obtained between platelet MAO B activity with executive neurocognitive task and hostility component may support the involvement of plateletMAOB activity in the further development of an impulsive cognitive style 1.4.3.4 monoamine oxidase medicine MAOA deficiency is associated with increased sleep apnea in mice and suggest that an acute or chronic excess of serotonin contributes to this phenotype 1.4.3.4 monoamine oxidase medicine MAOA genotype and cerebrospinal fluid testosterone interact to predict antisocial behaviors 1.4.3.4 monoamine oxidase medicine MAOA polymorphisms do not play a major role in pathogenesis of bipolar disorder or its clinical subtypes in Han Chinese 1.4.3.4 monoamine oxidase medicine MAOA-dependent metabolism of the biological amines may be partly related to high-activated MAO-A, allele 3, in the occurrence of fibromyalgia syndrome among Turkish population 1.4.3.4 monoamine oxidase medicine MAOA-L (the low-expressing allele of the MAOA u-variable-number tandem repeat), by causing an ontogenic excess of 5-hydroxytryptamine, labilizes critical neural circuitry for social evaluation and emotion regulation, thereby amplifying the effects of adverse early-life experience and creating deleterious sociocognitive biases 1.4.3.4 monoamine oxidase medicine methylation of the MAOA promoter is associated with nicotine dependence and alcohol dependence in females 1.4.3.4 monoamine oxidase medicine monoamine oxidase A gene polymorphism predicts adolescent outcome of attention-deficit/hyperactivity disorder 1.4.3.4 monoamine oxidase medicine MPTP-induced apoptosis of neural progenitor cells in the subventricular zone and rostral migratory stream is, at least in part, involved in the mechanism of MAO-B-mediated conversion of MPTP into 1-methyl-4-phenylpyridinium in vivo 1.4.3.4 monoamine oxidase medicine no association among this intergenic haplotype combination and suicidal behaviour in bipolar disorder 1.4.3.4 monoamine oxidase medicine no difference in allelic distributions of two MAOA polymorphisms is found, the risk haplotype 114S is associated with bipolar affective disorder in male patients. The significance is not found in female patients with 114S haplotype. MAOA may have a gender-specific and small effect on the etiology of bipolar affective disorder in Taiwan 1.4.3.4 monoamine oxidase medicine no evidence for interaction between MAOA and childhood adversity for antisocial behavior 1.4.3.4 monoamine oxidase medicine no significant evidence of association between the variable number tandem repeat and T941G polymorphisms and schizophrenia 1.4.3.4 monoamine oxidase medicine non-selective MAO and selective MAO-A inhibitors can induce 5-hydroxytryptamine syndrome in humans when co-administered with antidepressants. Furthermore, the risk of 5-hydroxytryptamine syndrome may be lower with the selective MAO-B inhibitor selegiline 1.4.3.4 monoamine oxidase medicine platelet MAO activity may be a marker of severity of obsessive-compulsive disorder. Low platelet monoamine oxidase activity may be associated with aggressive obsessions in patients with obsessive-compulsive disorder 1.4.3.4 monoamine oxidase medicine presence of the long (4-repeat) variant of the MAO-A gene in females interacted significantly with an unfavourable environment (poor family relations or maltreatment/abuse/sexual abuse) to increase the risk for high scores of alcohol-related problems 1.4.3.4 monoamine oxidase medicine quantification of MAO-B activity may be a useful diagnostic tool for differentiating glial tumours from other types of brain tumours or surrounding normal brain tissue 1.4.3.4 monoamine oxidase medicine selegiline is an effective and well-tolerated monoamine oxidase inhibitor for the treatment of depression. The selegiline transdermal system provides several advantages compared to orally administered monoamine oxidase inhibitors, including minimal interaction with dietary tyramine and prolonged exposure to the parent compound, while offering a favorable side effect profile. Treatment at the lowest effective dose of 6 mg/24 hours can be administered without the need for dietary modifications 1.4.3.4 monoamine oxidase medicine strongest evidence for the involvement of MAOB gene in the etiology of attention deficit hyperactivity disorder (ADHD), at least in Han Chinese population 1.4.3.4 monoamine oxidase medicine the fibroblast growth factor 20 (FGF20) and monoamine oxidase B (MAOB) genes are associated with Parkinson Disease risk. Variants in FGF20 and MAOB show evidence of statistical interactions, which emphasizes the importance of considering them jointly in genetic analysis of Parkinson Disease 1.4.3.4 monoamine oxidase medicine the in vivo MAO-B inhibiting effect of lamotrigine might contribute in part to its antidepressant activity 1.4.3.4 monoamine oxidase medicine the MAO B inhibitor rasagiline is initiated at 1 mg once-daily dosage as monotherap in early Parkinson’s disease patients and at 0.5–1 mg once-daily as adjunctive to levodopa in advanced Parkinson’s disease patients. Rasagiline treatment is not associated with cheese effect and up to 20 mg per day is well tolerated. In Parkinson’s disease patients with hepatic impairment, rasagiline dosage should be carefully adjusted. Rasagiline should not be administered with other MAO inhibitors and coadministration with certain antidepressants and opioids should be avoided. This drug provides an additional tool for Parkinson’s disease therapy improvement in motor performance 1.4.3.4 monoamine oxidase medicine the MAO B inhibitor selegiline is efficacious in the therapeutic management of Parkinson's disease 1.4.3.4 monoamine oxidase medicine the MAO inhibitor moclobemide is promising in the therapeutic management of post-traumatic stress disorder and panic disorder 1.4.3.4 monoamine oxidase medicine the monoamine oxidase B inhibitor N-propargyl-l(R)-aminoindan (i.e. rasagiline) is well tolerated and effective in the treatment of early Parkinson's disease and as adjunctive treatment in levodopa-treated patients with Parkinson's disease experiencing motor fluctuations 1.4.3.4 monoamine oxidase medicine the monoamine oxidase inhibitor rasagiline may provide a much lower risk of serotonin syndrome than the monoamine oxidase inhibitor selegiline in parkinsonian patients treated with an serotonin reuptake inhibitor 1.4.3.4 monoamine oxidase medicine theoretical and experimental support for the notion that cigarette smoke–induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring 1.4.3.4 monoamine oxidase medicine tobacco smoke contains monoamine oxidase inhibitors. Gestational nicotine and monoamine oxidase inhibitors both influence brain development 1.4.3.4 monoamine oxidase medicine when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood 1.4.3.4 monoamine oxidase medicine MAO-A is a target for a series of therapeutically valuable drugs. Thus, selective MAO-A inhibitors are used as antidepressants 1.4.3.4 monoamine oxidase medicine MAO-B is a target for a series of therapeutically valuable drugs. Thus, selective MAO-B inhibitorsare used in the treatment of Parkinson’s disease 1.4.3.4 monoamine oxidase medicine Rhodiola rosea roots have potent antidepressant activity by inhibiting MAO A and may also find application in the control of senile dementia by their inhibition of MAO B 1.4.3.4 monoamine oxidase medicine monoamine oxidase is an important drug target for the treatment of neurological disorders 1.4.3.11 L-glutamate oxidase medicine Pt/polyethyleneimine/GluOx/poly(o-phenylenediamine) biosensors of both cylinder and disk configurations display superb sensitivity in the linear glutamate calibration region, would provide excellent glutamate sensitivity and spatial resolution in neurochemical monitoring involving small brain areas or layered structures in vivo 1.4.3.11 L-glutamate oxidase medicine recombinant l-GlOx may be used for food analysis or in the monitoring of L-glutamate as a neurotransmitter, can be used to construct micro sensors and microanalysis systems, performs very similarly to the commercially available wild-type l-GlOx, the recombinant l-GlOx is suitable for mass production 1.4.3.13 protein-lysine 6-oxidase medicine cutis laxa, indicated by hyperextensible skin with marked deficiency of skin elastic fibers, is caused by deficiency of lysyl oxidase expression. Fibrosis is a symptom of scleroderma, where lysyl oxidase is markedly elevated in affected tissues. Menkes syndrome may involve abnormalities in the expression of several genes coding for connective tissue proteins 1.4.3.13 protein-lysine 6-oxidase medicine increase in the expression of lysyl oxidase during wound healing in skin and in aorta, lung and skin of developing and aging rats. Implication of lysyl oxidase as a target gene for IRF-1 in tumor suppression. Lysly oxidase has unusual and important roles in cellular homeostasis 1.4.3.13 protein-lysine 6-oxidase medicine chronic inhalation of cadmium induces emphysema. Long-term Cd exposure induces inhibition of Cu-dependent lysyl oxidase and its substrates, by upregulation of Cu scavenging thiols in pulmonary fibroblasts. Downregulation of lysyl oxidase results from limitated Cu bioavailability as a central event contributing to Cd-induced extracellular matrix damage. Restoration of LO levels in Cd-insulted lung cells or tissues by replenishing Cu may have a protective or therapeutic effect on Cd-induced emphysema 1.4.3.13 protein-lysine 6-oxidase medicine LOXL is a target to reinduce elastogenesis 1.4.3.13 protein-lysine 6-oxidase medicine treatment of rat dermal wound with lysyl oxidase-producing gene activated matrix leads to significantly enhanced mechanical strength of the wound site 1.4.3.13 protein-lysine 6-oxidase medicine genetic variation in the LOXL1 gene might play a role as a risk factor for spontaneous cervical artery dissection 1.4.3.13 protein-lysine 6-oxidase medicine LOX could play a key role in vascular homeostasis and, hence, it emerges as a new player in cardiovascular diseases 1.4.3.13 protein-lysine 6-oxidase medicine LOX is a potent metastasis-promoting gene in breast carcinomas that facilitates metastatic tumor progression by inducing cell motility and migration and has the potential for novel anti-metastatic cancer therapeutics 1.4.3.13 protein-lysine 6-oxidase medicine LOXL1 and LOXL4 are frequently hypermethylated and lose expression in primary bladder tumors 1.4.3.13 protein-lysine 6-oxidase medicine LOXL1 deficiency leads to pelvic organ prolapse 1.4.3.13 protein-lysine 6-oxidase medicine Loxl1 knockout mice have lower urinary tract dysfunction, most likely due to urethral dysfunction 1.4.3.13 protein-lysine 6-oxidase medicine LOXL2 can be used as a poor prognosis indicator in human squamous cell carcinomas promoting malignant transformation 1.4.3.13 protein-lysine 6-oxidase medicine LOXL2 may play an important role in susceptibility to intracranial aneurysm 1.4.3.13 protein-lysine 6-oxidase medicine lysyl oxidase like-1 protein knockout mice develop pelvic organ prolapse 1.4.3.13 protein-lysine 6-oxidase medicine LOX inhibition might be useful in metastasis prevention, metastasis model and drug administration study in mice, overview 1.4.3.13 protein-lysine 6-oxidase medicine an extracellular matrix (ECM)-targeting nanotherapeutic is engineered using a lipid-based nanoparticle chemically linked to an inhibitor of the ECM-related enzyme, lysyl oxidase 1 (LOX), that inhibits the crosslinking of elastin and collagen fibers. When the conjugated vesicles are loaded with the chemotherapeutic epirubicin, superior inhibition of triple negative breast cancer (TNBC) cell growth is observed both in vitro and in vivo 1.4.3.14 L-lysine oxidase medicine - 1.4.3.14 L-lysine oxidase medicine antitumor activity 1.4.3.14 L-lysine oxidase medicine suppresses efficiently genital herpes simplex virus type II (HSV-2) infection in guinea pig, showing the best results after combined treatment with enzyme gel and intramuscular injection on day 5 postinfection 1.4.3.14 L-lysine oxidase medicine the enzyme is an anticancer agent for the treatment of solid tumors in vivo 1.4.3.14 L-lysine oxidase medicine the enzyme severely inhibits growth of cancer cells but shows relatively low cytotoxicity fo normal cells 1.4.3.14 L-lysine oxidase medicine the enzyme may be used to reduce levels of L-Lys and polyamines in the brain. The enzyme enetrates into the brain and is retained there for up to 48 h after intravenous injection. The most significant impact of the enzyme is towards amino acids, which are directly exposed to its action (L-Lys, L-Orn, L-Arg). In addition, the enzyme significantly affects the redistribution of amino acids directly associated with the tricarboxylic acid cycle (L-Asp and l-Glu). The depletion of L-Orn, the precursor of polyamines, leads to a significant and long-term decrease in the concentration of polyamines, which are responsible for regulation of many processes including cell proliferation 1.4.3.20 L-lysine 6-oxidase medicine L-lysine epsilon-oxidase can be used for diagnosis based on plasma L-lysine concentration 1.4.3.21 primary-amine oxidase medicine hexakis(benzylammonium) decavanadate (V) dihydrate acts as a prodrug of peroxovanadate insulin mimetics. SSAO oxidizes hexakis(benzylammonium) decavanadate (V) dihydrate to the same extent as it does benzylamine 1.4.3.21 primary-amine oxidase medicine VAP-1 might be a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium 1.4.3.22 diamine oxidase medicine determination of fresh plasma diamine oxidase activity may serve as an effective tool to diagnose Cu deficiency in the bovine 1.4.3.22 diamine oxidase medicine histaminase exerts a clear-cut protective effect in splanchnic artery occlusion/reperfusion-induced splanchnic injury, likely caused by oxidative catabolism of proinflammatory histamine and antioxidant effects resulting in hindrance of free radicalYmediated tissue injury, endothelial dysfunction, and leukocyte recruitment. Histaminase could be used therapeutically in intestinal ischemia 1.4.3.22 diamine oxidase medicine the balance between histamine and DAO seems to be crucial for an uncomplicated course of pregnancy. Reduced DAO activities are found in multiple heterogeneous complications of pregnancy such as diabetes, threatened and missed abortion and trophoblastic disorders. Low activities of the histamine-degrading enzyme DAO might indicate high-risk pregnancies, although high intra- and interindividual variations limit its value as a screening tool 1.4.3.22 diamine oxidase medicine excess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles 1.4.4.2 glycine dehydrogenase (aminomethyl-transferring) medicine mutations of the glycine decarboxylase gene are found in patients with nonketotic hyperglycinemia, NKH 1.4.4.2 glycine dehydrogenase (aminomethyl-transferring) medicine serum GLDC is associated with increased lung cancer risk. Years of smoking are associated with serum GLDC in patients with lung cancer. The association is attenuated in the serum of matched controls. Overexpression of GLDC protein contributes to malignant transformation and inhibits microRNA-29 family expression in normal human bronchial epithelial cells 1.4.4.2 glycine dehydrogenase (aminomethyl-transferring) medicine in eight-week-old Zucker diabetic fatty rats (ZDF, a type-II diabetic animal model) receiving either 1% glycine or 1.19% L-alanine in drinking water for 6 weeks, glycine concentrations in serum and liver are markedly lower than in a group of control lean Zucker rats. Enteral glycine supplementation restores both serum and hepatic glycine levels, while reducing mesenteric and internal white fat mass compared with alanine-treated Zucker diabetic fatty rats rats. Blood glucose and non-esterified fatty acid concentrations do not differ between the control and glycine-supplemented Zucker diabetic fatty rats rats. Both mRNA and protein expression of aminomethyltransferase and decarboxylating glycine dehydrogenase are increased in the livers of obese versus lean rats. In contrast, glycine cleavage system H hepatic mRNA expression is downregulated in obese versus lean rats 1.5.1.2 pyrroline-5-carboxylate reductase medicine mediating apoptosis in tumor cells 1.5.1.2 pyrroline-5-carboxylate reductase medicine overexpression of proline oxidase causes apoptotic cell death in a variety of cancer cells 1.5.1.2 pyrroline-5-carboxylate reductase medicine proline oxidase can mediate apoptosis through generation of reactive oxygen species 1.5.1.2 pyrroline-5-carboxylate reductase medicine pyrroline-5-carboxylate reductase is related to virulence of Mycobacterium tuberculosis 1.5.1.2 pyrroline-5-carboxylate reductase medicine identification of a single homozygous region near the telomere of chromosome 17 in a cohort of patients with cutis laxa type 2. The single nucleotide change leads to a missense mutation adjacent to a slice junction in the gene encoding pyrroline-5-carboxylate reductase 1 which results in exon skipping and leads to deletion of reductase functional domain-coding region and an obligatory downstream frameshift 1.5.1.2 pyrroline-5-carboxylate reductase medicine micro-RNA miR-23b*, by targeting POX, may function as an oncogene. Pairs of human renal carcinoma and normal tissues show a negative correlation between miR-23b* and POX protein expression, providing its clinical corroboration. Ectopic overexpression of miR-23b* in normal renal cells results in striking downregulation of POX, whereas POX expression increases markedly when endogenous miR-23b* is knocked down by its antagomirs in renal cancer cells 1.5.1.2 pyrroline-5-carboxylate reductase medicine both PYCR1 mRNA and protein expression are significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Higher PYCR1 mRNA levels are significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor status. Inhibition of PYCR1 by small-hairpin RNA significantly reduces the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor negative). Chemotherapy significantly improves survival in early-stage breast cancer patients with low PYCR1 expression levels 1.5.1.2 pyrroline-5-carboxylate reductase medicine PYCR1 expression is upregulated in different gastric cancer cohorts. High PYCR1 protein expression is correlated with advanced tumor stage, aggressive histological type and high Ki-67 index. High PYCR1 expression in gastric cancer tissues is an indicator of poor outcome in gastric cancer patients. In vitro, PYCR1 knockdown markedly attenuates gastric cancer cells growth and promoted apoptosis, while overexpression produces the opposite effects. PI3K/Akt axis is strongly correlated with PYCR1 expression and PIK3CB and AKT1 mRNA expression are positively associated with PYCR1 in gastric cancer tissues. PI3K inhibition significantly reduces PYCR1 mRNA and protein expression. Nutrient stress induced by glucose deprivation also regulates PYCR1 expression 1.5.1.2 pyrroline-5-carboxylate reductase medicine PYCR2 is highly expressed in colorectal cancer patients and high PYCR2 expression is associated with advanced stage, adenocarcinoma, nodal metastasis, and poor survival rate. PYCR2 knockdown reduces cell viability, proliferation, migration, and invasion and increases apoptosis. PYCR2 knockdown increases Bax, cleaved caspase-3, and cleaved PARP levels and decreases Bcl-2, MMP-2, MMP-9, p-PI3K, p-AKT, and p-mTOR levels in colorectal cancer cells 1.5.1.3 dihydrofolate reductase medicine drug target 1.5.1.3 dihydrofolate reductase medicine potentially target for the discovery of novel insecticides and anthelminthics 1.5.1.3 dihydrofolate reductase medicine biomarker, key target in chemotherapy 1.5.1.3 dihydrofolate reductase medicine enzyme is a target of several anti-folate inhibitory drugs to combat bacteria, protozoa and cancer 1.5.1.3 dihydrofolate reductase medicine sequence analysis of enzyme isolated from strains in different regions of India. Prevalence of double enzyme mutants and some with triple mutants in isolates from mainland, presence of qudruple mutants in isolates from Car Nicobar Island. Association between the degree of malaria transmission and the number of enzyme mutations 1.5.1.3 dihydrofolate reductase medicine a 19-bp deletion polymorphism is not associated with overall breast cancer risk, although a borderline significant additive interaction between the dihydrofolate reductase genotype and multivitamin use is observed. Multivitamin supplements may place a subgroup of women, i.e., those with the19-bp allele, at elevated risk of developing breast cancer. A dose-dependent relation between dihydrolfolated reductase expression and the 19 bp deletion genotype is observed 1.5.1.3 dihydrofolate reductase medicine analysis of intronic 19-bp deletion polymorphism and two polymorphisms within the 3' untranslated region as candidates for risk of neural tube defect. The 829C>T polymorphism is not found to be variable within the Irish population. The 19-bp intron deletion and the 721A>T polymorphisms are found to be in linkage disequilibrium. The 19-bp intron deletion allele shows a significant protective effect in mothers of neural tube defect cases when present in one or two copies 1.5.1.3 dihydrofolate reductase medicine analysis of polymorphisms among 129 isolates from different geographical areas in India. A gradual increase in the frequency of mutant genotypes is observed from north to south, while isolates from the Car-Nicobar islands show only mutant genotypes 1.5.1.3 dihydrofolate reductase medicine analysis of the impact of the dihydrofolate reductase c.86 + 60_78 insertion/deletion polymorphism on folate and homocysteine concentrations. Among men the polymorphism is not signficantly associated with serum or red blood cell folate concentrations, or with homocysteine concentrations. Among women the polymorphis mexplains 2% of the variation in red blood cell folate levels and 5% of the variation in serum folate levels, but does not appear to have an independent effect on homocysteine 1.5.1.3 dihydrofolate reductase medicine c-Myc oncoprotein protein level is elevated in cervical intraepithelial neoplasia 1, cervical intraepithelial neoplasia 2, cervical intraepithelial neoplasia 3 biopsies. Concomitantly, dihydrofolate reductase gene amplification is detected. The degrees of dihydrofolate reductase gene amplification and of c-Myc protein levels are a measure of the progressive degree of the lesion 1.5.1.3 dihydrofolate reductase medicine Double knock-out lines of bifunctional dihydrofolate reductase-thymidylate synthase are unable to infect mice, whereas the virulence of single knock-out lines is similar to wild-type 1.5.1.3 dihydrofolate reductase medicine identification of synonymous and non-synonymous single nucleotide polymorphisms in the Plasmodium vivax dihydrolfolate reductase gene isolated from patients from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, thailand, and Vanuatu. The double mutant 58R/117N allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple 58R/61M/117T and quadruple 57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu 1.5.1.3 dihydrofolate reductase medicine in 451 blood samples from Plasmodium vivax cases in Sri Lanka, 68.9% showed dihydrofolate reductase wild-type haplotype. The double mutant F57L/S58R haplotype was the most frequently observed mutant with 24.4%, while the triple mutant F57L/S58R/S117N was only identified once. A significantly higher frequency of mutant haplotypes is observed in the Northern districts 1.5.1.3 dihydrofolate reductase medicine in a total of 92 Plasmodium falsiparum-infected blood samples from children in Mozambique, the frequency of the sulphadoxine/pyrimethamine resistance-associated dihydrofolate reductase triple mutants 51I/59R/108N and of dihydrofolate reductase /dihydropteroate synthetase quintuple mutants 51I/59R/108N + 437G/540E was 93% and 47%, respectively. However, no dihydrolfolate reductase 164L mutants were detected 1.5.1.3 dihydrofolate reductase medicine in clinical samples, a worse outcome is associated with increased levels of dihydrofolate reductase and C-MYC at diagnosis in osteosarcoma patients treated with a methotrexate-based protocol and of C-MYC in patients treated with a standard four-drug regimen. The assessment of C-MYC and dihydrolfolate reductase at diagnosis, together with that of other known prognostic markers, can be considered for an early identification of subgroups of OS patients with higher risk of adverse outcome 1.5.1.3 dihydrofolate reductase medicine in parasites isolated from Sudanese patients treated with sulphadoxine/pyrimethamine or sulphadoxine/pyrimethamine plus chloroquine, mutations have been detected in dihydrofolate reductase at N51I, S108N, and C59R, plus mutations in dihydropteroate synthetase. There is no significant correlation between multiplicity of mutation and response to sulphadoxine/pyrimethamine 1.5.1.3 dihydrofolate reductase medicine knock-down of dihydrofolate reductase or heart and neural crest derivatives expressed transcript HAND2 in fertilized eggs causes cardiac malformation. Expression of HAND2 is reduced in dihydrofolate reductase knock-down embryos. Microinjection of HAND2 mRNA into fertilized eggs can induce HAND2 overexpression which rescues the cardiac malformation phenotypes of dihydrofolate knock-down embryos 1.5.1.3 dihydrofolate reductase medicine renal ischemia-reperfusion decreases dihydrofolate reductase mRNA and protein levels, both of which are restored by angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, whereas GTP-cyclohydrolase 1 expression is unaltered. Renal ischemia-reperfusion suppresses endothelial nitric oxide synthase dimer while enhancing the monomer and augments inducible nitric oxide synthase mRNA, total inducible nitric oxide synthase protein and monomer, which are attenuated by angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker 1.5.1.3 dihydrofolate reductase medicine screening for the 19-bp deletion and the 9-bp repeat in dihydrolfolate reductase gene of 121 mothers of a spina bifida affected child, 109 spina bifida patients, 292 control women and 234 pediatric controls. The 19-bp del/del genotype is not associated with spina bifida risk in mothers and children and both the WT/del and the del/del genotype do not aVect expression relative to the WT/WT genotype. The 9-bp repeat is not associated with spina bifida risk in mothers and children. Expression of the 6/6 allele is 73% increased compared to the 3/3 allele, although not significantly 1.5.1.3 dihydrofolate reductase medicine study on Plasmodium falciparum isolates from 118 children in Cote d'Ivoire. 39.5% are highly resistant to pyrimethamine, with IC50 values above 2000 nM. 39% of the isolates have mutant dihydrofolate reductase and 94% mutant dihydropteroate synthetase genes, and mutant dihydrofolate reductase is associated with resistance to pyrimethamine in vivo and in vitro 1.5.1.3 dihydrofolate reductase medicine study on prevalence and frequency of dihydrofolate reductase and dihydropteroate synthetase mutations associated with sulfadoxine-pyrimethamine resistance at surveillance sites in Southern Mozambique. Frequency of dihydrofolate triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. Parasites with both dihydrofolate reductase triple mutation and dihydropteroate synthetase double mutations had increased in 2001, but decreased by 2004. The peaking of sulfadoxine-pyrimethamine resistance markers in 2001 coincided with a sulfadoxine-pyrimethamine resistant malaria epidemic in neighboring regions 1.5.1.3 dihydrofolate reductase medicine study on the association between the clinical and parasitological response to sulfadoxinepyrimethamine and allelic combinations of dihydrofolate reductase and dihydropteroate synthase genes. Determination of dihydrofolate reductase and dihydropteroate synthase genotypes is of limited value to predict the treatment outcome in individual patients, mostly due to few treatment failures and few wild-type haplotypes. The majority of clinical isolates is characterized as quadruple, i.e. 196 isolates with mutations N51I-C59R-S108N in dihydrofolate reductase and A437G dihydropteroate synthase, or triple mutants, i.e. 97 isolates with mutations N51I-C59R-S108N in dihydrofolate reductase and wild-type dihydropteroate synthase, or S108N + N51I or C59R in dihydrofolate reductase and A437G in dihydropteroate synthase. Wild-type, single mutation, and double mutation were observed in 29, 20, and 13 parasites, respectively 1.5.1.3 dihydrofolate reductase medicine study on the association of polymorphisms in dihydrofolate reductase gene and treatment response in children with acute lymphoblastic leukemia. Lower event-free survival is associated with homozygosity for the allele A-317 and C-1610, and with the haplotype *1, and mRNA analysis shows higher dihydrofolate reductase levels for haplotype *1 carriers 1.5.1.3 dihydrofolate reductase medicine study on the effect of co-trimoxazole prophylaxis on Plasmodium falciparum antifolate resistance development among HIV-infected persons. Mutation I164L is not associated with high-level sulfadoxine-pyrimethamine resistance or poor outcome among adults living where malaria is highly endemic 1.5.1.3 dihydrofolate reductase medicine the naturally occurring single nucleotide polymorhism C829T, near the miR-24 binding site in the 3' UTR of human dihydrofolate reductase leads to a decrease in microRNA binding, which in turn leads to overexpression of its target and results in resistance to methotrexate 1.5.1.3 dihydrofolate reductase medicine the prevalence of dihydrofolate reductase 19-bp deletion polymorphism and of the methylenetetrahydrofolate reductase C677T polymorphism is similar in cancer patients with and without thrombosis. The frequency of factor V Leiden polymorphism is significantly higher in cancer patients with thrombosis. Thus routine screening for dihydrofolate reductase 19-bp deletion polymorphism is not suggested 1.5.1.3 dihydrofolate reductase medicine target for therapy of acute lymphoblastic leukemia 1.5.1.3 dihydrofolate reductase medicine significantly reduced inflammatory responses and mortality are observed in zebrafish infected with Staphylococcus aureus pre-incubated with grape seed extract. Grape seed extract might serve as an effective natural alternative for the control of food poisoning caused by Staphylococcus aureus with proper safety measure 1.5.1.3 dihydrofolate reductase medicine amplification of a DHFR gene from field isolate PKNY146CSP collected from Southern Thailand. Aanalysis shows 11 polymorphisms in the DHFR domain of the bifunctional DHFR-TS gene. One polymorphism is a non-synonymous substitution (R34L) that has been reported but not associated with antifolate resistance 1.5.1.5 methylenetetrahydrofolate dehydrogenase (NADP+) medicine Leishmania major is shown to require 10-formyl tetrahydrofolate metabolism, thus this is a possible target for chemotherapy in Leishmania major and potential other protozoan parasites 1.5.1.5 methylenetetrahydrofolate dehydrogenase (NADP+) medicine MTHFD1 G1958A polymorphism might be a weak risk factor for early onset Alzheimer’s disease in the age group below 65 years 1.5.1.6 formyltetrahydrofolate dehydrogenase medicine formic acidemia: toxicity of methanol in humans is correlated with formate accumulation as a result of low rates of formate oxidation, which is in vivo dependent on enzyme activity and on hepatic tetrahydrofolate levels 1.5.1.6 formyltetrahydrofolate dehydrogenase medicine methanol-induced toxicity in Müller cells of the retina, role of 10-FDH in formate intoxination both as a protectant and as a toxicity-provoking element 1.5.1.6 formyltetrahydrofolate dehydrogenase medicine enzyme-induced suppressor effects are strictly dependent on p53 tumor suppressor protein in A549 cells. Enzyme elevation results in p53 phosphorylation at S6 and S20 in the p53 transactivation domain, and S392 in the C-terminal domain, but only S6 is strictly required to mediate enzyme effects 1.5.1.6 formyltetrahydrofolate dehydrogenase medicine feeding of ethanol decreases hepatic enzyme activity, decrease occurs irrespective of folate status 1.5.1.7 saccharopine dehydrogenase (NAD+, L-lysine-forming) medicine target for antimicrobial drug development 1.5.1.8 saccharopine dehydrogenase (NADP+, L-lysine-forming) medicine hyperlysinemia: genetic disease, deficiency of lysine-ketoglutarate reductase results in extreme elevations of serum lysine 1.5.1.8 saccharopine dehydrogenase (NADP+, L-lysine-forming) medicine hyperlysinemia 1.5.1.8 saccharopine dehydrogenase (NADP+, L-lysine-forming) medicine autosomal recessive familial hyperlysinemia type I: combined deficiency in lysine-ketoglutarate reductase and saccharopine dehydrogenase activities, EC 1.5.1.8 and EC 1.5.1.9 1.5.1.15 methylenetetrahydrofolate dehydrogenase (NAD+) medicine - 1.5.1.15 methylenetetrahydrofolate dehydrogenase (NAD+) medicine enzyme distribution suggests it can be useful as an oncodevelopmental marker 1.5.1.15 methylenetetrahydrofolate dehydrogenase (NAD+) medicine NAD+ dependent isoenzyme is genuinely tumor-specific, it may provide a novel therapeutic target for cancer therapy and/or an important diagnostic tool 1.5.1.15 methylenetetrahydrofolate dehydrogenase (NAD+) medicine the enzyme (MTHFD2) is highly relevant as an anticancer target 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine mutation in gene for methylenetetrahydrofolate reductase is a cause of moderate homocysteinaemia, which is a risk factor for arteriosclerosis and thrombosis, patients with MTHFR deficiency have low methionine concentrations in plasma 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine methylenetetrahydrofolate reductase deficiency causes homocystinuria 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine deficiency and thermolability of enzyme as cause of mild homocysteinemia with premature vascular disease 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine methylenetetrahydrofolate reductase deficiency as cause of homocysteinuria 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine C677T mution of MTHRF gene is the most frequent genetic cause of mild hyperhomocysteinemia, a risk factor for cardiovascular disease 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine association of A222V genotype with the Gc2 polymorphism of the vitamin D-binding protein. A222V mutant individuals additionally show a quantitative reduction of apolipoprotein A-I 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine MTHFR deficiency in mice is accompanied with hyperhomocysteinemia and decreased hematocrit, hemoglobin, and red blood cell numbers, increased nephrotoxicity und hepatotoxicity compared to wild type animals 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine MTHFR inhibition may be a novel anticancer approach 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine MTHFR is important for postnatal growth and vitality and 5-methyltetrahydrofolate deficiency contributes to the high postnatal mortality, Mefolinate may be a good candidate drug for treatment of severe MTHFR deficiency 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine the consequences of a deficient MTHFR genotype are probably dependent on the folate intake status, there is no clear conclusion regarding the influence of MTHFR polymorphisms on 5-fluorouracil-based treatment in colorectal cancer 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine homozygosity for the C677T natural polymorphism presents a 3fold increased risk of colorectal cancer. Low intake of methyl-donor nutrients is associated with an increased risk of colorectal cancer in homozygous participants for the C677T polymorphism 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine in Parkinson patients, plasma homocysteine elevation may be caused by levodopa administration, and further promoted by MTHFR C677T heterozygotes and homozygote C677T/C677T, but not by A1298C genotypes. The promoting elevation in 1298A homozygotes is attributed to combining the 677T allele. Neither C677T nor A1298C genotypes contribute to elevating plasma homocysteine in Parkinson patients without levodopa treatment 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine maternal MTHFR and dietary folate deficiencies in Mthfr +/- mice result in increased developmental delays and smaller embryos. Folate-deficient mice also have increased embryonic losses and severe placental defects, including placental abruption and disturbed patterning of placental layers. Folate-deficient placentae have decreased ApoA-I expression, and there is a trend toward a negative correlation between ApoA-I expression with maternal homocysteine concentrations 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine meta-analysis of Mthfr polymorphisms affecting methotrexate toxicity. Polymorphism C677T is associated with increased toxicity of methotrexate,while polymorphism A1298C is not 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine mice carrying a mutation in the adenomatous polyposis coli gene Apc, a model for intestinal polyposis, fed with high folate diets from weaning develop more adenomas than those fed the folic acid deficient diet or the control diet. Mthfr deficiency does not affect adenoma number. When the folic acid deficient diet and control diet are administered to dams prior to conception, throughout pregnancy and continued in offspring post-weaning, Apc -/+ offspring fed folic acid deficient diet develop fewer adenomas than those fed control diet. Mthfr+/- genotype of the mother or of the offspring also reduces adenoma numbers in the Apc -/+ offspring. Adenoma number is inversely correlated with plasma homocysteine, intestinal dUTP/dTTP ratios, and levels of intestinal apoptosis 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine MTHFR mutant C677T homozygotes who are also carriers of cystathione beta-synthase 844ins68 polymorphism have homocysteine and folate concentrations similar to those of individuals with the MTHFR heterozygous C677C/C677T and wild-type genotypes. Homocysteine levels in MTHFR double mutant subjects carrying the cystathione beta-synthase 844ins68 allele are 24.1% lower than in non-carriers, and serum folate levels are 27.7% higher. These suggests that the cystathione beta-synthase 844ins68 allele normalizes homocysteine and folate levels in MTHFR C677T/C677T individuals 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine mutations in the MTHFR gene decrease the onset risk of acute lymphoblastic leukemia with relapse in the setting of no folate supplementation in pregnancy, but not of relapse-free acute lymphoblastic leukemia 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine No significant difference is found in either Mthfr allele frequencies or genotype distribution between patients with bipolar disorder and controls in an association study in the Chinese population. The meta-analysis result shows no significant association between Mthfr C677T and bipolar disorder 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine no significant differences in plasma homocysteine levels and MTHFR genotypes are found in patients with systemic sclerosis compared to controls or in systemic sclerosis patients with limited cutaneous compared to diffuse disease. Seventy-one percent of patients with macrovascular disorders have MTHFR polymorphism C677T. In addition, 45% of patients with hyperhomocysteinemia have pulmonary hypertension. The presence of MTHFR C677T mutation influences the incidence of macrovascular abnormalities in SSc patients 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine plasma homocysteine levels are significantly elevated in patients lacking Mthfr activity or cystathione beta-synthase activity 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine study on association of factor V-Leiden and methylenetetrahydrofolate reductase C677T and A1298C mutations with stroke. MTHFR C677T/C677T and A1298C/A1298C, but not factor V-Leiden, genotypes are associated with stroke. The C677T but not A1298C MTHFR mutation is associated with elevated homocysteine levels in patients and control subjects. In addition to hypertension, the significant predictors for stroke are MTHFR C677T and C677T/C677T and A1298C/A1298C genotypes, together with hyperhomocysteinemia, indicating a synergistic effect of MTHFR mutations with elevated homocysteine and other risk factors in pathogenesis of stroke 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine MTHFR variant allele C677T has a protective effect on colorectal cancer development, whereas the variant allele of the A1298C does not produce any effect on disease risk. Both MTHFR polymorphisms are relevant and independent factors of patient outcome after 5-fluorouracil-based treatment of colorectal cancer 1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H] medicine obese women without comorbidities and carrying the T variant of the 677C>T (p.A222V) polymorphism of gene MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels 1.5.1.30 flavin reductase (NADPH) medicine FlaR's roles in pneumococcal physiology and virulence, combined with its lack of significant homology to human proteins, point towards rFlaR as a vaccine candidate 1.5.1.33 pteridine reductase medicine enzyme is a target for development of improved therapies for infection by trypanosomatid parasites 1.5.1.33 pteridine reductase medicine enzyme is an important chemotherapeutic target for drugs against Leishmania 1.5.1.34 6,7-dihydropteridine reductase medicine enzyme deficiency leads to progressive mental and physical retardation despite dietary phenylalanine restriction. Overview on genomic structure and location of natural mutations in the QDPR gene coding for enzyme 1.5.1.53 methylenetetrahydrofolate reductase (NADPH) medicine patients with severe methylenetetrahydrofolate reductase deficiency show neurologic disorders, mental retardation, and rapid deterioration 1.5.1.53 methylenetetrahydrofolate reductase (NADPH) medicine testing of 478 individuals with myelomeningocele for attention-deficit hyperactivity disorder (ADHD) behavior plus genotyping for seven single nucleotide polymorphisms in the MTHFR gene. 28.7% of myelomeningocele participants exhibit rating scale elevations consistent with ADHD, of these 70.1% have scores consistent with the predominantly inattentive subtype. There is a positive association between the SNP rs4846049 in the 39-untranslated region of the MTHFR gene and the attention-deficit hyperactivity disorder phenotype in myelomeningocele participants 1.5.3.1 sarcosine oxidase (formaldehyde-forming) medicine a photobioelectrochemical sensor based on CdSe/ZnS quantum dot and sarcosine oxidase is developed to determine sarcosine concentrations. The linear range is from 0.1 mM to 1 mM and the sensitivity depends on the number of immobilised enzyme layers.It is demonstrated that the [SOD/PAH]6-layer system is well suited for sensitive sarcosine detection. Sarcosine is an intermediate in the enzymatic analysis of creatinine, and thus, a sarcosine sensor can be beneficial for the diagnosis of kidney diseases 1.5.3.1 sarcosine oxidase (formaldehyde-forming) medicine developement of a simple and low cost electrochemical enzymatic biosensor for the determination of sarcosine in urine, based on the covalent immobilization of sarcosine oxidase, using N-ethyl-N-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, on the surface of the screen-printed carbon electrode.The biosensor presents high analytical performance features, such as large concentration linear range (10-100 nM), low detection limit (16 nM) and large storage stability (60 days). The biosensor is successfully applied to the analysis of sarcosine in synthetic urine samples 1.5.3.1 sarcosine oxidase (formaldehyde-forming) medicine the enzyme can be used as biosensor for the analysis of sarcosine in urine samples 1.5.3.7 L-pipecolate oxidase medicine L-pipecolic acid is formed by the catabolism of lysine in humans, and its accumulation is one of the first biochemical abnormalities detected in the Zellweger syndrome 1.5.3.7 L-pipecolate oxidase medicine L-pipecolic oxidase activity is deficient in patients with peroxisome biogenesis disorders 1.5.3.7 L-pipecolate oxidase medicine the L-pipecolate pathway for degradation of lysine is the principal one in the brain 1.5.3.13 N1-acetylpolyamine oxidase medicine high expression of APAO in A549 cells inhibits accumulation of antitumor polyamine analogue, N1-cyclopropylmethyl-N11-ethylnorspermine, decreases their sensitivity to the toxicity of N1-cyclopropylmethyl-N11-ethylnorspermine and prevents N1-cyclopropylmethyl-N11-ethylnorspermine-induced apoptosis 1.5.3.14 polyamine oxidase (propane-1,3-diamine-forming) medicine exogenous spermine and PAO treatment decrease cell viability in a spermine dose- and time-dependent manner, particularly, the viability of the multidrug-resistant colon adenocarcinoma cells, LoVo DX, when compared with drug-sensitive ones. H2O2 derived from spermine is mainly responsible for the cytotoxicity. Treatment with PAO and spermine increases the apoptotic population of LoVo wild-type and multidrug-resistant LoVo cells. Treatment with PAO and spermine markedly reduces mitochondrial membrane potential in the multidrug-resistant LoVo cells 1.5.3.16 spermine oxidase medicine the inhibitor MDL 72145 might be a chemical lead compound for the design of new chemotherapeutic agents against nematode infections 1.5.3.16 spermine oxidase medicine alterations in the levels of spermine synthase SMS and spermine oxidase SMOX have previously been observed in brains of suicide completers. SMS and SMOX display several promoter haplotypes, without consistent effects of haplotype on expression levels in either the brain or in reporter gene assays performed in three different cell lines. There are no overall effects of epigenetic factors in determining expression, with the exception of a relationship between CpG methylation at one site in the promoter of SMOX and its expression in Brodmann area 8/9. The genetic and epigenetic factors examined in this study show little influence on the expression levels of SMS and SMOX 1.5.3.16 spermine oxidase medicine both the expression level of SMO mRNA and SMO enzyme activity are significantly lower in breast cancer samples compared to nontumor samples 1.5.3.16 spermine oxidase medicine treatment of human C-28/I2 chondrocytes with polyamine analogue N1,N11-diethylnorspermine rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels 1.5.3.16 spermine oxidase medicine spermine oxidase is an important positive regulator of muscle fiber size whose expression is strongly downregulated by conditions that cause muscle atrophy. This reduction in spermine oxidase enables the atrophy process and represents a potential target for therapeutic intervention 1.5.3.16 spermine oxidase medicine the selective inhibitors of spermine oxidase represent an important tool for the development of novel anti-neoplastic drugs 1.5.3.16 spermine oxidase medicine spermine oxidase, as a hydrogen peroxide producer, may be involved in the oxidative stress during epilepsy. In a mouse model overexpressing SMOX specifically in the brain cortex, transgenic mice compared to controls showed a higher susceptibility towards pentylentetrazole and display an altered polyamine content with rise of 8-oxo-7,8-dihydro-2'-deoxyguanosine level, and an augmentation of system xc as a defence mechanism 1.5.3.16 spermine oxidase medicine during C2-C12 myotube differentiation, linear and circular RNA derived from SMOX gene show the same trend of expression. In atrophy, circSMOX levels significantly increase compared to the physiological state, in both in vitro and in vivo models. In both amyotrophic lateral sclerosis mouse models studied, an increased expression of circSMOX and a decreased expression of the linear SMOX mRNA are observed 1.5.3.16 spermine oxidase medicine SMOX is overexpressed in hepatocellular carcinoma cell lines and clinical hepatocellular carcinoma tissues. SMOX expression levels are gradually increased in normal liver, chronic hepatitis, and hepatocellular carcinoma tissues. Increased SMOX expression is correlated with poor clinical features of hepatocellular carcinoma. Positive SMOX expression in tumor tissues indicate worse overall survival of patients and shorter relapse-free survival. Knockdown of SMOX inhibits hepatocellular carcinoma cell proliferation, arrested cell cycle at S phase, and results in an increase of apoptosis 1.5.3.17 non-specific polyamine oxidase medicine the inhibitor MDL 72145 might be a chemical lead compound for the design of new chemotherapeutic agents against nematode infections 1.5.5.1 electron-transferring-flavoprotein dehydrogenase medicine mutations in the ETFDH gene lead to a secondary myopathic form of CoQ10 deficiency and to the late-onset form of glutaric aciduria type II 1.5.5.1 electron-transferring-flavoprotein dehydrogenase medicine in THP-1 monocytes during acute (16 h) and chronic (72 h) hypoxia, levels of electron-transferring flavoproteins are elevated. Expression of ETFDH decreases under acute hypoxia, but increases under chronic conditions. siRNA-mediated knockdown of ETFDH lowers mitochondrial respiration under chronic hypoxia 1.5.5.1 electron-transferring-flavoprotein dehydrogenase medicine mutations A84T/S307C identified in a chinese woman with late-onset glutaric aciduria type II reveal lipid storage myopathy. Blood biochemical test and urine organic acid analyses are consistent with glutaric aciduria type II 1.5.5.3 hydroxyproline dehydrogenase medicine the enzyme is a therapeutic target for the treatment of primary hyperoxaluria 1.5.5.3 hydroxyproline dehydrogenase medicine creation of a ProDH2 knock out mouse model. The lack of hydroxyproline dehydrogenase in primary hyperoxalurias mouse models results in lower levels of urinary oxalate excretion. In the double knockout mouse, lacking both glyoxylate reductase/hydroxypyruvate reductase Grhpr and ProDH2, calcium-oxalate crystal deposition in the kidney is prevented, when placed on a 1% hydroxyproline diet 1.5.8.3 sarcosine dehydrogenase medicine sarcosine dehydrogenase is defective in patient with sarcosinemia 1.5.8.3 sarcosine dehydrogenase medicine kidney tumors with clinically aggressive features such as a high tumor stage, positive lymph nodes, distant metastases or a previously advanced tumor status exhibit significantly lower methylation of a locus in the SARDH gene. SARDH gene methylation is a significant prognostic factor for recurrence-free survival in renal cell carcinoma patients showing statistical independence from the clinical prognosticators, grade, stage and state of metastasis 1.5.8.4 dimethylglycine dehydrogenase medicine expression of DMGDH is decreased in hepatocellular carcinoma. the enzyme can be applied as valuable biomarker for both diagnosis and prognosis 1.5.8.4 dimethylglycine dehydrogenase medicine the enzyme is biomarker for both diagnosis and prognosis for hepatocellular carcinoma 1.5.8.4 dimethylglycine dehydrogenase medicine the enzyme may be a valuable biomarker of hepatocellular carcinoma diagnosis 1.5.99.B2 proline dehydrogenase (acceptor) medicine proline dehydrogenase is involved in type I hyperprolinemia 1.6.2.2 cytochrome-b5 reductase medicine - 1.6.2.2 cytochrome-b5 reductase medicine potentially an important enzyme required for the reductive activation of bioreductive drugs that can be used in the treatment of solid tumours 1.6.2.2 cytochrome-b5 reductase medicine enzyme and cytochrome b5 play a direct role in metabolic activation of antimicrobial prodrug DB289 to furamidine 1.6.2.2 cytochrome-b5 reductase medicine isolation of mutations leading to type I recessive congenital methaemoglobinaemia 1.6.2.2 cytochrome-b5 reductase medicine natural mutant P275L from a patient with recessive congenital methemoglobinemia shows significant decrease in the affinity toward the physiological reducing substrate, NADH, without affecting the activity 1.6.2.2 cytochrome-b5 reductase medicine reduction of arylhydroxylamine carcinogens by enzyme and ferricytochrome b5 as a source of individual variability with respect to cancer susceptibility following exposure to arylhydroxylamines 1.6.2.2 cytochrome-b5 reductase medicine to establish a diagnosis of recessive congenital methaemoglobinaemia (RCM), it is important to demonstrate enzyme deficiency of cb5r and this is usually done using a spectrophotometric method,. RCM type I patients manifest a deficiency of cb5r in erythrocytes only whereas type II patients harbour the deficiency in both erythrocytes and leucocytes 1.6.2.4 NADPH-hemoprotein reductase medicine medical research, expression systems allows examinations on the activation of promutagenic drugs 1.6.2.4 NADPH-hemoprotein reductase medicine presence of quercetin and (-)-epigallocatechin gallate in human diet may increase P-450 reductase activity during doxorubicin therapy (antitumour drug) with subsequent increased risk of toxicity 1.6.2.4 NADPH-hemoprotein reductase medicine manifesting heterozygosity is a possible feature of P450 oxidoreductase deficiency 1.6.2.4 NADPH-hemoprotein reductase medicine nitrofurantoin-induced redox cycling and subsequent generation of reactive oxygen intermediates are not sufficient to mediate cytotoxicity. Cytochrome P450 reductase is not a determinant of sensitivity to redox-active chemotherapeutic agents 1.6.2.4 NADPH-hemoprotein reductase medicine the POR genotype contributes to breast cancer risk among African American women 1.6.2.4 NADPH-hemoprotein reductase medicine triple mutant L86F/L219F/P456A or a double mutant L86F/L219F enzyme will serve as a good model of mosquito CYPOR in future structural studies and in the development of new antimalarial agents 1.6.2.4 NADPH-hemoprotein reductase medicine a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine administration of thrombin to endothelial cells leads to upregulation of enzyme subunit p22phox accompanied by a delayed increase in generation of reactive oxygen species and enhanced proliferation. Existence of a positive feedback mechanism, whereby reactive oxygen species lead to elevated levels of p22phox and thus, sustained generation of reactive oxygen species as is observed in endothelial dysfunction 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine mutations in enzyme gene should be considered as the molecular cause of congenital hypothyroidism in young patients with thyroid dyshormogenesis 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine proliferation of microglial cells induced by fibrillar beta-amyloid peptide Abeta1-40 is mediated both by microglial release of TNF-alpha and by production of hydrogen peroxide by enzyme. TNF-alpha and enzyme, and its products, are potential targets to prevent Abeta-induced inflammatory neurodegeneration 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine TNF-alpha activates enzyme, resulting in an increase in intracellular H2O2 that stimulates Ca2+ sparks and transient Kca currents, leading to a reduction in global concentration of Ca2+ and vasodilation 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine (pro)renin receptor is constitutively expressed in renal glomeruli and tubules. Expression of the receptor is upregulated in diabetes via enhancement of angiotensin subtype 1 receptor-NADPH oxidase activity 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine after 14 days, local treatment with apocynin via the adventitia, reduces superoxide generation. Apocynin significantly reduces neointima formation and proliferation of cells in both the neointima and adventitia. Nitric oxide-dependent vasorelaxation to acetylcholine, which is normally impaired in collared arteries, is improved, and apocynin suppresses the endothelial expression of intracellular adhesion molecule- and vascular cell adhesion molecule- 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine after addition of thrombin to cell culture, expression of NADPH oxidase subunits p47phox and p67phox occurs, accompanied by up-regulation in the expression of cytosolic enzyme components Rac 1 and p67phox, and the translocation of cytosolic subunits p47phox and p67phox to the membrane. Thrombin-induced reactive oxygen species production, protein oxidation, and loss of cultured hippocampal neurons are partially attenuated by NADPH oxidase inhibition and/or by several antioxidants 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine after myocardial infarction, NAD(P)H oxidase activity is markedly increased in remote left ventricular myocardium of wild-type mice but not in mice deficient in subunit p47phox. Increased myocardial xanthine oxidase activity is observed in wild-type, but not in p47phox-deficient mice after myocardial infarction. Left ventricular cavity dilatation and dysfunction 4 weeks after infarction are markedly attenuated in p47phox-deficient mice and cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis are substantially reduced as compared with wild-type. The survival rate is markedly higher in mice deficient in subunit p47phox 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine analysis of pre-interventional intravascular ultrasound images and histological specimens obtained by directional coronary artherectomy of patients with atherosclerosis. Reactive oxygen positive area ratio in directional coronary artherectomy probes correlates positiviely with vessel cross-sectional area, and relative plaque area. The area immunopositive for subunit p22phox also correlates positively with vessel cross-sectional area, and relative plaque area 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine angiotensin-(1-7) decreases the elevated levels of renal NADPH oxidase activity and attenuates the activation of subunit NOX-4 gene expression in the diabetic hypertensive kidney. Angiotensin-(1-7) treatment increases sodium excretion but does not affect mean arterial pressure in diabetic hypertensive rats. The significant increase in urinary protein in the diabetic compared to control hypertensive rat is reduced by angiotensin-(1-). Angiotensin-(1-7) treatment also attenuates the diabetes-induced increase in renal vascular responsiveness to endothelin-1, norepinephrine, and angiotensin II in hypertensive rats, but significantly increases the vasodilation of the renal artery of hypertensive and diabetic hypertensive rats to the vasodilator agonists 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine aortas of transgenic rats harboring the mouse renin transgene exhibit greater NADPH oxidase activity, reactive oxygen species levels, C-reactive protein, tumor necrosis factor-alpha expression, apoptosis, and wall thickness, which are significantly attenuated by in vivo treatment with angiotensin type 1 receptor blockade by valsartan or the superoxide dismutase/catalase mimetic tempol 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine apocynin reduces avascularity and apoptosis in the oxygen-indunced retinopathy model. The antioxidant properties of N-acetylcysteine are not effective in reducing intravitreous neovasicularization or avascular retina 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine application of HIV regulatory protein Tat to microglia or macrophages causes dose- and time-dependent increases in superoxide formation that are prevented by both pharmacologic NADPH oxidase inhibitors and by specific decoy peptides gp91ds. Inhibition of NADPH oxidase attenuates Tat-induced release of IL-6 and TNFalpha, and MCP-1, and decreases microglial-mediated neurotoxicity. Macrophages derived from NADPH oxidase deficient mice display reduced superoxide production, released lower levels of cytokines/chemokines, and induce less neurotoxicity in response to Tat compared to wild-type macrophages 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine characterization of mutant V674G. Thyroid glands of mutant mice are goitrous and contain few normal follicles, anterior pituitaries are dysplastic. Serum thyroxine in homozygotes is about one-tenth the level of controls.. the weight of adult mutant mice is approximately half that of littermate controls, and serum IGF-I is reduced. The cochleae of mutant mice exhibit abnormalities characteristic of hypothyroidism, including a delayed formation of the inner sulcus and tunnel of Corti and an abnormally thickened tectorial membrane. Hearing thresholds of adult mutant mice are on average 50-60 decibels above those of controls 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine chronic administration of agents that induce hypertension can also produce changes in the subcellular localization in subunit p47phox in dorsomedial nucleus tractus solitarius neurons. Systemic hypertension may produce alterations in the trafficking of proteins associated with superoxide production in central autonomic neurons. Administration of angiotensin over 7 days, which produces elevated systemic blood pressure, is associated with a redistribution of p47phox immunolabeling away from intracellular organelles in the distal dendritic compartment, and toward non-vesicular targets in less distal, intermediate areas of dorsomedial nucleus tractus solitarius neurons. Chronic administration of phenylephrine, which produces increases in systolic blood pressure, is associated with a repartitioning of p47phox immunolabeling away from intracellular organelles in distal dendritic areas, andtoward the plasma membrane of intermediate dendritic areas of dorsomedial nucleus tractus solitarius neurons 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine diabetes-induced translocation of protein kinase C, specifically PKC-alpha to renal membranes is associated with increased NADPH-dependent superoxide production. In both diabetic animals and in advanced glycation end products-treated mesangial cells, blockade of NADPH oxidase or PKC-alpha attenuates cytosolic superoxide and protein kinase C activation and increases vascular endothelial growth factor 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine experimental model of spontaneous intracranial hemorrhage in transgenic mice expressing human renin and human angiotensinogen treated with high-salt diet and Nomega-nitro-L-arginine methyl ester. In these mice, NAD(P)H oxidase activity is significantly increased. Increased enzyme activity preceeds signs of spontaneous intracranial hemorrhage and increases further whith development of intracranial hemorrhage 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine exposure of porcine coronary artery endothelial cells, PCAECs, to hypoxia for 2 h followed by 1 h of reoxygenation significantly increases reactive oxygen species formation. Pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium and apocynin, significantly attenuates hypoxia/reoxygenation-induced reactive oxygen species formation. Exposure of PCAECs to hypoxia/reoxygenation causes a significant increase in serine-threonine kinase Akt and ERK1/2 activation. Exposure of PCAEC spheroids to hypoxia/reoxygenation significantly increases endothelial spheroid sprouting and vessel outgrowth, whereas pharmacological inhibition of NADPH oxidase or genetic deletion of the NADPH oxidase subunit p47phox significantly suppresses these changes 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine expression of isoform Nox4 mRNA in glioblastomas of WHO grade IV is significantly higher than other astrocytomas of WHO grades II and III. Knock-down of isoform Nox4 expression by RNAi results in cell-growth inhibition and enhances induction of apoptosis by chemotherapeutic agents in cultured glioma cell lines 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine glucose-mediated down-regulation of protein kinase G-I expression in vascular smooth muscle cells occurs through protein kinase C-dependent activation of NAD(P)H oxidase derived superoxide production, contributing to diabetes-associated vessel dysfunctions 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine hydrophobic, proapoptotic bile salts induce hepatocyte shrinkage largely through NADPH oxidase-derived oxidative stress. Because cell shrinkage in turn activates NADPH oxidase, which blunts cell volume recovery, a vicious cycle ensues between oxidative stress and cell shrinkage, which propagates CD95 activation and may finally lead to apoptosis 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine hypoosmotic swelling of cardiac myocytes activates volume-sensitive Cl- current via the angiotensin II-reactive oxygen species signalling cascade. In several models of cardiac disease, volume-sensitive Cl- current is persistently activated 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine hypoxic conditions lead to upregulation exclusively of NOX4 mRNA in lung, concomitant with increased levels in microdissected pulmonary arterial vessels. NOX4 mRNA and protein are localized predominantly in the media of small pulmonary arteries, with increased labeling intensities after chronic exposure to hypoxia. In isolated pulmonary arterial smooth muscle cells, NOX4 is localized primarily to the perinuclear space 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in brain capillary endothelial cells, hypoxia/reoxygenation induces translocation of the NAD(P)H oxidase activator Rac-1 to the membrane. Inhibition of Rac-1 prevents the ischemia/reperfusion-induced blood-brain barrier disruption. Activation of NAD(P)H oxidase promotes cerebral reactive oxygen species formation, which then leads to Rho kinase-mediated endothelial cell contraction and disruption of the blood-brain barrier 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in cells continuously treated with nitric oxide donors, including nitroglycerin, over 2-3 days, basal production of nitrite and nitrate is diminished. The diminished basal nitric oxide levels are mitigated by intermittent treatment allowing an 8-h daily nitrate-free interval during the 2- to 3-day treatment period. Addition of the NAD(P)H oxidase inhibitor apocynin restores the basal levels of nitric oxides that are decreased by continuous nitroglycerin treatment. Apocynin causes significant improvement of increased mRNA and protein levels of endothelial nitric oxide synthase in cells given nitroglycerin continuously over the treatment period. Apocynin also reduces endothelial production of reactive oxygen species after continuous nitroglycerin treatment 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in lungs from patients with idiopathic pulmonary arterial hypertension, expression levels of NOX4, which is localized in the vessel media, are 2.5-fold upregulated 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in macula densa, increasing luminal NaCl induces superoxide anion production during tubuloglomerular feedback. Superoxide anion generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in obese, diabetic, leptin-receptor deficient db-/db- mice, mRNA levels of enzyme subunits Nox-1, Nox-2, and Nox-4 as well as Nox-2 protein expression are elevated, whereas aortic Cu/Zn superoxide dismutase protein and PPARgamma mRNA levels are reduced 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in peripheral blood lymphocytes from children with acute asthma, activity of NAD(P)H oxidase is significantly increased. Plasma levels of malondialdehyde, and nitric oxide are also markedly elevated, while catalase activity is decreased. Treatment of lymphocytes with salbutamol at 10 microg per ml, prevents the attenuation of catalase activity but significantly increases the levels of nitroc oxide and NAD(P)H oxidase activity. Levels of isoform NOX-1 mRNA are significantly increased in peripheral blodd lymphocytes following treatment with NO donor, S-nitroso-N-acetyl penicillamine. Subunit gp91phox protein is also two- to threefold increased following treatment with S-nitroso-N-acetyl penicillamine and leads to increased NAD(P)H oxidase activity 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in rabbits with heart failure induced by myocardial infarction, treatment with inhibitor apocynin reduces NADPH oxidase activity, subunit p47phox protein, oxidative stress, myocyte apoptosis, and Bax protein, increases Bcl-2 protein, and ameliorates left ventricular dilatation and dysfunction 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in sarcoplasmic reticulum vesicles isolated after exercise and tachycardia, increase in NAD(P)H oxidase activity, ryanodine receptor-2 S-glutathionylation, and calcium release rates. Apocynin prevents the increase in ryanodine receptor-2 S-glutathionylation, reduced calcium release activity, and completely prevents the protective effects of exercise and tachycardia on infarct size 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine increased oxidative stress in the vasculature of streptozotocin-induced diabetic apoE-deficient mice is linked to changes in endothelial nitric oxide synthase, superoxide dismutase and NADPH oxidase expression 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine increases in myocardial serine-threonine kinase Akt and ERK1/2 activation and vascular endothelial growth factor expression are markedly blunted in the subunit p47phox-deficient mouse subjected to myocardial ischemia-reperfusion compared with the wild-type mouse 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine incubation of microglial cultures in the presence of fibrillar amyloid beta1-42 induces the assembly and the activation of NADPH oxidase, and triggers the production of superoxide anion-derived reactive oxygen species. Pretreatment of microglia with melatonin dosedependently prevents the activation of NADPH oxidase and decreases the production of reactive oxygen species. Melatonin inhibits the phosphorylation of the p47phox subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47phox and p67phox subunit to the membrane, down-regulates the binding of p47phox to gp91phox, and impairs the assembly of NADPH oxidase 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine induction of sterile hyperinflammation by injection of fungal cell wall preparations in chronic granulomatous disease mouse model. Preparations from Aspergillus fumigatus, Candida albicans, or Saccharomyces cerevisiae cause prolonged and severe skin inflammation, but not preparations from bacteria such as Staphylococcus aureus, Pseudomonas aerginosa, or Escherichia coli. Components most responsible for the inflammatory effect are branched fungal beta-glucans 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine induction of superoxide production by doxorubicin is much higher in hearts of wild-type mice than in subunit gp91phox knock-out mice. Superoxide production is similarly induced by addition of NADPH cytochrome P450 reductase 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine inhibition of NAD(P)H oxidase by apocynin in ischemia-induced mice prevents blood-brain barrier damage in the ischemic hemisphere I after reperfusion. In mice deficient in subunit gp91phox, middle cerebral artery occlusion-induced blood-brain barrier disruption and lesion volume in ischemia-induced animals are largely attenuated. Activation of NAD(P)H oxidase promotes cerebral reactive oxygen species formation, which then leads to Rho kinase-mediated endothelial cell contraction and disruption of the blood-brain barrier 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine inhibition of subunit Nox4 expression by small interfering RNA reduces angiogenic responses, in both human microvascular and umbilical vein endothelial cells. Overexpression of wild-type Nox4 enhances, whereas expression of a dominant negative form of Nox4 suppresses the angiogenic responses in endothelial cells. These effects are mimicked by exogenous H2O2 and the antioxidant compound ebselen, respectively. Overexpression of Nox4 enhances receptor tyrosine kinase phosphorylation and the activation of extracellular signal-regulated kinase. Nox4 expression also promotes proliferation and migration of endothelial cells, and reduces serum deprivation-induced apoptosis 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine intrarenal infusions of angiotensin II both in vitro and in vivo increase renal vascular resistance, and alpha2-adrenoceptor agonist UK14,304 enhances this response. The interaction between angiotensin II and UK14,304 is blocked by inhibitors of NAD(P)H oxidase 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine intravitreal injections of angiotensin II can result in retinal leukostasis, which appears to be mediated via increasing superoxide generation by NAD(P)H oxidase, and by vasular endothelial growth factor. The activity of NAD(P)H oxidase is required for leukostasis to occur in the diabetic retina 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine isoform Nox4 is expressed at high levels in white and brown preadipocytes. Differentiation into adipocytes results in a decrease in their NOX4 mRNA content. In intact adipose tissue, the majority of NOX4 expressing cells are localized within the preadipocyte containing stromal/vascular fracftion. Alterations in NOX4 expression reflects changes in the ratio of adipocyte/interstitial fractions 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine isoobtusilactone A elicits a concentration-dependent growth impediment with IC50 value of 37.5 microM. Treated cells also display transient increase of reactive oxygen species during the earlier stage of the experiment, followed by the disruption of mitochondrial transmembrane potential. The presence of a reactive oxygen species scavenger N-acetyl-L-cysteine and the inhibitor of NADPH oxidase diphenyleneiodonium chloride block reactive oxygen species production and the subsequent apoptotic cell death 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine long-term survival mechanisms in niacin deficient HaCaT keratinocyte cells involve accumulation of reactive oxygen species and increased DNA damage with concomitant increase in expression and activity of NAD(P)H oxidase 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine mice deficient in NAD(P)H oxidase p47phox show an increase of 17% of the area occupied by airway smooth muscle cells in trachea, compared with wild-type. They exhibit a significantly reduced airway smooth muscle cell relaxation during electric field stimulation and after the end of stimulation. NAD(P)H oxidase may have a role in the structural arrangement and mechanical properties of the airway tissue 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine mice lacking the NAD(P)H oxidase gp91phox subunit respond to exposure to single-walled carbon nanotubes with a marked accumulation of polymorphnuclear neutrophils and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-beta, and significantly lower levels of collagen deposition 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine microinjection of lipopolysaccharide bilaterally into the rostral ventrolateral medulla induces progressive hypotension, bradycardia, and reduction in sympathetic vasomotor outflow. This is accompanied by an increase in superoxide anion production for 60-240 min, alongside phosphorylation of subunits p47phox or p67phox, upregulation of gp91phox or p47phox protein, and increase in Rac-1 or NADPH oxidase activity during 60-120 min, and a depression of mitochondrial respiratory enzyme activity during 120-240 min. Inhibition of NADPH oxidase or knockdown of the gp91phox or p47phox gene blunts the early phase of 60-150 min, coenzyme Q10 or mitochondrial KATP channel inhibitor antagonizes the delayed phase of 120-240 min of lipopolysaccharide-nduced increase in superoxide anion production in rostral ventrolateral medulla and cardiovascular depression 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine monocytes from sickle cell disease patients show higher levels of NAD(P)H oxidase subunit gp91phox gene expression and p47phox phosphorylation, along with increased interferon-gamma release by lymphocytes 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide i.e. FLZ, squamosamide derivative. FLZ inhibits the translocation of the cytosolic subunit p47phox to the membrane and thus inhibits the activation of NAD(P)H oxidase. In vivo, FLZ significantly protects against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced dopaminergic neuronal loss 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine NADPH oxidase is involved in killing of Candida albicans by dendritic cells, which is increased by interferon-alpha or interferon-gamma. However, Candida escapes the oxidative damage by inhibiting NADPH oxidase and by entering dendritic cells through receptors not involved in NADPH oxidase activation 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine neuroblastoma cell, cells differentiated by retinoic acid die after exposure to glycated albumin, a model of advanced glycation end product-modified protein. Undifferentiated cells are resistant to glycated albumin. Differentiated cells pre-treated with NAD(P)K oxidase inhibitor diphenyleneiodinium or with rottlerin, an inhibitor of protein kinase C delta, are able to prevent neuronal death induced by glycated albumin 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine neutrophil cytosolic factor 1-deficient mice lacking functional NADPH oxidase are resistant to skin blistering by the passive transfer of antibodies against type VII collagen. Recruitment of granulocytes into the skin is required for tissue injury, as demonstrated by the resistance to experimental blistering of wild-type mice depleted of neutrophils and of CD18-deficient mice. Granulocyte-derived NADPH oxidase is a key molecular effector engaged by pathogenic autoantibodies and provides relevant targets for prevention of tissue damage in granulocyte-mediated autoimmune diseases 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine neutropjhil NAD(P)H oxidase activation, induced by hemorrhagic shock/resuscitation and as mediated by high-mobility group box HMGB1/TLR4 signaling, is an important mechanism responsible for hemorrhagic shock/resuscitation-mediated inflammation and organ injury after hemorrhage 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine on a high-salt diet of 4% NaC1, male and obese rats have significantly higher mean arterial blood pressure relative to female and lean rats and reduced renal cortical nitric oxide synthase activity. Lean female rats have the highest outer medullary protein levels of several NADPH oxidase subunits, including gp91phox, p47phox, and p67phox, however, renal NADPH activity is not increased in lean females, but is significantly increased in obese rats of both sexes 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine overweight and obese adults demonstrate increased vascular endothelial expression of NAD(P)H oxidase subunit p47phox and evidence of endothelial oxidative stress, with selective compensatory upregulation of antioxidant enzymes and Ser1177-phosphorylated endothelial nitric oxide synthase. Endothelin-1 and nuclear factor kappaB protein expression also appear to be elevated in obese compared with lean adults 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine pharmacological inhibition or deficiency of human NADPH oxidase abolishes dermal-epidermal separation caused by autoantibodies and granulocytes ex vivo. Granulocyte-derived NADPH oxidase is a key molecular effector engaged by pathogenic autoantibodies and provides relevant targets for prevention of tissue damage in granulocyte-mediated autoimmune diseases 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine pivotal role of myeloid Src family kinases and complement receptor 3 in mounting an effective defense against infection with Streptococcus pneumonia by regulating phagocytosis and NADPH oxidase-dependent superoxide production. Leukocyte recruitment into the cerebrospinal fluid space and bacterial clearance is hampered in mice deficient in all three myeloid Src family kinases during pneumococcal meningitis. The mice develop increased intracranial pressure and a worse clinical outcome with increased neurologic deficits and mortality, compared with wildtype mice. In neutrophils of mice deficient for myeloid Src family kinases p59/61hck, p58c-fgr, and p53/56lyn, phosphorylation of NAD(P)H oxidase subunit p40phox is absent, indicating a defect in enzyme activation 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine platelets and leukocytes from high cholesterol-fed mice exhibit elevated generation of reactive oxygen species compared to normal diet mice. Hypercholesterolemia-induced leukocyte recruitment is attenuated in Cu,Zn-superoxide dismutase transgenic, and NAD(P)H oxidase-knockout mice on high cholesterol diet. Platelets from NAD(P)H oxidase-knockout mice on high cholesterol diet exhibit low levels of adhesion comparable to those of wild-type on normal diet. Overexpression of Cu,Zn-superoxide dismutase or, to a lesser extent, NAD(P)H oxidase subunit gp91 deficiency restores arteriolar vasorelaxation responses toward normal diet wild-type levels 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine pre-treatment of NB-4 cells with inhibitor diphenyleneiodinium blocks arsenic trioxide-induced apoptosis 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine reactive oxygen species produced upstream of Ca2+ influx by NADPH oxidase and downstream of Ca2+ influx by the mitochondria regulate the proinflammatory response of mast cells 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine rosiglitazone activates 5'-AMP-activated protein kinase which, in turn, prevents hyperactivity of NAD(P)H oxidase induced by high glucose, possibly through protein kinase C inhibition. Rosiglitazone protects endothelial cells against glucose-induced oxidative stress with an 5'-AMP-activated protein kinase-dependent and a PPARgamma-independent mechanism 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine rosuvastatin reduces systolic blood pressure in spontaneously hypertensive rats but does not change plasma lipid levels. Rosuvastatin treatment in spontaneously hypertensive rats significantly decreases reactive oxygen species levels , NAD(P)H activity in retinal ganglion cells, and increases retinal plasmalogen content in spontaneously hypertensive rats, but does not modify the electroretinogram response 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine salt sensitivity in the salt-sensitive rat is associated with upregulations of the intrarenal angiotensin system, reactive oxygen species-generating and proinflammatory/profibrotic proteins and an inability to raise antioxidant enzymes and maximally suppress plasma renin activity in response to high salt intake 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine single nucleotide polymorphisms 242C/T and 640A/G in the gene encoding p22phox subunit of NAD(P)H oxidase are marginally significantly associated with asthma, but single nucleotide polymorphisms 640A/G shows a significant association with sensitization to two allergens tested. Haplotype 930G/242T/640A is associated with an increased risk of asthma 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine study on the aggregation of platelets from high-risk cardiac patients with aspirin resistance in presence of adenosine diphosphate, collagen, and epinephrine. Inhibition of NAD(P)H oxidase effectively suppresses collagen and epinephrine-induced aggregation 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine the morphinan analog, sinomenine inhibits NAD(P)H oxidase cytosolic subunit p47phox translocation to the cell membrane and thus reduces lipopolysaccharide-induced extracellular reactive oxygen species production. Sinomenine protects neuron-glial cell cultures at both micro- and sub-picomolar concentrations against dopaminergic neuron death, but not protection is seen at nanomolar concentrations 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine treatment of animals by oral administration of isoobtusilactone A for two weeks does not result in significant difference between control animals and treated animals with respect to the body weight gain, the body weight ratio of liver, spleen and kidney, haematological and clinical chemistry parameters 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine treatment of fibroblasts with tumor necrosis factor induces the formation of a signaling complex containing TNF-R1-associated death domain protein TRADD, receptor interacting protein RIP1, NAD(P)H oxidase Nox1, and the small GTPase Rac1. Formation of this complex plays a key role in tumor necrosis factor-induced necrotic cell death 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine treatment with peptidyl inhibitor gp91ds-tat reduces proliferation and migration of cultured microvascular endothelial cells 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine vascular cell adhesion molecule-1 induction of NADPH oxidase in the endothelium is necessary for the eosinophil recruitment during allergic inflammation 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine water-soluble components of cigarette smoke activate the vascular NAD(P)H oxidase. NAD(P)H oxidase-derived H2O2 activates NF-kappaB, leading to proinflammatory alterations in vascular phenotype, which likely promotes development of atherosclerosis 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine wild-type mice fed with high-cholesterol diet exhibit impaired endothelium-dependent vasodilation, enhanced superoxide generation, and increased expression of NAD(P)H oxidase subunit Nox-2 mRNA. In severe combined immunodeficient mice, in mice genetically deficient for interferon IFN-gamma, and CD4+ T-lymphocyte-deficient mice, the impaired endothelium-dependent vasodilation and enhanced superoxide generation are significantly blunted. Effects are similar in high-cholesterol fed mice genetically deficient in NAD(P)H oxidase subunit Nox-2 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine wild-type mice with myocardial infarction display significantly increased gp91phox and 3-nitrotyrosine in the infarcted myocardium, accumulated macrophages and myofibroblasts at the infarct site, abundant apoptotic myocytes primarily at border zones on day 3, and numerous apoptotic inflammatory/myofibroblasts in the later stages. Transforming growth factor 1, tissue inhibitor of metalloprotease 2, and type 1 collagen gene expression is increased, collagen volume in the infarcted myocardium continuously increases, and noninfarcted myocardium displays hypertrophy. Compared to wild-type mice with myocardial infarction, subunit gp91phox knockout mice do not display significant difference in infarct size/thickness, cardiac hypertrophy, myocyte apoptosis, inflammatory/fibrogenic responses, as well as cardiac oxidative stress 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine Burkholderia cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane. This phenomenon may contribute to preventing the efficient clearance of this opportunistic pathogen from the infected airways of susceptible patients 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components. Clinical, functional, and molecular investigation of chronic granulomatous disease in nine Jordanian families 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine inactivating mutations of Duox2 are linked to congenital hypothyroidism, and epigenetic silencing of Duox is frequently observed in lung cancer 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine as NAD(P)H oxidase activation may have dual actions in diabetes, selective targeting of the deleterious effects of sustained NAD(P)H oxidase activation, such as eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant gene expression, may prove beneficial in the treatment of diabetes 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine NADPH oxidase type 4 is a major source of oxidative stress and an effective therapeutic target in acute stroke 1.6.3.1 NAD(P)H oxidase (H2O2-forming) medicine in apolipoprotein E-knockout mice, aequous extract of Tessaria absinthioides and Prosopis strombulifera significantly reduce triglycerides and lipid peroxidation, increase plasma total antioxidant status, and improve glutathione peroxidase activity in the liver. Under high-fat diet, both extracts are able to inhibit O2 anion generation in the aortic tissue and cause a significant regression of atheroma plaques 1.6.3.5 renalase medicine plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects 1.6.3.5 renalase medicine renalase deficiency is associated with increased renal dopamine synthesis, stimulated phosphate excretion, and moderately severe hypophosphatemia. The signal to increase renal dopamine synthesis is strong since it overcomes a compensatory increase in catechol-O-methyl transferase activity 1.6.3.5 renalase medicine renalase infusion in rats causes a decrease in cardiac contractility, heart rate, and blood pressure and prevents a compensatory increase in peripheral vascular tone 1.6.3.5 renalase medicine renalase is a cardiovascular drug for ischemia/ischemia reperfusion injury 1.6.3.5 renalase medicine in chronic pancreatitis, renalase immunoreactivity localizes to peri-acinar spindle-shaped cells in some samples and is also widely present in pancreatic ductal adenocarcinoma precursor lesions and pancreatic ductal adenocarcinoma tissue. Among 240 patients with pancreatic ductal adenocarcinoma, elevated plasma renalase levels are associated with worse tumor characteristics, including greater angiolymphatic invasion and greater node positive disease. Overall survival is worse in patients with high plasma renalase levels. Renalase levels also predict whether patients with locally advanced/borderline resectable pancreatic ductal adenocarcinoma undergo resection 1.6.3.5 renalase medicine renalase levels are significantly lower in schizophrenia patients than in the control group, whereas dopamine levels are significantly higher. The epinephrine levels of both groups are similar, while the norepinephrine levels in patients with schizophrenia are significantly lower than those in the control group 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine activation of antitumor prodrugs 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine acetaminophen is bioactivated by cytochrome P450 to the reactive intermediate N-acetyl-p-benzoquinone imine. Enhanced levels of hepatic enzyme may detoxify N-acetyl-p-benzoquinone imine by reducing it back to acetaminophen 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine antitumour quinones 2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone and 2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone, i.e. RH1 and MeDZQ resp., induce apoptosis via enzyme-linked formation of alkylating species rather than via enzyme-linked redox cycling 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine ascorbic acid may potentiate the therapeutic efficacy of As3+ in treatment of acute promyelotic leukemia by enhancing the expression of enzyme together with heme oxygenase-1 and glutathione S-transferase Ya 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine clofibrate-mediated hepatoprotection against acetaminophen does not appear to be dependent upon enhanced expression of enzyme. Conditions of 94% inhobition of enzyme do not increase the susceptibility of hepatocytes from clofibrate treated mice to acetaminophen 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine enzyme is highly upregulated in active and chronic multiple sclerosis lesions, particularly in hypertrophic astrocytes and myelin-laden macrophages 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine enzyme protein is low in normal liver. Livers from patients with damage due to acetaminophen overdose or primary biliary cirrhosis show a strong induction of enzyme protein and activity 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine higher levels of enzyme expression in pancreatic adenocarcinomas compared to nontumourous tissues from nonsmokers. High levels are also found in pancreas of smokers and in pancreatitis tissues. No differences are found in genotype distribution and frequencies of the variant alleles between normal and cancer tissues. Use of enzyme expression as a biomarker for pancreatic cancer 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine presence of significant interethnic differences in polymorphic hepatic enzyme activity. Black donors show about twofold higher enzyme activity than white donors, and cytosolic enzyme activities differ significantly by enzyme genotype status in white, but not in black donors 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine statistically significant risk for colorectal cancer is associated with variant enzyme genotypes 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 guards against oxidative stress and carcinogenesis and stabilizes p53, a homozygous common missense variant, NQO1*2, P187S that disables NQO1 predicts poor survival of women with breast cancer, NQO1 deficiency implicates cancer progression and treatment resistance to epirubicin, the NQO1 status is important for the response to epirubicin, ionizing radiation or 5-FU is not, NQO1 genotype is a prognostic and predictive marker for breast cancer 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 polymorphism analysis is performed to investigate the relationship between prostate cancer and NQO1 C609T polymorphism in a turkish population, no correlation is found 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 polymorphism analysis is performed using genomic DNA from blood samples, NQO1 polymorphisms, C/T and T/T genotypes, are associated with the risk of urothelial cancer, particularly among those who have ever smoked 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 polymorphism analysis is performed using genomic DNA from buccal cell samples, anthracycline-related congestive heart failure is an important long-term complication among childhood cancer survivors, NQO1 polymorphism analysis indicated no association between the NQO1 polymorphism and the risk of anthracycline-related congestive heart failure 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 polymorphism analysis is performed using genomic DNA from rectal biopsy samples, genotypes of C609T, T609T and C609C, G718G, A718A and A718G polymorphisms of NQO1 are compared, C609C genotype shows higher activity, C609T polymorphism is a important predictor for rectal NQO1 activity, fruit and vegetable consumption have no influence on NQO1 activity 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine series of indolequinones are synthesized and tested as inhibitors for NQO1 in pancreatic tumor cells, NQO1 inhibition does not correlate with growth inhibitory activity in MiaPaCa-2 cells 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine 3-nitrobenzanthrone is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine 3H-1,2-dithiole-3-thione potently induces neuronal cellular GSH and NQO1 as well as mitochondrial GSH. Such upregulated endogenous defenses are accompanied by increased resistance to oxidative and electrophilic neurocytotoxicity, e.g. in Parkinson's disease 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine acute manganese intoxication, similarly to that of cadmium and other heavy metals, increases both the hepatic level of Nrf2 and its transfer from the cytoplasm to the nucleus where it actively regulates the induction of phase II enzymes, e.g. NQO1 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine dependence of copper neurotoxicity on DT-diaphorase inhibition 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine exposed workers to benzene in the petroleum refining industry with the T/T genotype for NQO1 show significant 1.9fold and 2.6fold increases in micronuclei and chromosome aberrations frequencies, respectively, compared to controls with C/C and C/T genotypes, after adjusting for age, smoking status, and alcohol intake 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine genetic variation, especially the NQO1 609CT polymorphism, is a more important predictor of rectal NQO1 phenotype than fruit and vegetable consumption. White blood cell NQO1 activity is not a good surrogate for rectal activity 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine individuals with the NQO1*2 allele are more susceptible to the toxic effects of benzene metabolites. Quinones that are good substrates for human NQO1 are more toxic to the NQO1 containing or expressing tumour cell lines than the NQO1-deficient cell lines. Quinones such as the biphenyl and naphthyl derivatives that are poor substrates show no selectivity or have no measurable cytotoxicity 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine main function of QR1 is probably the detoxification of dietary quinones but it may also contribute to the reduction of vitamin K for its involvement in blood coagluation 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine neuroprotective role of DT-diaphorase against aminochrome neurotoxicity 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine no association between NQO1 polymorphism and the risk of anthracycline-related congestive heart failure among childhood cancer survivors 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 and SULT1A1 polymorphisms are associated with the risk of urothelial cancer, particularly among those who have ever smoked 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 gene polymorphism influences interleukin-6 levels and therefore attenuates the inflammatory response after cardiopulmonary bypass 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1-induced bioreduction of beta-lap is an essential step in beta-lap-induced cell death. Combined radiotherapy and beta-lap treatment can have a significant effect on human tumor xenografts 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine plays a protective role against the induction of renal tumors by diethylstilbestrol 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine strain difference where Sprague Dawley rats possess a sex-dependent expression and activity of Nqo1 and August Copenhagen x Irish rats exhibit no sexual dimorphism may provide an important tool when using these rat models for oxidative stress and cancer studies 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine synthesis of novel heterocyclic quinones (benzimidazole- and benzothiazole-quinones) as excellent substrates for recombinant human NQO1 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine there is no significant relationship between NQO1 gene C609kT polymorphism and prostate cancer in a Turkish population, but an increased frequency of the TT genotype in patients compared to controls. Carrying the T allele may have an effect on serum prostate specific antigen and alkaline phosphatase levels in prostate cancer patients 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine trend toward lower drug response in patients with the NQO1 null genotype. Inhibiting NQO1 activity decreases p53 levels and drug induced apoptosis in chronic lymphocytic leukemia cells. NQO1 polymorphism may be a risk factor for chronic lymphocytic leukemia especially in males, and a predictor of response to chemotherapy 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine combination therapy employing a member of the group of non-cytotoxic NQO1 inhibitors together with a 2,6-dichlorophenolindophenol-like molecule may provide therapeutic efficacy against tumors that display high NQO1 enzymatic activity 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine isoform NQO1-KO mice exhibit a marked increase of permeability and spontaneous inflammation in the gut. In the dextran sulfate sodium salt-induced colitis model, NQO1-KO mice show more severe inflammatory responses than NQO1-wild-type mice. The transcript levels of claudin and occludin, the major tight junction molecules of gut epithelial cells, are significantly decreased in NQO1-KO mice. The colons of NQO1-KO mice also show high levels of reactive oxygen species and histone deacetylase activity 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine protein expression but not activity of NQO1 is weakly negatively correlated with age. No sex differences are observed for either protein expression or activity and for ethnicity. Caucasians have greater NQO1 activity than Asians. Overweight children have statistically significantly higher NQO1 activity as compared with ideal weight children 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine (+-)-dunnione and its ortho-quinone analogues act as substrates. The biological activity is favored by the presence of methyl group at the C ring and methoxy group at the A ring. The ortho-quinones exert their antitumor activity through NQO1-mediated reactive oxygen species production by redox cycling 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine development of an NQO1-targeted radiolabeled agent to establish an internal radiation therapy that amplifies the therapeutic effects when combined with external radiation therapy. The uptake of [125I]-marked compound 3-([[4-iodophenyl]thio]methyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione is specific and is dependent on the expression of NQO1. In NQO1-expressing tumor cells, over 85% of the initial radioactivity of [125I]-marked 3-([[4-iodophenyl]thio]methyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione is observed as an intact form at 1 h after incubation 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine in sub-chronic studies upon oral exposure to sulphoraphane for 30 days a 2- to 3fold increase in GSTM1, Gclc and NQO1 transcript levels, and a 2fold increase in NQO1 activity in adult livers is observed 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine levels of NQO1 protein and mRNA are significantly elevated in fresh tissue samples of small cell lung cancer. The rate of strong positive NQO1 protein expression is significantly higher in small cell lung cancer when compared with the rate in either adjacent non-cancerous or normal lung tissues and correlated with large tumor size, late pathologic stage and the presence of lymph node metastasis. High?level expression of NQO1 protein is significantly correlated with lower disease-free survival and 5-year survival rates in patients 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine low hepatic expression of the active glutathione S-transferases and NQO1 may increase the susceptibility of patients to amodiaquine idiosyncratic hepatotoxicity. NQO1 inactivates protein reactive quinonimines such as amodiaquine by reduction 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine natural polymor­phism C609T may affect amrubicin-related pharmacokinetics and clinical outcomes in lung cancer treatment. At a dose of 40 mg/m2, the T/T genotype exhibits a tendency toward a relationship with decreased concentrations of amrubicinol on days 2 and 4 of treatment. The genotype also shows a significant decrease of hematological toxicities 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 is highly expressed in normal melanocytes and in several melanoma cell lines in the presence of wild-type KEAP1, whose mutation elicits constitutive NRF2 activation and resistance to cisplatin. NQO1 expression is dependent on NRF2 activation. Synergistic cytotoxicity of HSP90 inhibitor 17-AAG, i.e. 17-(allylamino)-17-demethoxygeldanamycin, and cisplatin is detected in four out of five NQO1-low cell lines, but not in a cell line with KEAP1 mutation 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 overexpression induces hepatocellular carcinoma cell apoptosis and proliferation inhibition through the AMPK/PGC-1a pathway 1.6.5.2 NAD(P)H dehydrogenase (quinone) medicine NQO1 overexpression is a main determinant for a potential chemotherapy resistance or an increased sensitivity to quinone-bearing compounds 1.6.5.5 NADPH:quinone reductase medicine QAO does not possess a protective role in menadione-induced free radical production and DNA damage in human cancer cells. Under aerobic conditions, menadiol produced by QAR is readily oxidized to menadione by two 1-electron steps producing the semiquinone and the parent quinone with concomitant production of superoxide anion, which leads to generation of hydroxyl radicals 1.6.5.5 NADPH:quinone reductase medicine NfsA has potential applications in the anticancer strategy gene-directed enzyme prodrug therapy 1.6.5.10 NADPH dehydrogenase (quinone) medicine arsenic exposure is associated with an increased risk of urothelial carcinoma, inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid, are determined in urothelial carcinoma patients from arsenic-contaminated areas of southwestern Taiwan, no correlation of the arsenic methylation capability of the patients and C609T genotype of NQO1 is found 1.6.5.10 NADPH dehydrogenase (quinone) medicine Pro187Ser polymorphism in NQO1 has a limited role in the development of Tardive dyskinesia (a potentially irreversible side effect of antipsychotic medication treatment that occurs in approximately 25% of chronically treated schizophrenia patients) 1.7.1.3 nitrate reductase (NADPH) medicine the purified native enzyme is successfully used for synthesis of silver nanoparticles in an NADPH-dependent manner using gelatin as a capping agent, analysis by X-ray diffraction, dynamic light scattering spectroscopy, and transmission and scanning electron microscopy, overview. The stable nonaggregating nanoparticles are spherical in shape with an average size of 50 nm and a zeta potential of -34.3. The synthesized nanoparticles show a strong growth inhibitory antimicrobial activity against all tested human pathogenic fungi and bacteria, overview 1.7.1.B3 aromatic nitroreductase [NADPH] medicine NfsA has potential applications in the anticancer strategy gene-directed enzyme prodrug therapy 1.7.1.7 GMP reductase medicine potential target for the treatment of leukemia 1.7.2.1 nitrite reductase (NO-forming) medicine study on use of stabilized hemoglobin as alternative to red cells. Cross-linked hemoglobin bis-tetramers with good oxygen delivery potential have 3fold enhanced nitrite reductase activity, compared to native protein and cross-linked tetramers. Conjugation of four polyethylene glocol chains to the bis-tetramer at each beta-Cys-93 produces a material with additionallly 2.5fold increased nitrite reductase activity while retaining cooperativity 1.7.2.3 trimethylamine-N-oxide reductase medicine detection of the enzyme in blood is associated with gut leakage and systemic inflammation. The enzyme is a biomarker for chronic kidney disease vascular complications 1.7.3.3 factor-independent urate hydroxylase medicine determining the urate concentration in blood and urine 1.7.3.3 factor-independent urate hydroxylase medicine determination of the urate concentration in blood and urine is required for the diagnosis of gout as urate accumulation is a causative factor of gout in humans 1.7.3.3 factor-independent urate hydroxylase medicine substitute for allopurinol in the management of gout and hyperuricaemia 1.7.3.3 factor-independent urate hydroxylase medicine the enzyme might be useful in the treatment of patients with refractory gout, overview 1.7.3.3 factor-independent urate hydroxylase medicine treatment od tumor lysis syndrome, recombinant urate oxidase is effective in reducing uric acid and preventing uric acid accumulation in patients with hematologic malignancies with hyperuricemia or at high risk of developing it, rasburicase represents an effective alternative to allopurinol to promptly reduce uric acid levels, improve patients electrolyte status, and reverse renal insufficiency 1.7.3.3 factor-independent urate hydroxylase medicine urate oxidase is used to reduce toxic urate accumulation during chemotherapy 1.7.3.3 factor-independent urate hydroxylase medicine uricase is an important medical enzyme which can be used to determine urate in clinical analysis, to therapy gout, hyperuricemia, and tumor lysis syndrome 1.7.3.3 factor-independent urate hydroxylase medicine treatment of patients with high risk for tumor lysis syndrome with 0.2 mg/kg intravenously over 30 min, daily, for 4 days leads to 75.3% reduction in plasma uric acid at 4 h as compared to baseline. Recombinant rasburicase that is indigenously developed is effective for prevention and management of hyperuricemia in patients who are at high risk of developing tumor lysis syndrome 1.7.3.3 factor-independent urate hydroxylase medicine oral uricase therapy significantly decreases plasma uric acid concentrations in pigs with chronic kidney disease 1.7.3.3 factor-independent urate hydroxylase medicine the enzyme can be used as biosensor for uric acid measurements in biofluids of sweat and wounds 1.7.3.3 factor-independent urate hydroxylase medicine the enzyme can be used for treating gout disease 1.7.3.3 factor-independent urate hydroxylase medicine the enzyme is used for the treatment of gout and hyperuricemia occurring in tumor lysis syndrome 1.7.3.3 factor-independent urate hydroxylase medicine the enzyme, when engineered as bifunctional protein with uricase and peroxidase activities (constructed by direct fusion of Candida utilis uricase and Vitreoscilla hemoglobin), can be used for evaluation and measurement of uric acid from lyophilized serum 1.8.1.B1 thioredoxin glutathione reductase medicine identification of oxadiazole 2-oxides (TGR inhibitors) as new lead compounds for schistosomiasis chemotherapy 1.8.1.B1 thioredoxin glutathione reductase medicine quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade, several of which are highly potent and should serve both as mechanistic tools for probing the redox balance in Schistosome mansoni, and starting points for developing medicinal leads for treatments for schistosomiasis 1.8.1.B1 thioredoxin glutathione reductase medicine TGR is a key target for antischistosomal drug development 1.8.1.B1 thioredoxin glutathione reductase medicine the enzyme presents a target for anti-schistosomiasis drug development 1.8.1.B1 thioredoxin glutathione reductase medicine the enzyme is a drug target for schistosomiasis 1.8.1.B1 thioredoxin glutathione reductase medicine the enzyme is a drug target in schistosomiasis 1.8.1.B1 thioredoxin glutathione reductase medicine the enzyme is a potential target for development of novel agents against schistosomes 1.8.1.B1 thioredoxin glutathione reductase medicine the enzyme is a promising target for anti Fasciola treatments 1.8.1.B1 thioredoxin glutathione reductase medicine enzyme can be used as a diagnostic target antigen for Schistosama mansoni infection in serum and urine. Sandwich ELISA detects the protein with high diagnostic efficiency in individuals with high or low worm burden 1.8.1.2 assimilatory sulfite reductase (NADPH) medicine potential use of vaccine against Actinobacillus pleuropneumoniae infections 1.8.1.4 dihydrolipoyl dehydrogenase medicine mutations of the enzyme cause the often-fatal human disease known as E3 deficiency 1.8.1.4 dihydrolipoyl dehydrogenase medicine brain DLDH expression and activity undergo independent postnatal maturational increases. Senescence does not confer any detectable change in the activity of DLDH or its susceptibility to inactivation by mitochondrial oxidative stress 1.8.1.4 dihydrolipoyl dehydrogenase medicine dihydrolipoyl dehydrogenase is an important source of reactive oxygen species leading to life span limitation 1.8.1.4 dihydrolipoyl dehydrogenase medicine direct involvement of LpdC in the prolonged retention of coronin-1 on the phagosome, thus promoting phagosome maturation arrest. Under the influence of IFNgamma, LRG-47 is recruited to the phagosome and mediates dislocation of coronin-1 leading ultimately to phagosome acidification and recruitment of lysosomal vacuoles and phagolyosome fusion 1.8.1.4 dihydrolipoyl dehydrogenase medicine linkage and association analysis of diplotypes in the DLD gene with Alzheimer's from the National Institute of Mental Health-National Cell Repository for Alzheimer's disease and Italian data series, controlling for Gender and ApoE e4 status. Significant evidence of association of DLD with Alzheimer's disease. Combining the linkage and association study results for DLD together, leads to a p-value that is more significant than any of the individual p-value results for DLD. Only with sufficiently large sample sizes it is possible to rule out whether the DLD gene is in fact associated with Alzheimer’s disease 1.8.1.4 dihydrolipoyl dehydrogenase medicine lipoamide dehydrogenase activity and metallothionein levels may be critical for dopaminergic neuronal survival in Parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine can affect the lipoamide dehydrogenase activity and metallothionein content to exert its neurotoxicity 1.8.1.4 dihydrolipoyl dehydrogenase medicine NADH diaphorase staining can establish tissue non-viability after radiofrequency ablation, but the timing of staining after treatment must be considered when interpreting results to avoid false positive tests. Tissue that is apparently viable by NADH diaphorase staining within 2.5 hours of radiofrequency ablation may in fact have been ablated 1.8.1.4 dihydrolipoyl dehydrogenase medicine enzyme is surface-exposed and contributes to survival of Pseudomonas aeruginosa in human serum. Enzyme binds the four human plasma proteins, Factor H, factor H-like protein-1, complement factor H-related protein 1, and plasminogen. Factor H contacts the enzyme via short consensus repeats 7 and 18-20. Factor H, factor H-like protein-1, and plasminogen when bound to enzyme are functionally active. Bacterial survival is reduced when the enzyme is blocked on the surface prior to challenge with human serum. Similarly, bacterial survival is reduced up to 84% when the bacteria are challenged with complement active serum depleted of factor H, factor H-like protein-1, and complement factor H-related protein 1 1.8.1.4 dihydrolipoyl dehydrogenase medicine due to its TiO2 binding ability, the enzyme may serve as a molecular bridge between Ti-based medical structures and human tissues 1.8.1.4 dihydrolipoyl dehydrogenase medicine Arg-Gly-Asp-modified enzyme enhances the adhesion of bone forming cells to titanium dioxide implant surfaces 1.8.1.4 dihydrolipoyl dehydrogenase medicine the enzyme is a DNA chelating agent. Enzyme binding to DNA presents a moonlight activity which may be used for DNA alkylating in cancer treatment 1.8.1.7 glutathione-disulfide reductase medicine potential target for chemotherapy 1.8.1.7 glutathione-disulfide reductase medicine mimicking of favism by inhibiting the enzyme with specific inhibitors to protect against malaria 1.8.1.7 glutathione-disulfide reductase medicine potential target of antimalarial and cytostatic agents 1.8.1.7 glutathione-disulfide reductase medicine antimalarial dual drugs based on potent inhibitors of glutathione reductase from Plasmodium falciparum 1.8.1.9 thioredoxin-disulfide reductase medicine target for a chemotherapeutic intervention of malaria 1.8.1.9 thioredoxin-disulfide reductase medicine target for immunostimulating effect of 1-chloro-2,4-dinitrobenzene as agent in AIDS treatment 1.8.1.9 thioredoxin-disulfide reductase medicine development of novel anticancer agents 1.8.1.9 thioredoxin-disulfide reductase medicine potential drug target for malaria chemotherapy 1.8.1.9 thioredoxin-disulfide reductase medicine both pharmacological and toxicological effects of anti-cancer drug cisplatin involve TrxR inactivation, and the large enhancement on cisplatin cure rate in H22 ascites model by using amifostine is, at least in part, ascribed to its selective modulation on TrxR 1.8.1.9 thioredoxin-disulfide reductase medicine TR1 acts largely as a pro-cancer protein and it is a primary target in cancer therapy 1.8.1.9 thioredoxin-disulfide reductase medicine TrxR1 may be one putative cause for glucocorticoid resistance in alopecia areata, AA, through the impact on intracellular redox system 1.8.1.9 thioredoxin-disulfide reductase medicine tumor-bearing mice treated with 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane shows an increase of life span with a comparable effect to cyclophosphamide. Potential usage of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane as a therapeutic agent against non-solid tumors 1.8.1.9 thioredoxin-disulfide reductase medicine thioredoxin reductase is a antimalarial drug target 1.8.1.9 thioredoxin-disulfide reductase medicine inhibition of thioredoxin reductase represents a potential target in pancreatic cancer and provides a biomarker of effect of lead indolequinones in this type of cancer 1.8.1.9 thioredoxin-disulfide reductase medicine TrxR is a target for cancer chemotherapy 1.8.1.10 CoA-glutathione reductase medicine potential point of intervention in the treatment of staphylococcal infections 1.8.1.12 trypanothione-disulfide reductase medicine - 1.8.1.12 trypanothione-disulfide reductase medicine target enzyme for chemotherapy against Chagas' disease 1.8.1.12 trypanothione-disulfide reductase medicine good target for structure/function studies and trypanicidal inhibitor design 1.8.1.12 trypanothione-disulfide reductase medicine potential target for drug design against trypanosomiasis 1.8.1.12 trypanothione-disulfide reductase medicine target for rational approach to design new anti-leishmanial chemotherapeutic agents 1.8.1.12 trypanothione-disulfide reductase medicine nitrofuran derivatives show antiparasitic effect on the trypanocidal drug design target trypanothione reductase 1.8.1.12 trypanothione-disulfide reductase medicine inhibition of the enzyme by naphthoquinone and nitrofuran derivatives abolish the cell penetration by the parasite trypomasstigotes, alternate approach to chemotherapy of trypanosomiasis and leishmaniasis, Chagas' disease 1.8.1.12 trypanothione-disulfide reductase medicine enzyme substrate trypanothione disulfide is the primary target for arsenical drugs against african trypanosomes 1.8.1.12 trypanothione-disulfide reductase medicine enzyme is a target for development of antileishmanial drugs 1.8.1.12 trypanothione-disulfide reductase medicine enzyme is a therapeutic target 1.8.1.12 trypanothione-disulfide reductase medicine hypnophilin is good candidate for developing new drugs against Chagas disease 1.8.1.12 trypanothione-disulfide reductase medicine promising trypanothione reductase inhibitors 1.8.1.12 trypanothione-disulfide reductase medicine promising TryR inhibitors 1.8.1.15 mycothione reductase medicine the enzyme is sensitive to free radical generating antituberculosis drugs and may be useful target for new drug development 1.8.2.6 S-disulfanyl-L-cysteine oxidoreductase medicine the amount of H2S produced by periodontopathic bacteria or oral bacteria collected from human subjects decreases after an incubation with recombinant Sox enzymes. The combination of recombinant Sox enzymes is useful for the prevention of oral malodor 1.8.3.1 sulfite oxidase medicine deficiency in SO, due to either a defect in molybdopterin cofactor biosynthesis or a mutation in the apo-enzyme gene itself, leads to dramatic neurological problems that can cause death in early infancy 1.8.3.1 sulfite oxidase medicine low plasma total homocysteine is a valuable early indicator of sulfite oxidase dysfunction, providing a crucial first-line screen, whereas plasma cystine is not always informative in the first few days of life 1.8.3.1 sulfite oxidase medicine magnetic resonance imaging and magnetic resonance spectroscopy measurements may help differentiate isolated sulfite oxidase deficiency from hypoxic-ischemic condition in patients in whom this diagnosis is not clinically suspected and may lead to further genetic antenatal inquiry that may prevent the birth of other infants affected with this severe and incurable congenital disease 1.8.3.1 sulfite oxidase medicine molybdenum trioxide (MoO3) nanoparticles display an intrinsic biomimetic sulfite oxidase activity under physiological conditions, and, functionalized with a customized bifunctional ligand containing dopamine as anchor group and triphenylphosphonium ion as targeting agent, they selectively target the mitochondria while being highly dispersible in aqueous solutions. Chemically induced sulfite oxidase knockdown cells treated with MoO3 nanoparticles recover their sulfite oxidase activity in vitro, which makes MoO3 nanoparticles a potential therapeutic for sulfite oxidase deficiency and opens new avenues for cost-effective therapies for gene-induced deficiencies. Molybdenum trioxide (MoO3) is a well-known model compound for selective oxidation catalysis 1.8.3.2 thiol oxidase medicine protective role of QSOX1 against apoptosis 1.8.3.2 thiol oxidase medicine protective role of QSOX1 against apoptosis. QSOX1 short transcript overexpression slows down proliferation and protects cells from oxidative stress-induced cell death 1.8.3.2 thiol oxidase medicine mutation R194H has been isolated from a rare autosomal recessive myopathy connected with the development of cataract and respiratory-chain deficiency. In a Saccharomyces cerevisiae model, under restrictive conditions, the presence of the mutant form of human ALR, R194H, impairs the accumulation of human Mia40 and other mitochondrial intermembrane space proteins 1.8.3.2 thiol oxidase medicine te enzyme might be useful in therapeutic strategies for treating prion diseases 1.8.3.3 glutathione oxidase medicine ALT-2074, a catalytic mimic of glutathione oxidase, inhibits human cytochrome P450 3A isoforms in vitro 1.8.3.7 formylglycine-generating enzyme medicine coexpression of formylglycine-generating enzyme is essential for gene therapy of metachromatic leukodystrophy 1.8.4.2 protein-disulfide reductase (glutathione) medicine DsbA protein is a target for treatment of pathogenic bacteria 1.8.4.8 phosphoadenylyl-sulfate reductase (thioredoxin) medicine in Mycobacterium tuberculosis, APR is a validated target against the latent phase of infection 1.8.4.11 peptide-methionine (S)-S-oxide reductase medicine interventions focusing on the enzymatic reduction of oxidized methionine catalyzed by MSRA represents a new prevention and therapeutic approach for Parkinson’s disease and potentially for other neurodegenerative diseases involving oxidative stress 1.8.4.11 peptide-methionine (S)-S-oxide reductase medicine MsrA efficiently reduces oxidized methionine residues in recombinant alpha-synuclein. Enhancing MsrA function may be a reasonable therapeutic strategy in Parkinson's disease 1.8.4.11 peptide-methionine (S)-S-oxide reductase medicine MSRA gene on chromosome 8p might possess metastasis suppressor activity in hepatocellular carcinoma 1.8.4.11 peptide-methionine (S)-S-oxide reductase medicine Caenorhabditis elegans model of the human amyloidogenic disease inclusion body myositis. In a constitutive transgenic Abeta strain that lacks MSRA-1, the number of amyloid aggregates decreases while the number of oligomeric Abeta species increases. The results correlate with enhanced synaptic dysfunction and mislocalization of the nicotinic acetylcholine receptor ACR-16 at the neuromuscular junction 1.8.4.11 peptide-methionine (S)-S-oxide reductase medicine mouse model of Alzheimer's disease, a mouse that overexpresses amyloid precursor protein and Abeta in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins. MsrA-deficient mice expressing amyloid precursor protein exhibit higher levels of soluble Abeta in brain. Mitochondrial respiration and the activity of cytochrome c oxidase are compromised in the MsrA-deficient mice expressing amyloid precursor protein compared with control mice 1.8.5.1 glutathione dehydrogenase (ascorbate) medicine significant association with the age-at-onset of Alzheimer's disease and Parkinson's disease 1.8.5.4 bacterial sulfide:quinone reductase medicine termination of endogenous H2S signalling in the colonic muscularis externa occurs via catabolism to thiosulfate and sulfate partially via a mechanism involving sulfide:quinone reductase. In the brain, H2S signal termination occurs partially through protein sequestration and partially through catabolism not involving sulfide:quinone reductase 1.8.7.1 assimilatory sulfite reductase (ferredoxin) medicine potential target for the development of antituberculosis agents 1.8.98.2 sulfiredoxin medicine increased sulfiredoxin has been linked with oncogenic transformation, data support a role for Srx in controlling the phosphorylation status of key regulatory kinases 1.8.98.2 sulfiredoxin medicine oxidative stress results in protein oxidation and is involved in the pathogenesis of lung diseases such as chronic obstructive pulmonary disorder, COPD, in lungs from COPD patients the expression of Srx1 is dramatically decreased 1.10.3.2 laccase medicine inhibitory activity of enzyme against HIV-1 reverse transcriptase, 50% inhibition at 0.0095 mM 1.10.3.2 laccase medicine no inhibitory activity of enzyme against HIV-1 reverse transcriptase 1.10.3.3 L-ascorbate oxidase medicine reagent for clinical analysis of L-ascorbic acid 1.10.3.5 3-hydroxyanthranilate oxidase medicine enzyme activity increases in the brains of Huntington disease victims 1.10.3.6 rifamycin-B oxidase medicine rifamycin is used for the treatment of tuberculosis 1.10.3.6 rifamycin-B oxidase medicine starting material for synthesis of many clinically important rifampicins 1.10.3.6 rifamycin-B oxidase medicine rifamycin S is used for the production of the antibiotic rifampicin for treatment of leprosy and tuberculosis 1.10.3.6 rifamycin-B oxidase medicine rifamycin, an ansa-macrolide antibiotic, is used for production of antituberculosic agents 1.10.5.1 ribosyldihydronicotinamide dehydrogenase (quinone) medicine anti-cancer therapy 1.10.5.1 ribosyldihydronicotinamide dehydrogenase (quinone) medicine the high NQO2 activity of intraperitoneal ovarian metastases relative to other tissues indicates a potential for tretazicar therapy in the treatment of this disease 1.10.5.1 ribosyldihydronicotinamide dehydrogenase (quinone) medicine estrogen quinones, including estradiol estradiol-3,4-quinone, generated by estrogen metabolism, are thought to be responsible for estrogen-initiated carcinogenesis. NQO2 could be a novel target for prevention of breast cancer initiation 1.10.5.1 ribosyldihydronicotinamide dehydrogenase (quinone) medicine quinone reductase 2 can play important roles in the regulation of catecholamine oxidation processes that may be involved in the etiology of Parkinson disease 1.10.5.1 ribosyldihydronicotinamide dehydrogenase (quinone) medicine QR2 inhibitors possibly represent a therapeutic strategy toward the treatment of learning deficits especially observed in the aged brain 1.10.5.1 ribosyldihydronicotinamide dehydrogenase (quinone) medicine an increased risk of breast cancer is associated with the NQ2 I-29 allele. The I-29-containing genotype is significantly correlated with breast cancer under a dominant model. There is a significant association of the I-29/D polymorphism with luminal-like breast cancer but not with HER2-enriched or triple-negative subtypes 1.10.5.1 ribosyldihydronicotinamide dehydrogenase (quinone) medicine NQO2 protein level is significantly higher in non-small cell lung cancer tissues as compared with their normal tissues. NQO2 score at clinical stages III and IV is higher than stage I, and there exists a significant correlation between tumor NQO2 expression level and the pathologic T stage 1.11.1.6 catalase medicine systemic reduction in catalase activity by dsRNA-mediated knock-down significantly reduces the reproductive output of mosquito females. Mutation S2W leads to strain G3 which shows a lower specific activity and higher Km value than the wild-type Ser-isoform. Mutation S2W destabilizes the functional tetrameric form of the enzyme. Ser/Ser females have a significantly higher fecundity than Trp/Trp females 1.11.1.6 catalase medicine catalase A1 is a good candidate for the development of an immunoassay for serodiagnosis of infections caused by the Scedosporium apiospermum complex in patients with cystic fibrosis 1.11.1.6 catalase medicine design and production of a bifunctional protein with mitochondrial superoxide dismutase and catalase activities plus cell penetrating peptide from HIV-1 Tat to enable cellular internalization. Coexpression of catalase-superoxide dismutase and superoxide dismutase -Tat fusion genes allows simultaneous self-assembly of the protein sequences. The protein complex is expected to contain one tetrameric structure of catalase, four tetrameric structures of superoxide dismutase and twelve units of Tat. The complex shows cellular internalization and superior protection against paraquat-induced cell death 1.11.1.7 peroxidase medicine biosensors for direct and mediated electron transfer, determination of hydrogen peroxide in RDE mode (mediatorless) 1.11.1.7 peroxidase medicine the enzyme shows high antibacterial activity in 100 mM thiocyanate, 100 mM H2O2 medium for some pathogenic bacteria, such as Aeromonas hydrophila ATCC 79666, Micrococcus luteus LA 2971, Mycobacterium smegmatis RUT, Bacillus subtilis IMG22, Pseudomonas pyocyanea, Bacillus subtilis var. niger ATCC 10, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 15753, Bacillus brevis FMC3, Klebsiella pneumoniae FMC5, Corynebacterium xerosis UC9165, Bacillus cereus EÜ, Bacillus megaterium NRS, Yersinia enterocolitica, Listeria monocytogenes scoot A, Bacillus megaterium EÜ, Bacillus megaterium DSM32, Klebsiella oxytoca, Staphylococcus aerogenes, Streptococcus faecalis, Mycobacterium smegmatis CCM 2067. The lactoperoxidase(100 mM)/thiocyanate(100 mM)/H2O2 system is purposed as an effective agent against many of the diseases causing organisms in human and animals 1.11.1.7 peroxidase medicine QPO is a potential drug target to inhibit the expression of leukotoxin LtxA from Aggregatibacter actinomycetemcomitans for the treatment and prevention of localized aggressive periodontitis 1.11.1.8 iodide peroxidase medicine amino acids from TPO region 713-717 are the key residues, recognized by IDR/B-specific anti-TPO autoantibodies in autoimmune thyroid disease. These data are of great importance to rationally design therapeutic peptides able to block undesired autoimmune responses 1.11.1.8 iodide peroxidase medicine R646 and D707 together with R225 constitute a functional epitope within IDR-A, and that residues E604, D620, and D630, together with K627, constitute a functional epitope within IDR-B. The identification of key residues within the autoreactive epitopes will help in understanding the structural basis for the breakdown of immune tolerance to TPO in thyroid autoimmune disease 1.11.1.8 iodide peroxidase medicine identification of TPO gene defects in a cohort of patients with thyroid dyshormonogenesis from Slovenia, Bosnia, and Slovakia. The high percentage of single allele mutations implies possible intronic or regulatory TPO gene mutations or monoallelic expression 1.11.1.8 iodide peroxidase medicine two patients with iodide organification defect caused by two compound heterozygous mutations, c.215delA/c.2422T-->C [p.Q72fsX86/p.C808R] and c.387delC/c.1159G-->A [p.N129fsX208/p.G387R], in the TPO gene and four patients with monoallelic TPO defect. Identification of the molecular basis of this disorder might be helpful for understanding the pathophysiology of congenital hypothyroidism 1.11.1.8 iodide peroxidase medicine addition of TPO stain and proliferation marker Ki-67 stain to routine Papanicolaou stain may improve the diagnostic reliability of fine-needle aspiration cytology for follicular carcinoma with high degree of malignancy 1.11.1.8 iodide peroxidase medicine analysis of of TPO immunohistochemical expression in thyroid nodules with signs or symptoms suspicious for malignancy. TPO may be useful in confirming or ruling out benign diseases from differentiated thyroid carcinoma, with the exception of low-risk carcinoma such as minimally invasive follicular carcinoma 1.11.1.8 iodide peroxidase medicine TPO transcripts are present in both normal and cancer tissue samples patients with breast cancer. TPO levels are lower in more advanced cancers. The antigenicity of the immunodominant regions in breast TPO resembles that of thyroid TPO 1.11.1.9 glutathione peroxidase medicine the enzyme has potential therapeutic value as an antioxidant, but its pharmacological development is limited because the enzyme uses a selenocysteine as its catalytic group and it is difficult to generate selenium-containing proteins with traditional recombinant DNA technology 1.11.1.9 glutathione peroxidase medicine in liver, by 24 h, exposure to alow dose of Cd causes 13% loss of Gpx4a expression. At higher dose, Cd leads to 40% decrease in Gpx4a expression. Longer exposure periods cause about 20% loss of liver Gpx4a expression by low Cd dose 1.11.1.9 glutathione peroxidase medicine olfactory isoform Gpx4b mRNA expression is not extensively modulated by presence of cadmium ions. In liver, by 24 h, exposure to alow dose of Cd causes 18% loss of Gpx4b expression. At higher dose, Cd leads to 37% decrease in Gpx4b expression. Longer exposure periods cause about 22% loss of liver Gpx4b expression by low Cd dose, whereas at higher Cd exposures, a 33% loss in Gpx4b expression is observed 1.11.1.9 glutathione peroxidase medicine for patients with sepsis, geometric mean Gpx3 bioactivity is 78.13 U/l , significantly lower than for normal subjects with 108.21 U/l. The GPx3 protein concentration is significantly lower in patients with sepsis than in normal subjects, with the mean Gpx3 value of 0.78 vs 3.10 microg/ml, respectively. A positive correlation is observed between the Gpx3 bioactivity and its corresponding protein concentration in septic serum samples, regardless of gender or age difference 1.11.1.9 glutathione peroxidase medicine the activities of superoxide dismutase and glutathione peroxidase in a population chronically exposed to high levels of radon indoors does not differ from those in the control group (0.37 versus 0.28 U/mg protein and 8.46 versus 8.34 U/mg protein). For both populations, there is a significant positive correlation between superoxide dismutase and glutathione peroxidase activities. No significant effects of gender, age, smoking habit, and body mass index on superoxide dismutase and glutathione peroxidase activities are found for both groups 1.11.1.12 phospholipid-hydroperoxide glutathione peroxidase medicine tumor growth inhibitor 1.11.1.12 phospholipid-hydroperoxide glutathione peroxidase medicine PHGPx downregulation could be related with a poorer prognosis in breast invasive ductal carcinoma 1.11.1.12 phospholipid-hydroperoxide glutathione peroxidase medicine PHGPx is useful as a biomarker to screen for detrimental effects of exogenous endocrine disrupting chemicals in testes 1.11.1.12 phospholipid-hydroperoxide glutathione peroxidase medicine overexpression of GPx4 inhibits the development of atherosclerosis by decreasing lipid peroxidation and inhibiting the sensitivity of vascular cells to oxidized lipids 1.11.1.12 phospholipid-hydroperoxide glutathione peroxidase medicine MPHGPx transgenic mice made diabetic by multiple low-dose streptozotocin injections show decreased ejection fraction and fractional shortening in diabetic hearts that is reversed with hydroperoxide glutathione peroxidase mPHDPx4 overexpression. MPHGPx overexpression increases electron transport chain function while attenuating hydrogen peroxide production and lipid peroxidation in diabetic mPHGPx interfibrillar mitochondria. mPHGPx overexpression lessens proteomic loss observed in diabetic interfibrillar mitochondria. Posttranslational modifications, including oxidations and deamidations, are attenuated with mPHGPx overexpression. Mitochondrial protein import dysfunction in diabetic interfibrillar mitochondria is reversed with mPHGPx overexpression correlating with protein import constituent preservation. Oxidative phosphorylation, tricarboxylic acid cycle, and fatty acid oxidation processes most influenced in diabetic interfibrillar mitochondria are preserved by mPHGPx overexpression 1.11.1.21 catalase-peroxidase medicine catalase-peroxidase activates the core anti-tuberculosis drug isoniazid 1.11.1.21 catalase-peroxidase medicine KatG is responsible for activation of the antituberculosis antibiotic isoniazid (isonicotinic acid hydrazide) 1.11.1.21 catalase-peroxidase medicine the enzyme activates the pro-antitubercular drug isoniazid 1.11.1.21 catalase-peroxidase medicine the enzyme responsible for the activation of isoniazid as an antibiotic 1.11.1.21 catalase-peroxidase medicine the toxicity of the anti-tuberculosis drug isoniazid is mediated by catalase-peroxidase 1.11.1.21 catalase-peroxidase medicine the gene is used for detection of Mycobacterium avium-intracellulare complex disease in HIV patients 1.11.1.23 (S)-2-hydroxypropylphosphonic acid epoxidase medicine fosfomycin is a clinically useful antibiotic for the treatment of limb-threatening diabetic foot infections and lower urinary tract infections. It is effective against ciprofloxacin-resistant Escherichia coli, as well as methicillin-resistant and vancomycin-resistant strains of Staphylococcus aureus. The antimicrobial activity of fosfomycin is due to the inactivation of UDP-GlcNAc-3-O-enolpyruvyltransferase, which catalyzes the first committed step in the biosynthesis of peptidoglycan, the main component of the bacterial cell wall 1.11.1.23 (S)-2-hydroxypropylphosphonic acid epoxidase medicine fosfomycin is a clinically utilized antibiotic of low toxicity, blocking bacterial cell wall biosynthesis by acting as an analogue of phosphoenolpyruvate 1.11.1.24 thioredoxin-dependent peroxiredoxin medicine the enzyme is a potential vaccine candidate against trichinosis 1.11.1.26 NADH-dependent peroxiredoxin medicine epitope AhpC4-16 shows effective protective role against Campylobacter jejuni and is a candidate epitope of vaccine against this pathogen 1.11.1.26 NADH-dependent peroxiredoxin medicine the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fusobacterium nucleatum in the intestinal tract, which can provide a practical strategy for the prevention of colorectal cancer associated with Fusobacterium nucleatum infection 1.11.1.27 glutathione-dependent peroxiredoxin medicine regulating PRDX6 may improve the clinical utility of stem cell-based regenerative medicine for the treatment of bone diseases 1.11.1.28 lipoyl-dependent peroxiredoxin medicine AhpCis a critical element of the antioxidant defense system of Mycobacterium tuberculosis and may be suitable target for the development of novel anti-tuberculosis strategies 1.11.1.28 lipoyl-dependent peroxiredoxin medicine AhpD is a critical element of the antioxidant defense system of Mycobacterium tuberculosis and may be suitable target for the development of novel anti-tuberculosis strategies 1.11.1.28 lipoyl-dependent peroxiredoxin medicine immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract. AhpC as a potential vaccine candidate against inhabitation or infection of Fusobacterium nucleatum in the intestinal tract, which could provide a practical strategy for the prevention of colorectal cancer associated with Fn infection 1.11.1.28 lipoyl-dependent peroxiredoxin medicine the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fusobacterium nucleatum in the intestinal tract, which can provide a practical strategy for the prevention of colorectal cancer associated with Fusobacterium nucleatum infection 1.11.2.2 myeloperoxidase medicine loading macrophages with exogenous myeloperoxidase could enhance their microbicidal activity, potentially useful therapeutic application 1.11.2.2 myeloperoxidase medicine the enzyme is an interesting target for anti-inflammatory therapy 1.13.11.5 homogentisate 1,2-dioxygenase medicine - 1.13.11.5 homogentisate 1,2-dioxygenase medicine HGO gene is responsible for alkaptonuria 1.13.11.5 homogentisate 1,2-dioxygenase medicine alkaptonuria: rare hereditary disorder of the phenylalanine catabolism, patients are deficient in homogentisate 1,2-dioxygenase and carry two copies of a loss-of-function allele of HGO gene, disease causes homogentisic aciduria, ochronosis and arthritis 1.13.11.5 homogentisate 1,2-dioxygenase medicine HGO deficiency causes alkaptonuria, inherited as a recessive Mendelian trait, HGO inhibitors may be useful in the treatment of hereditary tyrosinemia type I, HT1 1.13.11.5 homogentisate 1,2-dioxygenase medicine inactivation of enzyme in kidney and liver causes the basic defect of alkaptonuria 1.13.11.5 homogentisate 1,2-dioxygenase medicine missense mutation in exon 13 (G360R) and exon 3 (K57N) affecting homogentisate 1,2-dioxygenase function by interfering with substrate traffic at active site causing alkaptonuria, a rare recessive phanylalanine/tyrosine metabolism disorder 1.13.11.6 3-hydroxyanthranilate 3,4-dioxygenase medicine plays a role in disorders, associated with altered tissue levels of quinolinic acid 1.13.11.11 tryptophan 2,3-dioxygenase medicine the enzyme is a therapeutic target in cancer treatment 1.13.11.12 linoleate 13S-lipoxygenase medicine 15-LO-1 expression in colorectal carcinoma may contribute to the inhibition of metastatic capacity in vitro and can be exploited for therapeutic purposes 1.13.11.12 linoleate 13S-lipoxygenase medicine the LOX/4-nitroso-N,N-dimethylaniline method is able to highlight high antioxidant activity values in durum wheat grains, as well as synergistic interactions among antioxidants from different extracts, and so provide a more comprehensive and integrated determination of antioxidant activity, which is essential for a total antioxidant activity assessment and may provide a more realistic quantification of food antioxidant effectiveness in preventing diseases 1.13.11.12 linoleate 13S-lipoxygenase medicine induction of 15-LOX-1-mediated down-regulation of a PPAR-gamma and COX-2 pathway by honokiol is a therapeutic strategy for gastric cancer 1.13.11.12 linoleate 13S-lipoxygenase medicine 15 lipoxygenase 1 is abundant in asthmatic human airway epithelial cells and binds phosphatidylethanolamine-binding protein 1 (PEBP1), leading to generation of hydroperoxy-phospholipids, which drive ferroptotic cell death. 15LO1, PEBP1, and glutathione peroxidase 4 GPX4 activity drives abnormal asthmatic redox biology, to enhance type 2 inflammatory responses. In vitro, type 2 inflammatory cytokine IL-13 induces 15LO1 generation of hydroperoxy-phospholipids, which lowers intracellular GSH and increased extracellular GSSG levels. Lowering GSH further by inhibiting cystine transporter SLC7A11 enhances type 2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances correspond to 15LO1 and SLC7A11 expression, type 2 inflammatory biomarkers, and worsen clinical outcomes 1.13.11.12 linoleate 13S-lipoxygenase medicine when treating type 2 diabetic wild-type mice and transgenic mice ubiquitously overexpressing 15-LOX-1 with menhaden (fish) oil, there is a trend for the severity of diabetic peripheral neuropathy-related deficits to be less in the diabetic transgenic mice compared to the diabetic wild-type mice. Treating diabetic wild-type and transgenic mice with menhaden oil improves the diabetic peripheral neuropathy-related endpoints with a trend for greater improvement or protection by menhaden oil observed in the diabetic transgenic mice 1.13.11.18 persulfide dioxygenase medicine the combined oral treatment with metronidazole and N-acetylcysteine is an effective therapy for ethylmalonic encephalopathy which is caused by mutations in the mitochondrial matrix sulfur dioxygenase ETHE1 1.13.11.19 cysteamine dioxygenase medicine ADO functions as an oxygen sensor by modifying N-degron substrates to transduce responses to hypoxia 1.13.11.20 cysteine dioxygenase medicine lack of methionine sulfoxide reductase MsrA in liver of MsrA -/- mice leads to a significant drop in the cellular level of thiol groups and lowers the level of cysteine dioxygenase expression. Following selenium deficient diet applied to decrease the expression levels of selenoproteins like MsrB, the latter effect is maintained while the basal levels of thiol decreased in both wild-type strains and strains deficient for methionine dioxygenase 1.13.11.20 cysteine dioxygenase medicine CDO1 is preferentially silenced by promoter methylation in human non-small cell lung cancers harboring mutations in KEAP1, the negative regulator of transcription factor NRF2. CDO1 silencing promotes proliferation of non-small cell lung cancer cells by limiting the futile metabolism of cysteine to the wasteful and toxic byproducts CSA and sulfite, and depletion of cellular NADPH 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase medicine mechanism of binding of the inhibitor 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione used to treat type I tyrosinemia. Enzyme-Fe(II)-inhibitor complex does not oxidize, dissociation rate constant is essentially zero 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase medicine 4-hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase medicine compounds N-(4-methoxyphenyl)-7-nitro-2,1,3-benzoxadiazol-4-amine and 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one can be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase medicine HPD is highly expressed in lung cancer and expression correlates with poor prognosis in lung cancer patients. Suppressed HPD expression is sufficient to decrease oxidative pentose phosphate pathway flux, leading to reduced RNA biosynthesis and enhanced reactive oxygen species level, attenuated cancer cell proliferation, and tumor growth 1.13.11.31 arachidonate 12-lipoxygenase medicine prevention of increased 12-LO expression or activity in pancreatic beta cells could be a new way to prevent inflammation and damage to beta cells 1.13.11.31 arachidonate 12-lipoxygenase medicine the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimer‘s disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder. Thus, drugs that specifically reduce or block the 12/15-LOX metabolic pathway activation may warrant consideration as potential therapeutic interventions for Alzheimer‘s disease 1.13.11.31 arachidonate 12-lipoxygenase medicine psoralen plus ultraviolet A decreases 12-LOX expression, thus this UVA photochemotherapy is considered to be first-line treatment for patients with moderate to severe psoriasis. Interruption of 12-LOX catalytic activity and the 12-hydroxyeicosatetraenoic acid signaling pathway by increasing 15-LOX metabolites may be a promising target for psoriasis therapies 1.13.11.31 arachidonate 12-lipoxygenase medicine blood platelet enzyme 12-LOX modulates FcgammaRIIa signaling and presents a viable therapeutic target in the prevention of immune-mediated thrombosis 1.13.11.31 arachidonate 12-lipoxygenase medicine selective ALOX 12 inhibitors may constitute a good approach to limit adipose tissue inflammation in human obesity 1.13.11.31 arachidonate 12-lipoxygenase medicine the enzyme is a target in treatment of cardiomyopathy 1.13.11.31 arachidonate 12-lipoxygenase medicine 15 lipoxygenase 1 is abundant in asthmatic human airway epithelial cells and binds phosphatidylethanolamine-binding protein 1 (PEBP1), leading to generation of hydroperoxy-phospholipids, which drive ferroptotic cell death. 15LO1, PEBP1, and glutathione peroxidase 4 GPX4 activity drives abnormal asthmatic redox biology, to enhance type 2 inflammatory responses. In vitro, type 2 inflammatory cytokine IL-13 induces 15LO1 generation of hydroperoxy-phospholipids, which lowers intracellular GSH and increased extracellular GSSG levels. Lowering GSH further by inhibiting cystine transporter SLC7A11 enhances type 2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances correspond to 15LO1 and SLC7A11 expression, type 2 inflammatory biomarkers, and worsen clinical outcomes 1.13.11.31 arachidonate 12-lipoxygenase medicine activity of 12S-lipoxygenase is hardly observed in liver cytosol of normal chow-fed mice but is clearly detectable in that of nonalcoholic steatohepatitis model mice prepared by feeding a methionine and choline-deficient diet 1.13.11.31 arachidonate 12-lipoxygenase medicine application of 14(S)-hydroxy docosahexaenoic acid suppresses IL-33-mediated eosinophilic inflammation in 12/15-LOX-deficient mice. 14(S)-hydroxy docosahexaenoic acid and 10(S),17(S)-dihydroxy docosahexaenoic acid markedly attenuate ILC2 proliferation and cytokine production at micromolar concentration in vitro. Maresin 1 (MaR1) and resolvin D1 (RvD1), 12/15-LOX-derived specialized proresolving mediators (SPMs), inhibited cytokine production of ILC2s at nanomolar concentration 1.13.11.31 arachidonate 12-lipoxygenase medicine humans acutely treated with specific beta3-adrenergic agonist mirabegron display elevated levels of 12-LOX metabolites in the circulation, and significantly higher levels of 12-hydroxyeicosapentaenoic acid and 14-hydroxydocosahexaenoic acid are found in the media of brown adipocytes treated with the beta3-adrenergic agonist CL316,243 for 4 hours 1.13.11.31 arachidonate 12-lipoxygenase medicine hypoxia increases the formation of endogenous 12-hydroxyeicosatetraenoic acid through stimulation of 12-lipoxygenase. 12-hydroxyeicosatetraenoic acid promotes endothelial cell migration and tube formation, whereas it inhibits the serum deprivation-induced apoptotic responses under hypoxia. The regulatory effects of 12-lipoxygenase/12-hydroxyeicosatetraenoic acid on pulmonary artery endothelial cells, at least in part, depend on phosphatidylinositol 3-kinase (PI3K)/Akt signaling activatio 1.13.11.31 arachidonate 12-lipoxygenase medicine older normal human fibroblasts (NHFs) have significantly increased arachidonic acid 12-lipoxygenase (ALOX12) expression and elevated levels of its mitogenic metabolite, 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-(S)-HETE) compared with their younger counterparts. In cocultures with older rather than with younger NHFs, pancreatic ductal adenocarcinoma cells exhibit increases in mitogen-activated protein kinase signaling and cellular metabolism, as well as a lower oxidation state that correlates with their enhanced proliferation and resistance to radiation therapy. Expression of ALOX12 is significantly lower in pancreatic ductal adenocarcinoma cell lines and tumor biopsies 1.13.11.31 arachidonate 12-lipoxygenase medicine Streptococcus pneumoniae infection of the respiratory epithelium induces the production of the 12-lipoxygenase-dependent lipid inflammatory mediator hepoxilin A3, which promotes recruitment of neutrophils into the airways, tissue damage, and lethal septicemia. A pneumolysin-deficient S. pneumoniae mutant is impaired in triggering human neutrophil transepithelial migration in vitro 1.13.11.31 arachidonate 12-lipoxygenase medicine when treating type 2 diabetic wild-type mice and transgenic mice ubiquitously overexpressing 15-LOX-1 with menhaden (fish) oil, there is a trend for the severity of diabetic peripheral neuropathy-related deficits to be less in the diabetic transgenic mice compared to the diabetic wild-type mice. Treating diabetic wild-type and transgenic mice with menhaden oil improves the diabetic peripheral neuropathy-related endpoints with a trend for greater improvement or protection by menhaden oil observed in the diabetic transgenic mice 1.13.11.33 arachidonate 15-lipoxygenase medicine tumorigenesis 1.13.11.33 arachidonate 15-lipoxygenase medicine 15-LOX-1 and its metabolites (13-S-hydroxyoctadecadienoic acid and 15-S-hydroxyeicosatetraenoic acid) have anti-carcinogenic effects in colorectal cancer. 15-LOX-1 is possibly of prognostic value in stage IV colon cancer survival 1.13.11.33 arachidonate 15-lipoxygenase medicine 15-LOX-2 is a negative regulator of tumor growth via downregulating angiogenesis 1.13.11.33 arachidonate 15-lipoxygenase medicine 15-LOX-2 may be a potential target in radiation-targeted therapy of head-and-neck cancer 1.13.11.33 arachidonate 15-lipoxygenase medicine has anti-carcinogenic effects in colorectal cancer 1.13.11.33 arachidonate 15-lipoxygenase medicine interruption of 12-LOX catalytic activity and the 12-hydroxyeicosatetraenoic acid signaling pathway by increasing 15-LOX metabolites may be a promising target for psoriasis therapies 1.13.11.33 arachidonate 15-lipoxygenase medicine pro-tumorigenic feedback loop for 13-(S)-hydroxyoctadecadienoic acid against 15-hLO-2 1.13.11.33 arachidonate 15-lipoxygenase medicine under cellular conditions (low fatty acid and low oxygen concentrations), the allosteric binding of 12(S)-hydroxyeicosatetraenoic acid to 15-hLO-1 can increase the substrate specificity of 15-hLO-1 toward arachidonic acid over linoleic acid significantlysignificantly, which may have important implications in cancer progression 1.13.11.33 arachidonate 15-lipoxygenase medicine gene ALOX15 has potential as a therapeutic target for eradicating leukemia stem cells in chronic myeloid leukemia 1.13.11.33 arachidonate 15-lipoxygenase medicine the enzyme is a target in treatment of cardiomyopathy 1.13.11.33 arachidonate 15-lipoxygenase medicine 15 lipoxygenase 1 is abundant in asthmatic human airway epithelial cells and binds phosphatidylethanolamine-binding protein 1 (PEBP1), leading to generation of hydroperoxy-phospholipids, which drive ferroptotic cell death. 15LO1, PEBP1, and glutathione peroxidase 4 GPX4 activity drives abnormal asthmatic redox biology, to enhance type 2 inflammatory responses. In vitro, type 2 inflammatory cytokine IL-13 induces 15LO1 generation of hydroperoxy-phospholipids, which lowers intracellular GSH and increased extracellular GSSG levels. Lowering GSH further by inhibiting cystine transporter SLC7A11 enhances type 2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances correspond to 15LO1 and SLC7A11 expression, type 2 inflammatory biomarkers, and worsen clinical outcomes 1.13.11.33 arachidonate 15-lipoxygenase medicine application of 14(S)-hydroxy docosahexaenoic acid suppresses IL-33-mediated eosinophilic inflammation in 12/15-LOX-deficient mice. 14(S)-hydroxy docosahexaenoic acid and 10(S),17(S)-dihydroxy docosahexaenoic acid markedly attenuate ILC2 proliferation and cytokine production at micromolar concentration in vitro. Maresin 1 (MaR1) and resolvin D1 (RvD1), 12/15-LOX-derived specialized proresolving mediators (SPMs), inhibited cytokine production of ILC2s at nanomolar concentration 1.13.11.33 arachidonate 15-lipoxygenase medicine when treating type 2 diabetic wild-type mice and transgenic mice ubiquitously overexpressing 15-LOX-1 with menhaden (fish) oil, there is a trend for the severity of diabetic peripheral neuropathy-related deficits to be less in the diabetic transgenic mice compared to the diabetic wild-type mice. Treating diabetic wild-type and transgenic mice with menhaden oil improves the diabetic peripheral neuropathy-related endpoints with a trend for greater improvement or protection by menhaden oil observed in the diabetic transgenic mice 1.13.11.34 arachidonate 5-lipoxygenase medicine selenium -induced apoptosis in prostate cancer cells may be mediated thgroufgh inhibition of the activity of arachidonate 5-lipoxygenase. The anti-cancer effects of selenium may be substantially compromised by consumption of high-fat diets rich in arachidonic acid or its precursor fatty acids 1.13.11.34 arachidonate 5-lipoxygenase medicine powerful inhibitory properties of anthocyanins (delphinidin glycosides) towards lipoxygenases in relation to their currently known availability in human metabolism may in vivo prevent inflammatory diseases 1.13.11.34 arachidonate 5-lipoxygenase medicine direct 5-LO inhibitors are able to suppress the viability of various human tumour cells independently of 5-LO inhibition 1.13.11.34 arachidonate 5-lipoxygenase medicine the enzyme is a promising target for anti-inflammatory therapy 1.13.11.34 arachidonate 5-lipoxygenase medicine the enzyme is an attractive drug target for the pharmacotherapy of inflammatory and allergic diseases 1.13.11.40 arachidonate 8-lipoxygenase medicine therapeutic effect of inhibitors of arachidonic acid metabolism on inflammatory skin diseases and epidermal tumors and on tumor development 1.13.11.52 indoleamine 2,3-dioxygenase medicine yellowing of the aged lens may be preventable by drug-induced suppression of IDO activity 1.13.11.52 indoleamine 2,3-dioxygenase medicine enzyme catalyzes the first and rate-limiting step in kynurenine pathway 1.13.11.52 indoleamine 2,3-dioxygenase medicine first and probably rate-limiting enzyme in UV filter biosynthesis 1.13.11.52 indoleamine 2,3-dioxygenase medicine first and rate-limiting enzyme in tryptophan metabolism, plays a role in pathogenesis of many diseases 1.13.11.52 indoleamine 2,3-dioxygenase medicine IDO induces suppression of antitumoral immune response, inhibits tumor cell proliferation by tryptophan depletion 1.13.11.52 indoleamine 2,3-dioxygenase medicine inhibits T-cell activation and proliferation 1.13.11.52 indoleamine 2,3-dioxygenase medicine plays a role in the antiparasitic defense in humans 1.13.11.52 indoleamine 2,3-dioxygenase medicine plays a role in the antiparasitic defense in humans, inhibits the growth of tumor cell lines in vitro, inhibits T lymphocyte proliferation 1.13.11.52 indoleamine 2,3-dioxygenase medicine rate-limiting enzyme in kynurenine pathway 1.13.11.52 indoleamine 2,3-dioxygenase medicine reduced tryptophan and increased kynurenine concentrations, chronic immune activation which can be referred to increased IDO activation 1.13.11.52 indoleamine 2,3-dioxygenase medicine expression of indoleamine 2,3-dioxygenase may be deleterious during renal inflammation, because it enhances TEC self-injury through Fas/FasL interactions. Attenuation of indoleamine 2,3-dioxygenase may represent a novel strategy to promote kidney function following ischemia and renal allograft rejection 1.13.11.52 indoleamine 2,3-dioxygenase medicine in patients with acute myeloid leukemia, activity of indoleamine 2,3-dioxygenase can be monitored by measuring its metabolites in sera, and appears correlated with outcome. Monitoring indoleamine 2,3-dioxygenase activity provides a useful tool for future clinical trials of IDO inhibitors in acute myeloid leukemia 1.13.11.52 indoleamine 2,3-dioxygenase medicine indoleamine 2,3-dioxygenase activity might be of therapeutic utility in allergen immunotherapy. Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model 1.13.11.52 indoleamine 2,3-dioxygenase medicine target for therapeutic intervention. Inhibition of inappropriate IDO activity in tumours in vivo may attenuate the ability of tumours to evade immune surveillance and promote clearance. Strategies that enhance IDO activity during autoimmune or inflammatory diseases may be beneficial via inhibition of undesirable T cell activities 1.13.11.52 indoleamine 2,3-dioxygenase medicine the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults, and could constitute a novel marker of immune activation in early atherosclerosis in females 1.13.11.52 indoleamine 2,3-dioxygenase medicine identification of genetic variants, which have altered enzyme activity 1.13.11.52 indoleamine 2,3-dioxygenase medicine indole 2,3-dioxygenase acitvity in bacteremic patients 1.13.11.52 indoleamine 2,3-dioxygenase medicine indole 2,3-dioxygenase is potentially useful as a non-invasive marker for organ transplant rejection 1.13.11.52 indoleamine 2,3-dioxygenase medicine review of multifaceted activity of indole 2,3-dioxygenase in infections 1.13.11.52 indoleamine 2,3-dioxygenase medicine engraftment of IDO expressing skin substitutes on the back of rats significantly improves healing progression over 7 days compared with both nontreated and non-IDO-expressing skin substitutes 1.13.11.52 indoleamine 2,3-dioxygenase medicine genetic alteration of fetal IDO gene is not a primary cause of pre-eclampsia 1.13.11.52 indoleamine 2,3-dioxygenase medicine systemic IDO activity, determined as the kynurenine/tryptophan ratio in serum, correlates with the presence of palpable tumor. IDO mediates immune suppression in the early stages of prostate cancer progression. IDO expression in the tumor tissue is irrelevant for transgenic adenocarcinoma of mouse prostate tumor incidence 1.13.11.52 indoleamine 2,3-dioxygenase medicine tryptophan 2,3-dioxygenase is considered as a drug target for cancer immunotherapy 1.13.11.53 acireductone dioxygenase (Ni2+-requiring) medicine the enzyme level positively associates with postoperative recurrence-free survival in patients with hepatocellular carcinoma 1.13.11.54 acireductone dioxygenase [iron(II)-requiring] medicine matrix metalloproteinase MT1-MMP physically interacts with claudin-1 and acireductone dioxygenase 1, both associated with hepatitis C virus cell entry. Positive cytoplasmic ADI1 in liver biopsies is associated with higher serum hepatitis C virus RNA levels. Positive MT1-MMP and ADI1 interaction is associated with lower tissue hepatitis C virus RNA levels. Hepatic hepatitis C virus RNA levels are positively associated with ADI1 levels in the MT1-MMP and ADI1 coimmunoprecipitates 1.13.11.63 beta-carotene 15,15'-dioxygenase medicine Modulation of intestinal beta-carotene uptake and its conversion to vitamin A using specific fatty acids. Improved absorption and metabolism of beta-carotene by feeding mixed micelles with oleic acid or eicosapentanoic acid compared with linoleic acid 1.13.11.63 beta-carotene 15,15'-dioxygenase medicine BCM gene expression in the liver and intestine might affect retinol levels in type 2 diabetes 1.13.11.63 beta-carotene 15,15'-dioxygenase medicine changes in the metabolism of retinol and beta-carotene might have an important role in the protection against the development of nephrosis 1.13.12.7 firefly luciferase medicine luciferase gene is a useful reporter gene in vivo, allowing noninvasive imaging of tumor growth, metastasis, gene transfer, drug treatment, and gene expression. The use of thermostabilized luciferases may allow monitoring of micro-metastses and the early stages of tumor growth 1.13.12.7 firefly luciferase medicine observing tumours 1.13.12.7 firefly luciferase medicine use in endotoxin detection method 1.13.99.1 inositol oxygenase medicine the enzyme is a possible target for treatment of diabetic kidney disease. MIOX enzyme inhibitor D-glucarate might be a potential therapeutic agent for the amelioration of diabetic kidney disease 1.13.99.1 inositol oxygenase medicine the enzyme is a marker in the diagnosis of acute kidney injury 1.13.99.3 tryptophan 2'-dioxygenase medicine use for tryptophan depletion in patients with refractory acute lymphocytic leukemia 1.14.11.1 gamma-butyrobetaine dioxygenase medicine effects of hyperthyroidism and hypothyroidism on enzyme activity 1.14.11.1 gamma-butyrobetaine dioxygenase medicine activity of gamma-butyrobetaine dioxygenase in the liver is lower in pigs treated with clofibrate than in control pigs. Concentrations of gamma-butyrobetaine does not differ between both groups. Pigs treated with clofibrate have higher relative mRNA concentrations of organic cation transporter OCTN2 in liver, skeletal muscle and epithelial cells from small intestine than control pigs. Pigs treated with clofibrate have also higher concentrations of free and total carnitine in the liver and a higher concentration of free carnitine in skeletal muscle than control pigs 1.14.11.1 gamma-butyrobetaine dioxygenase medicine both enhancement of carnitine biosynthesis due to increased ?-butyrobetaine dioxygenase activity, extra-hepatic gamma-butyrobetaine synthesis and increased hepatic carnitine import contributes to the increased hepatic carnitine levels after fasting 1.14.11.1 gamma-butyrobetaine dioxygenase medicine BBOX is a therapeutic target in humans, the BBOX inhibitor mildronate is used to decrease fatty acid oxidation in patients after myocardial infarction 1.14.11.1 gamma-butyrobetaine dioxygenase medicine inhibition of BBOX is reported to aid in recovery after acute stroke 1.14.11.2 procollagen-proline 4-dioxygenase medicine in aortic smooth muscle cell, expression of prolyl-4-hydroxylase is suppressed by tumor necrosis factor TNFalpha via the MKK4-JNK1 pathway, which induces histone 4 lysine 12 acetylation within the TNFalpha response element in the prolyl-4-hydroxylase promoter 1.14.11.2 procollagen-proline 4-dioxygenase medicine in culture, gingival fibroblasts from Chinese patients with hereditary gingival fibromatosis show similar growth characteristics to fibroblasts isolated from control. mRNA and protein levels of prolyl 4-hydroxylase alpha and type I collagen are higher than those in control. For prolyl 4-hydroxylase alpha(II), prolyl 4-hydroxylase alpha(II) and prolyl 4-hydroxylase beta, no differences between control and hereditary gingival fibromatosis are detected 1.14.11.2 procollagen-proline 4-dioxygenase medicine potential applications of human recombinant collagen, produced by transgenic tobacco expressing the recombinant enzyme, in regenerative medicine 1.14.11.2 procollagen-proline 4-dioxygenase medicine enzyme P4Halpha1 overexpression might be a potential therapeutic target in stabilizing vulnerable plaques to prevent rupture and erosion of atherosclerotic plaque and thus thrombosis 1.14.11.2 procollagen-proline 4-dioxygenase medicine P4Halpha1 overexpression might be a valuable therapeutic modality in stabilizing advanced but not early plaque because of the adverse event of accelerated lesion formation 1.14.11.2 procollagen-proline 4-dioxygenase medicine the prolyl-4-hydroxylase alpha subunit 2 is a potential therapeutic target for the disorders associated with increased collagen deposition and a biomarker for breast cancer progression 1.14.11.4 procollagen-lysine 5-dioxygenase medicine deficiency in enzyme activity causes the Ehler-Danlos syndrome type 6 1.14.11.4 procollagen-lysine 5-dioxygenase medicine LH2b is an interesting target to interfere with osteoarthritis-related persistent fibrosis 1.14.11.4 procollagen-lysine 5-dioxygenase medicine isozyme LH2 is of interest as candidate mediator of a p21-independent transcriptional program that regulates the metastatic propensity of KC cells. LH2 promotes lung cancer metastatic behavior and predicts poor prognosis in patients 1.14.11.16 peptide-aspartate beta-dioxygenase medicine insulin-like growth factor-1 stimulates peptide-aspartate beta-dioxygenase protein expression and directional motility. Ethanol reduces the stimulation without inhibition of the mRNA expression, and phosphorylation of the enzyme is higher in ethanol-treated compared with control cells 1.14.11.16 peptide-aspartate beta-dioxygenase medicine isolation of human single-chain Fv fragments directed against human aspartyl-asparaginyl beta-hydroxylase. Antibodies show significant binding to recombinant enzyme in ELISA, tumor cell lines, and tumor tissues. They target different domains of the enzyme. A goat-anti-human IgG saporin conjugate can be delivered into tumor cells by antibody 6-22 and elicits cytotoxicity toward the tumor cells in vitro 1.14.11.16 peptide-aspartate beta-dioxygenase medicine biomarker to prognosticate non-small cell lung cancer 1.14.11.16 peptide-aspartate beta-dioxygenase medicine insulin/IGF-1 stimulation of asparaginyl-beta-hydroxylase and Notch are enhanced by inhibiting kinases that could phosphorylate asparaginyl-beta-hydroxylase protein. Targeted manipulation of the phosphorylation state of asparaginyl-beta-hydroxylase may have therapeutic value for reducing asparaginyl-beta-hydroxylase-Notch activation and attendant infiltrative growth of hepatocellular carcinomas 1.14.11.16 peptide-aspartate beta-dioxygenase medicine ASPH gene alterations have prognostic value both in prostate cancer and castration-resistant prostate cancer patients. ASPH expression promotes a more aggressive malignant phenotype. In castration-resistant prostate cancer cells, inhibition of ASPH expression reduces cell proliferation, invasion and cyclin D1 expression through modulation of the NOTCH signaling. ASPH and HIF1alpha crosstalk might be transiently driven by the oxidative stress evidenced inside castration-resistant prostate cancer cells. ASPH silencing leads to increased phosphorylation of GSK3beta 1.14.11.18 phytanoyl-CoA dioxygenase medicine treatment of Refsum disease 1.14.11.27 [histone H3]-dimethyl-L-lysine36 demethylase medicine fisetin induces DNA damage via critical transcription factor RFXAP/KDM4A-dependent histone H3K36 demethylation, thus causing inhibition of proliferation in pancreatic adenocarcinoma (PDAC). Fisetin inhibits cell proliferation and induces DNA damage and S-phase arrest in PDAC. Expression of RFXAP and other DNA-damage response genes is upregulated by fisetin. RFXAP expression is relatively low in PDAC and correlates with tumor stage and poor prognosis. Fisetin enhances the effect of chemotherapy on pancreatic cancer cells 1.14.11.27 [histone H3]-dimethyl-L-lysine36 demethylase medicine JmjC domain histone H3K36me2/me1 demethylase KDM2B is highly expressed in glioblastoma surgical specimens compared to normal brain. Targeting KDM2B function genetically or pharmacologically impairs the survival of patient-derived primary glioblastoma cells through the induction of DNA damage and apoptosis and sensitizes them to chemotherapy. KDM2B loss decreases the cancer stem-like cells pool, which is potentiated by coadministration of chemotherapy 1.14.11.27 [histone H3]-dimethyl-L-lysine36 demethylase medicine JMJD2A overexpression increases the mRNA and protein level of brain-derived neurotrophic factor Bdnf, a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf 1.14.11.27 [histone H3]-dimethyl-L-lysine36 demethylase medicine JMJD2A responds to neuropathic pain and participates in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain. Jmjd2a responds to 5-hydroxytryptamine and promotes the expression of the brain-derived neurotrophic factor (Bdnf), a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf. JMJD2A promotes the expression of Bdnf during neuropathic pain and neuron-specific knockout of Jmjd2a blocks the hypersensitivity of mice undergoing chronic neuropathic pain 1.14.11.29 hypoxia-inducible factor-proline dioxygenase medicine during disc degeneration PHD2 may offer a therapeutic target to mitigate the deleterious actions of TNF-alpha, a key proinflammatory cytokine 1.14.11.29 hypoxia-inducible factor-proline dioxygenase medicine PHD2 represents a potential contributing factor for hepatocellular carcinoma-associated erythrocytosis. Selective inhibition of PHD2 in HCC cells might be considered as a way to manage erythrocytosis in hepatocellular carcinoma (HCC) patients 1.14.11.30 hypoxia-inducible factor-asparagine dioxygenase medicine the high constitutive activities of the proteins with both Pro and Asn substitutions confirm that the relevant prolyl and asparaginyl hydroxylases are attractive targets for therapeutic regulation of hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha 1.14.11.51 DNA N6-methyladenine demethylase medicine ALKBH1 overexpression decreases hepatocellular carcinoma cell viability, induces apoptosis, and decreases migration and invasion. 23779 gain-of-6 mA regions and 11240 loss-of-6 mA regions are differentially identified in hepatocellular carcinoma tissues. The differential gain and loss of 6 mA regions are considerably enriched in intergenic regions. 7% of the differential 6 mA modifications are associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes, and 17 are common to oncogenes and TSGs 1.14.11.51 DNA N6-methyladenine demethylase medicine during the progression of vascular calcification in a model of chronic kidney disease, increased ALKBH1 expression is linked to decreased 6mA levels 1.14.11.51 DNA N6-methyladenine demethylase medicine expression levels of ALKBH1 in lung cancer tissues and cells are up regulated. The invasion and migration abilities of lung cancer cells are significantly suppressed in vitro upon the silencing of ALKBH1 while they are significantly promoted upon its overexpression 1.14.11.51 DNA N6-methyladenine demethylase medicine in patients with chronic kidney disease, leukocyte 6mA levels are significantly reduced as the severity of vascular calcification increases. Decreased 6mA demethylation results from the upregulation of ALKBH1. ALKBH1 overexpression aggravates whereas its depletion blunts vascular calcification progression and osteogenic reprogramming in vivo and in vitro 1.14.11.53 mRNA N6-methyladenine demethylase medicine FTO is up-regulated in human breast cancer. High level of FTO is significantly associated with lower survival rates in patients with breast cancer. FTO promotes breast cancer cell proliferation, colony formation and metastasis in vitro and in vivo. BNIP3, a pro-apoptosis gene, is a downstream target of FTO-mediated m6A modification. BNIP3 acts as a tumor suppressor and is negatively correlated with FTO expression in clinical breast cancer patients. BNIP3 dramatically alleviates FTO-dependent tumor growth retardation and metastasis 1.14.11.53 mRNA N6-methyladenine demethylase medicine FTO level is increased in human melanoma. Knockdown of FTO increases m6A methylation in critical protumorigenic melanoma cell-intrinsic genes including PD-1, CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma 1.14.11.53 mRNA N6-methyladenine demethylase medicine FTO mRNA and protein levels are overexpressed in non-small cell lung cancer tissues and cell lines, associated with a reduced m6A content. FTO loss-of-function mutations reduce the proliferation rate of cancer cells. FTO knockdown also inhibits the colony formation ability of lung cancer cells. FTO knockdown reduces lung cancer cells growth in vivo. FTO decreases the m6A level and increases mRNA stability of ubiquitin-specific protease (USP7), which relies on the demethylase activity of FTO. USP7 mRNA level is overexpressed in human lung cancer tissues and USP7 expression was positively correlated with FTO mRNA level 1.14.11.53 mRNA N6-methyladenine demethylase medicine FTO nhances melanoma tumorigenesis in mice. Knockdown of FTO increases m6A methylation in critical protumorigenic melanoma cell-intrinsic genes including PD-1, CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma and sensitizes melanoma to anti-PD-1 treatment in mice 1.14.11.53 mRNA N6-methyladenine demethylase medicine substrate NEAT1 is a potential binding long noncoding lncRNA of ALKBH5. NEAT1 is overexpressed in gastric cancer cells and tissue. Knockdown of NEAT1 significantly represses invasion and metastasis of gastric cancer cells. ALKBH5 affects the m6A level of NEAT1. The binding of ALKBH5 and NEAT1 influences the expression of EZH2 (a subunit of the polycomb repressive complex) and thus affects gastric cancer invasion and metastasis 1.14.11.54 mRNA N1-methyladenine demethylase medicine human adenocarcinomas and squamous cell carcinomas of the lung show overexpression of Alkbh3 and the percentage of cells positive for Alkbh3 also correlates statistically to recurrence-free survival in adenocarcinoma. Knockdown of Alkbh3 by siRNA transfection induces expression of p21WAF1/Cip1 and p27Kip1 in the human lung adenocarcinoma cell line A-549, resulting in cell cycle arrest, senescence and strong suppression of cell growth in vitro. In vivo, peritoneal tumour growth and dissemination is inhibited in nude mice, previously inoculated with the A-549 cell line, by intraperitoneal injection of Alkbh3 siRNA plus atelocollagen 1.14.11.54 mRNA N1-methyladenine demethylase medicine the enzyme is a prostate cancer marker 1.14.11.54 mRNA N1-methyladenine demethylase medicine ALKBH3 promoter CpG island hypermethylation is most frequent in Hodgkin lymphoma cell lines (44%; 4 of 9), followed by Burkitt lymphoma (38%; 5 of 13), other non-Hodgkin lymphoma cell lines (37%; 12 of 32), and anaplastic large cell lymphoma. ALKBH3 promoter hypermethylation is detected in detected in18% (14 of 80) of the primary Hodgkin lymphoma cases. ALKBH3 CpG island hypermethylation is associated with protein loss. ALKBH3 epigenetic silencing is also associated with COL1A2 and COL1A1 overexpression, whereas an unmethylated ALKBH3 CpG island is linked to the absence of collagen expression. ALKBH3 hypermethylation is associated with shorter overall survival in the studied Hodgkin lymphoma cohort 1.14.11.54 mRNA N1-methyladenine demethylase medicine the alteration of ALKBH3 expression regulates the cytokine CSF-1 mRNA stability. Actions of cytokine CSF-1 lead to poor prognosis in ovarian and breast cancers. Demethylation of m1A by ALKBH3 increases the half-life of CSF-1 mRNA without affecting the translation efficiency. Overexpression of ALKBH3 increases CSF-1 expression and the degree of cancer cell invasiveness without affecting cell proliferation or migration 1.14.11.63 peptidyl-lysine (3S)-dioxygenase medicine in head and neck squamous cell carcinoma, a read-through fusion gene JMJD7-PLA2G4B is present, splicing neighboring JMJD7 and phospholipase A2, group IVB (PLA2G4B) genes together. Ablation of JMJD7-PLA2G4B significantly inhibits proliferation of head and neck squamous cell carcinoma cells by promoting G1 cell cycle arrest and increased starvation-induced cell death compared to JMJD7-only knockdown head and neck squamous cell carcinoma cells. JMJD7-PLA2G4B modulates phosphorylation of protein kinase B to promote head and neck squamous cell carcinoma cell survival. JMJD7-PLA2G4B also regulates an E3 ligase S-phase kinase-associated protein 2 to control the cell cycle progression from G1 phase to S phase by inhibiting cyclin-dependent kinase inhibitor 1 and 1B expression 1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase medicine KDM3A expression in human breast cancer cell lines and tumors is defective 1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase medicine KDM3B represses leukemia cell differentiation and is upregulated in blood cells from acute lymphoblastic leukemia-type leukemia patients 1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase medicine fisetin induces DNA damage via critical transcription factor RFXAP/KDM4A-dependent histone H3K36 demethylation, thus causing inhibition of proliferation in pancreatic adenocarcinoma (PDAC). Fisetin inhibits cell proliferation and induces DNA damage and S-phase arrest in PDAC. Expression of RFXAP and other DNA-damage response genes is upregulated by fisetin. RFXAP expression is relatively low in PDAC and correlates with tumor stage and poor prognosis. Fisetin enhances the effect of chemotherapy on pancreatic cancer cells 1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase medicine JMJD2A overexpression increases the mRNA and protein level of brain-derived neurotrophic factor Bdnf, a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf 1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase medicine JMJD2A responds to neuropathic pain and participates in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain. Jmjd2a responds to 5-hydroxytryptamine and promotes the expression of the brain-derived neurotrophic factor (Bdnf), a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf. JMJD2A promotes the expression of Bdnf during neuropathic pain and neuron-specific knockout of Jmjd2a blocks the hypersensitivity of mice undergoing chronic neuropathic pain 1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase medicine KDM3A deficiency delays cancer cell growth and migration, which is rescued by YAP1 expression. KDM3A expression is correlated with YAP1 and hippo target genes in colorectal cancer patient tissues 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine histone demethylase JMJD2B is a therapeutic target in breast cancer patients 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine JMJD2B is a feasible molecular target for anticancer therapy 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine a significant upregulation of KDM4D is observed in gastrointestinal stromal tumour tissue compared with matched normal tissue. KDM4D directly interacts with the HIF1beta gene promoter and regulates its activity, promoting tumour angiogenesis and gastrointestinal stromal tumour progression both in vitro and in vivo. KDM4D transcriptionally activates HIF1beta expression via H3K9me3 and H3K36me3 demethylation at the promoter region 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine fisetin induces DNA damage via critical transcription factor RFXAP/KDM4A-dependent histone H3K36 demethylation, thus causing inhibition of proliferation in pancreatic adenocarcinoma (PDAC). Fisetin inhibits cell proliferation and induces DNA damage and S-phase arrest in PDAC. Expression of RFXAP and other DNA-damage response genes is upregulated by fisetin. RFXAP expression is relatively low in PDAC and correlates with tumor stage and poor prognosis. Fisetin enhances the effect of chemotherapy on pancreatic cancer cells 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine histone H3.3 G34R substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 level by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induces chromatin alterations that are comparable to a KDM4 A/B/C triple-knockout. H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine JMJD2A displays higher expression in glioma tissues than that in normal brain tissues and lower levels of H3K9me3/H3K36me3are found in glioma tissues 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine JMJD2A responds to neuropathic pain and participates in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain. Jmjd2a responds to 5-hydroxytryptamine and promotes the expression of the brain-derived neurotrophic factor (Bdnf), a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf. JMJD2A promotes the expression of Bdnf during neuropathic pain and neuron-specific knockout of Jmjd2a blocks the hypersensitivity of mice undergoing chronic neuropathic pain 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine KDM4A expression is upregulated in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in prostate cancer cells inhibits their proliferation and survival in vivo and vitro. Upregulation of KDM4A expression with high USP1 expression is observed in most prostate tumors and inhibition of USP1 promotes prostate cancer cells response to therapeutic agent enzalutamide 1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylase medicine KDM4D is a key regulator of adipogenesis in C3H10T1/2 mesenchymal stem cells 1.14.11.67 [histone H3]-trimethyl-L-lysine4 demethylase medicine in human tumors, KDM5B expression is inversely associated with STING expression in multiple cancer types, with the level of intratumoral CD8+ T cells, and with patient survival in cancers with a high level of cytosolic DNA, such as human papilloma virus-positive head and neck cancer 1.14.11.67 [histone H3]-trimethyl-L-lysine4 demethylase medicine paclitaxel-resistant lung adenocarcinoma PTX-Calu-3 cells show significantly higher IC50 value (7 microM) upon paclitaxel treatxadment than lung adenocarcinoma SK-LI-1 (3.6 nM), Calu-3 (4.3 nM), and A549 (4.5 nM) cells. Expression of KDM5A and P-glycoprotein are significantly higher in PTX-Calu-3 cells compared to SK-LI-1, Calu-3, and A549 cells. A significantly higher number of PTX-Calu-3 cells are inxadvasive and motile compared to SK-LI-1, Calu-3, and A549 cells. A significantly higher expression of KDM5A is observed in lung adenocarcixadnoma patients' samples compared with adjacent normal tissues as well as in PTX-Calu-3 cells 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine demethylase Kdm6a expression is significantly upregulated in a rat acute myocardial infarction model and in hypoxia induction 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine H3K27 methylation imposes ligand-dependent regulation of the estrogen receptor alpha-dependent apoptotic response via Bcl-2 in breast cancer cells. The activation of BCL2 transcription is dependent on the simultaneous inactivation of the H3K27 methyltransferase, EZH2, and the demethylation of H3K27 at a poised enhancer by the estrogen receptor alpha-dependent recruitment of JMJD3 in hormone-dependent breast cancer cells. This pathway is modified in cells resistant to anti-estrogen, which constitutively express BCL2 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine in renal cell carcinoma, UTX and JMJD3 transcripts are significantly increased compared to normal tissues. The level of trimethylated H3K27 is lower in cancer tissues compared to normal tissues, but expression of the H3K27 methyltransferase EZH2 is increased 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine inhibition of JMJD3 and UTX blocks reactivation-induced H3K27me3 demethylation of herpes simplex virus genomes 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine JMJD3 is upregulated in prostate cancer, and its expression is higher in metastatic prostate cancer 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine JMJD3 upregulation and NF-kappaB activation occur in the region of the wound edge during keratinocyte wound healing. JMJD3 interacts with NF-kappaB, resulting in increased expression of the inflammatory matrix metalloproteinase, and growth factor genes via demethylation of H3K27me3 at the gene promoters. Inactivation of JMJD3 or NF-kappaB results in aberrant keratinocyte wound healing 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine presence of nickel chloride upregulates the expression of H3K27me3 demethylase Jmjd3 in kidney cancer cells, which is accompanied by the reduction in the protein level of H3K27me3 1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylase medicine upon exposure of macrophages to Bacillus anthracis, lethal toxin, substantial cell death is induced with a survival rate of around 40%. The expression of Jmjd3 is induced 8fold in intoxication-resistant cells generated by treatment with lipopolysaccharides of RAW 264.7 cells. These intoxication-resistant cell lines are maintained for 8 passages and have a survival rate of around 100% on secondary exposure to lethal toxin and lipopolysaccharides 1.14.11.69 [histone H3]-trimethyl-L-lysine36 demethylase medicine KDM4A is both amplified and deleted across many disparate cancer types, and KDM4A expression correlates with copy number in these samples. 46% of ovarian cancer cells display KDM4A amplification, which correlates with expression 1.14.11.69 [histone H3]-trimethyl-L-lysine36 demethylase medicine fisetin induces DNA damage via critical transcription factor RFXAP/KDM4A-dependent histone H3K36 demethylation, thus causing inhibition of proliferation in pancreatic adenocarcinoma (PDAC). Fisetin inhibits cell proliferation and induces DNA damage and S-phase arrest in PDAC. Expression of RFXAP and other DNA-damage response genes is upregulated by fisetin. RFXAP expression is relatively low in PDAC and correlates with tumor stage and poor prognosis. Fisetin enhances the effect of chemotherapy on pancreatic cancer cells 1.14.11.69 [histone H3]-trimethyl-L-lysine36 demethylase medicine histone H3.3 G34R substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 level by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induces chromatin alterations that are comparable to a KDM4 A/B/C triple-knockout. H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity 1.14.11.69 [histone H3]-trimethyl-L-lysine36 demethylase medicine JMJD2A displays higher expression in glioma tissues than that in normal brain tissues and lower levels of H3K9me3/H3K36me3are found in glioma tissues 1.14.11.69 [histone H3]-trimethyl-L-lysine36 demethylase medicine JMJD2A responds to neuropathic pain and participates in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain. Jmjd2a responds to 5-hydroxytryptamine and promotes the expression of the brain-derived neurotrophic factor (Bdnf), a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf. JMJD2A promotes the expression of Bdnf during neuropathic pain and neuron-specific knockout of Jmjd2a blocks the hypersensitivity of mice undergoing chronic neuropathic pain 1.14.11.69 [histone H3]-trimethyl-L-lysine36 demethylase medicine KDM4A expression is upregulated in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in prostate cancer cells inhibits their proliferation and survival in vivo and vitro. Upregulation of KDM4A expression with high USP1 expression is observed in most prostate tumors and inhibition of USP1 promotes prostate cancer cells response to therapeutic agent enzalutamide 1.14.11.79 protein-L-histidine (3S)-3-hydroxylase medicine MINA53 is overexpressed in multiple cancer types, blocking MINA53 expression limits the proliferative capacity of several tumor cell lines in vitro. MINA53 acts as an immuno-modulator 1.14.11.79 protein-L-histidine (3S)-3-hydroxylase medicine NO66 inhibits the ability of Osterix to drive osteoblast-specific gene transcription. Overexpression of NO66 is sufficient to suppress the transactivation domain of Osterix. Mesenchymal-specific ablation of NO66 increases the expression of genes that promote bone growth and development in mice 1.14.13.9 kynurenine 3-monooxygenase medicine enzyme is a therapeutical target for treatment of Huntigton disease 1.14.13.9 kynurenine 3-monooxygenase medicine the enzyme is an attractive target for the treatment of ischemic stroke 1.14.13.9 kynurenine 3-monooxygenase medicine T helper 17 cells preferentially express kynurenine 3-monooxygenase. Enzyme inhibition, either with a specific inhibitor or via siRNA-mediated silencing, markedly increases IL-17 productionin vitro, whereas IFN-gamma production by T helper 1 cells is unaffected. Inhibition of kynurenine 3-monooxygenase significantly exacerbates disease in a Th17-driven model of autoimmune gastritis 1.14.13.9 kynurenine 3-monooxygenase medicine inhibition of the enzyme shows benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. It is a target for acute pancreatitis multiple organ dysfunction syndrome 1.14.13.9 kynurenine 3-monooxygenase medicine inhibition of the enzyme shows benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. It is a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS) 1.14.13.9 kynurenine 3-monooxygenase medicine the enzyme is a potential drug target for treatment of neurodegenerative disorders such as Huntington's and Alzheimer's diseases 1.14.13.9 kynurenine 3-monooxygenase medicine the enzyme is a potential therapeutic target for neurodegenerative and neurologic disorders 1.14.13.9 kynurenine 3-monooxygenase medicine importance of KMO as a drug target in neurological disease, benefits of brain permeable inhibitors in modulating kynurenine pathway metabolites in the central nervous system teeating brain neurological diseases. KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites 1.14.13.9 kynurenine 3-monooxygenase medicine KMO and its enzymatic product QUIN are potential broad-spectrum antiviral factor therapeutics against emerging pathogenic viruses 1.14.13.9 kynurenine 3-monooxygenase medicine rationale for enzyme KMO inhibition as a therapeutic strategy to protect against acute kidney injury (AKI) during critical illness. Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) 1.14.13.29 4-nitrophenol 2-monooxygenase medicine malaria decreases the activity of p-nitrophenol-hydroxylase in liver microsomes by 33%, mRNA levels are lowered compared to uninfected mice 1.14.13.32 albendazole monooxygenase medicine albendazole as an anthelmintic drug is an important tool for the control of lancet fluke infections in small ruminants 1.14.13.39 nitric-oxide synthase (NADPH) medicine enzyme induces relaxation of endothelium-denuded rat aortic rings precontracted with phenylepinephrine, possible participation in pathogenesis of invasive amebiasis 1.14.13.39 nitric-oxide synthase (NADPH) medicine no evidence for altered enzyme function of mutant E298D that could explain endothelial dysfunction associated with the E298D polymorphism 1.14.13.39 nitric-oxide synthase (NADPH) medicine nitric oxide synthase inhibitors, e.g. L-N(G)-nitro-arginine-methylester, may serve as an alternative adjunct with antibiotic therapy for Pseudomonas keratitis, especially for reducing ocular inflammation without affecting the antimicrobial efficacy of the antibiotic 1.14.13.128 7-methylxanthine demethylase medicine methylxanthine intermediates of caffeine catabolism obtained by the action of N-demethylases have many applications. In medicine, theobromine and theophylline are used as diuretics, vasodilators, and myocardial stimulants. Monomethylxanthines can be converted to effective caffeine derivatives by chemical derivatization and hence can serve as interesting alternatives to caffeine. Xanthine also finds pharmaceutical application in drugs for treatment of asthma. The biotechnological potential of N-demethylases therefore lies not only in general decaffeination purposes but also in specific product recovery from caffeine 1.14.13.146 taxoid 14beta-hydroxylase medicine manipulation of the hydroxylase gene can permit redirection of the pathway to increase flux toward taxol and can allow the preparation of 13alpha,14beta-hydroxy taxoids as new therapeutic agents 1.14.13.225 F-actin monooxygenase medicine elevated MICAL1 gene expression is observed in invasive breast cancer samples from human patients relative to normal tissue, while MICAL1 amplification or point mutations are associated with reduced progression free survival 1.14.14.1 unspecific monooxygenase medicine 2fold increase in enzyme activity on diet of total parenteral nutrition plus choline 1.14.14.1 unspecific monooxygenase medicine plasma concentration of 4beta-hydroxycholesterol may be used as an endogenous marker of CYP3A activity. Concentration of 4beta-hydroxycholesterol increases with the number of active CYP3A5 alleles in Koreans, Swedes and Tanzanians 1.14.14.1 unspecific monooxygenase medicine the two major mechanisms that confer resistance to permethrin in Culex mosquitoes are target site insensitivity (i.e. kdr) and enhanced detoxification by cytochrome P450 monooxygenases 1.14.14.1 unspecific monooxygenase medicine during degradation of permethrins, potential dispositional differences may occur with permethrin enantiomers. Cleavage of pyrethroid esters leads to detoxification of the acute neurological effects, but formation of the benzyl alcohol and hydroxylated metabolite may lead to estrogenic responses 1.14.14.1 unspecific monooxygenase medicine in transgenic mice with altered cytochrome P450 lipid biosynthetic pathways in a mouse model of laser-induced choroidal neovascularization, overexpression of the human monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase enzyme leads to increased levels of epoxydocosapentaenoic acids and epoxyeicosatetraenoic acids with attenuated choroidal neovascularization development. The molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment 1.14.14.3 bacterial luciferase medicine expression in Staphylococcus aureus Xen29. In the absence of antibiotics, staphylococcal bioluminescence increases over time until a maximum after ca. 6 h of growth, and subsequently decreases to the detection threshold after 24 h of growth. Up to minimal inhibitory concentrations of the antibiotics vancomycin, ciprofloxacin, erythromycin or chloramphenicol, bioluminescence increases according to a similar pattern up to 6 h of growth, but after 24 h, bioluminescence is higher than in the absence of antibiotics. Antibiotic pressure impacts the relation between bioluminescence per organism and bioluminescence. Under antibiotic pressure, bioluminescence is not controlled by luxA expression but by cofactors impacting the bacterial metabolic activity 1.14.14.3 bacterial luciferase medicine transient and stable transfection of human kidney, breast cancer, and colorectal cancer cell lines by a codon optimized lux expression cassette using viral 2A elements as linker regions. The expression product produces autobioluminescent phenotypes in all cell lines tested without the induction of cytotoxicity and allows for repeated interrogation of populations and self-directed control of bioluminescent activation with detection limits and EC50 values similar to traditional reporter systems 1.14.14.B9 fatty acid omega2/3-hydroxyase medicine missense mutation Y125F in substrate recognition site-1 occurs naturally in low frequency. The variant oxidizes two prostaglandin H2 analogs U-51605 and U-44069, but 4,7,10,13,16-(Z)-docosatetraenoic acid and 4,7,10,13,16-(Z)-docosapentaenoic acid are not oxidized 1.14.14.14 aromatase medicine comparison of cerebrocortical microvascular responses to the endothelium-dependent vasodilator ACh between male and female wild-type and aromatase knockout (ArKO) mice. Wild-type female mice have significantly greater responses to ACh compared with wild-type males, which is associated with higher aromatase expression in female compared with male cerebral vessels 1.14.14.14 aromatase medicine in an animal model of familial Amyotrophic lateral sclerosis, i.e. copper-zinc superoxide dismutase-1-G93A transgenic mice, the motor neurons in the spinal anterior horn express aromatase under normal and nearly normal (pre-symptomatic stage) conditions. After disease onset, astrocytes begin to express aromatase. The total level of aromatase expression decreases with disease progression 1.14.14.14 aromatase medicine increased adipose tissue aromatase activity reduces adipose tissue inflammation and improves insulin sensitivity in male mice 1.14.14.14 aromatase medicine allelic variants of CYP19A1 when present with a variant form of cytochrome P450 oxidoreductase POR may show different activities, and combined effects of natural variations in both the enzymes should be considered when genetic data are available 1.14.14.14 aromatase medicine in the trophoblast choriocarcinoma cell line, JEG-3, the expression of let-7g microRNA is downregulated, but upregulated in primary term trophoblast. Aromatase is upregulated in JEG-3 cells but downregulated in primary trophoblast. Let-7g antagomirs and mimics increase and decrease aromatase expression, respectively, and Let-7g directly targets the 3'-untranslated region of CYP19A1 mRNAlet-7g antagomirs and mimics robustly increase and decrease production of estradiol, respectively 1.14.14.14 aromatase medicine phenolic endocrine-disrupting compounds DDT, methoxychlor, benzophenone-2, bisphenol A, bisphenol S, 4-phenylphenol and n-butylparaben upregulate aromatase mRNA expression, increase aromatase activity, significantly increase the aromatase-induced biosynthesis of 17beta-estradiol, and increase ERalpha positive breast cell proliferation 1.14.14.14 aromatase medicine tumor-associated stroma tissues display high aromatase activities. High progesterone receptor intensity levels decrease this activity level. Tumor tissue specific aromatase activity levels of postmenopausal patients' tend to be lower compared to healthy premenopausal subjects'. Low aromatase activity in tumor tissues is associated with low grade and late stage cancers 1.14.14.16 steroid 21-monooxygenase medicine dominant negative effect of mutant enzymes involved in congenital adrenal hyperplasia on wild-type alleles 1.14.14.16 steroid 21-monooxygenase medicine molecular analysis of enzyme gene from Middle European patients with congenital adrenal hyperplasia. CYP21 enzyme gene deletion and In2 and I172N mutation account for 72.7% of the affected alleles in the whole study group. With exception of I172N and P30L mutations, a good genotype-phenotype correlation is observed. Using high-resulotion genotyping, the causative mutation could be identified in 341 out of 348 patients 1.14.14.16 steroid 21-monooxygenase medicine study on the effects of enzyme-specific monoclonal antibodies on enzyme activity by comparative structural modelling. Antibodies with epitopes located distant from the enzyme active sites have no effect on activity. An antibody with epitope close to the redox binding protein binding site results in almost 50% decrease in activity 1.14.14.16 steroid 21-monooxygenase medicine localization of mutations leading to congenital adrenal hyperplasia within the protein. The severity of the congenital adrenal hyperplasia clinical manifestations can be directly correlated with the degree of mutation-induced damage in terms of protein fold stability and active site changes in the structural model. The nonclassical phenotype is typically associated with mutations that have a compensatory effect, i.e. H-bonding replacing hydrophobic interactions and vice versa 1.14.14.17 squalene monooxygenase medicine cholesterol lowering effect of green tea may be attributed to the enzyme inhibitory activities of its gallocatechins 1.14.14.17 squalene monooxygenase medicine breast, ovarian, and colorectal cancers show the highest copy number-driven gene expression among 8783 cases from 22 cancer types, with breast camcer presenting the strongest one. Squalene epoxidase overexpression is more prevalent in aggressive breast cancer, and is an independent prognostic factor of unfavorable outcome. Squalene epoxidase inhibition results in a copy-dosage correlated decrease in cell viability, and in a noticeable increase in replication time, only in lines with detectable Squalene epoxidase transcript 1.14.14.17 squalene monooxygenase medicine expression of squalene epoxidase mRNA and protein in lung squamous cancerous tissues is significantly higher than in pericarcinoma tissues. The positive expression rate of squalene epoxidase mRNA is not associated with gender, age, smoking, or tumor size but closely correlated with poor differentiation, clinical stages, and lymphatic metastasis. The expression of mRNA is negatively associated with overall survival rate 1.14.14.18 heme oxygenase (biliverdin-producing) medicine cells pretreated with curcumin at 37°C or during a programmed decrease in temperature exhibit increased resistance to oxidative stress-mediated injury, feasibility of modulating HO-1 expression during hydpothermic storage to confer tissues a better protection against damages characteristic of organ transplantation 1.14.14.18 heme oxygenase (biliverdin-producing) medicine involved in the control of wound healing, heme-induced influx of leukocytes is highly elevated after inhibition of enzyme 1.14.14.18 heme oxygenase (biliverdin-producing) medicine treatment of streptozotocin-induced diabetic rats with enzyme inhibitor sn protoporphyrin IX. No significant alterations of the enzyme sytem following one week of diabetes. One month of diabetes caused increased oxidative stress in association with 2.5-fold increase in enzyme activity. Sn protoporphyrin IX treatment reduces the number of 8-hydroxy-2’deoxyguanosine-positive cardiomycetes and enzyxme activity. Non-diabetic animals treated with hemin exhibit abnormalities similar to diabetic rats 1.14.14.18 heme oxygenase (biliverdin-producing) medicine potential therapeutic target in cancer 1.14.14.18 heme oxygenase (biliverdin-producing) medicine chronic ethanol feeding induces 5-aminolevulinic acid synthase-1 (ALAS1) mRNA, cytosolic ALAS1 and mature ALAS1 protein levels, but not those of HO-1 in rat livers, which provides novel insights into the effects of chronic ethanol consumption on hepatic heme biosynthesis and porphyrias 1.14.14.18 heme oxygenase (biliverdin-producing) medicine outstanding capacity of HO-1-specific CD8+ Tregs to efficiently suppress T cell responses opens new opportunities for therapeutic intervention to modulate immune responses 1.14.14.18 heme oxygenase (biliverdin-producing) medicine reduction in HO activity may contribute to the protective effect of MEK and ERK inhibitors against heme-mediated neuronal injury 1.14.14.18 heme oxygenase (biliverdin-producing) medicine modulation of Nox4 activity via heme oxygenase-1 may represent a promising therapeutic tool in osteoarthritis 1.14.14.18 heme oxygenase (biliverdin-producing) medicine the enzyme is a potentially useful parameter for distinguishing active from latent or treated pulmonary tuberculosis 1.14.14.18 heme oxygenase (biliverdin-producing) medicine activity of heme oxygenase-1 interferes with porcine reproductive and respiratory syndrome virus PRRSV replication. The host cell antiviral effect depends on a heme oxygenase-1-biliverdin/bilrubin-nitric oxide-cGMP/PKG cascade 1.14.14.18 heme oxygenase (biliverdin-producing) medicine Hmox1 protects against amyloid beta toxicity via production of CO. Protection does not arise from inhibition of apoptosis-associated K+ efflux, but rather by inhibition of AMP-dependent protein kinase activation 1.14.14.18 heme oxygenase (biliverdin-producing) medicine induction or exogenous overexpression of heme oxygenase HO-1 effectively inhibits Dengue virus DENV replication in DENV-infected Huh-7 cells. This antiviral is attenuated by inhibitor tin protoporphyrin. Biliverdin but not carbon monoxide and ferrous ions, mediates the HO-1-induced anti-DENV effect by non-competitively inhibiting DENV protease. HO-1 induction or its exogenous overexpression, rescues DENV-suppressed antiviral interferon response. HO-1 induction by cobalt protoporphyrin and andrographolide leads to a significant delay in the onset of disease and mortality, and virus load in the infected mice's brains 1.14.14.19 steroid 17alpha-monooxygenase medicine inhibition of steroid 17alpha-monooxygenase is an important therapeutic strategy in order to inhibit tumor growth in prostate cancer 1.14.14.19 steroid 17alpha-monooxygenase medicine women with epilepsy have a higher incidence of polycystronic ovary syndrome. At concentrations normally used in antiepileptic drug therapy, the drugs valproic acid, carbamazepine, topiramate, lamotrigine do not influence 17alpha-hydroxylase/17,20-lyase and 3beta-hydroxysteroid dehydrogenase type 2 activities 1.14.14.19 steroid 17alpha-monooxygenase medicine CYP17 inhibitors are synthesized for the potential treatment of prostate cancer 1.14.14.19 steroid 17alpha-monooxygenase medicine partial 17alpha-hydroxylase/17,20-lyase deficiency is a very rare form of congenital adrenal hyperplasia 1.14.14.19 steroid 17alpha-monooxygenase medicine the vital role of CYP17 in androgen biosynthesis makes it a potential molecular target for gene therapetutic strategy 1.14.14.19 steroid 17alpha-monooxygenase medicine low apparent CYP17A1 activity, i.e. the combined 17alpha-hydroxylase/17,20-lyase activity, is associated with elevated daytime ambulatory blood pressure when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly 1.14.14.23 cholesterol 7alpha-monooxygenase medicine association of CYP7A1 gene polymorphisms with the risk of gallbladder cancer. This polymorphism plays a significant role in the pathogenesis of gallbladder cancer which is causatively related to depressed bile acid production. The proposed tumorigenic mechanism for gallbladder cancer is independent of gallstone pathway and appears to be mediated by increase in concentration and accumulation of toxic substances in gallbladder, generated in liver as a consequence of lipid peroxidation and other catabolic reactions 1.14.14.23 cholesterol 7alpha-monooxygenase medicine polymorphisms/mutations described so far at the CYP7A1 promoter do not impair enzyme activity and most likely do not contribute directly to hypercholesterolemia and/or increased cardiovascular risk 1.14.14.23 cholesterol 7alpha-monooxygenase medicine Chlamydia pneumoniae and human cytomegalovirus infections significantly decrease isoform CYP7A1 promoter activity in a dose-dependent manner, with maximal inhibitions of 33% and 32%, respectively 1.14.14.23 cholesterol 7alpha-monooxygenase medicine CYP7A1 overexpression in transgenic mice leads to marked activation of the steroid response element-binding protein 2-regulated cholesterol metabolic network and absence of bile acid repression of lipogenic gene expression in livers. Cyp7a1-tg mice show significantly elevated hepatic cholesterol synthesis rates, but reduced hepatic fatty acid synthesis rates, which is accompanied by increased 14C-glucose-derived acetyl-coenzyme A incorporation into sterols for fecal excret 1.14.14.23 cholesterol 7alpha-monooxygenase medicine in inborn error of metabolism known as Smith-Lemli-Opitz syndrome, 7-oxocholesterol levels may also be elevated in tissue and fluids as a result of CYP7A1 oxidation of 7-dehydrocholesterol 1.14.14.23 cholesterol 7alpha-monooxygenase medicine upregulation of CYP7A1 mRNA in hypercholesterolemic rats treated with extracts from steamed and dried roots of Panax ginseng C.A. Meyer. Treatment leads to decreased ratios of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol. In-vitro studies also show the upregulation of CYP7A1 mRNA and protein levels by the addition of ginsenosides Ro, Rg3, Re, Rg1, and Rg2 to rat primary hepatocytes 1.14.14.23 cholesterol 7alpha-monooxygenase medicine manipulation of hormone signaling pathways can provide a strategy to enhance Cyp7a1 activity in human patients 1.14.14.24 vitamin D 25-hydroxylase medicine experimental autoimmune encephalomyelitis development is markedly suppressed in mice lacking the vitamin D receptor and partially suppressed in vitamin D-insufficient mice. The absence of either of the two key hydroxylases, i.e., 25-hydroxylase and 1alpha-hydroxylase, neither inhibits nor enhances the development of experimental autoimmune encephalomyelitis 1.14.14.24 vitamin D 25-hydroxylase medicine mutation L99P has been identified in a patient with low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency. This individual is homozygous for a transition mutation in exon 2 of the CYP2R1 gene on chromosome 11p15.2, leading to the substitution of a proline for an evolutionarily conserved leucine and eliminating vitamin D 25-hydroxylase enzyme activity 1.14.14.24 vitamin D 25-hydroxylase medicine genes CYP2R1 encoding vitamin D 25-hydroxylase, CYP27B1 encoding 25-hydroxyvitamin D-1 alpha hydroxylase and CYP24A1 encoding 1,25-dihydroxyvitamin D(3) 24-hydroxylase are upregulated in clear cell renal cell carcinomas compared with normal tissue. CYP24A1 displays a significantly higher expression in tumours than CYP27B1 and CYP2R1, whereas no differences in the expression of these genes are found in healthy renal tissue. Gene expression of CYP2R1, CYP27B1 and CYP24A does not differ between pathological classifications 1.14.14.24 vitamin D 25-hydroxylase medicine testis samples from patients with hypospermatogenesis and Sertoli-cell-only syndrome show a lower gene and protein expression of isoform CYP2R1 and a colocalization with INSL-3, a Leydig cell marker. In all testiculopathic patients 25-hydroxyvitamin D levels are significantly lower and parathyroid hormone levels higher compared to controls. Testiculopathic patients show osteopenia and osteoporosis despite normal testosterone levels compared with controls both with increased bone-marker levels and altered dual-energy X-ray absorptiometry in the femoral neck and lumbar spine 1.14.14.24 vitamin D 25-hydroxylase medicine vitamin D analogus can be potential therapeutic agents to control oral squamous cell carcinoma tumor cell tumor progression 1.14.14.25 cholesterol 24-hydroxylase medicine CYP46A1 affects the pathophysiology of AD and provides insight into how polymorphisms in the CYP46A1 gene might influence the pathophysiology of this prevalent disease 1.14.14.25 cholesterol 24-hydroxylase medicine genotyping of CYP46A1 gene polymorphisms (associated with the risk of Alzheimer's disease in Chinese) 1.14.14.25 cholesterol 24-hydroxylase medicine abnormal expression of cholesterol 24S-hydroxylase in astrocytes in Alzheimer's disease, which may limit the usefulness of the plasma marker 24S-hydroxycholesterol in this specific disease 1.14.14.25 cholesterol 24-hydroxylase medicine restoring CYP46A1 activity in the striatum promises a therapeutic approach in Huntington's disease 1.14.14.25 cholesterol 24-hydroxylase medicine the enzyme is a potential target for Alzheimers disease as it can be activated pharmacologically by some of the marketed drugs as exemplified by efavirenz (EFV), the anti-HIV medication 1.14.14.29 25/26-hydroxycholesterol 7alpha-hydroxylase medicine identification of mutations in CYP7B1 associated with hereditary spastic paraplegias provide direct evidence for abnormalities in cholesterol metabolism in the pathogenesis of motor-neuron degeneration 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine inhibition of EC 4.1.2.30 is a potential therapeutic approach for the treatment of both breast and prostrate cancers 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine homology modelling of the enzyme cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450c17)-a target for prostate cancer chemotherapy-from the crystal structure of P450BM-3 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine combined 17alpha-hydroxyprogesterone aldolase/17,20-lyase deficiency is a rare, autosomal recessive form of congenital adrenal hyperplasia 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine inhibition of 17alpha-hydroxylase-C(17,20)-lyase can block androgen synthesis at an early stage, and may therefore be useful in the treatment of prostatic carcinoma 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine inhibitors of 17alpha-hydroxylase/17,20 lyase are a class of anti-prostate cancer agents 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine inhibitors of 17alpha-hydroxylase/17,20 lyase are a new class of anti-prostate cancer agents 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine partial 17alpha-hydroxylase/17,20-lyase deficiency is a very rare form of congenital adrenal hyperplasia 1.14.14.32 17alpha-hydroxyprogesterone deacetylase medicine inhibitor VT-464 displays selective suppression of androgen synthesis through CYP17 lyase inhibition. VT-464 shows a greater decrease in androgen receptor transactivation than inhibitor abiraterone 1.14.14.55 quinine 3-monooxygenase medicine green tea extract use may cause significant interactions with drugs metabolized by CYP3A4. Effect on CYP3A4 varies among different brands of green tea extract, possibly due to variations in their content of the herbal product's active ingredients 1.14.14.55 quinine 3-monooxygenase medicine plasma concentration of 4beta-hydroxycholesterol may be used as an endogenous marker of CYP3A activity 1.14.14.57 taurochenodeoxycholate 6alpha-hydroxylase medicine vitamin D receptor deficiency in the intestine of mice exacerbates lithocholic acid-induced hepatotoxicity manifested by increased necrosis and inflammation, due in part to overaccumulation of hepatic bile acids including taurocholic acid and taurodeoxycholic acid. Intestinal expression of CYP3A4 in the Vitamin D receptor-deficient mouse line reduces lithocholic acid-induced hepatotoxicity through elevation of lithocholic acid metabolism and detoxification, and suppression of bile acid transporter expression in the small intestine 1.14.14.73 albendazole monooxygenase (sulfoxide-forming) medicine enzyme is able to modify antihistamine drugs such as albendazole, amiodarone, astemizole, thioridazine, mesoridazine, and danazol with in vitro intrinsic clearance values ranging from 0.06 to 3.98 microl/min/pmol CYP2J2. Whereas isoform CYP3A4 commonly metabolizes compounds at multiple sites, CYP2J2 metabolism is more restrictive and limited, in general, to a single site for large compounds 1.14.14.80 long-chain fatty acid omega-monooxygenase medicine specific inhibition of either the CYP2C epoxygenase or the CYP4A omega-hydroxylase abrogates peroxisomal proliferation induced by the hypolipidemic drug cirpofibrate 1.14.14.80 long-chain fatty acid omega-monooxygenase medicine hepatic CYP4A14 expression is up-regulated in three murine models of nonalcoholic fatty liver disease. Overexpression of CYP4A14 in the livers of C57BL/6 mice results in a fatty liver phenotype with a significant increase in hepatic fatty acid translocase (FAT/CD36) expression. CYP4A14 gene-deficient mice fed a high-fat diet or a methionine and choline-deficient diet exhibit attenuated liver lipid accumulation and reduced hepatic FAT/CD36 expression. Hepatic inflammation and fibrosis is markedly ameliorated in methionine and choline-deficient diet-fed CYP4A14-deficient mice 1.14.14.88 isoflavone 3'-hydroxylase medicine Astragalus membranaceus var. mongholicus is a medicinal plant in traditional Chinese medicine, the enzyme products calycosin and calycosin-7-O-beta-D-glucoside are two major isoflavones related to the bioactivity of the herb 1.14.14.92 benzoate 4-monooxygenase medicine the enzyme is involved in detoxification of benzoate, a key intermediate in aromatic compound metabolism in fungi. Because this enzyme is unique to fungi, it is a promising drug target in fungal pathogens of other eukaryotes 1.14.14.102 N-methylcoclaurine 3'-monooxygenase medicine traditional Chinese medicinal plant containing benzylisoquinoline alkaloids as active agents 1.14.14.154 sterol 14alpha-demethylase medicine - 1.14.14.154 sterol 14alpha-demethylase medicine target enzyme for azole antifungal agents. These specific inhibitors are of great importance as plant growth regulators, fungicides and herbicides in the agricultural and medical fields 1.14.14.154 sterol 14alpha-demethylase medicine target for cholesterol-lowering drugs 1.14.14.154 sterol 14alpha-demethylase medicine fluconazole-resistant strain isolated from patients receiving long-term azole treatment shows Y132H and F145L substitutions 1.14.14.154 sterol 14alpha-demethylase medicine the enzyme is a potential drug target for treatment of Chagas disease 1.14.14.154 sterol 14alpha-demethylase medicine the enzyme is a target for antifungal inhibitors 1.14.14.154 sterol 14alpha-demethylase medicine the enzyme is a target in treatment of the chronic lung disease caused by Mycobacterium avium 1.14.14.154 sterol 14alpha-demethylase medicine Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14alpha-demethylase inhibitors 1.14.14.154 sterol 14alpha-demethylase medicine the chemotherapy of leishmaniasis is a serious problem in the field of neglected tropical diseases. Since the biosynthesis of specific sterols is vital for effective survival, normal proliferation and infectivity of Leishmania parasites, the sterol 14alpha-demethylase inhibitors obtained from azole antifungal drug discovery programs can be used in antileishmanial therapy 1.14.14.154 sterol 14alpha-demethylase medicine the enzyme constitutes an important biological target for the most popular class of antifungals 1.14.14.176 taxadiene 5alpha-hydroxylase medicine enzyme may be useful in the biological production of the potent antimitotic drug taxol which shows activity against a range of cancers 1.14.14.177 ultra-long-chain fatty acid omega-hydroxylase medicine CYP4F22 is one of the autosomal recessive congenital ichthyosis-causative genes. Ichthyosis-mutant proteins exhibit reduced enzyme activity. Lipid analysis of a patient with ichthyosis shows a drastic decrease in acylceramide production 1.14.15.4 steroid 11beta-monooxygenase medicine inhibitors for P-45011beta, against aldosterone overproduction which leads to oedematous diseases and hypertension 1.14.15.4 steroid 11beta-monooxygenase medicine increased sensitivity of adrenocortical stereoidgenesis to adrenocorticotropic hormone in Milan hypertensive rats, enzyme is not affected 1.14.15.4 steroid 11beta-monooxygenase medicine treatment of hyperaldosteronism, congestive heart failure, and myocardial fibrosis by lowering the elevated plasma aldosterone levels via blockade of aldosterone synthase, CYP11B2, the key enzyme of mineralocorticoid biosynthesis 1.14.15.4 steroid 11beta-monooxygenase medicine blocking of aldosterone synthesis by mediating aldosterone synthase activity is a possible pharmacological therapy for hypertension 1.14.15.6 cholesterol monooxygenase (side-chain-cleaving) medicine treatment of certain hormone-related pathologies 1.14.15.6 cholesterol monooxygenase (side-chain-cleaving) medicine significant inversed statistical correlation of enzyme immunoreactivity with residual size of tumor in epithelial ovarian carcinoma, but correlation is not an independent prognostic value 1.14.15.6 cholesterol monooxygenase (side-chain-cleaving) medicine P450scc overexpression in the ventral tegmental area significantly reduces ethanol self-administration of alcohol preferring rats trained to self-administer ethanol, by 20% over the 3 week test period. P450scc overexpression in the nucleus accumbens, does not alter ethanol self-administration. P450scc overexpression produces a 36% increase in (3alpha,5alpha)-3-hydroxypregnan-20-one-positive cells in the ventral tegmental area, but does not increase (3alpha,5alpha)-3-hydroxypregnan-20-one immunoreactivity in nucleus accumbens 1.14.15.15 cholestanetriol 26-monooxygenase medicine 7-dehydrocholesterol is catabolized by isoform CYP27A1 to metabolites that act as selective liver X receptor LXR modulators. Metabolites detected in serum of a patient with Smith-Lemli-Opitz syndrome are 25-hydroxy-7-dehydrocholesterol which activates liver X receptors LXRalpha, LXRbeta and vitamin D receptor and 26/27-hydroxy-7-dehydrocholesterol which induces activation of LXRalpha and LXRbeta, although the activities of both compounds on LXRs are weak 1.14.15.15 cholestanetriol 26-monooxygenase medicine treatment of enzyme with iso[4]levuglandin E2 in vitro diminishes enzyme activity. Lys residues Lys134, Lys358, and Lys476, readily interact iso[4]levuglandin E2 in vitro, and modified CYP27A1 is present in the retina. The post-translational modifications may exemplify a general mechanism whereby oxidative stress and inflammation deleteriously affect protein function, contributing, for example, to cholesterol-rich lesions associated with age-related macular degeneration and cardiovascular disease 1.14.15.15 cholestanetriol 26-monooxygenase medicine the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway, role of marinobufagenin in highly prevalent human cardiovascular diseases 1.14.15.16 vitamin D3 24-hydroxylase medicine elevated tumor CYP24A1 expression is associated with a poor prognosis 1.14.15.18 calcidiol 1-monooxygenase medicine the enzyme is a target in cancer therapy and prevention 1.14.15.18 calcidiol 1-monooxygenase medicine genes CYP2R1 encoding vitamin D 25-hydroxylase, CYP27B1 encoding 25-hydroxyvitamin D-1 alpha hydroxylase and CYP24A1 encoding 1,25-dihydroxyvitamin D(3) 24-hydroxylase are upregulated in clear cell renal cell carcinomas compared with normal tissue. CYP24A1 displays a significantly higher expression in tumors than CYP27B1 and CYP2R1, whereas no differences in the expression of these genes are found in healthy renal tissue. Gene expression of CYP2R1, CYP27B1 and CYP24A does not differ between pathological classifications 1.14.15.18 calcidiol 1-monooxygenase medicine hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. 25-hydroxyvitamin D3 1alpha-hydroxylase is expressed at much higher levels in oxyphil cells than in chief cells in these patients. The calcimimetic cinacalcet increases the expression of the enzyme in human parathyroid cultures. The enzyme in human parathyroid cultures is functionally active 1.14.15.30 3-ketosteroid 9alpha-monooxygenase medicine KSH inhibitory compounds may find application in combatting tuberculosis 1.14.16.4 tryptophan 5-monooxygenase medicine the two distinct serotonin systems in the brain (TPH2) and in the periphery (TPH1) can be targeted independently by pharmacological agents and new therapeutical options are available for psychiatric diseases on one side and disorders of haemostasis and the immune system on the other side 1.14.16.4 tryptophan 5-monooxygenase medicine TPH2 is a good candidate gene for 5-hydroxytryptophan related psychiatric diseases such as bipolar affective disorders. The two distinnct serotonin systems in the brain (TPH2) and in the periphery (TPH1) can be targeted independently by pharmacological agents and new therapeutical options are available for psychiatric diseases on one side and disorders of haemostasis and the immune system on the other side 1.14.16.4 tryptophan 5-monooxygenase medicine the serotonin transporter gene-linked promoter region 5-HTTLPR and tryptophan hydroxylase-2 genes act in concert to modulate the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders 1.14.17.1 dopamine beta-monooxygenase medicine ethanol causes concentration- and time-dependent increase in DBH gene transcription. Protein kinase A, mitogen-activated protein kinase/extracellular signal -regulated kinase kinase, and casein kinase II inhibitors block induction of dopamine beta-hydroxylase and a large subset of ethanol-responsive genes. Ethanol regulation of dopamine beta-hydroxylase requires a functional cAMP-response element and its binding protein and may require interaction of multiple kinase pathways. These studies may have implications for behavioral responses to ethanol or mechanisms underlying ethanol-related neurological disease 1.14.17.1 dopamine beta-monooxygenase medicine the antidepressant drug imipramine counteracts the chronic mild stress-induced reduction of plasma dopamine beta-hydroxylase activity 1.14.17.1 dopamine beta-monooxygenase medicine a -1021C/T polymorphism in human dopamine-beta-hydroxyase shows an correlation with fasting plasma glucose in association with hypertension. CC homozygotes show a steeper increase in probability of hypertension with FPG than T allele carriers 1.14.17.1 dopamine beta-monooxygenase medicine adequate dietary Cu is essential to support DBM function in vivo 1.14.17.1 dopamine beta-monooxygenase medicine simple photometric method in clinical chemistry for determining the DBH activity in human blood, which parallels the protein level, and the high interest in DBH activity in the blood in various diseases that affect central and peripheral catecholamine systems, such as DBH deficiency and pheochromocytoma 1.14.17.1 dopamine beta-monooxygenase medicine inhibitors of enzyme DBH nepicastat and etamicastat are currently in clinical development for treatment of cocaine dependence 1.14.17.3 peptidylglycine monooxygenase medicine enzyme is an attractive target for anti-tumor compounds 1.14.17.3 peptidylglycine monooxygenase medicine PHM is a potential target for the development of inhibitors as drugs for the teratment of human disease 1.14.17.3 peptidylglycine monooxygenase medicine PHM is a potential target for the development of inhibitors as drugs for the treatment of human disease 1.14.17.3 peptidylglycine monooxygenase medicine PHM is a potential target for the development of insecticides 1.14.18.1 tyrosinase medicine tyrosinase purified from Agaricus bisporus is a potential source for medical applications 1.14.18.B1 5,6-dihydroxyindole-2-carboxylic acid oxidase medicine H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss 1.14.18.B1 5,6-dihydroxyindole-2-carboxylic acid oxidase medicine histone demethylase JMJD3 might serve as a therapeutic target for treatment of systemic lupus erythematosus, SLE 1.14.18.B1 5,6-dihydroxyindole-2-carboxylic acid oxidase medicine regulation of JMJD3 may provide a therapeutic intervention for treating the chronic skin wounds 1.14.18.2 CMP-N-acetylneuraminate monooxygenase medicine the results pinpoint the crucial need for totally xenofree culturing and expansion conditions for human therapeutic stem cells 1.14.18.6 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase medicine in blood and fibroblasts from patients harboring a deleterious FA2H mutatation, hydroxylated fatty acid sphingomyelin is present in normal amounts in patient lymphocytes, but decreases to a different extent in fibroblasts and erythrocytes 1.14.18.6 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase medicine silencing of sphingolipid fatty acyl 2-hydroxylase Fa2h turns the cells resistant to synthetic antitumor drug PM02734, i.e. elisidepsin. Overexpression of Fa2H leads to an increased sensitivity to PM02734. Exogenous addition of the 2-hydroxylated fatty acid 2-hydroxy palmitic acid to different human cell lines increases their sensitivity to the cytotoxic compound 1.14.18.9 4alpha-methylsterol monooxygenase medicine enzyme is an antifungal target 1.14.19.1 stearoyl-CoA 9-desaturase medicine potential use of SCD1 as a target in the treatment of some eye diseases 1.14.19.1 stearoyl-CoA 9-desaturase medicine treatment with enzyme-specific antisense oligonucleotide inhibitors results in prevention of diet-induced obesity with reductions in the ratio of oleate to stearoyl-CoA in tissues and plasma. Correlation with reduced body adiposity, hepatomegaly and steatosis 1.14.19.1 stearoyl-CoA 9-desaturase medicine DELTA9 desaturase and abdominal adiposity are positively associated independently of insulin resistance and dietary saturated fatty acids intake, DELTA9 desaturase is positively associated with blood lipids independent of the insulin resistance, abdominal adiposity, and dietary saturated fatty acid intake 1.14.19.1 stearoyl-CoA 9-desaturase medicine the gene combination of macrophage migration inhibitory factor and stearoyl-CoA desaturase 1 is a prognostic marker for the overall outcome of soft tissue sarcomas 1.14.19.1 stearoyl-CoA 9-desaturase medicine isozyme SCD1 may represent a therapeutic target to control obesity and the progression of related metabolic diseases including type 2 diabetes and hepatic steatosis 1.14.19.1 stearoyl-CoA 9-desaturase medicine targeting SCD1 in combination with sorafenib may be another therapeutic strategy against liver cancer. SCD1 may be a biomarker for sorafenib response and personalized medicine for hepatocellular carcinoma 1.14.19.19 sphingolipid 10-desaturase medicine the enzyme can be useful for production of fusaruside, a 10,11-unsaturated immunosuppressive fungal sphingolipid with medical potentials for treating liver injury and colitis 1.14.19.22 acyl-lipid omega-6 desaturase (cytochrome b5) medicine use of enzyme as a molecular target for the development of chemotherapeutic approaches against Chagas disease 1.14.19.25 acyl-lipid omega-3 desaturase (cytochrome b5) medicine consuming high levels of long-chain OMEGA-3 polyunsaturated fatty acids (PUFAs) is been shown to reduce prostate cancer risk and increase chemotherapy sensitivity in humans 1.14.19.30 acyl-lipid (8-3)-desaturase medicine a higher serum concentration of the n-6 polyunsaturated fatty acid dihomo-gamma-linoleic acid and lower DELTA5-desaturase activity are associated with an increased risk of type 2 diabetes, independent of BMI, in Japanese adults 1.14.19.30 acyl-lipid (8-3)-desaturase medicine Delta5 desaturase inhibitors are expected to drive anti-inflammatory properties through reduction of arachidonic acid biosynthesis and simultaneous accumulation of dihomo-gamma-linolenic acid 1.14.19.68 (S)-canadine synthase medicine a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale 1.14.19.70 mycocyclosin synthase medicine CYP121 is a potential target for the treatment of Mycobacterium tuberculosis infections 1.14.19.70 mycocyclosin synthase medicine the CYP121 gene is essential for survival of Mycobacterium tuberculosis in vitro and the enzyme is believed to be the molecular target responsible for the anti-tubercular efficacy of azole antifungal compounds pharmacology 1.14.20.1 deacetoxycephalosporin-C synthase medicine antibiotic cephalosporin production 1.14.20.4 anthocyanidin synthase medicine fruit extracts of Fragaria ananassa transgemic lines exert cytotoxic effects on human liver cancer cells, increasing cellular apoptosis and free radical levels and impaired mitochondrial functionality 1.14.20.14 hapalindole-type alkaloid chlorinase medicine synthesis of 13R-bromo-12-epi-fischerindole U, which is selective against the gram-positive bacterium Staphylococcus aureus 1.14.99.1 prostaglandin-endoperoxide synthase medicine inhibition of prostaglandin synthesis by suppression of enzyme expression using isomallotochromanol 1.14.99.1 prostaglandin-endoperoxide synthase medicine use of peroxidase activity for luminol assay of inflammation 1.14.99.1 prostaglandin-endoperoxide synthase medicine study of aspirin acetylated enzyme in order to inhibit prostaglandin synthesis 1.14.99.1 prostaglandin-endoperoxide synthase medicine amphetamines, bioactivated by prostaglandin H synthase, cause reactive oxygen species formation, implicated in amphetamine-initiated neurodegeneration 1.14.99.1 prostaglandin-endoperoxide synthase medicine clinical important drug target 1.14.99.1 prostaglandin-endoperoxide synthase medicine inhibition of cyclooxygenases is a mode of antiinflammatory drugs 1.14.99.24 steroid 9alpha-monooxygenase medicine - 1.14.99.24 steroid 9alpha-monooxygenase medicine enzyme catalyzes the production of 9alpha-hydroxy-4-androstene-3,17-dione, an important intermediate for the semi-synthesis of potent anti-inflammatory drugs such as 9alpha-fluorocorticoids from 4-androstene-3,17-dione 1.14.99.24 steroid 9alpha-monooxygenase medicine 9alpha-steroid hydroxylating activity is used for conversion of different steroid compounds into valuable 9alpha-hydroxy derivatives used in the pharmaceutical industry 1.14.99.29 deoxyhypusine monooxygenase medicine ciclopirox inhibits cell proliferation and angiogenesis in vitro 1.14.99.29 deoxyhypusine monooxygenase medicine inhibition of DOHH leads to a decrease of hypusine-containing eIF5A and inhibition of eukaryotic cell growth, consequently, these results suggest that eIF5A and DOHH could be promising targets for antitumor and anti-HIV-1 therapies 1.14.99.29 deoxyhypusine monooxygenase medicine the results support the concept that drugs targeting DOHH should be tested clinically for HIV-1 inhibition and could be developed as antiretrovirals 1.14.99.38 cholesterol 25-monooxygenase medicine genetic variability in the set of cholesterol metabolism genes: cholesterol 25-hydroxylase, cholesterol 24-hydroxylase and ATP-binding cassette transporter A1 does not influence the development of Alzheimer‘s disease 1.14.99.38 cholesterol 25-monooxygenase medicine patients with Alzheimer’s disease show high expression of cholesterol 25-hydroxylase gene in specifically vulnerable brain regions. The common enzyme haplotype CH25Hchi4 is a putative susceptibility factor for sporadic Alzheimer’s disease 1.14.99.65 4-amino-L-phenylalanyl-[CmlP-peptidyl-carrier-protein] 3-hydroxylase medicine upon treatment with phenobarbital, the content of cytochrome P450 isozymes CMLa, CMLb and CMLc increases about 12.8, 2.3 and 2.7fold, respectively 1.15.1.1 superoxide dismutase medicine recombinant protein is useful as serodiagnostic marker for identification of Aspergillus fumigatus infections, crossreactive antibodies 1.15.1.1 superoxide dismutase medicine investigations with help of mutants to elucidate structure-function relation in familial amyotrophic lateral sclerosis 1.15.1.1 superoxide dismutase medicine potential target for drug design 1.15.1.1 superoxide dismutase medicine differences in oxidative stress between human arteries and veins are unlikely to be caused by superoxide dismutase activity. However enzyme plays an important role in amelioration of oxidative stress in both types of vessels 1.15.1.1 superoxide dismutase medicine enzyme deletion mutants are avirulent in a murine model of inhaled cryptococcosis 1.15.1.1 superoxide dismutase medicine patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia show significantly lowered immunoreactivity of extracellular superoxide dismutase in fibrotic compared to non-fibrotic areas of the diseased lung 1.15.1.1 superoxide dismutase medicine pronounced reaction of enzyme with sera from patients infected by Clonorchis sinensis and extensive cross-reactions with sera of patients infected by other trematodes or cestodes 1.15.1.1 superoxide dismutase medicine superoxide dismutase enzyme mutations causing familial amyotrophic lateral scerosis FALS cluster in protein regions influencing architectural integrity. FALS mutants H43R and A4V show reduced stability and drastically increased aggregation propensity, promoting the formation of filamentous aggregates. Free-cysteine-independent aggregation of FALS mutant enzyme is an intregral part of pathology 1.15.1.1 superoxide dismutase medicine SOD3 has the potential as a therapeutic drug for various diseases 1.16.1.8 [methionine synthase] reductase medicine cloning of the cDNA will permit the diagnostic characterization of cblE patients and investigation of the potential role of polymorphisms of this enzyme as a risk factor in hyperhomocysteinemia-linked vascular disease 1.16.1.8 [methionine synthase] reductase medicine the common variant I22M in methionine synthase reductase combined with low vitamin B12 increases risk for spina bifida 1.16.1.8 [methionine synthase] reductase medicine variant M22/S175 is a genetic determinant of plasma homocysteine levels and has been linked to premature coronary artery disease, Down‘s syndrome, and neural tube defects 1.16.1.8 [methionine synthase] reductase medicine study on association of natural polymorphisms I22M (A66G) and S175L (C524T) with bone mineral density and serum osteocalcin levels. No significant association between these two polymorphisms and bone mineral density and serum osteocalcin levels, but the 66G/524C haplotype affects bone turnover rate 1.16.3.1 ferroxidase medicine mutations in human ceruloplasmin which result in a loss of activity, cause aceruloplasminemia, a neurodegenerative disease 1.16.3.1 ferroxidase medicine clinical interest relates to its critical role in the diagnosis of Wilson's disease in serum from patients, marked reduction in serum of patients 1.16.3.1 ferroxidase medicine homogenous ceruloplasmin with ferroxidase activity for the treatment of aplastic anemics, aplastic anemics have low levels of this enzyme, clinical trials have shown effective in 56% of cases 1.16.3.1 ferroxidase medicine different forms of normal and pathological ceruloplasmins, increasing ceruloplasmin activity in the blood of schizophrenics 1.16.3.1 ferroxidase medicine unusual antioxidant property of caeruloplasmin have important implications in vivo for conditions such as rheumatoid joint disease and Wilson's disease, where changes in copper homeostasis, caeruloplasmin and oxygen radicals are known to occur 1.16.3.1 ferroxidase medicine clinical importance because of its role in iron and copper metabolism and transport 1.16.3.1 ferroxidase medicine production of monoclonal antibodies for use in diagnostic kits for ceruloplasmin related diseases 1.16.3.1 ferroxidase medicine both hypoxia and CuCl2 increase ceruloplasmin mRNA levels in hepatoma cells due to transcriptional induction of enzyme gene promoter 1.16.3.1 ferroxidase medicine after induction of cerebral ischemia by ligating bilateral common carotid arteries, the expression of ceruloplasmin mRNA in the cortex and hippocampus decreases, and the longer the animals experience ischemia, the lower the expression. Iron concentration correlates negatively with ceruloplasmin expression 1.16.3.1 ferroxidase medicine in fluid from patients with Parkinson's disease, Alzheimer's disease, and Huntington's disease, a significantly decreased ferroxidase activity is found agreeing with findings of iron deposition in these entities, while free copper is found to be increased in cerebrospinal fluid and appears to be a good biomarker of Parkinson's disease. The sum of nitrites and nitrates as end products of nitric oxide are increased in the degenerative diseases Parkinson's disease, Alzheimer's disease, Huntington's disease and lateral amyotrophic sclerosis, and fluorescent lipoperoxidation products in three of them, excepting lateral amyotrophic sclerosis 1.16.3.1 ferroxidase medicine serum ceruloplasmin concentrations of less than 0.20, of 0.14 and 0.10 g per l show positive predictive values of 48.3%, 100%, and 100%, respectively, for Wilson disease, and negative predictive values of 98.7%, 97.1%, and 91.9%, with measurement of ceruloplasmin concentration according to a nephelometric method, in ATP7B genotyped subjects. The diagnostic accuracy for Wilson disease using a serum ceruloplasmin concentration of 0.14 g per l as the local decision threshold is therefore better than using a threshold of 0.20 g per l 1.16.3.1 ferroxidase medicine Serum transferrin, albuminumin and Zinc concentrations are lower in patients with chronic lymphocytic leukemia while serum alpha-1-acid glycoprotein, ceruloplasmin, copper concentrations, and ceruloplasmin oxidase activity are higher in chronic lymphocytic leukemia patients when compared with the control group. Serum ceruloplasmin level positively correlates with serum ceruloplasmin oxidase activity in patients from the early stage group and in patients with advanced stage 1.16.3.1 ferroxidase medicine study on children with Henoch-Schönlein purpura. Patients at active stage have significantly higher myeloperoxidase activity, higher ceruloplasmin and total oxidant values than the control. Patiens have significantly lower arylesterase activity and lower free thiol levels. Significantly positive correlations are found between total oxidant status and myeloperoxidase, and total oxidant status and ceruloplasmin at disease onset, whereas a negative correlation is found between myeloperoxidase and thiol during remission 1.16.3.1 ferroxidase medicine the requirement for a ferroxidase to maintain iron transport activity may explain brain iron overload in patients with aceruloplasminemia 1.16.3.1 ferroxidase medicine treatment of rabbits with standard common rabbit diet and water ad libitum containing 40 mg fluoride per liter results in significant decrease of ceruloplasmin level in serum by days 35 and 70, with concomitant increase of serum adenosine eaminase and C-reactive protein 1.17.1.4 xanthine dehydrogenase medicine modification of xanthine oxidoreductase by disulfiram that is used in the management of chronic alcolism 1.17.1.4 xanthine dehydrogenase medicine enzyme null mutant mice demonstrate 50% reduction in adipose mass compared to control, while obese mice exhibit increased concentrations of xanthine oxidoreductase mRNA and urate in adipose tissues. In vitro, knockdown of xanthine oxidoreductase inhibits adipogenesis and nuclear receptor PPARgamma activity. Xanthine oxidoreductase is a potential therapeutic target for metabolic abnormalities beyond hyperuricemia 1.17.1.4 xanthine dehydrogenase medicine lung xanthine oxidoreductase activity is significantly increased after 2 h of mechanical ventilation without changes in enzyme expression. Increase occurs via activation of p38 MAP kinase and ERK and plays a critical role in the pathogenesis of pulmonary edema associated with ventilator-induced lung injury 1.17.1.4 xanthine dehydrogenase medicine oral adminstration of cassia oil significantly reduces serum and hepatic urate levels in hyperuricemic mice. At 600mg/kg, cassia oil is as potent as allopurinol. This hypouricemic effect is explained by inhibiting activities of liver xanthine oxidase and xanthine oxidoreductase 1.17.1.4 xanthine dehydrogenase medicine cocaine-induced cardiac disfunction is associated with an increase in NADPH oxidase and xanthine oxidoreductase activities by 59% and 29%, respectively, and a decrease in catalase activity. Apocynin or allopurinol treatment prevents the cocaine-induced cardiac alteration by restoration of cardiac output, stroke volume and fractional shortening. This is associated with a reduction of the myocardial production of superoxide anions and an enhancement of catalase activity. Apocynin treatment prevents anthine oxidoreductase up-regulation supporting the hypothesis that NADPH oxidase-derived reactive oxygen species play a role in modulating reactive oxygen species production by xanthine oxidoreductase 1.17.1.4 xanthine dehydrogenase medicine demonstration of a functional link between xanthine oxidoreductase expression and mammary epithelial cell migration, potential role in enzyme in suppressing breast cancer pathogenesis. Level of xanthine oxidoreductase is markedly reduced in highly invasive mammary tumor cells, and over-expression of enzyme cDNA in cell lines possessing weak expression and high migratory capacity inhibits their migration in vitro 1.17.1.4 xanthine dehydrogenase medicine demonstration of a functional link between xanthine oxidoreductase expression and mammary epithelial cell migration, potential role in enzyme in suppressing breast cancer pathogenesis. Over-expression of enzyme cDNA in cell lines possessing weak expression and high migratory capacity inhibits their migration in vitro 1.17.1.4 xanthine dehydrogenase medicine the enzyme inhibitor 4-(5-pyridin-4-yl-1H-[1,2,4]triazol-3-yl) pyridine-2-carbonitrile, i.e. FYX-051, is modified in vivo by N1- and N2-glucuronidation, mainly catalyzed by UDP-glucuronosyltransferase UGT1A9 1.17.1.4 xanthine dehydrogenase medicine xanthine oxidoreductase is activated in a p38 MAP kinase-dependent manner following high tidal volume mechanical ventilation and is involved in resulting increased alveolar cell apoptosis 1.17.1.8 4-hydroxy-tetrahydrodipicolinate reductase medicine - 1.17.1.8 4-hydroxy-tetrahydrodipicolinate reductase medicine potential drug target in therapy of tuberculosis caused by resistent strains of Mycobacterium tuberculosis, molecular modeling for identification of potential inhibitors 1.17.1.8 4-hydroxy-tetrahydrodipicolinate reductase medicine design and evaluation of dihydropicolinate reductase inhibitors as broad spectrum antibiotics and herbicides 1.17.1.9 formate dehydrogenase medicine enzyme-loaded erythrocytes along with equimolar solution of sodium carbonate and hydrogencarbonate facilitate removal of formate in methanol poisoning of folate-deficient rats 1.17.1.9 formate dehydrogenase medicine immobilization of enzyme with N-hydroxysuccinimidyl ester of methoxy polyethylene glycol propionic acid in order to reduce immunogenicity of enzyme when applied intravenously during detoxification of formate in methanol poisoning. Coupled enzyme has a longer half-life and lower immunogenicity than native enzyme and a better in vivo efficacy in eliminating formate 1.17.3.2 xanthine oxidase medicine in Helicobacter pylori positive and negative pediatric patients, the activities of xanthine oxidase, myeloperoxidase, and superoxide dismutase in gastric mucosa are not affected by presence/absence of Helicobacter pylori 1.17.3.2 xanthine oxidase medicine increased activity of xanthine oxidase in cells exposed to CoCl2 and subsequent increase in reactive oxygen species derived from enzyme activity, which results in accumulation of hypoxia-inducible factor 1alpha. Blockade of enzyme activity by allopurinol, N-acetyl-L-cysteine or siRNA significantly attenuates expression of hypoxia-inducible factor 1alpha and thus the induction of genes such as erythropoietin and vascular endothelial growth factor 1.17.3.2 xanthine oxidase medicine oral adminstration of cassia oil significantly reduces serum and hepatic urate levels in hyperuricemic mice. At 600 mg/kg, cassia oil is as potent as allopurinol. This hypouricemic effect is explained by inhibiting activities of liver xanthine oxidase and xanthine oxidoreductase 1.17.4.1 ribonucleoside-diphosphate reductase medicine in transgenic human lung and colon cancer lines expressing xanthine oxidase regulatory subunit RRM1, G2 cell cycle arrest, apoptosis, and efficient DNA damage repair are induced 1.17.4.1 ribonucleoside-diphosphate reductase medicine in transgenic mice expressing xanthine oxidase regulatory subunit RRM1, carcinogen-induced lung tumor formation is significantly suppressed. RRM1 transgenic animals repair chemically induced DNA damage with greater efficiency than control animals 1.17.4.1 ribonucleoside-diphosphate reductase medicine ribonucleotide reductase is a therapeutic target for DNA replication-dependent diseases such as cancer in humans 1.17.4.1 ribonucleoside-diphosphate reductase medicine the enzyme is a target for cancer therapy 1.17.4.1 ribonucleoside-diphosphate reductase medicine combination of (2E)-2-(anthracen-9-ylmethylidene)-N-hydroxyhydrazinecarboximidamide with the first-line antileukemic agent arabinofuranosylcytosine, Ara-C, synergistically potentiates the antineoplastic effects of Ara-C 1.17.4.1 ribonucleoside-diphosphate reductase medicine skin fibroblasts isolated from a patient with a lethal homozygous missense mutation of ioform p53R2 grow normally in culture with an unchanged complement of mtDNA. During active growth, the four dNTP pools do not differ in size from normal controls, whereas during quiescence, the dCTP and dGTP pools decrease to 50% of the control. On withdrawal of ethidium bromide depleting cell of mitochondrial DNA, mitochondrial DNA recovers equally well in cycling mutant and control cells, whereas during quiescence, the mutant fibroblasts remain deficient. Addition of deoxynucleosides to the medium increases intracellular dNTP pools and normalizes mtDNA synthesis. Quiescent mutant fibroblasts are also deficient in the repair of UV-induced DNA damage 1.17.4.1 ribonucleoside-diphosphate reductase medicine thiosemicarbazone chelators 2-[di(pyridin-2-yl)methylidene]-N,N-dimethylhydrazinecarbothioamide and 2-(diphenylmethylidene)-N,N-dimethylhydrazinecarbothioamide possess potent and selective antitumor activity and may have an additional mechanism of ribonucleotide reductase inhibition via their effects on major thiol-containing systems 1.17.4.1 ribonucleoside-diphosphate reductase medicine high expression of ribonucleotide reductase subunit M2 (RRM2) correlates with poor prognosis of hepatocellular carcinoma. High RRM2 protein expression might be a useful marker for predicting early recurrence and may be a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy 1.17.4.1 ribonucleoside-diphosphate reductase medicine the thiazolyl hydrazones VG12, VG19, and VG22 plus arabinofuranosylcytosine might be able to improve conventional chemotherapeutic regimens for the treatment of human malignancies such as acute promyelocytic or chronic myelogenous leukemia 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine the enzyme is the therapeutic target site for warfarin, an anticoagulant that is prescribed widely for the treatment and prevention of thrombosis. Point mutations in VKORC1 may be an important, though rare, cause of warfarin resistance in anticoagulation clinic populations 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine comparison of the effect of single nucleotide polymorphisms in African Americans and Caucasians. Subjects carrying an 1173T allele have a lower warfarin maintenance compared with subjects with the CC genotype in African americans and Caucasians. Before reaching maintenance dose, only Caucasians with the T allele have significantly increased risk of international normlized ratio > 3 compared with Caucasians with the CC genotype. Polymorphisms may not be useful in predicting over-coagulation among African Americans 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine patient with warfarin resistance due to a T383G transition in exon 2 of the VKORC1 gene, patient is heterozygous for the mutation 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine study on the association between the 1173C>T polymorphism in the VKORC1 gene and calcification of the aortic far wall. Persons with at least one T-allele have a statistically significant 19% risk increase of calcification of the aortic far wall compared to CC homozygous persons, adjusted for age and gender 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine the single nucleotide polymorphism G1639A is a suitable biomarker for warfarin dosing across ethnic populations. Preferential association of the promoter -1639 G allele with active chromatin 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine polymorphisms in the VKORC1 gene are important determinants of warfarin dose requirements in Turkish patients 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine the determination of VKORC1-3 and VKORC1-4 haplotypes may be an important addition to CYP2C9 and VKORC1-2 genotyping to identify patients at risk of being outside the target range during initial anticoagulation with acenocoumarol 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine VKORC1 genotype affects daily dose requirements and time to therapeutic international normalized ratio in Turkish patients receiving warfarin for anticoagulation 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine VKORC1 haplotypes influence the performance characteristics of protein induced by vitamin K absence II for screening of hepatocellular carcinoma 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine the enzyme is regulated by microRNA miR-133a, which may have potential importance for anticoagulant therapy or aortic calcification 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine vitamin K 2,3-epoxide reductase complex subunit 1 is is the target of oral anticoagulant drugs and a relevant molecule for cardiovascular diseases 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine the T-allele of the VKORC1 1173CT polymorphism is associated with a significantly higher risk of aortic calcification in Whites 1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive) medicine VKORC1 gene rs7294 polymorphism is important for the development of essential hypertension 1.21.1.1 iodotyrosine deiodinase medicine study on enzyme expression in thyroid pathology. The highest DEHAL1 mRNA levels are found in Graves' disease thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurrs in papillary thyroid carcinomas and anaplastic thyroid carcinomas. DEHAL1 protein is overexpressed in toxic thyroid nodules and Graves' disease thyroids with predominant apical staining in all samples. A weaker and patchy staining pattern is found in benign cold thyroid nodules and normal thyroids. In differentiated thyroid cancers such as follicular thyroid carcinomas and papillary thyroid carcinomas, a diffuse cytoplasmic DEHAL1 expression is found. In partially differentiated thyroid cancers and anaplastic thyroid carcinomas, DEHAL1 expression is faint or absent 1.21.3.1 isopenicillin-N synthase medicine isopenicillin N synthase is a potential target in the design of novel antibiotic compounds 1.21.3.3 reticuline oxidase medicine a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale 1.21.99.3 thyroxine 5-deiodinase medicine expression and function of the 5-deiodinase and 5’-deiodinase isozymes are sensitive to thyroid hormone status, various cytokines and growth factors, severe illness, reactive oxygen species, a variety of hormones and signaling compounds, circadian rythm, and pharmacological agents, and therefore might be useful in sensor function of physiology and pathophysiology 1.21.99.3 thyroxine 5-deiodinase medicine sonic hedgehog pathway plays a critical role in hair follicle physiology and is constitutively active in basal cell carcinomas, induces D3 in proliferating keratinocytes and in BCCs through Gli2, reversing this T3 deficiency may be a therapeutic approach for BCCs and perhaps other D3-expressing tumors 1.21.99.3 thyroxine 5-deiodinase medicine sonic hedgehog pathway plays a critical role in hair follicle physiology and is constitutively active in basal cell carcinomas, induces TYPE 3 DEIODINASE in proliferating keratinocytes and in BCCs through Gli2, reversing this T3 deficiency may be a therapeutic approach for BCCs and perhaps other TYPE 3 DEIODINASE-expressing tumors 1.21.99.3 thyroxine 5-deiodinase medicine type 3 deiodinase activity is robustly induced 1 week after myocardial infarction only in the infarcted myocardium and leads to an acute decrease in serum T4 and T3 after infarction 1.21.99.4 thyroxine 5'-deiodinase medicine expression and function of the 5-deiodinase and 5’-deiodinase isozymes are sensitive to thyroid hormone status, various cytokines and growth factors, severe illness, reactive oxygen species, a variety of hormones and signaling compounds, circadian rythm, and pharmacological agents, and therefore might be useful in sensor function of physiology and pathophysiology 1.21.99.4 thyroxine 5'-deiodinase medicine Dio2 plays a significant role in the photoperiodic response of gonads, melatonin is involved in the signal transduction mechanisms controlling the photoperiodic response of gonads by acting on Dio2 expression 1.21.99.4 thyroxine 5'-deiodinase medicine thyroglobulin gene mutations induce defective intracellular transport of thyroglobulin leading to increased thyroidal type 2 iodothyronine deiodinase activity, increased thyroidal type 2 deiodinase activity accounts for a relatively high serum free T3 level with a disproportionately low serum free T4 level 1.21.99.4 thyroxine 5'-deiodinase medicine expression and alternative splicing of DIO mRNA is disturbed in renal cancer, possibly due to changes in expression of splicing factors SF2/ASF and hnRNPA1 1.21.99.4 thyroxine 5'-deiodinase medicine exposure of animals to ventilator-induced lung injury leads to ignificant increases in enzyme immunorectivity and activity. Treatment of knock-out mice with 3,3',5-triiodothyronine reverses many of the lung chemokine and cytokine profiles seen in response to ventilator-induced lung injury 1.21.99.4 thyroxine 5'-deiodinase medicine the enzymatic activity of isoform Dio1 is not significantly altered in focal nodular hyperplasia and hepatocellular carcinomas when compared to matched normal liver parenchyma controls 1.97.1.4 [formate-C-acetyltransferase]-activating enzyme medicine in dental plaque, under anaerobic conditions, enzyme is always kept active 2.1.1.1 nicotinamide N-methyltransferase medicine enzyme protein level is significantly elevated in younger patients with Parkinson's disease 2.1.1.1 nicotinamide N-methyltransferase medicine significantly increased levels of enzyme protein and activity in brain of patients with Parkinson´s disease, study on brain tissue distribution 2.1.1.1 nicotinamide N-methyltransferase medicine enzyme activity correlates with tumor growth and morphological changes resembling apoptosis 2.1.1.1 nicotinamide N-methyltransferase medicine possibly involved in response to radiation 2.1.1.1 nicotinamide N-methyltransferase medicine levels of hepatic enzyme activity are closely associated with the degree of weight loss, use as marker of cancer cachexia 2.1.1.1 nicotinamide N-methyltransferase medicine expression of enzyme is significantly higher in cerebellum of patients with idiopathic Parkinson's disease than in control groups 2.1.1.1 nicotinamide N-methyltransferase medicine significantly higher enzyme activity in papillary thyroid carcinoma cell lines than in controls 2.1.1.1 nicotinamide N-methyltransferase medicine epidemiologic study to analyze risk factors for complex congenital heart defects (CHDs) and multifactorial aetiology 2.1.1.1 nicotinamide N-methyltransferase medicine inhibition of NNMT activity is a promising therapeutic target for cancer therapy 2.1.1.1 nicotinamide N-methyltransferase medicine the enzyme may serve as a potential biomarker for tumor diagnosis and a therapeutic target 2.1.1.1 nicotinamide N-methyltransferase medicine down-regulation of NNMT in colorectal cancer HT-29 cells diminishes 5-fluorouracil resistance, while overexpression of NNMT in SW-480 cells enhances it 2.1.1.1 nicotinamide N-methyltransferase medicine patients with manifest type 2 diabetes have an approximately twofold higher NNMT expression both in omental and subcutaneous white adipose tissue compared with controls. Plasma 1-methylnicotinamide concentration correlates with increased tissue NNMT expression and the degree of insulin resistance 2.1.1.1 nicotinamide N-methyltransferase medicine the expression level of NNMT is elevated in the peripheral blood and tissues of patients with prostate cancer. The overexpression of NNMT enhances PC-3 cell viability, invasion and migration capacity. The overexpression of NNMT significantly increases the mRNA level of sirtuin 1 in PC-3 cells. Nicotinamide treatment significantly suppresses the expression of SIRT1 even in PC-3 cells transfected with adeno-associated virus-NNMT 2.1.1.2 guanidinoacetate N-methyltransferase medicine GAMT deficiency in mouse is associated with increased neonatal mortality, muscular hypotonia, decreased male fertility and a non-leptin-mediated life-long reduction in body weight due to reduced body fat mass 2.1.1.2 guanidinoacetate N-methyltransferase medicine GAMT is a key enzyme in the biosynthesis of creatine, deficiency leads to severe clinical symptoms, including mental retardation, muscle hypotonia, extrapyramidal movement abnormalities and epileptic seizures 2.1.1.2 guanidinoacetate N-methyltransferase medicine guanidinoacetate methyltransferase deficiency is a rare autosomal recessive inborn error of creatine synthesis leading to accumulation of guanidinoacetate and lack of creatine in all tissues, particularly in the brain and muscle 2.1.1.2 guanidinoacetate N-methyltransferase medicine guanidinoacetate methyltransferase deficient patients show intellectual disability, epilepsy and sigificant movement disorder 2.1.1.2 guanidinoacetate N-methyltransferase medicine since creatine plays an important role in the buffering and transfer of high-energy phosphate bonds in the heart, it is hypothesized that lack of creatine would be detrimental for resting cardiac performance during ageing 2.1.1.5 betaine-homocysteine S-methyltransferase medicine methionine-deficient diet produces large increase in enzyme activity 2.1.1.5 betaine-homocysteine S-methyltransferase medicine decreased plasma homocysteine in various models of diabetes may be due to enhanced homocysteine removal brought about by a combination of increased transsulfuration of homocysteine to cysteine and increased remethylation of homocysteine to methionine by BHMT 2.1.1.5 betaine-homocysteine S-methyltransferase medicine transient inhibition of BHMT in vivo causes transient hyperhomocysteinemia 2.1.1.5 betaine-homocysteine S-methyltransferase medicine upregulation of BHMT may indicate an increased choline requirement in the diabetic rat 2.1.1.5 betaine-homocysteine S-methyltransferase medicine Zucker diabetic fatty rats show increased BHMT activity and mRNA levels 2.1.1.5 betaine-homocysteine S-methyltransferase medicine a polymorphisms in betaine-homocysteine S-methyltransferase might be linked to an increased risk for placental abruption 2.1.1.5 betaine-homocysteine S-methyltransferase medicine effect of extrahepatic expression of homo sapiens betaine-homocysteine methyltransferase on alcohol or homocysteine-induced fatty liver is shown in transgenic mice 2.1.1.5 betaine-homocysteine S-methyltransferase medicine BHMT1 is a auto-antigen associated with anti-Golgi immune reactivity. Antibodies to BHMT1 were found in four of 80 samples with a Golgi-pattern on indirect immunofluorescence. The antibodies are not associated with a specific clinical condition 2.1.1.5 betaine-homocysteine S-methyltransferase medicine in serum from healthy individuals, the median value is 1.83 ng/ml. In serum from patients with acute liver injury, the median value of BHMT is 748.48 ng/ml. The detection range of the ELISA assay is from 1.56 to 100 ng/ml with good sensitivity and specificity. In five acute liver injury cases with time course samples available, BHMT and alanine transaminase both follow the rise and fall temporal pattern with the disease progression. The slopes of BHMT curves are steeper than alanine transaminase curves. In three out of the five cases, BHMT levels peak 1 day earlier than alanine transaminase levels 2.1.1.5 betaine-homocysteine S-methyltransferase medicine treatment of hepatocytes with homocysteine to follow the impact of hyperhomocysteinemia and concomittant inhibition of betaine-homocysteine S-methyltransferase BHMT. Inhibition and 0.1 mM homocysteine treatment induce only moderate changes in the hepatocyte proteome and secretome, while the changes induced by 2 mM homocysteine treatment are extensive: phosphatidylethanolamine carboxykinase and ornithine aminotransferase are up-regulated about twofold indicating an intervention into metabolism. Cellular proliferation is suspended, secretome composition is changed and signs of apoptosis are discernible. Fibrinogen gamma dimers can be detected and maturation of apolipoprotein A1 fails 2.1.1.6 catechol O-methyltransferase medicine COMT activity may alter neurotransmitter deposition and transport 2.1.1.6 catechol O-methyltransferase medicine comparison of COMT isoforms and implications for breast cancer risk 2.1.1.6 catechol O-methyltransferase medicine genetic variation in COMT gene (MIM 116790) is associated with altered prefrontal cortex function and higher risk for schizophrenia. A common single-nucleotide polymorphism within COMT, Val158Met, significantly affects protein abundance and enzyme activity but not mRNA expression levels. Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function 2.1.1.6 catechol O-methyltransferase medicine inhibition of catechol-O-methyltransferase is an important approach in the treatment of Parkinson's disease 2.1.1.6 catechol O-methyltransferase medicine a functional COMT polymorphism (Val158Met) predicts performance in tasks of prefrontal executive function and the neurophysiological response measured with electroencephalography and functional magnetic resonance imaging in tasks assessing working memory. In fact, individuals with the Val/Val genotype, which encodes for the high-activity enzyme resulting in lower dopamine concentrations in the prefrontal cortex, perform less well and are less efficient physiologically than Met/Met individuals 2.1.1.6 catechol O-methyltransferase medicine association between the COMT Val158Met polymorphism and anger-related personality traits in suicide attempters. COMT Val158Met shows a strong effect on Trait Anger and Anger Control scores in female suicide attempters and a weaker effect on the Trait Anger score in violent suicide attempters of both genders 2.1.1.6 catechol O-methyltransferase medicine association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder. 62.5% of the patients showing a good response to methylphenidate treatment have the Val/Val genotype, 41.7% and 11.7% of the patients showing a poor response to methylphenidate treatment as assessed by their teachers have the Val/Met and Met/Met genotypes 2.1.1.6 catechol O-methyltransferase medicine catechol-O-methyltransferase activity and protein expression are increased in the substantia nigra after inflammation induced by lipopolysaccharides. These changes in glial and perivascular catechol-O-methyltransferase activity may have clinical relevance for Parkinson’s disease drug treatment due to increased metabolism of levodopa in the brain 2.1.1.6 catechol O-methyltransferase medicine COMT activity and increased formation of depurinating adducts can be critical factors leading to initiation of breast cancer 2.1.1.6 catechol O-methyltransferase medicine COMT activity has an influence on cell transforming activity and its related genetic effects of catechol estrogens imply that an individual activity of COMT may be one of the etiological factors in endogenous estrogen-induced carcinogenesis 2.1.1.6 catechol O-methyltransferase medicine COMT genotype directly influences cognitive phenotype in Parkinson’s disease through altering activation in a frontoparietal executive neural network. COMT genotype has differing effects on prefrontal function according to underlying dopaminergic state 2.1.1.6 catechol O-methyltransferase medicine COMT Val158Met polymorphism modulates the association between physical activity, areal bone mineral density, and trabecular volumetric bone mineral density, suggesting that this polymorphism is of importance for bone mineral density in subjects with a low level of physical activity 2.1.1.6 catechol O-methyltransferase medicine in boys there appeared to be a population shift toward higher verbal IQ with increasing Met allele dose (Val108/158Met polymorphism). The effects on IQ are significantly greater in pubertal than in prepubertal boys. In girls, there are no significant effects of genotype on cognition 2.1.1.6 catechol O-methyltransferase medicine L-dopa treatment is an acquired cause of hyperhomocysteinemia. The mechanism underlying L-dopa-related hyperhomocysteinemia is the O-methylation of the drug catalyzed by the enzyme catechol-O-methyltransferase. L-Dopa is the gold standard in the symptomatic management of Parkinson’s disease, but its long-term treatment is complicated by the elevation in plasma homocysteine concentrations, due to the O-methylation by COMT 2.1.1.6 catechol O-methyltransferase medicine low COMT activity leads to increased pain sensitivity via a beta2/3-adrenergic mechanism. These findings are of considerable clinical importance, suggesting that pain conditions resulting from low COMT activity and/or elevated catecholamine levels can be treated with pharmacological agents that block both beta2- and beta3-adrenergic receptors 2.1.1.6 catechol O-methyltransferase medicine significant association between the COMT Val158Met polymorphism and specific clinical features related to the onset of psychosis in a large and representative sample of first episode patients. These results suggest that COMT genotype may have a role in the pathogenesis of psychotic disorders and therefore takes part in the etiological model for schizophrenia and other psychoses 2.1.1.6 catechol O-methyltransferase medicine single nucleotide polymorphisms rs6269, rs4633, rs4818, and rs4680, tagging the common putative functional COMT haplotypes, are genotyped in 435 adult subjects with a clinical diagnosis of ADHD and 383 controls and analyzed for association with attention-deficit/hyperactivity disorder and the hyperactivity/impulsivity and in attention dimensions from the Adult ADHD Self-Report Scale. Haplotype analysis reveales that the rs6269 risk allele tags the suggested high COMT-activity haplotype, which is associated with the highest hyperactivity/impulsivity score 2.1.1.6 catechol O-methyltransferase medicine the COMT Val158Met polymorphism is associated with fracture risk in elderly men, through a mechanism independent of bone mineral density 2.1.1.6 catechol O-methyltransferase medicine the functional catechol-O-methyltransferase (COMT) Val158Met polymorphism interacts significantly with total Childhood Trauma Questionnaire abuse scores to impact perceived dissociation. The Val/Val genotype is associated with increasing levels of dissociation in participants exposed to higher levels of childhood trauma. The opposite is observed in people with Met/Met genotypes who display decreased dissociation with increasing self-reported childhood trauma. COMT Val158Met polymorphism is involved in mediating the relationship between trauma and psychopathology 2.1.1.6 catechol O-methyltransferase medicine the present meta-analysis provides tentative support for the COMT Val158met polymorphism as a possible risk factor for panic disorder, with differential effects in Caucasian and Asian populations, and suggests a female-specific effect 2.1.1.6 catechol O-methyltransferase medicine therapeutic potential of manipulating COMT activity to alter dopaminergic neurotransmission in the prefrontal cortex 2.1.1.6 catechol O-methyltransferase medicine best-characterized single nucleotide polymorphism of the COMT gene consists of a valine-to-methionine substitution at codon 108/158. In homozygous carriers of Met, but not Val alleles, the activity of COMT and methionine sulfoxide reductase are significantly correlated throughout all tested brain regions 2.1.1.6 catechol O-methyltransferase medicine both melanotic melanoma SK-mel-1 and Ha-Cat cells express COMT activity. In SK-mel-1, COMT activity is reduced nearly 50% both 24 h and 48 h after a high dose UVB. In Ha-Cat cells, COMT activity increases 24 h after a high dose UVB but decreases at 48 h. Tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation only in HaCat. High concentrations of tolcapone reduce melanin levels in melanoma cells parallel to reduced cell numbers 2.1.1.6 catechol O-methyltransferase medicine despite successful lesioning of dopaminergic and noradrenergic neurons, no changes in COMT protein expression or activity are observed 2.1.1.6 catechol O-methyltransferase medicine enzymatic activities of functional COMT single-nucleotide polymorphisms in red blood cells in 24 healthy human volunteers, supplemented with750 mg of epigallocatechin-3-gallate.The homozygousVal-Met substitution in the SNPrs 4680 results in significantly decreased COMT activity. Enzymatic COMT activities are also affected by the other COMT polymorphisms. Epigallocatechin-3-gallate plasma levels significantly increase after intervention.They are not influenced by any of the COMT SNPs and different enzyme activities. Ingestion of 750 mg epigallocatechin-3-gallate does not result in impairment of COMT activity. However, COMT activity is significantly increased by 24% after epigallocatechin-3-gallate consumption 2.1.1.6 catechol O-methyltransferase medicine subjects carrying the Val/Val genotype of the Val108/158Met polymorphism show increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs placebo, whereas subjects carrying the Met/Met genotype react similarly to green tea and placebo ingestion. The differences in responses are due to the different responses on PL ingestion, but similar responses to green tea ingestion. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for energy expenditure and fat oxidation after green tea treatment 2.1.1.6 catechol O-methyltransferase medicine inhibition of catechol-O-methyltransferase enzyme by entacapone decreases the antiproliferative effects of fisetin and quercetin on Hep-G2 cells 2.1.1.8 histamine N-methyltransferase medicine in patients with food allergy, median enzyme activity, as well as median diamone oxidase activity, are significantly decreased compared to controls. Histamine content is elevated 2.1.1.8 histamine N-methyltransferase medicine T105I mutation is more abundant among alcoholics from Finnish Caucasion and Plains Indian American populations. Decreased histamine level in central nervous system may be a risk factor in alcoholism and associated with higher levels of trait anxiety 2.1.1.8 histamine N-methyltransferase medicine elevation of endogenous histamine by amodiaquine may play a protective role through the regulation of TNF-alpha production in endotoxin-induced hepatic injury mice 2.1.1.8 histamine N-methyltransferase medicine in German Caucasians the association of the HNMT Thr105Ile polymorphism with alcoholism is not replicated, but a congruent association is found between the Ile105 allele and family history of alcoholism supporting the protective role of the Ile105 allele against alcoholism 2.1.1.8 histamine N-methyltransferase medicine results suggest that alterations of histamine homeostasis are associated with the risk of movement disorders 2.1.1.8 histamine N-methyltransferase medicine the HNMT T314 allele frequency is lower in Chinese population than in American Caucasians. No association can be found in the involvement of HNMT C314T polymorphism in the susceptibility to duodenal ulcer 2.1.1.8 histamine N-methyltransferase medicine Iodinated contrast media can cause pseudoallergic reactions associated with histamine release in significant numbers of patients. The iodinated contrast media tested in vitro do not exhibit inhibition of histamine inactivating enzymes diamine oxidase and histamine N-methyltransferase at physiologically relevant concentrations 2.1.1.8 histamine N-methyltransferase medicine histamine-N-methyltransferase is increased in atopic dermatitis patients and atopic dermatitis model mice. Micro-RNA miR-223 is upregulated in the whole blood cells of a large group of atopic dermatitis patients. HNMT expression is not inhibited by miR-223 2.1.1.9 thiol S-methyltransferase medicine enzyme activity in cholestatic liver 2.1.1.9 thiol S-methyltransferase medicine enzyme activity in inflammatory bowel disease 2.1.1.9 thiol S-methyltransferase medicine clopidogrel, a thienopyridine antiplatelet prodrug, is metabolized by oxidation to 2-oxo-clopidogrel, followed by conversion to its pharmacologically active thiol metabolite. In liver microsomes, thiol isomers H3 and H4 are further S-methylated, and the S-methylation is inhibited by 2,3-dichloromethyl benzylamine, indicating the involvement of thiol S-methyltransferase. The intrinsic clearance value for the S-methylation of H3 in microsomes is 98.1fold higher than that for H4. The stereoselective formation of H3 from 2-oxo-clopidogrel and the stereoselective S-methylation of H3 may lead to the similar exposure levels of H3 and H4 previously reported in humans 2.1.1.9 thiol S-methyltransferase medicine in some patients with type 2 diabetes mellitus who are treated with 11beta-hydroxysteroid dehydrogenase inhibitor BI 187004, the plasma exposure of N-methylbenzimidazole metabolite 1-(1-methyl-1H-benzimidazole-5-carbonyl)-1,2,3,4,5,5a,10,10a-octahydroindeno[2,1-b]azepine-7-carbonitrile is 7fold higher than in the other patients. Thiol S-transferase catalyzes the formation of the metabolite 2.1.1.10 homocysteine S-methyltransferase medicine determination of total homocysteine in plasma and serum 2.1.1.13 methionine synthase medicine comparison of enzyme in methionine dependent HTC cells and methionine independent Phi-1 cells 2.1.1.13 methionine synthase medicine B12-deficient diet leads to extremely low activity of enzyme possibly due to effects of coenzyme stabilization 2.1.1.13 methionine synthase medicine the A2756G polymorphism is not a risk factor for deep vein thrombosis among South Indians 2.1.1.13 methionine synthase medicine fibroblasts of patients with cblG-variant megaloblastic anaemia, i.e. undetectable methionine synthase activity, show decreased conversion of cyanocobalamin to hydroxocobalamin, similar to that observed in cblC fibroblasts. Alternative splicing in cells from the cblG variant produces an MTR-201 transcript that encodes a truncated methionine synthase, and a MTR-001 transcript with two insertions containing stop codons. Interactions between methionine synthase and cytosolic cobalamin trafficking chaperone MMACHC suggest a regulatory role of methionine synthase in the intracellular metabolism of cobalamin, through splicing of two transcripts that encode the full-size enzyme and a non-functional truncated protein, respectively 2.1.1.17 phosphatidylethanolamine N-methyltransferase medicine animals with homozygous disruption of enzyme gene, develop severe steatosis when fed a diet deficient in choline. Animals have substantially diminished concentrations of docosahexaenoic acid and arachidonic acid in plasma 2.1.1.17 phosphatidylethanolamine N-methyltransferase medicine a multiple isotopomer distribution analysis approach is presented, based on transfer of deuterated methyl groups to S-adenosylmethionine and subsequent sequential methylations of phosphatidylethanolamine, to quantify absolute flux rates through the PEMT pathway that are applicable to studies of liver dysfunction in clinical studies 2.1.1.17 phosphatidylethanolamine N-methyltransferase medicine inhibition of PEMT and/or reduction of intestinal sodium concentration may be helpful in attenuating liver damage and prolonging hepatic function in intrahepatic cholestasis 2.1.1.17 phosphatidylethanolamine N-methyltransferase medicine both low and high levels of global DNA methylation are associated with the risk of bladder cancer. This risk follows a nonlinear association with LINE-1 methylation which significantly increases among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene 2.1.1.17 phosphatidylethanolamine N-methyltransferase medicine in Pemt-/- mice, treatment with vitamin E (0.5 g/kg) for 3 weeks improves very low-density lipoprotein-triglyceride secretion and normalizes cholesterol metabolism, but fails to reduce hepatic triglyceride content. Vitamin E treatment is able to reduce hepatic oxidative stress, inflammation and fibrosis. Pemt-/- mice fed a high-fat diet show abnormal ceramide metabolism, with elevation of ceramides and other sphingolipids and higher expression of mRNAs for acid ceramidase (Asah1) and ceramide kinase (Cerk) 2.1.1.17 phosphatidylethanolamine N-methyltransferase medicine PEMT deficiency reduces the phosphatidylcholine/phosphatidylethanolamine ratio in the ER and induces ER stress,which sensitizes the mice to high-fat-induced steatohepatitis 2.1.1.20 glycine N-methyltransferase medicine feeding with excess methionine leads to upregulation of hepatic enzyme 2.1.1.20 glycine N-methyltransferase medicine patients with mutations Leu49Pro and His176Asn suffer from mild liver disease 2.1.1.20 glycine N-methyltransferase medicine activation and induction of enzyme by retinoids are tissue- and gender-specific 2.1.1.20 glycine N-methyltransferase medicine vitamin A may induce enzyme, induction by all-trans-retinoic acid can lead to impairment of essential transmethylation processes 2.1.1.20 glycine N-methyltransferase medicine all-trans-retinoic acid and dexamethasone independently induce GNMT in liver, thereby having substantial implications for the potential interaction of retinoic administration with diabetes 2.1.1.20 glycine N-methyltransferase medicine diabetes increases the activity and abundance of GNMT, lack of dietary folate results in the highest activity of GNMT in diabetic rats without the abundance of the protein being altered 2.1.1.20 glycine N-methyltransferase medicine GNMT 1289 C->T polymorphism influences plasma homocysteine and is responsive to folate intake, plasma homocysteine concentrations do not differ among the GNMT C1289T genotypes at baseline. After folate restriction, women with the GNMT 1289 TT genotype have higher homocysteine concentrations than women with the CT or CC genotype. The influence of the GNMT 1289 C->T variant on homocysteine is dependent on the MTHFR C677T genotype. In subjects with the MTHFR 677 CC genotype, homocysteine is greater for GNMT 1289 TT subjects relative to 1289 CT or CC subjects. In subjects with the MTHFR 677 TT genotype, plasma homocysteine concentrations do not differ among the GNMT C1289T genotypes 2.1.1.20 glycine N-methyltransferase medicine GNMT is a tumor susceptibility gene for prostate cancer, three major GNMT haplotypes in our populations, haplotype C conferred protection from the development of prostate cancer and exhibits the highest promoter activity 2.1.1.20 glycine N-methyltransferase medicine GNMT sequesters benzo[a]pyrene, diminishes benzo[a]pyrene's effects to the liver detoxification pathway and prevents subsequent cytotoxicity 2.1.1.20 glycine N-methyltransferase medicine glycine N-methyltransferase is a tumor susceptibility gene for both hepatocellular carcinoma and prostate cancer 2.1.1.20 glycine N-methyltransferase medicine GNMT is a tumor suppressor gene for liver cancer, and is associated with gender disparity in liver cancer susceptibility 2.1.1.20 glycine N-methyltransferase medicine GNMT may represent a novel marker of malignant progression and poor prognosis in prostate cancer 2.1.1.20 glycine N-methyltransferase medicine GNMT is strongly downregulated in human cancers and is undetectable in cancer cell lines while the transient expression of the protein in cancer cells induces apoptosis and results in the activation of ERK1/2. The antiproliferative effect of GNMT can be partially reversed by treatment with the pancaspase inhibitor zVAD-fmk but not by supplementation with high folate or SAM. GNMT exerts the suppressor effect primarily in cells originated from malignant tumors. High levels of GNMT, detected in regenerating liver and in NIH3T3 mouse fibroblasts, do not produce cytotoxic effects. GNMT, a predominantly cytoplasmic protein, is translocated into nuclei upon transfection of cancer cells. The induction of apoptosis is associated with the GNMT nuclear localization but is independent of its catalytic activity or folate binding 2.1.1.28 phenylethanolamine N-methyltransferase medicine strong relationship between PNMT gene expression and tissue epinephrine levels in human pheochromocytomas 2.1.1.34 tRNA (guanosine18-2'-O)-methyltransferase medicine an RNA preparation of an Escherichia coli trmH mutant that lacks Gm18 2'-O-methyltransferase activity is significantly more immunostimulatory in human peripheral blood mononuclear cells than the wild-type sample. The single methyl group on the 2'-oxygen of Gm18 is a natural modification in native tRNA that, beyond its primary structural role, has acquired a secondary function as an antagonist of toll-like receptor TLR7 2.1.1.34 tRNA (guanosine18-2'-O)-methyltransferase medicine bacterial tRNA induces type I interferon and inflammatory cytokines in mouse dendritic cells and human peripheral blood mononuclear cells. tRNA from an Escherichia coli knockout strain for tRNA (Gm18)-2'-O-methyltransferase regained immunostimulatory potential. In vitro methylation of this immunostimulatory Gm18-negative tRNA with recombinant trmH from Thermus thermophilus abolishes its interferon-alpha-inducing potential. Gm18-modified tRNA acts as toll-like receptor TLR7 antagonist and blocks IFN-alpha induction of influenza A virus-infected peripheral blood mononuclear cells 2.1.1.34 tRNA (guanosine18-2'-O)-methyltransferase medicine in vitro methylation of immunostimulatory Gm18-negative tRNA with recombinant trmH from Thermus thermophilus abolishes its interferon-alpha-inducing potential 2.1.1.38 O-demethylpuromycin O-methyltransferase medicine product puromycin is an antibiotic and antitumor agent 2.1.1.41 sterol 24-C-methyltransferase medicine target for drug development against pneumonitis caused by this pathogen based on its unique substrate preference for lanosterol and 24-methylenelanosterol 2.1.1.41 sterol 24-C-methyltransferase medicine the results indicate that SMT/MPL-SE can be an effective vaccine candidate for use against visceral leishmaniasis 2.1.1.41 sterol 24-C-methyltransferase medicine vaccine development, visceral leishmaniasis 2.1.1.41 sterol 24-C-methyltransferase medicine SMT is a vaccine antigen for multiple forms of leishmaniasis 2.1.1.45 thymidylate synthase medicine - 2.1.1.45 thymidylate synthase medicine important drug target, fungus causes opportunistic pneumonia infections in immune-compromised patients and is among the leading causes of death of AIDS patients, inhibitors selective for fungal TS over human TS will be greatly beneficial in combating this disease 2.1.1.45 thymidylate synthase medicine enzyme is believed to be the major site of the cytotoxic action of the cancer chemotherapeutic drug 5-fluorouracil, development of inhibitors as clinical useful drugs 2.1.1.45 thymidylate synthase medicine target enzyme for antitumor and antibacterial agents 2.1.1.45 thymidylate synthase medicine human TS mutants have potential applications in gene therapy by protecting hematopoietic progenitors from TS inhibitor toxicity, drug-resistant variants can be used to decrease the myelosuppressive side effects of TS-directed anticancer agents or to select genetically modified cells in vivo, clincal trials introduce chemoprotecting genes into hematopoietic cells 2.1.1.45 thymidylate synthase medicine development of effective chemotherapy of the eosinophilic meningoencephalitis angiostrongylosis 2.1.1.45 thymidylate synthase medicine target enzyme for malarial chemotherapy 2.1.1.45 thymidylate synthase medicine drug development against cryptococcosis, a pulmonary subclinical infection, in immunocompromised individuals having diseases such as leukemia, lymphoma or AIDS the infection seminates to the central nervous system, the fourth most common opportunistic infection complicating AIDS 2.1.1.45 thymidylate synthase medicine development of antimalarial drugs, selective chemoptherapy directed at malarial TS, inhibitors of pyrimidine biosynthesis shall be considered for malaria chemotherapy 2.1.1.45 thymidylate synthase medicine possible target for chemotherapeutic attack 2.1.1.45 thymidylate synthase medicine inhibition of human thymidylate synthase leads to apoptosis of rapidly dividing cells such as cancer cells, human thymidylate synthase is a target in the chemotherapy of colorectal cancer and some other neoplasms 2.1.1.45 thymidylate synthase medicine inhibition of thymidylate synthase and DHFR enzymes has found clinical utility as antitumor, antimicrobial and antiprotozoal agents 2.1.1.45 thymidylate synthase medicine inhibition of TS and DHFR enzymes has found clinical utility as antitumor, antimicrobial and antiprotozoal agent 2.1.1.45 thymidylate synthase medicine inhibition of TS and DHFR enzymes has found clinical utility as antitumor, antimicrobial and antiprotozoal agents 2.1.1.45 thymidylate synthase medicine inhibitors of thymidylate synthase are used in the treatment of advanced colorectal carcinoma 2.1.1.45 thymidylate synthase medicine Lovo 175X2 cells transfected with mutant tumor suppressor gene p53 are more resistant to 5-fluorouracil, nolatrexed, raltitrexed and pemetrexed in comparison with the wild-type p53 parental cells Lovo 92. Resistance is associated with an increase in thymidylate synthase protein expression and catalytic activity. Lovo li cells, characterized by functionally inactive p53, are 3-13fold more sensitive to nolatrexed, raltitrexed and pemetrexed, and have a lower thymidylate synthase mRNA, protein expression and catalytic activity than Lovo 92. Mutant p53 WiDr cells transfected with wt p53 are not significantly different from mutant p53 WiDr cells with respect to sensitivity to thymidylate synthase inhibitors or thymidylate synthase levels 2.1.1.45 thymidylate synthase medicine pharmacological treatment of colorectal cancer 2.1.1.45 thymidylate synthase medicine the combination of the oral fluorouracil S-1 and the epidermal growth factor receptor-tyrosine kinase inhibitor gefitinib in shows a synergistic antiproliferative effect in vitro in all non-small cell lung cancer cell lines tested. Gefitinib inhibits the expression of the transcription factor E2F-1, resulting in the down-regulation of thymidylate synthase at the mRNA and protein levels 2.1.1.45 thymidylate synthase medicine the use of the TS inhibitor RTX in the treatment of colorectal cancer has been approved in Europe, Canada, Australia and Japan 2.1.1.45 thymidylate synthase medicine thymidylate synthase as a target for antitubercular drugs 2.1.1.45 thymidylate synthase medicine thymidylate synthase is a target in the treatment of cancer 2.1.1.45 thymidylate synthase medicine thymidylate synthase is an important target for cancer chemotherapy 2.1.1.45 thymidylate synthase medicine thymidylate synthase is an important target of several chemotherapeutic agents including 5-fluorouracil and raltitrexed 2.1.1.45 thymidylate synthase medicine treatment of patients with advanced colorectal carcinoma with liposomal inhibitor OSI-7904L, in combination with oxaliplatin. At the highest dose level of OSI-7904L 9 mg/m2, oxaliplatin 130 mg/m2, one of nine patients experienced dose-limiting toxicity of grade 3 oral mucositis with cycle 1 and five further patients required dose reductions. The toxicity profile of stomatitis, diarrhea, nausea, fatigue, sensory neuropathy and skin rash was consistent with that expected for a thymidylate synthase inhibitor/oxaliplatin combination regimen. High interpatient variability with no detectable interaction between OSI-7904L and oxaliplatin 2.1.1.45 thymidylate synthase medicine treatment with thymidylate synthase inhibitors BGC 945 and BGC 9331 results in concentration-dependent increase in thymidine uptake in FR-positive epidermoid KB cells and in increase of membrane-associated equilibrative nucleoside transporter type 1 levels. Tumor [18F]-fluorothymidine accumulation in KB xenografts increases by more than 2fold with maximal levels at 1 to 4 hours and 4 to 24 hours after drug treatment. Quantitiative changes in tumor [18F]-fluorothymidine uptake are associated with increased tumor dUrd levels. BGC 9331 induces accumulation of [18F]-fluorothymidine in the intestine 2.1.1.45 thymidylate synthase medicine TS is a clinical target in cancer chemotherapy 2.1.1.45 thymidylate synthase medicine TS is an important target for colorectal cancer therapy 2.1.1.45 thymidylate synthase medicine TYMS is the target enzyme of fluorouracil, an antimetabolite widely used in the treatment of colorectal, head-and-neck, breast cancers, pancreatic cancer and hepatocellular carcinoma 2.1.1.45 thymidylate synthase medicine target for therapy of acute lymphoblastic leukemia 2.1.1.45 thymidylate synthase medicine octapeptide inhibitor LSCQLYQR and derivatives are expected to work in combination with more aggressive chemotherapeutic agents in cancer cells to improve the efficacy, fight platinum-induced drug resistance, and reduce the overall drug combination toxicities. The cellular half-life observed for the peptide suggests that more chemical changes should be performed for an acceptable in vivo pharmacokinetics 2.1.1.56 mRNA (guanine-N7)-methyltransferase medicine the enzyme is a therapeutic target in breast cancer 2.1.1.57 methyltransferase cap1 medicine the nsp10-nsp16 interface represents an attractive target for antivirals against human and animal pathogenic coronaviruses 2.1.1.61 tRNA 5-(aminomethyl)-2-thiouridylate-methyltransferase medicine the enzyme is a target for the prevention of aminoglycoside-induced hair cell death 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine the enzyme is important in cellular resistance to certain alkylating antitumor agents such as the methylating drug temozolomide. Cisplatin is able to decrease enzyme levels in Jurkat cells, probably via the inhibition of gene transcription. The clinical efficiacy of triazene compounds might be improved by combination with cisplatin using appropriate doses and schedules of administration 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine high level of enzyme in tumors and relative resistance to cyclophosphamide in lung cancer indicates that 6-O-methylguanine-DNA methyltransferase may be a predictive factor of resistance to cyclophosphamide 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine the efficiacy of 6-O-benzylguanine as a chemomodulator depends on the extent of depletion of 6-O-methylguanine DNA methyltransferase in normal tissues and the optimal therapeutic index for combination of 6-O-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea therapy should be achieved by depleting 6-O-methylguanine DNA methyltransferase in the target tumor for 24 h with minimal depletion in normal tissues 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine clonal selection of AGT mutants during trteatment with O6-benzylguanine plus an alkylator may produce resistance to this intervention in clinical settings 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine DNA hypermethylation and silencing of MGMT are frequent and rather early events in esophageal squamous cell carcinogenesis. Hypermethylation and inactivation of MGMT may be prevented or reversed by dietary polyphenols, (-)-epigallocatechin-3-gallate and genistein, for the prevention of carcinogenesis 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine O4-benzylfolic acid is 30times more active than O6-benzylguanine against the wild-type alkyltransferase, inactivation of P140K mutant alkyltransferase. Inhibitor shows promise as an agent for possible tumor-selective alkyltransferase inactivation superior toO6-benzylguanine as a chemotherapy adjuvant 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine AGT-DNA cross-linking is a likely mechanism of 1,2,3,4-diepoxybutane-mediated cytotoxicity in cells expressing this important repair protein 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine alkyltransferase activity in tumors protects them from therapeutic agents such as temozolomide and N,N'-bis(2-chloroethyl)-N-nitrosourea, polymorphisms in the AGT gene 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine cigarette smoking not only induces O6-alkylguanine lesions, it inhibits the repair of these adducts by MGMT, O6-alkylguanine adducts are well established carcinogenic lesions and decreased repair of such lesions may increase susceptibility to lung cancer in smokers 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine combining cisplatin and temozolomide is based on the potential for improved antitumour activity, combination is well tolerated in children and adolescents, generating no toxicity greater than that of the single agents 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine even slight alterations in the active site pocket of AGT do not prevent its ability to protect cells from alkylating agents, can block the paradoxical enhancement of the genotoxicity of the larger alpha,omega-dihaloalkanes by reducing the reaction with Cys145 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine expression of additional AGT in a variety of tissues in transgenic mice protects against carcinogenesis 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine highly significant correlation between AGT protein expression assessed by immunohistochemistry and AGT activity assessed by HPLC, marginal statistically significant correlation between immunohistochemistry and real-time methylation-specific PCR, and no significant correlation between AGT protein activity assessed by HPLC versus real-time methylation-specific PCR. Cross-tabulation of immunohistochemistry and real-time methylation-specific PCR data based on prognostic groups shows no significant relationship, suggesting that one assay cannot be used interchangeably for another, thus the results cannot be used to guide glioma therapy decisions 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine inhibition of tumor suppressor p53 by RNAi is accompanied by down-regulation of MGMT gene expression, but is not associated with a discernible change in the pattern of MGMT promoter methylation 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine MGMT can modulate cytotoxicity of camptothecin-derived topoisomerase I inhibitors, MGMT overexpression reveals more resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, camptothecin, 7-ethyl-10-hydrocamptothecin and topotecan, alteration of MGMT expression coincides with camptothecin-induced cell death and poly(ADP-ribose) polymerase cleavage 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine MGMT significantly protects against in vivo temozolomide-induced mutations 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine temozolomide appears to be a good candidate for use in conjunction with hyperthermia for regional chemotherapy of melanoma 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine transgenic rats expressing Ada-C are resistant to mammary tumor induction by N-methyl-N-nitrosourea but not by N-ethyl-N-nitrosourea 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine tumor suppressor p53 positively regulates MGMT gene expression in murine astrocytes 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine inhibition of tumour MGMT by pseudosubstrates to overcome tumour resistance is under clinical evaluation, MGMT overexpression in haematopoietic stems cells has been shown to protect normal cells against the myelosuppressive effects of chemotherapy 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine MGMT can confer resistance to the cancer chemotherapeutic effects of the class of DNA damaging drugs, inactivation of MGMT is thus a practical approach to improving the efficacy of such agents 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine the results suggest that expression of MGMT could enhance the capacity of bone marrow-derived cells to repopulate lung epithelium, and when used in combination with a gene of interest, MGMT could have therapeutic applications 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine determination of MGMT in peripheral blood mononuclear cells can identify patients at greatest risk of toxicity with O6-alkylating agent chemotherapy or who are suitable for dose intensification, MGMT protects against the toxic effects of O6-alkylating agents 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine MGMT is a factor of chemoresistance to alkylating drugs in anaplastic ependymomas 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine the combination of high thymidylate synthase and low O6-methylguanine-DNA methyltransferase expression is a significant predictor of a poor response to fluoropyrimidine treatment 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine the enzyme protein expression is an unfavorable prognostic factor for patients with gliosarcoma 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine a deficient enzyme status in pancreatic neuroendocrine tumors is not associated with a better response to temozolomide-based chemotherapy and cannot be used as a predictive marker to lead treatment decisions 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine a larger number of methylated CpG sites in the enzyme promoter region is associated with a favorable outcome of medulloblastoma 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase medicine the enzyme methylation status is associated with longer survival in female patients compared with unmethylated females 2.1.1.67 thiopurine S-methyltransferase medicine - 2.1.1.67 thiopurine S-methyltransferase medicine enzyme may be a target for clinically significant drug interactions, the common genetic polymorphism might be a risk factor for the occurence of therapy-dependent secondary leukemia 2.1.1.67 thiopurine S-methyltransferase medicine enzyme activity might represent one factor responsible for variations in the therapeutic or toxic effects of thiopurine and thiopyrimidine drugs used clinically to treat recipients of transplanted kidneys and patients with renal disease such as glomerulonephritis 2.1.1.67 thiopurine S-methyltransferase medicine identification of a novel non-functional allele of the thiopurine S-methyltransferase gene enhances the efficiency of genotyping methods to predict patients at risk of an inadequate response to thiopurine therapy 2.1.1.67 thiopurine S-methyltransferase medicine the knowledge of the genetic basis of interindividual variability in thiopurine S-methyltransferase activity could enhance the efficiency of genotyping methods to preduct patients at risk of inadequate response to thiopurine therapy 2.1.1.67 thiopurine S-methyltransferase medicine the knowledge of the genetic basis of interindividual variability in thiopurine S-methyltransferase activity could enhance the efficiency of genotyping methods to product patients at risk of inadequate response to thiopurine therapy 2.1.1.67 thiopurine S-methyltransferase medicine azathioprine sodium is a purine antagonist commonly used as an adjuvant immunosuppressive agent in treating Pemphigus Vulgaris, mercaptopurine is the active compound, TPMT is the principal inactivation enzyme for this cytotoxic metabolite in hematopoietic tissues 2.1.1.67 thiopurine S-methyltransferase medicine detecting TPMT genetic variants before the administration of azathioprine has the potential to prevent serious and costly adverse drug reactions, such as neutropenia 2.1.1.67 thiopurine S-methyltransferase medicine evaluation of a possible long-term effect of mesalazine or azathioprine on thiopurine methyltransferase activity is of particular clinical importance because both drugs can to be given for several years in inflammatory bowel disease 2.1.1.67 thiopurine S-methyltransferase medicine first case of azathioprine-associated AML linked to low thiopurine S-methyltransferase enzyme activity 2.1.1.67 thiopurine S-methyltransferase medicine genetic variation in thiopurine S-methyltransferase is a major factor for wide variation in the metabolism and safety of thiopurine drugs 2.1.1.67 thiopurine S-methyltransferase medicine genotyping at diagnosis identifies patients with a homozygous mutant TPMT and may prevent severe and life-threatening toxicity, ALL treatment monitoring should preferentially be based on repeated determinations of intracellular active metabolites, 6-TGN, and methylated metabolites 2.1.1.67 thiopurine S-methyltransferase medicine individuals with decreased TPMT activity are at great risk for adverse reactions if treated with conventional thiopurine doses 2.1.1.67 thiopurine S-methyltransferase medicine individuals with decreased TPMT activity are at high risk of fatal adverse reactions if treated with conventional thiopurine doses 2.1.1.67 thiopurine S-methyltransferase medicine myelosuppression occurs in 2-7% of inflammatory bowel disease patients treated with azothioprine, and can be associated with reduced activity of thiopurine methyltransferase in some patients 2.1.1.67 thiopurine S-methyltransferase medicine patients carrying a variant genotype have low TPMT activity and produce elevated levels of 6-thioguanine nucleotides in their red blood cells, 6-TGN accumulation may result in azathioprine-induced bone marrow myelosuppression in the course of treatment with the drug in a standard dosage regimen in patients following renal transplantation 2.1.1.67 thiopurine S-methyltransferase medicine patients carrying defective mutations in TMPT gene have elevated thioguanine nucleotides concentrations that finally result in severe or even fatal hematopoietic toxicities when they are treated with standard doses of 6-mercaptopurine 2.1.1.67 thiopurine S-methyltransferase medicine patients with inflammatory bowel disease may have different thiopurine dose requirements in relation to thiopurine methyltransferase genotype or phenotype 2.1.1.67 thiopurine S-methyltransferase medicine polymorphisms at the thiopurine S-methyltransferase coding gene determine enzyme activity and consequently, the development of toxicity secondary to thiopurines 2.1.1.67 thiopurine S-methyltransferase medicine single nucleotide polymorphisms are known to be responsible for variations in the metabolism of numerous drugs in humans, thiopurine S-methyltransferase displays polymorphisms with varying prevalence among different populations 2.1.1.67 thiopurine S-methyltransferase medicine the goal is to determine which metabolite of azathioprine has the most antiviral activity and to gain a better understanding of how this compound may act in vitro 2.1.1.67 thiopurine S-methyltransferase medicine the knowledge of the TPMT activity distribution in each population seems relevant, the incidence of hematologic adverse effects associated with azathioprine and 6-mercaptopurine treatment probably depends on that distribution 2.1.1.67 thiopurine S-methyltransferase medicine the murine model recapitulates many clinical features of the human polymorphism and provides a preclinical system for establishing safer regimens of genetically influenced antileukemic drug therapy 2.1.1.67 thiopurine S-methyltransferase medicine the remarkable change in enzyme activity of TPMT may be explained by differences in the age of red blood cells, as younger erythrocytes have a higher TPMT activity 2.1.1.67 thiopurine S-methyltransferase medicine the results suggest that coadministration of thiopurines and various nonsteriodal anti-inflammatory drugs may lead to drug interactions 2.1.1.67 thiopurine S-methyltransferase medicine the use of azothioprine and mercaptopurine is limited by toxicity, especially myelosuppression, which is related to activity of the enzyme thiopurine S-methyltransferase 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine methyltransferase activity inversely correlated with clinical response to thiopurine treatment in inflammatory bowel disease 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine methyltransferase is a genetically moderated key enzyme involved in the metabolism of azathioprine that can be used to stratify individuals into different levels of risk of developing neutropaenia 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine methyltransferase is the main enzyme responsible for inactivating toxic products of azathioprine metabolism 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine methyltransferase metabolises thiopurine drugs and influences their cytotoxic activity 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine S-methyltransferase activity is inversely related to the risk of developing severe hematopoietic toxicity in patients treated with azathioprine 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine S-methyltransferase is a key enzyme in the detoxification of thiopurine drugs widely used in the treatment of various diseases, such as inflammatory bowel diseases, acute lymphoblastic leukaemia and rheumatic diseases 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine S-methyltransferase is an enzyme responsible for the detoxification of the widely used thiopurine drugs 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine S-methyltransferase modulates the cytotoxic effects of thiopurine prodrugs such as 6-mercaptopurine by methylating them in a reaction using S-adenosyl-L-methionine as the donor 2.1.1.67 thiopurine S-methyltransferase medicine while factors other than TPMT status are likely to be involved in azathioprine toxicity, the majority of evidence suggests that TPMT deficiency is a significant independent risk factor for myelotoxicity 2.1.1.67 thiopurine S-methyltransferase medicine determination of TPMT and monitoring of thiopurine metabolites allows azathioprine treatment to be optimised 2.1.1.67 thiopurine S-methyltransferase medicine induction of thiopurine methyltransferase is associated with recalcitrant disease 2.1.1.67 thiopurine S-methyltransferase medicine mercaptopurine dose can be adjusted on the basis of TPMT genotype to mitigate toxicity in pediatric patients with acute lymphoblastic leukemia 2.1.1.67 thiopurine S-methyltransferase medicine TPMT activity is a good prediction factor for the toxicity and efficacy of the antileukemic thiopurine therapy 2.1.1.67 thiopurine S-methyltransferase medicine low enzyme level can lead to greater sensitivity to thiopurine therapy in astroglial cells 2.1.1.67 thiopurine S-methyltransferase medicine thiopurine S-methyltransferase gene polymorphisms are pharmacogenetic markers which enable the individualization of thiopurine drug therapy 2.1.1.67 thiopurine S-methyltransferase medicine enzyme polymorphisms are associated with 6-thioguanine levels in patients using azathioprine 2.1.1.71 phosphatidyl-N-methylethanolamine N-methyltransferase medicine adriamycin, an effective anticancer chemotherapeutic agent depresses enzyme activity in vivo and in vitro 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine confers antibiotic resistance in clinical isolates, important determinant of bacterial virulence, may be transmitted by horizontal gene transfer, potential drug target 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine Dam is essential for viability and mediates virulenc 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine epigenetic effects, in addition to genotoxic effects, need to be considered in chemical carcinogenesis initiated by r7,t8-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, since the inhibition of methylation may allow the expression of genes that promote tumor development 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine essential for the viability of the bacterium, overproduction of Dam in Aeromonas hydrophila SSU reduces the virulence of the pathogen, decreases the motility and T3SS-associated cytotoxicity, but increases both the cytotoxicity and hemolysis associated with Act, mice infected with the Dam-overproducing strain do not die over a tested period of 3 weeks, indicating bacterial attenuation as a result of Dam overproduction 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine methyltransferase activity associated with Dam is essential for attenuation of Aeromonas hydrophila virulence, immunization of mice with a native-Dam-overproducing strain at the same 50% lethal dose does not result in any lethality and provides protection to animals after subsequent challenge with a lethal dose of the control strain 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine potential targets for both vaccines and antimicrobials 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine upregulation of recombinational repair in dam mutants allows for the efficient repair of double-strand breaks whose formation is dependent on functional mismatch repair 2.1.1.72 site-specific DNA-methyltransferase (adenine-specific) medicine DNA adenine methyltransferase identification is a useful technology to map holocarboxylase synthetase binding sites in human chromatin 2.1.1.74 methylenetetrahydrofolate-tRNA-(uracil54-C5)-methyltransferase [NAD(P)H-oxidizing] medicine human pathogen, target for new antibiotics 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase medicine aging research, accumulation of damaged proteins have detrimental effects over the human lifespan 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase medicine a cloned source of this enzyme should be useful in the identification of cellular substrates and for quantitation and localization of isoaspartyl sites in purified proteins, including recombinant proteins used as pharmaceuticals 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase medicine L-isoaspartyl residue formation in extracellular matrix proteins such as type -I collagen could play an important role in reducing cell migration. PIMT could be a therapeutic tool to restore normal cell migration in pathological conditions where cell motility is crucial 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase medicine results show that PIMT expression is up-regulated by GSK-3 inhibition and beta-catenin stabilization upon treatments with lithium and valproic acid suggesting a possible therapeutic role for PIMT in certain brain diseases including epilepsy 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase medicine mutations in the PCMT1 gene are associated with premature ovarian failure 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase medicine PCMT1 is associated with the type 1 diabetes in groups defined by other risk genes (SUMO4 and HLA) 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase medicine strong enzyme expression is a predictive marker of poor prognosis for surgically resected lung adenocarcinoma 2.1.1.96 thioether S-methyltransferase medicine exposure of the mouse to arsenic during a critical period of fetal development may potentially alter adrenal genetic programming, leading to endocrine disruption and potentially enhancing tumor formation together with diethylstilbestrol at other sites much later in life 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine development of Icmt inhibitors as another approach to anticancer drug development 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine generation of Icmt inhibitors based on the structure of the minimal Icmt substrate N-acetyl-S-farnesyl-L-cysteine in hopes of developing potent anticancer agents 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine inhibition of the enzyme results in Ras mislocalization and loss of cellular transformation ability, making it an attractive and novel anticancer target 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine target in anticancer drug design 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine targeting the enzyme is an effective strategy for treating HGPS 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine a correlation exists between p53 status and ICMT expression in breast and lung cancers. ICMT overexpression is correlated with negative clinical outcomes 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine ICMT loss-of-function isogenic cell lines for both RAS-transformed human mammary epithelial cells (HME1) and human cancer cell lines MiaPaca-2 and MDA-MB-231 containing naturally occurring mutant KRAS. In both in vitro and in vivo tumorigenesis studies, ICMT loss-of-function abolishes the tumor initiation ability of all major isoforms of mutant RAS in HME1 cells, and the tumor maintenance capacity of MiaPaca-2 and MDA-MB-231 cells 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine Icmt mRNA and protein levels are increased in nasopharyngeal carcinoma cells after prolonged exposure to chemotherapy. Icmt inhibition is more effective against chemoresistant compared to chemosensitive nasopharyngeal carcinoma cells. The combination of Icmt inhibition with 5-fluorouracil or cisplatin results in greater efficacy than single chemotherapeutic agent alone in nasopharyngeal carcinoma cells. Icmt inhibition decreases Ras and RhoA activities, Ras may be the critical effector of Icmt in nasopharyngeal carcinoma cells 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine inhibition of ICMT significantly reduces cell migration in vitro and cancer invasion and metastasis in vivo. The role of ICMT is mediated by regulator RAB4A. ICMT catalyzed carboxylmethylation is critical for RAB4A activation and interaction with effectors, its localization to endosomes and recycling vesicles, and hence important for RAB4A-dependent integrin beta3 recycling to plasma membrane 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase medicine upregulation of Icmt expression is a common feature in patients with epithelial ovarian cancer regardless of age and disease stage. Ovarian cancer cell lines with higher Icmt levels are more resistant to chemotherapeutic agents. Icmt inhibition by siRNA or inhibitor cysmethynil suppresses growth and induces apoptosis in ovarian cancer cells. Icmt inhibition significantly augments chemotherapeutic agent's efficacy in vitro and in vivo. Ras activation is a critical effector of ICT in ovarian cancer cells 2.1.1.103 phosphoethanolamine N-methyltransferase medicine the enzyme is an antiparasitic target 2.1.1.103 phosphoethanolamine N-methyltransferase medicine development of an elisa assay using PMT protein to identify a Plasmodium knowlesi infection and to differentiate Plasmodium knowlesi from a Plasmodium falciparum or Plasmodium vivax infection. The assay uses a common epitope as well as species-specific epitopes for differentiation 2.1.1.104 caffeoyl-CoA O-methyltransferase medicine plays a role in the biosynthesis of curcuminoids, which are important pharmacologically active metabolites 2.1.1.104 caffeoyl-CoA O-methyltransferase medicine plays a role in the biosynthesis of gingerols, which are important pharmacologically active metabolites 2.1.1.114 polyprenyldihydroxybenzoate methyltransferase medicine the levels of SAM-dependent methyltransferases Coq3 and Coq5 are decreased in the myocardial infarction groups. In addition, short-chain (C3) and medium-chain (C4-C12) acylcarnitine levels gradually decrease, whereas long-chain acylcarnitine (C14-18) levels increase in myocardial infarction 2.1.1.116 3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase medicine a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale 2.1.1.117 (S)-scoulerine 9-O-methyltransferase medicine a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale 2.1.1.B123 16S rRNA (uridine1369-2'-O)-methyltransferase medicine mutation G189R identified in a 7-year-old boy with childhood-onset rapidly progressive encephalomyopathy and stroke-like episodes. Multiple OXPHOS defects and decreased mtDNA copy number (40%) are detected in muscle homogenate. Symptoms are similar to mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. A yeast MRM2 knockout mutant shows a defect in respiration and the reduction of the 2'-O-methylmodification at position U2791 in the yeast mitochondrial 21S rRNA. Complementation of the yeast knockout mutant with the human mutant Mrm2 fails to rescue the respiratory phenotype, which is instead completely rescued by expressing the wild-type allele 2.1.1.128 (RS)-norcoclaurine 6-O-methyltransferase medicine a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale 2.1.1.137 arsenite methyltransferase medicine the proliferation of NB4 cells is significantly inhibited in a transwell system cocultured with AS3MT-transfected HepG2 cells after exposure to arsenite. The therapeutic efficacy of As2O3 (i.e., iAsIII) in acute promyelocytic leukemia patients is probably associated with the production of methylated arsenic metabolites by AS3MT 2.1.1.140 (S)-coclaurine-N-methyltransferase medicine a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale 2.1.1.148 thymidylate synthase (FAD) medicine promising medical target, thyX is present in a number of pathogenic bacteria but absent in human 2.1.1.148 thymidylate synthase (FAD) medicine specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low cross-reactivity against mammalian thyA enzymes, EC 2.1.1.45 2.1.1.148 thymidylate synthase (FAD) medicine specific and selective inhibitors for thy1 can provide highly effective tools for therapeutic intervention with low crossreactivity against mammalian thyA enzymes, EC 2.1.1.45 2.1.1.148 thymidylate synthase (FAD) medicine the unique mechanism of FDTS makes it an attractive target for antibiotic drug development 2.1.1.148 thymidylate synthase (FAD) medicine antibiotic target 2.1.1.148 thymidylate synthase (FAD) medicine thymidylate synthase as a target for antitubercular drugs 2.1.1.182 16S rRNA (adenine1518-N6/adenine1519-N6)-dimethyltransferase medicine KsgA as a possible anti-microbial drug target 2.1.1.182 16S rRNA (adenine1518-N6/adenine1519-N6)-dimethyltransferase medicine the presence of a functional rRNA dimethylase enzyme belonging to the KsgA family in Chlamydia present an excellent chemotherapeutic target 2.1.1.184 23S rRNA (adenine2085-N6)-dimethyltransferase medicine ErmC' catalyzes S-adenosyl-L-methionine-dependent modification of a specific adenine residue in bacterial 23S rRNA, thereby conferring resistance to clinically important macrolide, lincosamide, and streptogramin B antibiotics. The crystal structure of ErmC’ methyltransferase is used as a target for structure-based virtual screening of a database composed of 58679 lead-like compounds. Among 77 compounds selected for experimental validation (63 predicted to bind to the catalytic pocket and 14 compounds predicted to bind to the putative RNA bindingsite), several novel inhibitors are found that decrease the minimal inhibitory concentration of a macrolide antibiotic erythromycin toward an Escherichia coli strain that constitutively expresses ErmC'. Analysis of docking models of the identified inhibitors suggests a novel strategy to develop potent and clinically useful inhibitors 2.1.1.184 23S rRNA (adenine2085-N6)-dimethyltransferase medicine the Erm family of adenine-N6 methyltransferases is responsible for the development of resistance to macrolide-lincosamide-streptogramin B antibiotics through the methylation of 23S ribosomal RNA. Hence, these proteins are important potential drug targets 2.1.1.201 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase medicine the levels of SAM-dependent methyltransferases Coq3 and Coq5 are decreased in the myocardial infarction groups. In addition, short-chain (C3) and medium-chain (C4-C12) acylcarnitine levels gradually decrease, whereas long-chain acylcarnitine (C14-18) levels increase in myocardial infarction 2.1.1.203 tRNA (cytosine34-C5)-methyltransferase medicine this methyltransferase is a novel downstream Myctarget which mediates Myc-induced cell proliferation and growth. Therefore, the characterization of hTrm4 substrate specificity can be essential since this enzyme is a potential target for cancer therapies 2.1.1.228 tRNA (guanine37-N1)-methyltransferase medicine the sequence and structural distinction of bacterial TrmD from the eukaryotic Trm5 suggests that strategies can be developed to specifically inhibit TrmD without a deleterious effect on humans 2.1.1.229 tRNA (carboxymethyluridine34-5-O)-methyltransferase medicine transurethral injection of ALKBH8 small interfering RNA (siRNA) offers promise as a new therapeutic strategy for bladder cancer 2.1.1.235 dTDP-3-amino-3,6-dideoxy-alpha-D-glucopyranose N,N-dimethyltransferase medicine the enzyme is involved in biosynthesis of D-mycaminose. D-Mycaminose is an unusual dideoxy sugar found attached to the antibiotic tylosin, a commonly used veterinarian therapeutic 2.1.1.237 mycinamicin III 3''-O-methyltransferase medicine the antibacterial activities of some mycinamicin products against Staphylococcus aureus are higher than those of clinical macrolide antibiotics erythromycin and leucomycin 2.1.1.238 mycinamicin VI 2''-O-methyltransferase medicine the antibacterial activities of some mycinamicin products against Staphylococcus aureus are higher than those of clinical macrolide antibiotics erythromycin and leucomycin 2.1.1.319 type I protein arginine methyltransferase medicine oxidative stress induces apoptosis both via isoform PRMT1 in a SIRT1-dependent manner and via PRMT4 in a SIRT1-independent manner 2.1.1.319 type I protein arginine methyltransferase medicine modulating PRMT1 activity may represent new avenues to regulate thermogenic fat and mediate energy homeostasis and may ultimately lead to therapeutic strategies against human obesity and associated metabolic disorders 2.1.1.319 type I protein arginine methyltransferase medicine potential application of PRMT1 inhibitors in cancer treatment 2.1.1.319 type I protein arginine methyltransferase medicine PRMT1 and PRMT5 have opposing effects on chemotherapeutic agent-mediated apoptosis in lung cancer cells. The identification of PRMT5 and PRMT1 as CFLARL regulators involved in cellular apoptosis may help in developing new strategies to increase the sensitivity of cancer cells to chemotherapy, which may eventually benefit lung cancer treatments 2.1.1.319 type I protein arginine methyltransferase medicine splive variant PRMT1 v.2 promotes the survival and invasiveness of breast cancer cells, while it could serve as a biomarker of unfavorable prognosis in colon cancer patients 2.1.1.320 type II protein arginine methyltransferase medicine abundant expression of isoform PRMT5 and its symmetric methylation mark H4R3 in lung carcinoma but not in non-neoplastic human pulmonary alveolar and bronchial epithelial cell lines. More than two thirds of lung tumors express PRMT5. High levels of cytoplasmic PRMT5 are detected in 20.5% of non-small cell lung carcinomas and in 16.5% of pulmonary neuroendocrine tumors. High levels of nuclear PRMT5 are detected in 38.0% of non-small cell lung carcinomas and 24.0% of pulmonary neuroendocrine tumors. Cytoplasmic PRMT5 is associated with high grade in both non-small cell lung carcinomas and pulmonary pulmonary neuroendocrine tumors, while nuclear PRMT5 is more frequent in carcinoid tumors 2.1.1.320 type II protein arginine methyltransferase medicine knockdown of isoform PRMT5 results in more paralysis in a Caenorhabditis elegans model of Alzheimer's disease 2.1.1.320 type II protein arginine methyltransferase medicine PRMT5 localizes in the nucleus in benign prostate epithelium, whereas it localizes in the cytoplasm in prostate premalignant and cancer tissues 2.1.1.320 type II protein arginine methyltransferase medicine PRMT1 and PRMT5 have opposing effects on chemotherapeutic agent-mediated apoptosis in lung cancer cells. The identification of PRMT5 and PRMT1 as CFLARL regulators involved in cellular apoptosis may help in developing new strategies to increase the sensitivity of cancer cells to chemotherapy, which may eventually benefit lung cancer treatments 2.1.1.321 type III protein arginine methyltransferase medicine isoform PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. Reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreases cell invasion in vitro and metastasis in vivo. Overexpression of PRMT7 in non-aggressive MCF-7 cells enhances their invasiveness. PRMT7 induces the expression of matrix metalloproteinase MMP9. Invasion of aggressive breast cancer cells depleted of PRMT7 may be rescued by the exogenous expression of MMP9 2.1.1.348 mRNA m6A methyltransferase medicine METTL3 expression is elevated in lung adenocarcinoma and promotes growth, survival, and invasion of human lung cancer cells 2.1.1.348 mRNA m6A methyltransferase medicine enzyme overexpression is associated with poor prognosis of patients with hepatocellular carcinoma 2.1.1.354 [histone H3]-lysine4 N-trimethyltransferase medicine SET1 regulates multiple processes important to the pathogenesis of candidiasis, antibody responses against a unique N-terminal fragment of Candida albicans Set1p distinguish patients with candidiasis from controls without disease, the Set1p N-terminal fragment does not exhibit significant homology to eukaryotic or microbial proteins, and might represent a novel therapeutic, preventive or diagnostic target 2.1.1.355 [histone H3]-lysine9 N-trimethyltransferase medicine G9a plays an important role in the hypoxia-induced dimethylated histone H3 lysine 9, which inhibits the expression of several genes that likely leads to solid tumor progression 2.1.1.355 [histone H3]-lysine9 N-trimethyltransferase medicine hepatocellular tumor tissues show high levels of H3K9me3 and H3K9-specific methyltransferase ESET proteins in 23 (54.8%) and 29 (69.0%) of 42 samples, respectively. Expression levels of isoform SUV39H1 but not those of ESET are significantly correlated with H3K9me3 levels. The cumulative HCC recurrence rate is significantly higher for patients with elevated SUV39H1 expression and H3K9me3 levels 2.1.1.355 [histone H3]-lysine9 N-trimethyltransferase medicine SUV39H1 knockdown reduces H3K9me3 levels and impairs HCC cell growth and sphere formation. The pharmacological inhibition of SUV39H1 by chaetocin results in cell growth inhibition and inducing cellular apoptosis in culture and xenograft subcutaneous tumors. 24 of 42 HCC surgical samples display high levels of SUV39H1 expression compared with corresponding nontumor tissues. Tumor tissues show high levels of H3K9me3 and H3K9-specific methyltransferase ESET proteins in 23 (54.8%) and 29 (69.0%) samples, respectively. Expression levels of SUV39H1 but not those of ESET are significantly correlated with H3K9me3 levels. The cumulative HCC recurrence rate is significantly higher for patients with elevated SUV39H1 expression and H3K9me3 levels 2.1.1.355 [histone H3]-lysine9 N-trimethyltransferase medicine treatment with inhibitor BIX-01294 specifically decreases global H3K9Me2 level but not H3K27Me2. The inhibition of EHMT2 decreases proliferation of NB cells and induces apoptosis by increasing caspase 8/caspase 3 activity. BIX-01294 inhibits NB cell mobility and invasion accompanied with a decreased expression of the MYCN oncogene. Inhibition of EHMT2 enhances a doxorubicin induced inhibitory effect on cell proliferation and modulates global DNA methylation levels in NB cells 2.1.1.360 [histone H3]-lysine79 N-trimethyltransferase medicine high levels of enzyme gene expression in human neuroblastoma tissues independently predict poor patient prognosis 2.1.1.360 [histone H3]-lysine79 N-trimethyltransferase medicine the enzyme is a prognostic marker for rectal cancer 2.1.1.361 [histone H4]-lysine20 N-methyltransferase medicine enzyme knockdown can inhibit proliferation and promote apoptosis of esophageal squamous cell carcinoma cells 2.1.1.361 [histone H4]-lysine20 N-methyltransferase medicine upregulation of the enzyme is positively correlated with a poor survival rate in hepatocellular carcinoma patients 2.1.1.366 [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase medicine expression of an inactivated form of SETDB1 in human pancreatic ductal adenocarcinoma cells with wild-type TP53 results in TP53-induced apoptosis 2.1.1.366 [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase medicine loss of SETDB1 from pancreas accelerates formation of premalignant lesions in mice with pancreata that express activated KRAS. Expression of genes in the apoptotic pathway is upregulated and genes are regulated by p53 in SETDB1-deficient pancreata. Deletion of Setdb1 from pancreas prevents formation of pancreatic ductal adenocarcinoma, concomitant with increased apoptosis and upregulated expression of Trp53 in mice heterozygous for disruption of Trp53. Pancreata of mice with homozygous disruption of Trp53 have no increased apoptosis, and pancreatic ductal adenocarcinomas develop. SETDB1 binds to the Trp53 promoter to regulate its expression 2.1.1.366 [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase medicine overexpression of SETDB1 contributes to melanoma tumorigenesis. SETDB1 is highly amplified in melanoma cells and in the patient tumors. Increased expression of SETDB1 correlates with SETDB1 amplification and is associated with a more aggressive phenotype in in vitro and in vivo studies. SETDB1 implements its effects via regulation of thrombospondin 1, and the SET-domain of SETDB1 is essential for the maintenance of its tumorigenic activity. Inhibition of SETDB1 reduces cell growth in melanomas resistant to targeted treatments 2.1.1.366 [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase medicine overexpression of SETDB1 contributes to melanoma tumorigenesis. SETDB1 is highly amplified in melanoma cells. Increased expression of SETDB1 correlates with SETDB1 amplification and is associated with a more aggressive phenotype in in vitro and in vivo studies. SETDB1 implements its effects via regulation of thrombospondin 1, and the SET-domain of SETDB1 is essential for the maintenance of its tumorigenic activity. Inhibition of SETDB1 reduces cell growth in melanomas resistant to targeted treatments 2.1.1.366 [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase medicine SETDB1 depletion effectively converts stem-like colorectal cancer cells into postmitotic cells and restores normal morphology in patient-derived colorectal cancer organoids. SETDB1 depletion recapitulates global gene expression profiles of normal differentiated cells by restoring the transcriptional activity of core transcription factors such as CDX2, ELF3, HNF4G, PPARG, and VDR, on their target genes 2.1.1.366 [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase medicine SETDB1 expression is highly amplified in colorectal cancer. SETDB1 downregulation in SW480 and HCT116 cells reduces cell proliferation, migration, invasion, and increased colorectal cancer cells apoptosis. SETDB1 overexpression promotes colorectal cancer cells proliferation, migration, and invasion. High expression of SETDB1 is associated with a more aggressive phenotype in vitro. Cell cycle is arrested in G1 phase after SETDB1 silencing. Depletion of SETDB1 in vivo suppresses colorectal cancer cells proliferation. p21 is the target of SETDB1. After transfection with siSETDB1, expression of p21 s distinctly increased. Expression of p21 is significantly decreased after overexpression of SETDB1. SETDB1 can bind to the promoter of p21 and regulate its H3K9me3 enrichment level. Silencing of SETDB1 inhibits colorectal cancer tumorigenesis in vivo 2.1.1.366 [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase medicine Setdb1 has a constant role in endogenous retrovirus silencing. Distinctive sets of endogenous retroviruses are reactivated in different types of Setdb1-deficient somatic cells, including the VL30-class of endogenous retroviruses in mouse embryonic fibroblasts. A viral defense response is induced in immortalized Setdb1 knock-out embryonic fibroblasts 2.1.1.370 [histone H3]-lysine4 N-dimethyltransferase medicine Nsd3 expression is increased in both acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) patients 2.1.1.371 [histone H3]-lysine27 N-dimethyltransferase medicine Nsd3 expression is increased in both acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) patients 2.1.1.371 [histone H3]-lysine27 N-dimethyltransferase medicine NSD3 expression is reduced by isoproterenol stimuli both in vitro and in vivo. Overexpression of NSD3 attenuates isoproterenol-induced cardiomyocyte hypertrophy. Isoproterenol treatment decreases H3K27me2/3 modifications on the atrial natriuretic factor promoter by suppressing NSD3 and inhibits the association between NSD3 and bromodomain-containing protein BRD4, thus suppressing the BRD4-mediated H3K27ac modifications, which ultimately promote atrial natriuretic factor transcription and cardiomyocyte hypertrophy 2.1.1.371 [histone H3]-lysine27 N-dimethyltransferase medicine silencing of NSD3 in osteosarcoma results in a marked decrease in the number of viable cancer cells, accompanied by increases in the cell population at the G2/M phase and the number of apoptotic cells. NSD3 negatively regulates a number of genes that are involved in the process of negative regulation of signal transduction as well as negative regulation of signaling and cell communication 2.1.2.1 glycine hydroxymethyltransferase medicine enzyme is a potential target for cancer chemotherapy 2.1.2.1 glycine hydroxymethyltransferase medicine enzyme is a target for antibiotics 2.1.2.1 glycine hydroxymethyltransferase medicine the cytosolic SHMT is a target enzyme for chemotherapy 2.1.2.1 glycine hydroxymethyltransferase medicine animal model for drug screening of SHMT 2.1.2.1 glycine hydroxymethyltransferase medicine drug target in Leishmania 2.1.2.1 glycine hydroxymethyltransferase medicine enzyme is distinct from its prokaryotic and eukaryotic counterparts, thus is a potential drug target 2.1.2.1 glycine hydroxymethyltransferase medicine ldSHMT is of medical importance as a drug target since ldSHMT is preferentially expressed in the amastigote stage of parasite which resides in human macrophages 2.1.2.1 glycine hydroxymethyltransferase medicine SHMT is a potential target for antimalarial chemotherapy 2.1.2.1 glycine hydroxymethyltransferase medicine isozyme SHMT2 is a possible target for anticancer therapies 2.1.2.2 phosphoribosylglycinamide formyltransferase 1 medicine - 2.1.2.2 phosphoribosylglycinamide formyltransferase 1 medicine inhibitor 5,10-dideazatetrahydrofolate is antiproliferate and cytotoxic against mammalian tumor cells in culture and have broad spectrum activity against transplantable mouse tumors and human tumor xenografts 2.1.2.2 phosphoribosylglycinamide formyltransferase 1 medicine target for structure-based drug design 2.1.2.2 phosphoribosylglycinamide formyltransferase 1 medicine pharmacological importance, target enzyme for chemotherapy, development of novel antifolate drugs, to be used as anti-cancer drugs 2.1.2.2 phosphoribosylglycinamide formyltransferase 1 medicine glycinamide ribonucleotide transformylase has emerged as a productive target for antineoplastic therapeutic intervention 2.1.2.2 phosphoribosylglycinamide formyltransferase 1 medicine glycinamide ribonucleotide transformylase is a validated target for cancer chemotherapy 2.1.2.2 phosphoribosylglycinamide formyltransferase 1 medicine high GART expression is observed in glioma and is related to the grade of malignancy. GART overexpression is significantly associated with overall survival. Transfecting cells with GART-siRNA suppresses proliferation and enhances temozolomide-induced apoptosis in glioma cells 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase medicine - 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase medicine animal model of systemic autoimmune disease 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase medicine target for development of inhibitors with potential use as chemotherapeutic agents 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase medicine potential target for development of antineoplastic drugs 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase medicine attractive anticancer target 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase medicine potential target for antineoplastic chemotherapy 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase medicine potential target for antineoplastic drug design 2.1.2.5 glutamate formimidoyltransferase medicine subcellular localization of protein may influence production of autoantibodies and their role in the pathogenesis of type 2 autoimmune hepatitis 2.1.2.10 aminomethyltransferase medicine a subset of nonketotic hyperglycinemia cases is due to mutations in the gene for the T-protein 2.1.2.10 aminomethyltransferase medicine strategy for molecular investigation of patients with nonketotic hyperglycinemia: defective glycine cleavage enzyme system, composed of P-, H-, T- and L-protein, 15% of patients have a T-protein defect 2.1.2.10 aminomethyltransferase medicine identification of several mutations and polymorphisms occurring in patients with glycine encephalopathy, NKH, and methods for their PCR-restriction enzyme analysis 2.1.2.13 UDP-4-amino-4-deoxy-L-arabinose formyltransferase medicine modification of the lipid A moiety of lipopolysaccharide by the addition of the sugar 4-amino-4-deoxy-L-arabinose is a strategy adopted by pathogenic Gram-negative bacteria to evade cationic antimicrobial peptides produced by the innate immune system. L-Ara4N biosynthesis is therefore a potential anti-infective target 2.1.3.1 methylmalonyl-CoA carboxytransferase medicine industrial antibiotic production 2.1.3.1 methylmalonyl-CoA carboxytransferase medicine use of enzyme as a molecular marker for specific detection of Propionibacterium freudenreichii in human microbiota. Rapid quantification of bacteria by real time PCR using enzyme operon. Propionibacterium freudenreichii not only survives but remains metabolically active in the human gut 2.1.3.3 ornithine carbamoyltransferase medicine after administration of carbon tetrachloride, allyl alcohol, D-galactosamine, lipopolysaccharide, and concanavalin A, the significant increase in the serum levels of the markers is faster in type-I arginase and ornithine carbamoyltransferase than aspartate aminotransferase and alanine aminotransferase. The extent of the increase at the peak is always higher in type-I arginase and ornithine carbamoyltransferase than in spartate aminotransferase and alanine aminotransferase 2.1.3.3 ornithine carbamoyltransferase medicine in patients with Alzheimer's disease, ornithine carbamoyltransferase is expressed in brain, but not in controls. Ornithine carbamoyltransferase expression is strictly restricted to vascular endothelial cells. Ornithine carbamoyltransferase activity is 880% increased in the cerebrospinal fluid of probable Alzheimer's disease cases compared with controls. Rare haplotypes may be associated with the risk of Alzheimer's disease through a possible modulation of the methylation of the ornithine carbamoyltransferase promoter 2.1.3.3 ornithine carbamoyltransferase medicine in patients with non-alcoholic steatohepatitis, the serum levels of ornithine carbamoyltransferase and the ratios of ornithine carbamoyltransferase:alanine amino transferase and ornithine carbamoyltransferase:aspartate amino transferase are increased in parallel with the progression of on-alcoholic steatohepatitis. Especially, ornithine carbamoyltransferase and both ratios are markedly increased in hepatocellular carcinoma. As for the relationship between fibrosis grade and ornithine carbamoyxltransferase, the serum ornthine carbamoyltransferase levels and theratio of ornithine carbamoyltransferase:alanine amino transferase levels are increased in parallel with liver fibrosis. In non-alcoholic steatohepatitis patients with alanine amino transferase within normal range, about 30% show elevation of ornithine carbamoyltransferase 2.1.3.3 ornithine carbamoyltransferase medicine ornithine carbamoyltransferase is acetylated at lysine resiudes, including K88, which is also mutated in ornithine carbamoyltransferase-deficient patients. K88 acetylation decreases the affinity for carbamoyl phosphate, and the maximum velocity, whereas the Km for ornithine is not affected 2.1.3.3 ornithine carbamoyltransferase medicine ornithine carbamyltransferase is present in urine of patients with pulmonary tuberculosis. Recombinant ornithine carboamyltransferase produced in Escherichia coli is recognized by immunoglobulin G antibodies from patients with active tuberculosis but not by IgG from uninfected healthy subjects. Protein is strongly recognized by peripheral blood mononuclear cells from both healthy tuberculin purified protein derivative-positive individuals and patients with pulmonary tuberculosis 2.1.3.3 ornithine carbamoyltransferase medicine the serum activities of ornithine carbamoyltransferase and glutamate dehydrogenase increase significantly by chronic ethanol feeding while other markers do not. Although the hepatic content of ornithine carbamoyltransferase and glutamate dehydrogenase also increase, the serum activities do not correlate with the hepatic activities and the extent of increase in the liver is much less than in serum 2.1.3.3 ornithine carbamoyltransferase medicine use of multiplex ligation-dependent probe amplification methodology to three ornithine transcarbamylase deficiency patients, two females and one male, reveals copy number alterations of ornithine transcarbamylase exons in all of them. The two females are heterozygous for deletions of either exon 2 or exons 6-9, and the male is confirmed to lack all exons. Females' characterization of the deletion breakpoints reveal mutations corresponding to exon 2 and exon 6-9 deletions, respectively. Exon 2 deletion probably results from replication slippage facilitated by a secondary structure formed by two inverted Alu repeats, whereas an Alu-Alu homologous recombination is probably responsible for the exon 6_9 deletion 2.1.3.3 ornithine carbamoyltransferase medicine enzyme downregulation is associated with poor prognosis in hepatocellular carcinoma 2.1.3.3 ornithine carbamoyltransferase medicine measurement of serum enzyme concentration is a useful marker of disease severity, and thus can be a useful marker for a high risk of hepatocellular carcinoma occurrence 2.1.4.1 glycine amidinotransferase medicine presence of the enzyme in serum or urine may prove useful in development of kidney disease diagnosis, hyperornithinemia, an autosomal recessive disease caused by decreased enzyme activity, enzyme activity is also dimished in thyrotoxicosis and myotonic muscular dystrophy 2.1.4.1 glycine amidinotransferase medicine enzyme is a target of the estrogen receptor, is involved in carcinogenesis, mental disorder, osteoporosis and cardiovascular disease 2.1.4.1 glycine amidinotransferase medicine diagnostic tool for biochemical diagnosis of creatine metabolism disorders 2.1.4.1 glycine amidinotransferase medicine diagnosis of AGAT deficiency can be conformed by enzymatic assays in various cell types. The genetic defects can be proven by mutation analysis of the gene involved. Prenatal diagnosis is possible by mutation analysis 2.1.4.1 glycine amidinotransferase medicine creatine deficiency syndromes, either due to AGAT, GAMT or SLC6A8 deficiencies, lead to a complete absence, or a very strong decrease, of creatine within the brain 2.1.4.1 glycine amidinotransferase medicine reaggregated brain cell three-dimensional cultures exposed to NH4Cl are used as an experimental model of hyperammonemia in the developing central nervous system 2.2.1.1 transketolase medicine both TKTL1 and p-Akt play an important role in the progression of cervical neoplasia, which may be due to their impact on glycolysis. Intensity of the expression of TKTL1 and the oncogene p-Akt increases significantly with an increase in the histopathological grade of cervical tissues. TKTL1 and p-Akt can be possibly valuable targets for nontoxic antitumor therapeutic approaches, especially in cervical precancerous lesions and cancer 2.2.1.1 transketolase medicine initially abnormal erythrocyte transketolase activity and/or the thiamin pyrophosphate effect, indicating intracellular cofactor deficiency, usually improves with thiamin administration 2.2.1.1 transketolase medicine is crucial for optimal brain function. Abnormal transketolase expression and/or activity are implicated in a number of diseases where thiamin availability is low, including Wernicke-Korsakoff’s Syndrome and alcoholism 2.2.1.1 transketolase medicine marked subset of breast cancers show a TKTL1 overexpression which correlates significantly with Her2/neu overexpression. In contrast to colon and urothelial cancer from previous studies, TKTL1 overexpression is not associated with a poor patient outcome in the examined study population. TKTL1 represents a novel metabolic biomarker in breast cancer, and a possible future target for mechanism-driven drug development 2.2.1.1 transketolase medicine the transketolase-like-1 gene plays an important role in total transketolase activity and in cell proliferation of human colon cancer. Transketolase-like-1 may serve as a target for novel anticancer therapies 2.2.1.1 transketolase medicine TktA interacts with MarR. TktA decreases MarR repressor activity. Overexpressing tktA decreases antibiotic susceptibility. Endogenous TktA enhances multiple antibiotic resistance to a small degree through release of MarR repression of the marRAB operon 2.2.1.1 transketolase medicine TKTL 1 is highest expressed in cell lines derived from more invasive tumors but the expression level is not strongly correlated to proliferation rate, to GLUT-1 expression or to the response to oxythiamine. Overexpression of TKTL-1 is not an indicator for responsiveness to oxythiamine 2.2.1.1 transketolase medicine TKTL1 gene influences total transketolase activity and cell proliferation in human nasopharyngeal carcinoma cells, suggesting that TKTL1 gene plays an important role on glycometabolism in tumors and may become a novel target for tumor gene therapy 2.2.1.1 transketolase medicine TKTL1 overexpression in papillary thyroid carcinoma bigger than 1.5 cm may be considered a factor that facilitates tumor growth and progression. Significant association between TKTL1 protein expression and the presence of multifocality, bilaterality, extrathyroidal extension, vascular invasion, sclerosis, and lymph-node metastases 2.2.1.1 transketolase medicine TKTL1 overexpression is associated with a more aggressive behavior and shorter survival of laryngeal squamous cell carcinomas 2.2.1.1 transketolase medicine TKTL1 plays a crucial role in ovarian cancer metabolism and its expression predicts poor prognosis. TKTL1 could thus have a possible value as target for nontoxic antitumoral therapeutic approaches especially in advanced ovarian cancer, a disease where really efficient treatment options are limited 2.2.1.1 transketolase medicine transketolase may emerge as a target of multiple sclerosis cerebro-spinal fluid autoimmune response 2.2.1.1 transketolase medicine treatment of hyperglycemic mice with BM-derived IPCs transplantation and benfotiamine, whereby activation of transketolase by benfotiamine can be playing a significant role in upregulation of both glucose metabolism and insulin protein synthesis 2.2.1.1 transketolase medicine upregulation of TKTL1 in the metabolism of astrocytic gliomas with different degrees of malignancy. Percentage of positive cells for TKTL1 and p-Akt are significantly correlated. These observations can lead to additional therapeutic options targeting a specific blockade of TKTL1 enzyme activity 2.2.1.1 transketolase medicine in HeLa cells, transketolase-like enzyme 1 mRNA is specifically overexpressed compared with normal human endocervical epithelial cells. After anti-transketolase-like enzyme 1 siRNA treatment, total transketolase activity is significantly reduced and cell proliferation is remarkably inhibited. In endocervical epithelia cells, total transketolase activity and cell proliferation have no significant differences after siRNA treatment 2.2.1.1 transketolase medicine six out of 15 anaplastic nephroblastomas analyzed show staining of transketolase-like enzyme 1 in 80–100% of the tumour. None of the 13 non-anaplastic nephroblastomas analyzed shows transketolase-like enzyme 1 staining in more than 80% of the tumour. Transketolase-like enzyme 1 expression is associated with the presence of anaplasia and may be a mechanism via which anaplastic tumour cells thrive under different conditions 2.2.1.1 transketolase medicine enzyme inhibition sensitizes cancer cells to sorafenib treatment 2.2.1.1 transketolase medicine high nuclear enzyme positivity in peritoneal metastases is significantly associated with reduced overall survival and a 2.8fold increased risk of ovarian cancer death 2.2.1.2 transaldolase medicine male mice lacking transaldolase are sterile because of defective forward motility of spermatozoa. Transaldolase -/- spermatozoa show loss of transmembrane potential and mitochondrial membrane integrity. Lack of enzyme influencies structure and function of mitochondria without compromising the nucleus and DNA integrity. Stimulation of de novo glutathione synthesis by oral N-acetyl-cysteine normalizes the low fertility rates of transaldolase +/- males without affecting the sterility of transaldolase -/- mice 2.2.1.2 transaldolase medicine clinical presentation and laboratory findings of a new patient with TALDO deficiency: a two-year-old Arabic boy presented with neonatal onset of anemia and thrombocytopenia, tubulopathy, and rickets and is subsequently found to have cirrhosis and deafness 2.2.1.2 transaldolase medicine the results provide preliminary evidence that genetic polymorphisms in TALDO1 are associated with squamous cell carcinoma of the head and neck 2.2.1.2 transaldolase medicine transaldolase-deficient patients have significantly increased urinary sedoheptulose and sedoheptulose 7-phosphate, associated with subtle elevations of mannoheptulose, sedoheptitol and perseitol. The development of a liquid chromatography-tandem mass spectrometry method for quantitation of the seven-carbon carbohydrates biomarkers in urine is shown 2.2.1.2 transaldolase medicine transaldolase shows a high mucin binding capacity. When exposed on the cell surface of Bifidobacterium bifidum, enzyme may act as an important colonization factor favoring its establishment in the gut. A recombinant Lactococcus lactis strain, engineered to secrete transaldolase, displays a mucin-binding level more than three times higher than the strain not producing the transaldolase 2.2.1.5 2-hydroxy-3-oxoadipate synthase medicine deficiency leads to hyperoxaluria, relative decrease in liver biomass 2.2.1.5 2-hydroxy-3-oxoadipate synthase medicine involved in renal stone formation, decreased activity due to thiamine deficiency may increase oxalate excretion by 35% 2.2.1.7 1-deoxy-D-xylulose-5-phosphate synthase medicine development of 1-deoxy-D-xylulose-5-phosphate synthase inhibitors to treat Plasmodium vivax malaria 2.3.1.1 amino-acid N-acetyltransferase medicine warly, accurate, and specific diagnosis of NAGS deficiency is critical since this condition can be successfully treated with N-carbamoylglutamate. Treatment with N-carbamoylglutamate should be initiated as soon as a patient is suspected of having NAGS deficiency. Molecular testing represents the most reliable method of diagnosis 2.3.1.1 amino-acid N-acetyltransferase medicine a polar body-based preimplantation genetic diagnosis for N -acetylglutamate synthase deficiency using multiplex and fluorescent single-cell PCR is described 2.3.1.4 glucosamine-phosphate N-acetyltransferase medicine analysis of the global protein expression profiles of lung cancer cell A549 treated with abraxane and paclitaxel. The superior drug effect of abraxane is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect 2.3.1.5 arylamine N-acetyltransferase medicine inactivation of antiopportunistic infection drugs 2.3.1.5 arylamine N-acetyltransferase medicine activity in umbilical cord tissue from different samples 2.3.1.5 arylamine N-acetyltransferase medicine activity in benign prostatic hyperplasia tissue 2.3.1.5 arylamine N-acetyltransferase medicine kinetics of several substrates for different genetic variants of enzyme 2.3.1.5 arylamine N-acetyltransferase medicine Nat2 expression may be useful as a marker in cardiac development 2.3.1.5 arylamine N-acetyltransferase medicine the enzyme is a target for antituberculosis therapy 2.3.1.5 arylamine N-acetyltransferase medicine a polymorphic homologue of human NAT2 is characterized in the rhesus macaque, to facilitate investigations of the postulated involvement of this isoenzyme in the toxicogenetics of endometriosis 2.3.1.5 arylamine N-acetyltransferase medicine altered expression of the human orthologue in breast tumours, in which there is endocrine signalling, suggests that human NAT1 should be considered as a potential biomarker for neuroendocrine tissues and tumours 2.3.1.5 arylamine N-acetyltransferase medicine C1095A SNP outside the NAT1 coding region is associated with increased homocysteine. The C1095A SNP is found most frequently in the NAT1 allele 1*10 and is shown to have increase NAT1 activity or to have no effect. C1095A SNP appears at increased frequency in bladder cancer and Alzheimer's disease 2.3.1.5 arylamine N-acetyltransferase medicine consensus gene nomenclature is necessary to report and interpret the results of human epidemiological studies, as well as to perform meta analysis and, or compare the results of different studies 2.3.1.5 arylamine N-acetyltransferase medicine epidemiological studies of birth defects indicate that NAT1 polymorphisms are associated with problems of neural tube closure in spina bifida and with cleft lip and palate. Limp formation defects are also associated with NAT1 polymorphism 2.3.1.5 arylamine N-acetyltransferase medicine genetic profile of the NAT2 gene in individuals from two different regions of Brazil: Rio de Janeiro and Goi´as States is examined in 404 individuals: 13 previously described SNPs are detected in these Brazilian populations, from which seven are the most frequent in other populations. Upon allele and genotype analysis, the most frequent NAT2 alleles are respectively NAT2*5B (33%), NAT2*6A (26%) and NAT2*4 (20%) being NAT2*5/*5 the more prevalent genotype (31.7%). Results demonstrate the predominance in the studied Brazilian groups of NAT2 alleles associated with slow over the fast and intermediate acetylator genotypes. Additionally, in Rio de Janeiro, a significantly higher frequency of intermediate acetylation status is found when compared to Goi´as (42.5% versus 25%),demonstrating that different regions of a country with a population characterized by a multi-ethnic ancestry may present a large degree of variability in NAT2 allelic frequencies 2.3.1.5 arylamine N-acetyltransferase medicine HIV-infection in human decreases NAT2 activity but not NAT1 2.3.1.5 arylamine N-acetyltransferase medicine it is shown that human NAT1 is induced by androgens, which may have implications for cancer risk in individuals 2.3.1.5 arylamine N-acetyltransferase medicine mutant alleles resulting in a decrease in NAT1 activity are found to be protective against spina bifida 2.3.1.5 arylamine N-acetyltransferase medicine NAT is involved in drug induced liver injury. NAT metabolizes drugs causing liver damages: acetylsalicylic acid, dapsone, dihydralazine, isoniazid, p-aminosalicylic acid, procainomide, sulfasalazine, sulfanamide, mesalamine, maprotiline, flutamide 2.3.1.5 arylamine N-acetyltransferase medicine NAT2 exerts the effects of drug combinations: NAT2 polymorphisms modify the doxycyline-rifampin interaction that occurs in individuals treated simulataneously with these drugs, that cause an inverse correlation between doxycycline rifampin plasma levels. Among individuals classified as rapid acetylators rifampin plasma levels are greater whereas doxycycline levels are lower, as compared to slow acetylators 2.3.1.5 arylamine N-acetyltransferase medicine NAT2 polymorphisms in both promoter and coding regions in the Indonesian population are examined: Promoter and coding regions of NAT2 displays 23 polymorphisms/variations. Seven haplotypes in the promoter region and six haplotypes in the coding region are inferred. Haplotypes in promoter and coding regions show limited combinations, and 13 combined haplotypes are inferred. The most frequent haplotypes are U1 (38.9%), U2 (33.5%) in the promoter region and NAT2*4 (37.3%), NAT2*6A (36.8%) in the coding region. When converted to predicted phenotypes, the studied population comprise 65.4% rapid acetylators and 35.6% slow acetylators according to bimodal distribution. Frequencies of NAT2 alleles for the Indonesian population resemble those of other Southeast Asian populations 2.3.1.5 arylamine N-acetyltransferase medicine ocular defects associated with a null mutation in the mouse arylamine N-acetyltransferase 2 gene 2.3.1.5 arylamine N-acetyltransferase medicine polymorphisms of arylamine N-acetyltransferase 2 are reportedly associated with the risk of drug toxicities and development of various diseases such as cancer and neurodegenerative diseases 2.3.1.5 arylamine N-acetyltransferase medicine present study examines an association of slow N-acetyltransferase 2 profile caused by classical N-acetylation polymorphism and anti-tuberculosis drug-induced hepatotoxicity in patients from Southern Brazil. 254 Brazilian tuberculosis patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) are tested in a prospective cohort study. Results demonstrate that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-tuberculosis drugs 2.3.1.5 arylamine N-acetyltransferase medicine results show that DNA hypomethylation in the NAT1 gene is present in cancerous breast tissues thus indicating that this type of methylation may significantly influence the transcriptional activation of the gene. Therefore, hypomethylation of the NAT1 gene plays a significant role in breast carcinogenesis 2.3.1.5 arylamine N-acetyltransferase medicine results show that human NAT1 is induced by androgens, which may have implications for cancer risk in individuals 2.3.1.5 arylamine N-acetyltransferase medicine results show that Warburgia salutaris is a useful source of anti-tubercular compounds for further analysis and supports the hypothesis of a link between NAT inhibition and antimycobacterial activity 2.3.1.5 arylamine N-acetyltransferase medicine results suggest that care should be taken to prevent the development of isoniazid-induced hepatic disorder in patients who have the NAT2 SA phenotype, a high concentration of rifampicin and who carry the GST M1 null genotype 2.3.1.5 arylamine N-acetyltransferase medicine TBNAT remains a potential drug target for the treatment of tuberculosis 2.3.1.5 arylamine N-acetyltransferase medicine the data pave the way for investigating NAT1 transcripts as candidate prognostic markers in ER-positive breast cancer 2.3.1.5 arylamine N-acetyltransferase medicine the evaluation of the NAT2 gene in Brazilians subjects demonstrated a considerable prevalence of slow acetylatots and established a basis for further investigations 2.3.1.5 arylamine N-acetyltransferase medicine the findings show that inflammation can supress NAT1, a key cellular defense enzyme, such a suppression may be implicated in drug toxicity and cancer risk 2.3.1.5 arylamine N-acetyltransferase medicine the internationally recommended dosage of isoniazid for patients with two active NAT2 alleles in order to achieve appropriate antituberculous efficiency should be increased 2.3.1.5 arylamine N-acetyltransferase medicine the present data do not support a relevant impact of the NAT1 genotype on colorectal cancer risk development in the study area 2.3.1.5 arylamine N-acetyltransferase medicine the results suggest that the irreversible inactivation of NAT1 by cysplatin may at least partly contribute to the pharmacological and, or toxicological effects of cisplatin 2.3.1.5 arylamine N-acetyltransferase medicine there is increasing evidence that arylamine N-acetyltransferases could contribute to antibiotic resistance in pathogenic bacteria 2.3.1.5 arylamine N-acetyltransferase medicine to better understand the possible relationship between the NAT2 gene and endometriosis, its homologue in the resus macaque is characterized 2.3.1.5 arylamine N-acetyltransferase medicine to estimate an optimal dosage for isoniazid (INH) RA-type patients (patients with two active NAT2 alleles due to genetic polymorphisms) a dose escalation study in healthy male volunteers is conducted carrying mutation NAT2*4/*4. In RA-type subjects, the pharmacokinetic parameters appear to lack linearity with the increased dose of isoniazid. It is proposed that the proper daily dose for RA-type patients is 1.5times higher than that currently recommended 2.3.1.5 arylamine N-acetyltransferase medicine tobacco smoking is shown to change the risk significance of individual alleles NAT2 to predisposition to multifactor diseases 2.3.1.5 arylamine N-acetyltransferase medicine Warburgia salutaris is a useful source of anti-tubercular compounds for further analysis and supports the hypothesis of a link between NAT inhibition and anti-mycobacterial activity 2.3.1.5 arylamine N-acetyltransferase medicine co-expression of Escherichia coli nitroreductase and arylamine N-acetyltransferase NAT2 in SKOV3 cells decreases the IC50 value of prodrug CB1954, i.e. 5-(aziridin-1-yl)-2,4-dinitrobenzamide, 16fold. The significantly decreased bystander effect may provide a greater clinical response at therapeutic concentrations of CB1954 2.3.1.5 arylamine N-acetyltransferase medicine exposure of lung epithelial cells to pathophysiologically relevant amounts of oxidants such as H2O2 or peroxyntrite, impairs the Nat1-dependent cellular biotransformation of aromatic amines 2.3.1.5 arylamine N-acetyltransferase medicine exposure of lung epithelial cells to pathophysiologically relevant amounts of oxidants such as H2O2 or peroxyntrite, impairs the Nat2-dependent cellular biotransformation of aromatic amines 2.3.1.5 arylamine N-acetyltransferase medicine increasing acetylation by introduction of the human NAT1 transgene is protective against sporadic dilantin-induced orofacial clefting defects in the mouse A/J strain 2.3.1.5 arylamine N-acetyltransferase medicine knock-down of enzymeby lentiviral shRNA reduces the invasion potential of MDA-MB-231 cells. Enzymic activity may be important in breast cancer growth and metastasis 2.3.1.5 arylamine N-acetyltransferase medicine knockout of NAT2 significantly decreases teratogen-induced orofacial clefting in the A/J strain, but not in the C57BL/6J strain 2.3.1.5 arylamine N-acetyltransferase medicine presence of *12A and the absence of *12B, *13, *14B, *14D, *6A, and *7A NAT2 haplotypes are risk factors for differentiated thyroid cancer. The inheritance of a rapid acetylation phenotype doubles the risk for a papillary carcinoma. No relationship between genotypes and clinical, pathologic, or laboratory features of patients or between genotypes and outcome 2.3.1.5 arylamine N-acetyltransferase medicine enzyme expression is correlated with improved overall survival of breast cancer patients. The enzyme is a possible prognostic biomarker for lymph node-positive breast cancer 2.3.1.5 arylamine N-acetyltransferase medicine a negative correlation is found between the expression of NAT1 and MMP9 in 1904 breast cancer samples 2.3.1.5 arylamine N-acetyltransferase medicine isoniazid N-acetylation rates in vitro exhibit a robust and highly significant NAT2 phenotype-dependent metabolism. N-acetylation rates in situ are isoniazid concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 mmol/l isoniazid, acetyl-isoniazid concentrations vary significantly across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. N-acetylation rates of N-(4-aminobenzoyl)-L-glutamate in vitro do not differ significantly between rapid, intermediate, and slow NAT2 acetylators. N-acetylation rates towards isoniazid in the identical samples exhibit a robust and highly significant NAT2 genotype-dependent metabolism 2.3.1.5 arylamine N-acetyltransferase medicine loss of NAT1 in in MDA-MB-231, HT-29 and HeLa cells increases adherence to collagen but migration of cells is unaffected. NAT1 deletion decreases invasion and induces changes to cell morphology. These effects are independent of matrix metalloproteinases but are related to integrin ITGalphaV expression 2.3.1.5 arylamine N-acetyltransferase medicine MOCA N-acetylation exhibits a robust gene dose response in cryopreserved human hepatocytes derived from individuals of rapid, intermediate and slow acetylator NAT2 genotype. 4,4'-methylenebis(2-chloroaniline)(MOCA) exhibits about 4fold higher affinity for recombinant human NAT2 than NAT1. Recombinant human NAT2 4 (reference) and 15 variant recombinant human NAT2 allozymes catalyze both the N-acetylation of MOCA and the O-acetylation of N-hydroxy-MOCA. Human NAT2 5, NAT2 6, NAT2 7 and NAT2 14 allozymes catalyze MOCA N-acetylation and N-hydroxy-O-acetylation at rates much lower than the reference NAT2 4 allozyme 2.3.1.5 arylamine N-acetyltransferase medicine there is no association between phenotypes of NAT2 polymorphisms and breast cancer. Ethnic and geographic differences in NAT2 polymorphism are present, but not associated with the risk of breast cancer in general. Intermediate acetylator is protective for particular ethnic groups 2.3.1.6 choline O-acetyltransferase medicine a severe case of congenital myasthenia gravis in a Chinese newborn is reported who presents with complete ptosis, severe hypotonia, dysphagia and respiratory insufficiency with recurrent apnea that requires mechanical ventilatory support since birth. The infant has heterozygous mutations in the choline acetyltransferase genes, p.T553N and p.S704P 2.3.1.6 choline O-acetyltransferase medicine ChAT 2384 A allele is a risk factor for Alzheimer’s disease and mild cognitive impairment 2.3.1.6 choline O-acetyltransferase medicine investigation of three ChAt gene polymorphisms in schizophrenia. Evidence for an influence of a 5' promoter polymorphism, rs1880676A/G, on susceptibility to the disorder among individuals of Basque origin. Evidence for a similar though less significant, influence for a second polymorphism of putative function, rs3810950 2.3.1.6 choline O-acetyltransferase medicine promoting ChAT activity and acetylcholine release can lead to treatments for neurodegenerative diseases with cholinergic deficits, such as Alzheimer’s disease 2.3.1.7 carnitine O-acetyltransferase medicine - 2.3.1.7 carnitine O-acetyltransferase medicine dysregulation of the enzyme can lead to serious diseases in humans, inherited deficiency in CRAT activity can lead to neurological and heart problems, patients suffering from Alzheimer 's disease also have reduced CRAT activity, promising target for therapeutic development against several human diseases like diabetes 2.3.1.7 carnitine O-acetyltransferase medicine pharmacological applications, patients suffering from CARAT deficiency, serious neurological, motor, repiratory and heart problems observed 2.3.1.7 carnitine O-acetyltransferase medicine CAT is clinically used in evaluating L-CA and its esters in body fluids and tissues 2.3.1.7 carnitine O-acetyltransferase medicine CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese type 2 diabetes mellitus patients. mRNA levels and protein abundance of CRAT are similar between from obese persons with or without type 2 diabetes mellitus and lean controls. Of 14 different acylcarnitine species measured, the levels of palmitoylcarnitine and octadecanoylcarnitine are slightly reduced in myotubes derived from type 2 diabetes mellitus patients compared to glucose-tolerant obese and lean controls 2.3.1.13 glycine N-acyltransferase medicine isoform Glyat expression is suppressed in all hepatocellular carcinomas, but not in other liver diseases. Glyat repression in cancerous cells in the liver is controlled at the transcriptional level 2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase medicine GPAT3 may be useful as a target for the treatment of obesity 2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase medicine elucidation of the metabolic pathways of triacylglycerol is critical to the understanding of chronic metabolic disorders such as obesity, cardiovascular disease and diabetes 2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase medicine GPAT1 is not an essential enzyme in hepatic triacylglycerol synthesis and GPAT1-deficiency does not protect against high-fat diet-induced obesity or glucose intolerance and does not increase whole body energy expenditure 2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase medicine Gpat1-/- mouse may be a useful model in which to study novel relationships between hepatic mitochondrial dysfunction, oxidative stress, apoptosis, proliferation, and cancer susceptibility 2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase medicine it has been implicated as one of the enzymes that can play a role in obesity and diabetes 2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase medicine major finding of the study is that overexpressing GPAT in liver causes hepatic steatosis and hepatic insulin resistance in the absence of obesity or high-fat feeding 2.3.1.15 glycerol-3-phosphate 1-O-acyltransferase medicine lack of GPAT1 activity affects both innate and adaptive immune mechanisms 2.3.1.16 acetyl-CoA C-acyltransferase medicine mutation in the thiolase gene causes severe health problems, such as ketoacidic attacks at the age of six months followed by severe retardation 2.3.1.16 acetyl-CoA C-acyltransferase medicine 3-ketoacyl coenzyme-A thiolase inhibition could be a treatment for patients with heart failure 2.3.1.17 aspartate N-acetyltransferase medicine patients with high levels of tumoral N-acetyl-L-aspartate and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), have worse overall survival than patients with low levels of N-acetyl-L-aspartate and NAT8L. The overall survival duration of patients with higher-than-median N-acetyl-L-aspartate levels (3.6 years) is lower than that of patients with lower-than-median N-acetyl-L-aspartate levels (5.1 years). High NAT8L gene expression in other cancers (melanoma, renal cell, breast, colon, and uterine cancers) is associated with worse overall survival. NAT8L silencing reduces cancer cell viability and proliferation. In orthotopic mouse models (ovarian cancer and melanoma), NAT8L silencing reduces tumor growth statistically significantly 2.3.1.20 diacylglycerol O-acyltransferase medicine enzyme expression is decreased in psoriatic skin 2.3.1.20 diacylglycerol O-acyltransferase medicine enzyme expression is increased in diabetic animals 2.3.1.20 diacylglycerol O-acyltransferase medicine increase in triglyceride accumulation in diet-induced hyperlipidemic, insulin-resistant animals corresponds with increase in microsomal enzyme activity. Isoform DGAT1 activity changes most in liver and adipose tissue, DGAT2 responses mainly in muscle and intestine 2.3.1.20 diacylglycerol O-acyltransferase medicine use of enzyme as target for antilacency drugs that prevent cells from surviving dormancy 2.3.1.20 diacylglycerol O-acyltransferase medicine diacylglycerol acyltransferase (DGAT), the only limited enzyme in the synthesis of triacylglycerol (TAG), is regarded as an important therapeutic target for human obesity and other metabolic syndromes 2.3.1.21 carnitine O-palmitoyltransferase medicine treatment of CPT2 deficiency is based upon avoidance of fasting and/or exercise, a low fat diet enriched with medium chain triglycerides and carnitine 2.3.1.21 carnitine O-palmitoyltransferase medicine enzyme inhibitors are used to shift the heart's reliance away from fatty acid oxidation to glucose as energy source to increase cardiac efficiency, overview 2.3.1.21 carnitine O-palmitoyltransferase medicine hypertrophied myocardium displays a significant shift in the relative isoform distribution of CPT1 isoforms, L-CPT1 expression dramatically increases relative to M-CPT1 expression 2.3.1.21 carnitine O-palmitoyltransferase medicine the data suggest that consuming a high-fat diet or inhibiting CPT-I do not result in cardiac hypertrophy or cardiac dysfunction in normal rats 2.3.1.21 carnitine O-palmitoyltransferase medicine isoform CPT1C expression is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1Cdepletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKalpha 2.3.1.21 carnitine O-palmitoyltransferase medicine overexpression of the enzyme correlates with a poor overall survival of ovarian cancer patients. CPT1A is a prognostic biomarker and rational target for therapeutic intervention of cancer 2.3.1.21 carnitine O-palmitoyltransferase medicine compared to isoforms CPT1A, CPT1B and CPT2, isoform CPT1C exerts the most significant effect on mitochondrial dysfunction-associated tumor cellular senescence among the members of the CPT family 2.3.1.21 carnitine O-palmitoyltransferase medicine problems in CPT2 deficiency originating from the S113L mutation might be at least partially related to an impaired thermal stability of the protein 2.3.1.21 carnitine O-palmitoyltransferase medicine triple-negative breast cancer cells resistant to glutaminase inhibitor CB-839 have increased CPT2 protein and CPT1 activity levels. CB-839-resistant triple-negative breast cancer cells mobilize more fatty acids into mitochondria for oxidation 2.3.1.21 carnitine O-palmitoyltransferase medicine triple-negative breast cancer cells resistant to glutaminase inhibitor CB-839 have increased CPT2 protein and CPT1 activity levels. CB-839-resistant triple-negative breast cancer cells mobilize more fatty acids into mitochondria for oxidation. Inhibition of both glutaminase and CPT1 decreases cell proliferation and migration of CB-839-resistant cells compared with single inhibition of each enzyme 2.3.1.21 carnitine O-palmitoyltransferase medicine when fatty acid oxidation is reduced approximately 90% by pharmacological inhibition of carnitine palmitoyltransferase I CPT1 with low concentrations of etomoxir, the proliferation rate of various cancer cells is unaffected. High concentrations of etomoxir (200 microM) have an off-target effect of inhibiting complex I of the electron transport chain. When fatty acid oxidation is reduced further by genetic knockdown of CPT1, the proliferation rate of these same cells decreases nearly 2fold and cannot be restored by acetate or octanoic acid supplementation. CPT1 knockdowns have altered mitochondrial morphology and impaired mitochondrial coupling, whereas cells in which CPT1 has been approximately 90% inhibited by etomoxir do not. Mitochondria isolated from CPT1 knockdowns show depleted concentrations of complex structural and signaling lipids. Expression of a catalytically dead CPT1 in CPT1 knockdowns does not restore mitochondrial coupling 2.3.1.22 2-acylglycerol O-acyltransferase medicine enzyme expression is not affected during diabetes, while total intestinal activity is significantly increased. Up-regulation of both enzyme expression and activity in animals fed with high fat diet 2.3.1.22 2-acylglycerol O-acyltransferase medicine enzyme deficiency protects mice from metabolic disorders (obesity, glucose intolerance, hypercholesterolemia, and fatty liver) despite high-fat diet, caloric intake is normal and dietary fat is absorbed fully but entry into the circulation is reduced, enzyme may be useful target to treat obesity and other metabolic diseases associated with excessive fat intake 2.3.1.22 2-acylglycerol O-acyltransferase medicine selective inhibition may provide a novel treatment for obesity and its related metabolic complications, defective triacylglycerol synthesis and storage can lead to severe insulin resistance, excess triacylglycerol accumulation leads to obesity, ectopic storage in nonadipose tissues such as liver and skeletal muscle is associated with insulin resistance 2.3.1.22 2-acylglycerol O-acyltransferase medicine expression of MGAT1 is robustly induced during adipocyte differentiation and its expression is suppressed in fat of genetically-obese mice 2.3.1.22 2-acylglycerol O-acyltransferase medicine expression of MGAT1 is robustly induced during adipocyte differentiation and its expression is suppressed in metabolically abnormal obese human subjects 2.3.1.23 1-acylglycerophosphocholine O-acyltransferase medicine LPCAT3 may have potential as a therapeutic target for diseases, including atherosclerosis, non-alcoholic steatohepatitis, and carcinoma 2.3.1.24 sphingosine N-acyltransferase medicine isoform CerS6 is specifically upregulated in experimental alcoholic steatosis in vivo and in vitro 2.3.1.24 sphingosine N-acyltransferase medicine isoform CerS6 is specifically upregulated in experimental alcoholic steatosis in vivo and in vitro. In vivo ceramide reduction by inhibition of de novo ceramide synthesis reduces PLIN2 and hepatic steatosis in alcohol-fed mice, and improves glucose homeostasis in control and Etoh mice, but only de novo synthesis inhibition. Inhibition of ceramide synthesis during alcohol feeding has minimal effect on body composition, food intake, and energy expenditure 2.3.1.26 sterol O-acyltransferase medicine identified as a major target for inhibition, based on the hypothesis that enzyme inhibitors may have a direct antiatherosclerotic effect within the arterial wall and a direct effect in blocking cholesterol absorption in the small intestine, and in reducing very-low-density lipoprotein secretion in the hepatocytes 2.3.1.26 sterol O-acyltransferase medicine for both isoform ACTA1 and ACAT2, overexpression in rat hepatoma McA-RH7777 cells results in increased synthesis, cellular accumulation, and secretion of cholesteryl esters. This leads to decreased intracellular degradation and increased secretion of very low density liporotein apoB. Overexpression of ACAT2 has significantly greater impact upon assembly and secretion of very low density liporotein from liver cells than that of ACAT1 2.3.1.26 sterol O-acyltransferase medicine inbred strains with high/low response in low-density lipoprotein cholesterol to dietary cholesterol and fat, resp. High responding animals have significantly higher percent cholesterol absorption, hepatic free and esterified cholesterol, and hepatic enzyme activity than low responding animals on high cholesterol and high fat diet. Hepatic enzyme activity, but not the intestinal activity is associated with hepatic cholesterol concentration and percent cholesterol absorption 2.3.1.26 sterol O-acyltransferase medicine elevated ACAT2expression may serve as a new biomarker for certain forms of hepatocellular carcinoma 2.3.1.26 sterol O-acyltransferase medicine hepatic ACAT2 plays a critical role in driving the production of atherogenic lipoproteins, and therapeutic interventions, such as the ACAT2-specific antisense oligonucleotide used here, which reduce acyltransferase 2 (ACAT2) function in the liver without affecting ACAT1, may provide clinical benefit for cardiovascular disease prevention 2.3.1.26 sterol O-acyltransferase medicine systemic ACAT inhibition reduces circulating tumor necrosis factor-alpha levels in hypercholesterolemic subjects and improves resistance-vessel endothelial function, with small effects on circulating cholesterol. This may be a novel therapeutic strategy to target vascular inflammation and endothelial dysfunction in atherosclerosis 2.3.1.26 sterol O-acyltransferase medicine ACAT is a key enzyme in controlling cholesterol metabolism and represents a promising target for the development of therapeutic agents and inhibitors to control hypercholesterolemia, atherosclerosis and Alzheimer's disease 2.3.1.26 sterol O-acyltransferase medicine an anti-oxidative ACAT inhibitor or the combination of an antioxidant and an ACAT inhibitor protects foam cells from oxidative stress and effectively reduces cholesterol levels, which would be a promising approach in anti-atherosclerotic therapy 2.3.1.26 sterol O-acyltransferase medicine statin treatment reduces ACAT2 activity in human liver and this effect, in combination with a reduced ApoE expression, may contribute to the favorable lowering of VLDL cholesterol seen in addition to the LDL lowering during statin treatment 2.3.1.26 sterol O-acyltransferase medicine the results suggest that the ACAT inhibitor VULM 1457 is a prospective hypolipidemic and anti-atherogenic drug which treats diabetes 2.3.1.26 sterol O-acyltransferase medicine the results suggest that this novel hypolipidaemic agent exert antiarrhythmic and infarct size-limiting effects in the diabetic-hypercholesterolaemic rat heart 2.3.1.26 sterol O-acyltransferase medicine the study provides evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis 2.3.1.26 sterol O-acyltransferase medicine feeding a diet suplemented with linoleic acid, conjugated linoleic acid, alpha-linolenic acid or conjugated linolenic acid results in decrease in plasma cholesterol, with conjugated linoleic acid being the most effective. Diets have no effect on sterol regulatory element binding protein-2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7-hydroxylase. The four octadecaenoic acids increase the excretion of fecal neutral sterols with conjugated linoleic acid being most effective followed by alphga-linolenic acid, linoleic acid and conjugated linolenic acid. Dietary conjugated linoleic acid is associated with the least intestinal acyl coenzyme A: cholesterol acyltransferase activity followed by alpha-linolenic acid, linoleic acid and conjugated linolenic acid in a decreasing trend 2.3.1.26 sterol O-acyltransferase medicine a panel of ovarian cancer cell lines (OC-314, SKOV-3 and IGROV-1) displays significant increase in the expression of ACAT1 and cholesterol ester levels compared to primary ovarian epithelial cells. ACAT1 knockdown ovarian cancer cell lines show significant suppression of cell proliferation, migration and invasion compared to their respective controls. ACAT-1 inhibition enhances apoptosis with a concurrent increase in caspases 3/7 activity and decreased mitochondrial membrane potential, and ACAT1-inhibited ovarian cancer cell lines display enhanced chemosensitivity to cisplatin treatment 2.3.1.26 sterol O-acyltransferase medicine treatment of 63 patients with metastatic adrenocortical carcinoma with oral nevanimibe at doses ranging from 1.6 mg/kg/day to 158.5 mg/kg/day. No patients experienced a complete or partial response. 13 of 48 (27%) patients who underwent imaging at 2 months had stable disease, and 4 of these had stable disease for more than 4 months 2.3.1.28 chloramphenicol O-acetyltransferase medicine probiotic mixture for the prevention of gastrointestinal side effects due to oral antibiotic therapy, no resistance transfer to Enterococcus faecalis JH2-2, Enterococcus faecium HM1070 (both resistant to rifampin and fusidic acid) and Bacillus subtilis UCN19 (resistant to ciprofloxacin) in mating experiments 2.3.1.28 chloramphenicol O-acetyltransferase medicine method development for a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain of Rattus norvegicus with therapeutic bioavailability, intranasal delivery of chloramphenicol acetyltransferase from Escherichia coli, a relatively large enzyme, in its active form into different regions of the brain, overview 2.3.1.30 serine O-acetyltransferase medicine in parasitic protists the L-cysteine biosynthetic pathway is present in contrast to mammals, therefore, enzymes in this pathway are a potential target for chemotherapeutic agents 2.3.1.30 serine O-acetyltransferase medicine inhibition of enzyme blocks growth of parasite trophozoites but not of mouse cell culture 2.3.1.31 homoserine O-acetyltransferase medicine using a mouse inhalation model of infection it is shown that MET2 is required for virulence, making fungal HTA a viable target for new antibiotic discovery 2.3.1.32 lysine N-acetyltransferase medicine pathogenesis of late-onset Alzheimer disease, post-translational regulation of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) levels, a membrane protein that acts as the rate-limiting enzyme in the generation of Alzheimer disease amyloid beta-peptide, acetylation protect the protein from degradation 2.3.1.37 5-aminolevulinate synthase medicine three-dimensional structural model of enzyme, mapping of a range of human mutants that give rise to X-linked sideroblastic anemia 2.3.1.37 5-aminolevulinate synthase medicine hypoxia induces the expression of TGF-beta1 and mitoferrin mRNAs through separate mechanisms in erythroid cells. TGF-beta1 subsequently induces erythroidspecific 5-aminolevulinate synthase ALAS2 expression 2.3.1.37 5-aminolevulinate synthase medicine in mouse model of erythropoietic protoporphyria, isoflurane induces 5-aminolevulinate synthase activity and increases excretion of porphyrin precursors. Mice homozygotically lacking ferrochelatase activity and receiving anaestesia show enhanced 5-aminolevulinate synthase and Cyp2E1 activities in the liver and increased urinary excretion of porphyrin precursors 2.3.1.37 5-aminolevulinate synthase medicine the relative expression of ALAS1 mRNA, the first and rate-limiting enzyme for heme biosynthesis under normal physiological conditions, is significantly reduced by nearly 90% in patients with Alzheimer's disease compared to control. The relative expression of porphobilinogen deaminase mRNA, the third enzyme in the heme synthesis pathway and a secondary rate-limiting enzyme in heme biosynthesis, is also significantly reduced by nearly 60% in brain of patients with Alzheimer's disease and significantly related to apolipoprotein E genotype. The relative expression of aminolevulinate dehydratase mRNA, the second and a non-rate-limiting enzyme for heme biosynthesis, is unchanged between the two groups 2.3.1.37 5-aminolevulinate synthase medicine delivery of stable and highly active ALAS2 variants has the potential to expand and improve upon current photodynamic therapies regimes 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase medicine enzyme is a potential target for antimycobacterial compounds 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I medicine target for the development of drugs for the treatment of cancer and tuberculosis 2.3.1.B41 protein-long-chain fatty-acyl-lysine deacylase (NAD+) medicine PfSir2A inhibitors may have therapeutic value in malaria treatment 2.3.1.B41 protein-long-chain fatty-acyl-lysine deacylase (NAD+) medicine the oncogenic role of SIRT6 in skin cancer suggest SIRT6 as a potential target for developing chemopreventive strategies to reduce the skin cancer 2.3.1.B41 protein-long-chain fatty-acyl-lysine deacylase (NAD+) medicine the enzyme is a therapeutic target for ovarian cancer therapy 2.3.1.B41 protein-long-chain fatty-acyl-lysine deacylase (NAD+) medicine SIRT6 and its downstream signaling can be targeted in Alzheimer's disease and age related neurodegeneration 2.3.1.B41 protein-long-chain fatty-acyl-lysine deacylase (NAD+) medicine SIRT6 as a potential therapeutic target to prevent astrocyte-mediated motor neuron death in amyotrophic lateral sclerosis (ALS) 2.3.1.B41 protein-long-chain fatty-acyl-lysine deacylase (NAD+) medicine small molecule activators for the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, such as for cancer 2.3.1.B41 protein-long-chain fatty-acyl-lysine deacylase (NAD+) medicine the enzyme is a potential therapeutic target for therapy of cancer and other metabolic diseases 2.3.1.42 glycerone-phosphate O-acyltransferase medicine DHPAT activity is decreased in fibroblast cell lines from patients with a deficient cytosolic receptor protein PEX5 2.3.1.42 glycerone-phosphate O-acyltransferase medicine the enzyme is highly correlated with poor clinical outcome in patients with hepatocellular carcinoma 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine the recombinant enzyme is utilized for enzyme replacement therapy in case of congenital enzyme deficiency 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine a complementary effect between myristic acid and alpha-linolenic acid that exerts a positive impact on the metabolism of plasma HDL by activating LCAT 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine carotid artery intima media thickness (IMT) is greater and plasma LCAT activity is higher in subjects with metabolic syndromes compared to control. Similar increases in IMT and LCAT are found in MetS subjects without type 2 diabetes mellitus. In addition, plasma LCAT activity is independently and positively related to insulin resistance, plasma triglycerides, non-HDL cholesterol and HDL cholesterol. LCAT activity may be a marker of subclinical atherosclerosis 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine haptoglobin from psoriatic patients exhibits decreased activity in binding haemoglobin and inhibiting LCAT 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine hemoglobine A1c concentration negatively correlates with LCAT activity in type 2 diabetes patients 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine in patients bearing a homozygous -629CC polymorphism of the cholesteryl ester transfer protein promoter a higher LCAT activity is measured 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine it is shown that LCAT activity is lower in pregnancy induced hypertension (PIH) and chronic hypertensive (CH) mothers than in normotensive controls. Similar changes are observed in small for gestational age (SGA) newborns of PHI mothers and in SGA newborns of CH mothers when compared to appropriate for gestational age newborns of control mothers (AGA-NC) 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine the correction of the aberrant HDL phenotypes by treatment with LCAT suggests a potential therapeutic intervention for HDL abnormalities that result from specific mutations in apoA-I 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine a therapeutic that increases enzyme LCAT activity may promote reverse cholesterol transport and prove beneficial for the treatment of dyslipidaemia and atherosclerosis 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine LCAT activity and phospholipid transfer protein PLTP activity are positively related to various obesity measures and homoeostasis model assessment. LCAT activity is associated with an fatty liver index FLI above 60, independent of type 2 diabetes and metabolic syndrome, the waist/hip ratio, or homoeostasis model assessment. PLTP activity is also associated with an FLI above 60 independent of these variables 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase medicine the plasma concentration of the LCAT enzyme significantly decreases during ST-segment-elevation myocardial infarction (STEMI) with a parallel significant reduction in LCAT activity. High-density lipoprotein isolated from STEMI patients progressively lose the capacity to promote NO production by endothelial cells, and the reduction is related to decreased LCAT concentration. In vitro incubation of STEMI patients' plasma with recombinant LCAT restores high-density lipoprotein ability to promote endothelial NO production 2.3.1.B43 protein-lysine desuccinylase (NAD+) medicine pharmacological interventions on SIRT5 expression may be useful in the treatment of oxidative stress-related cardiac injury 2.3.1.B43 protein-lysine desuccinylase (NAD+) medicine SIRT5 is involved in influencing oocyte quality and in-vitro-fertilisation outcomes 2.3.1.B43 protein-lysine desuccinylase (NAD+) medicine SIRT5 may have therapeutic value to treat hyperammonemia 2.3.1.B43 protein-lysine desuccinylase (NAD+) medicine SIRT5 may serve as a potential prognostic factor and drug target for intervention in non-small cell lung cancer. SIRT5 is overexpressed in human non-small cell lung cancer cells, high expression of SIRT5 predicts poor survival. SIRT5 knockdown makes lung cancer cells more sensitive to drug (cis-diamminedichloroplatinum, 5-fluorouracil or bleomycin) treatment in vitro and in vivo. Nrf2, which is a core transcription factor for lung cancer growth and drug resistance, is a target of SIRT5 2.3.1.45 N-acetylneuraminate 7-O(or 9-O)-acetyltransferase medicine high level of SOAT activity in lymphoblasts of childhood acute lymphoblastic leukaemia (ALL) is detected. SOAT in cell lysates or microsomal fractions of lymphoblasts of patients is up to 22fold higher than in healthy donors. SOAT activity increases at the diagnosis of leukaemia, decreases with clinical remission and sharply increases again in relapsed patients as determined by radiometric-assay. A newly developed non-radioactive ELISA can quickly detect SOAT, and serves as tool for ALL-monitoring in larger scale 2.3.1.47 8-amino-7-oxononanoate synthase medicine enzyme is a potential target for antimycobacterial drugs 2.3.1.48 histone acetyltransferase medicine allspice hot water extract reduces androgen receptor and histone acetylation and leads to decreased transcription of androgen receptor target genes, resulting in inhibition of prostate cancer cell growth 2.3.1.48 histone acetyltransferase medicine the dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats. Therefore, inhibition of p300 HAT activity by the nontoxic dietary compound curcumin may provide a novel therapeutic strategy for heart failure in humans 2.3.1.48 histone acetyltransferase medicine pathogenesis of late-onset Alzheimer disease, post-translational regulation of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) levels, a membrane protein that acts as the rate-limiting enzyme in the generation of Alzheimer disease amyloid beta-peptide, acetylation protect the protein from degradation 2.3.1.48 histone acetyltransferase medicine expression of isoform Tip60 is about 60% lower in samples from patients with acute myeloid leukemia 2.3.1.48 histone acetyltransferase medicine high mobility group domain-containing protein And-1 forms a complex with both histone H3 and isoform Gcn5. And-1 expression is increased in cancer cells in a manner correlating with increase in Gcn5 and acetylation of H3K9 and H3K56 2.3.1.48 histone acetyltransferase medicine histone acetylation is significantly increased in retinas from diabetic rats, and this acetylation is inhibited in diabetics treated with minocycline. Both the acetylation and induction of the inflammatory proteins in elevated glucose levels are significantly inhibited by inhibitors of histone acetyltransferase, such as garcinol and antisense against the histone acetylase, p300, or activators of histone deacetylase, such as theophylline and resveratrol, and are increased by the histone deacetylase inhibitor, suberolylanilide hydroxamic acid. Hyperglycemia causes acetylation of retinal histones and probably other proteins and the acetylation contributes to the hyperglycemia-induced upregulation of proinflammatory proteins and thereby to the development of diabetic retinopathy 2.3.1.48 histone acetyltransferase medicine CBP/p300 could be a promising therapeutic target in hepatocellular carcinoma 2.3.1.50 serine C-palmitoyltransferase medicine decreased expression of SPT protein is one of the important causative factors for decreased ceramide levels in psoriasis 2.3.1.50 serine C-palmitoyltransferase medicine results show that the inhibition of atherosclerosis by the serine palmitoyltransferase inhibitor myriocin in apolipoprotein-E gene knockout mice is associated with reduced plasma glycosphingolipid and plasma sphingomyelin concentration 2.3.1.50 serine C-palmitoyltransferase medicine results suggest that SPT activity might contribute to neuronal injury after kainate excitotoxicity in the rat hippocampus 2.3.1.50 serine C-palmitoyltransferase medicine the SPT inhibitor myriocin induces the regression of atherosclerotic plaques in hyperlipidemic ApoE-deficient mice 2.3.1.51 1-acylglycerol-3-phosphate O-acyltransferase medicine expression of isoform AGPAT11 mRNA is signifi cantly upregulated in human breast, cervical, and colorectal cancer tissues 2.3.1.51 1-acylglycerol-3-phosphate O-acyltransferase medicine expression of isoform CGI-58 in fibroblasts from humans with Chanarin-Dorfman increases the incorporation of fatty acids released from the lipolysis of stored triacylglycerols into phospholipids 2.3.1.51 1-acylglycerol-3-phosphate O-acyltransferase medicine expression of isoform LPAATbeta is readily detected in 8 of 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATbeta promotes osteosarcoma cell proliferation and migration, while silencing LPAATbeta expression inhibits these cellular characteristics. Exogenous expression of LPAATbeta effectively promotes tumor growth, while knockdown of LPAATbeta expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma 2.3.1.51 1-acylglycerol-3-phosphate O-acyltransferase medicine the role of isoforms AGPAT1 or AGPAT2 in liver lipogenesis is minimal and accumulation of liver fat is primarily a consequence of insulin resistance and loss of adipose tissue in Agpat2 -/- mice 2.3.1.56 aromatic-hydroxylamine O-acetyltransferase medicine - 2.3.1.56 aromatic-hydroxylamine O-acetyltransferase medicine metabolic activation by isoforms 1 and 2 of 3-nitrobenzanthrone and N-acetyl-N-hydroxy-3-aminobenzantrone, 2 compounds with high mutagenic and genotoxic potential, formation of DNA adducts 2.3.1.56 aromatic-hydroxylamine O-acetyltransferase medicine important for the activation of urinary metabolites of carcinogenic arylamines for the initiation of bladder carcinogenesis in the dog 2.3.1.56 aromatic-hydroxylamine O-acetyltransferase medicine bioactivation of N-hydroxy-2-acetylaminofluorenes by N,O-acytransfer resulting in mutagenic and carcinogenic compounds, DNA adduct formation 2.3.1.57 diamine N-acetyltransferase medicine induction of enzyme may be critical for the inhibition of tumor cell growth 2.3.1.57 diamine N-acetyltransferase medicine development of SSAT induction strategies to circumvent the ability of tumor cells to escape the antitumor activity of polyamine inhibitors such as alpha-difluoromethylornithine by salvaging exogenous polyamines 2.3.1.57 diamine N-acetyltransferase medicine logical target for tumor prevention 2.3.1.57 diamine N-acetyltransferase medicine the ability of polyamine analogues to induce N1SSAT activity correlates with the ability to inhibit growth and viability of human tumor-derived cells 2.3.1.57 diamine N-acetyltransferase medicine activation of the enzyme by aspirin and different non-steroidal anti-inflammatory drugs may be a common property of non-steroidal anti-inflammatory drugs that plays an important role in their chemopreventive actions in colorectal cancer 2.3.1.57 diamine N-acetyltransferase medicine in kidneys subjected to ischemia-reperfusion injury, one mechanism through which increased expression of SSAT may cause cellular injury and organ damage is through induction of DNA damage and the disruption of cell cycle 2.3.1.57 diamine N-acetyltransferase medicine the enzyme may be an important target for therapeutic intervention in colorectal cancer 2.3.1.57 diamine N-acetyltransferase medicine tumor progression in transgenic mouse lines overexpressing SSAT protein and susceptibility to skin carcinogenesis analyzed 2.3.1.57 diamine N-acetyltransferase medicine treatment of human C-28/I2 chondrocytes with polyamine analogue N1,N11-diethylnorspermine rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels. Caspase activation induced by N1,N11-diethylnorspermine plus cycloheximide is not prevented by a N1-acetylpolyamine oxidase inhibitor 2.3.1.57 diamine N-acetyltransferase medicine compared with wild-typet mice, the enzyme-deficient mice subjected to endotoxic acute kidney injury have less severe kidney damage as indicated by better preservation of kidney function. Animals treated with MDL72527, an inhibitor of both polyamine oxidase and spermine oxidase, show significant protection against endotoxin-induced acute kidney injury. Increased polyamine catabolism may contribute to kidney damage through generation of by-products of polyamine oxidation 2.3.1.57 diamine N-acetyltransferase medicine amantadine can be used to determine enzyme cellular activity by measuring excretion of N1-acetylamantadine which may indicate the presence of cancer 2.3.1.57 diamine N-acetyltransferase medicine the enzyme is a veritable therapeutic target in glioblastoma that controls tumor cell stemness and aggressiveness. The enzyme promotes resistance to radiotherapy 2.3.1.61 dihydrolipoyllysine-residue succinyltransferase medicine - 2.3.1.61 dihydrolipoyllysine-residue succinyltransferase medicine possible relationship between enzyme and familial Alzheimer's disease is discussed 2.3.1.61 dihydrolipoyllysine-residue succinyltransferase medicine enzyme may serve as a potential target antigen for diagnostic assays for Q fever 2.3.1.61 dihydrolipoyllysine-residue succinyltransferase medicine most pathogenic species for human 2.3.1.61 dihydrolipoyllysine-residue succinyltransferase medicine mounting of an anti-SucB response floows infection. Antibodies against Coxiella burnetti, Franciscella tularensis, and Rickettsia typhi also react with recombinant Bartonella SucB. Potential SuV antigenic cross-reactivity presents a challenge to the development of serodiagnostic tests for other intracellular pathogens that cause diseases such as Q fever, rickettsioses, brucelloses, tularemia, and other bartelloses 2.3.1.61 dihydrolipoyllysine-residue succinyltransferase medicine the DLST gene has two gene-products, one of which, gene product MIRTD, mediates the molecular assembly of the cytochrome c oxidase complex whose defect has been a candidate of the causes of Alzheimers disease. Since levels of MIRTD mRNA in the brains of Alzheimers disease patients are significantly low, a decrease in MIRTD could affect energy production 2.3.1.67 1-alkylglycerophosphocholine O-acetyltransferase medicine metabolic role in inflammatory disorders using experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS) 2.3.1.67 1-alkylglycerophosphocholine O-acetyltransferase medicine the results increases the understanding of the clinical implications of platelet-activating factor inhibition with regard to HIV infection 2.3.1.67 1-alkylglycerophosphocholine O-acetyltransferase medicine inhibitors 3-decanoyloxy-2-methoxy-5-methyl-1,4-benzoquinone and 2-methoxy-5-methyl-3-tetradecanoyloxy-1,4-benzoquinone at 2.5 mg/kg shod significant, 47.9-51.7%, inhibition in the carrageenan-induced mouse paw edema test, stronger than that of prednisolone at 10 mg/kg 2.3.1.67 1-alkylglycerophosphocholine O-acetyltransferase medicine study on the impact of diet on platelet-activating factor metabolism. Platelet-activating factor is inversely correlated with antioxidant-rich foods (herbal drinks and coffee), the dietary antioxidant capacity as well as a dietary pattern characterized by legumes, vegetables, poultry and fish. Platelet-activating factor is positively correlated to percentage of fat intake. Lyso-PAF acetyltransferase is also negatively associated with healthy patterns (fruits, nuts and herbal drinks, and a pattern rich in olive oil and whole-wheat products), as well as the dietary antioxidant capacity and percentage of monounsaturated fatty acids 2.3.1.68 glutamine N-acyltransferase medicine GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low-grade cancers have higher GLYATL1 expression compared to high-grade prostate tumors. GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbor ETV1 gene rearrangement. ETV1 knockdown in LNCaP cells shows downregulation of GLYATL1 2.3.1.71 glycine N-benzoyltransferase medicine isoform Glyat expression is suppressed in all hepatocellular carcinomas, but not in other liver diseases. Glyat repression in cancerous cells in the liver is controlled at the transcriptional level 2.3.1.71 glycine N-benzoyltransferase medicine in a small cohort of South African Caucasian individuals, the two most prominent GLYAT haplotypes in all populations analysed, are S156 (70%) and T17S156 (20%). The S156C199 and S156H131 haplotypes, which have a negative effect on the enzyme activity of a recombinant human GLYAT, are detected at very low frequencies. An additional Q61L SNP occurring at a high frequency (12%) was detected 2.3.1.71 glycine N-benzoyltransferase medicine study to investigate 4-aminobenzoic acid as an alternative glycine conjugation probe. All of the participants were homozygous for increased enzyme activity, but excretion of product 4-amino-N-benzoylglycine varies significantly (16-56%, hippurate ratio) 2.3.1.76 retinol O-fatty-acyltransferase medicine retinyl esterification: storage of vitamin A 2.3.1.76 retinol O-fatty-acyltransferase medicine keratinocyte growth and differentiation 2.3.1.76 retinol O-fatty-acyltransferase medicine neutral lipid synthesis enzyme acyl-CoA:diacylglycerol acyltransferase DGAT1 functions as the major acyl-CoA:retinol acyltransferase. When dietary retinol is abundant, DGAT1 deficiency results in elevated levels of retinoic acid in skin and cyclical hair loss, both are prevented by dietary retinol deprivation. DGAT1-deficient skin exhibits enhanced sensitivity to topically administered retinol. Deletion of the enzyme specifically in the epidermis causes alopecia 2.3.1.78 heparan-alpha-glucosaminide N-acetyltransferase medicine overview, design and synthesis of substrate and internal standard conjugates as substrates in enzyme assay for confirmation of enzyme deficiency using a combination of affinity chromatography and electrospray ionization mass spectrometry 2.3.1.78 heparan-alpha-glucosaminide N-acetyltransferase medicine mucopolysaccharidosis type IIIC or Sanfilippo syndrome type C is an autosomal recessive disorder caused by deficiency of heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase 2.3.1.78 heparan-alpha-glucosaminide N-acetyltransferase medicine direct method to assay HGSNAT enzymatic activity using fluorescent BODIPY-glucosamine, i.e. 1-[4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl-glycylamino]-beta-D-glucosamine, as a substrate. Cultured fibroblasts of mucopolysaccharidosis III type C patients show a profound deficiency of HGSNAT activity as compared to normal controls as well as to mucopolysaccharidosis III type A and D patients known to have normal HGSNAT activity 2.3.1.78 heparan-alpha-glucosaminide N-acetyltransferase medicine identification of HGSNAT mutations in six patients with non-syndromic retinitis pigmentosa. Homozygous HGSNAT variant c.370A>T leads to partial skipping of exon 3. In other patients with retinitis pigmentosa, a complex HGSNAT variant, c.[398G>C; 1843G>A] on one allele, and c.1843G>A on the other allele, is found. HGSNAT activity levels in blood leukocytes of patients are reduced compared with healthy controls, but usually higher than those in mucopolysaccharidosis type IIIC patients. All patients are diagnosed with non-syndromic retinitis pigmentosa and do not exhibit neurological deterioration, or any phenotypic features consistent with in mucopolysaccharidosis type IIIC. Four of the patients are over 60 years old, exceeding by far the life expectancy of mucopolysaccharidosis IIIC patients 2.3.1.80 cysteine-S-conjugate N-acetyltransferase medicine the frequently found single nucleotide polymorphisms, E104K or F143S, do not change enzymic activity or the expression of protein by more than 2fold 2.3.1.81 aminoglycoside 3-N-acetyltransferase medicine studies on the novel aminoglycoside antibiotic apramycin 2.3.1.81 aminoglycoside 3-N-acetyltransferase medicine mutation in the gene promoter affects the transcription level and enhances resistance to antibiotics 2.3.1.82 aminoglycoside 6'-N-acetyltransferase medicine aac(6')-Iz is an important contributor to aminoglycoside resistance in clinical strains of Stenotrophomonas maltophilia 2.3.1.82 aminoglycoside 6'-N-acetyltransferase medicine a C-14T mutation in eis confers kanamycin resistance in Mycobacterium tuberculosis 2.3.1.82 aminoglycoside 6'-N-acetyltransferase medicine aminoglycoside N-6'-acetyltransferases are important determinants of antibiotic resistance 2.3.1.82 aminoglycoside 6'-N-acetyltransferase medicine isolation of 85 clinical strains of Klebsiella pneumoniae and Escherichia coli that are believed to be aac(6')-Ib positive. Among them, 38 strains are wild-type, the remaining 47 strains harbour the aac(6')-Ib-cr variant that confers resistance against aminoglycoside and fluoroquinolone simultaneously. Of these 47 strains, 19 simultaneously harbor the aac(6')-Ib and aac(6')-Ib-cr gene 2.3.1.82 aminoglycoside 6'-N-acetyltransferase medicine two isolates resistant to fluoroquinolones and beta-lactam antimicrobials show mutations in the quinolone resistance-determining regions of gene GyrA and of ParC as well as carrying a 150 kb plasmid harbouring the quinolone resistance gene qnrA1, the ciprofloxacin-modifying enzyme-encoding gene aac(6')-Ib-cr and genes encoding for extended-spectrum beta-lactamases such as blaSHV and blaCTX-M-3. When this large plasmid is transferred to Escherichia coli by conjugation, the transconjugants show a 10-75fold increase in the minimum inhibitory concentrations of ciprofloxacin and norfloxacin 2.3.1.85 fatty-acid synthase system medicine androgen-independent expression of enzyme in oral SSC cells, enzyme activity is necessary for their proliferation 2.3.1.85 fatty-acid synthase system medicine anorectic effect of C75 is independent of its inhibition of enzyme in the hypothalamus 2.3.1.85 fatty-acid synthase system medicine in cancer cells, enzyme plays a major role in the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. Link between enzyme overexpression and dysregulation of membrane composition and functioning in tumor cells 2.3.1.85 fatty-acid synthase system medicine TRAMP mouse prostate adenocarcinoma cells show high enzyme expression and activity compared to nontransgenic littermates. Inhibition of enzyme expression and activity results in dose-dependent reduction in cell survival 2.3.1.85 fatty-acid synthase system medicine triclosan suppresses mammary carcinogenesis by inhibiting enzyme 2.3.1.85 fatty-acid synthase system medicine FAS could be a useful signal for early detection of ulcerative coliti 2.3.1.85 fatty-acid synthase system medicine FAS is a target for drug development against obesity and related diseases, and FAS inhibitors have antitumor activity 2.3.1.85 fatty-acid synthase system medicine the enzyme is a potential therapeutic target to treat cancer and obesity. Acylphloroglucinol derivatives could be considered to be a promising class of FAS inhibitors 2.3.1.85 fatty-acid synthase system medicine endogenously synthesized fatty acids do not fulfill a specific function in cancer cells. Cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, these fatty acids are esterified to the same lipid and phospholipid classes in the same proportions, and their distribution within neutral lipids is not different from untransformed cells. Anoxia increases glycolysis 2-3fold, with no concomitant increase in lipogenesis 2.3.1.85 fatty-acid synthase system medicine fatty acid synthase expression, which is upregulated in many human cancers, causes resistance to multiple anticancer drugs via inhibiting drug-induced ceramide production, caspase 8 activation, and apoptosis. Fatty acid synthase overexpression suppresses tumor necrosis factor-alpha production and nuclear factor-kappaB activation as well as drug-induced activation of neutral sphingomyelinase 2.3.1.85 fatty-acid synthase system medicine fatty acid synthase-dependent palmitoylation of epidermal growth factor receptor is required for epidermal growth factor receptor dimerization and kinase activation. Inhibition of fatty acid synthase or palmitoyl acyltransferases reduces the activity and down-regulated the levels of epidermal growth factor receptor, and sensitizes cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors 2.3.1.86 fatty-acyl-CoA synthase system medicine potential treatment of infection of humans with Candida parapsilosis 2.3.1.87 aralkylamine N-acetyltransferase medicine AANAT-specific immunoreactivity is observed in the nuclei of spinal neurons, and is significantly increased in aged dog spinal neurons compared to young adult spinal neurons. Melatonin receptor type 1B-specific immunoreactivity is found in the cytoplasm of spinal neurons, and is predominantly increased in the margin of the neuron cytoplasm in aged spinal cord compared to that in the young adult dogs 2.3.1.97 glycylpeptide N-tetradecanoyltransferase medicine target for antiviral and antifungal therapy 2.3.1.97 glycylpeptide N-tetradecanoyltransferase medicine since myristoylation has a central role in virus maturation and oncogenesis, specific NMT inhibitors might lead to potent antivirus and anticancer agents 2.3.1.97 glycylpeptide N-tetradecanoyltransferase medicine both NMT1 and hnRNP A2/B1 may take part in the regulation of HIV-1 RNA expression through their mutual opposite effects on the viral RNA expression in HIV-1-producing cells 2.3.1.97 glycylpeptide N-tetradecanoyltransferase medicine infection of HeLa cells with coxsackievirus B3 in the presence of NMT inhibitor DDD85646 decreases capsid protein VP0 acylation at least 100fold, resulting in a defect both early and late in virus morphogenesis, which diminishes the yield of viral progeny by about 90%. Virus particles still produced consist mainly of provirions containing RNA and uncleaved VP0 and, to a substantially lesser extent, of mature virions with cleaved VP0. Neither parechoviruses nor kobuviruses are affected by DDD85646. Individual knockout of the genes encoding the two human NMT isozymes in haploid HAP1 cells demonstrates the pivotal role for isoform NMT1, with little contribution by NMT2 2.3.1.97 glycylpeptide N-tetradecanoyltransferase medicine pharmacological inhibition of host cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. Inhibition of cotranslational myristoylation virus-encoded protein VP0 by inhibitor 1-(5-[3,4-difluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl]-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine potently blocks a key step in viral capsid assembly, delivering low nanomolar antiviral activity against multiple rhinovirus strains, poliovirus and foot-and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections 2.3.1.97 glycylpeptide N-tetradecanoyltransferase medicine upon inhibition of mTOR by treating MCF7 cells with rapamycin, the expression of NMT1 increases with rapamycin treatment over the period of time with a concomitant decrease in mTOR phosphorylation. Activated mammalian target of rapamycin (mTOR) is positively associated with overall survival and recurrence free survival in ER positive breast cancer patients who were later treated with tamoxifen 2.3.1.107 deacetylvindoline O-acetyltransferase medicine production of therapeutically valuable terpenoid indole alkaloids 2.3.1.122 trehalose O-mycolyltransferase medicine the enzyme is immunogenic in C57BL/6 mice and effective as tuberculosis vaccine, usage of vaccines combining mycolyl-transferase Ag85A and phosphate transport receptor PstS-3, overview 2.3.1.129 acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase medicine structures helps to design new inhibitors that target LpxA, antibiotics 2.3.1.135 phosphatidylcholine-retinol O-acyltransferase medicine LRAT mutations are likely a rare cause of Leber congenital amaurosis among patients from North America 2.3.1.135 phosphatidylcholine-retinol O-acyltransferase medicine study on the effects of ectopic expression of human lecithin:retinol acyltransferase on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide. In transgenic mice with targeted human LRAT expression to the basal layer of mouse skin and oral cavity epithelia, the retinyl ester levels in skin are 32% greater than those in wild-type mice, and topical treatment of the back skin with retinol results in greater increases in retinyl esters than in wild-type mouse skin. While 4-nitroquinoline 1-oxide treatment induces multifocal precancerous and cancer lesions in the tongues of both transgene positive and negative mice, higher percentages of transgene positive mice develop more severe tongue lesions of grades 3 and 4 than transgene negative mice after 4-nitroquinoline 1-oxide treatment. Carcinogen treatment also results in greater percentages of transgene positive mouse tongues with hyperplasia, dysplasia, and carcinoma than transgene negative mouse tongues. There are higher cyclooxygenase-2 and lower RARbeta(2) mRNA levels in transgene positive mouse tongues as compared to wild-type mouse tongues after 4-nitroquinoline 1-oxide treatment 2.3.1.135 phosphatidylcholine-retinol O-acyltransferase medicine expression of RPE65 involved in vitamin A metabolism is downregulated in malignant melanoma compared with benign melanocytic nevi. In contrast, expression of LRAT is not significantly different. High LRAT expression in melanoma metastases is inversely correlated with patient survival, Kaplan-Meier analysis reveals earlier melanoma-related death 2.3.1.135 phosphatidylcholine-retinol O-acyltransferase medicine among overweight/obese and lean children (aged 6-12 years), LRAT expression is remarkably lower in the overweight/obese group than in the lean group. Compared with the lean group, the overweight/obese group has elevated vitamin A level. The levels of 25-hydroxyvitamin D and its receptor are lower in overweight/obese subjects than in lean subjects. LRAT is negatively correlated with body mass index and waist circumference and positively correlated with high-density lipoprotein 2.3.1.147 glycerophospholipid arachidonoyl-transferase (CoA-independent) medicine disruption of arachidonic acid remodeling in a manner that increases intracellular arachidonic acid level involving inhibition of the enzyme may represent a novel therapeutic strategy to reduce cancer cell proliferation 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase medicine GlmU is a potential antituberculosis drug target, a microtiter plate assay for GlmU activity as read out is developed 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase medicine arylsulphatase AtsG , bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyl transferase GlmU and S-adenosyl-L-homocysteine hydrolase SahH are the Mycobacterium tuberculosis proteins that bind to human IL-8. The interactions with IL-8 are characterized by high binding affinity with KD values of 6.83x10-6 M, 5.24x10-6 M and 7.14x10-10 M, respectively. Strains overproducing the enzymes show a significantly increased number of intracellularly located bacilli compared with those of wild-type 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase medicine GlmUMtb is a strong candidate for intervention measures against established tuberculosis infections 2.3.1.161 lovastatin nonaketide synthase medicine production of cholesterol lowering drugs 2.3.1.161 lovastatin nonaketide synthase medicine antihypercholesterolemic activity 2.3.1.161 lovastatin nonaketide synthase medicine lovastatin is a fungal polyketide metabolite produced by Aspergillus terreus that has been used as a drug to lower cholesterol levels 2.3.1.162 taxadien-5alpha-ol O-acetyltransferase medicine understanding of biosynthetic pathway of taxol, target: possibly biological production of taxol, taxol or paclitaxel is now well established as a potent chemotherapeutic drug 2.3.1.165 6-methylsalicylic-acid synthase medicine production of 6-methylsalicylic acid which is used as human pharmaceutical 2.3.1.168 dihydrolipoyllysine-residue (2-methylpropanoyl)transferase medicine creation of a Drosophila model of maple syrup urine disease MSUD by knocking out the DBT gene, an ortholog of the human gene encoding the dihydrolipoamide branched chain transacylase (DBT) subunit of BCKDH. The homozygous DBT mutant larvae recapitulate an array of MSUD phenotypes, including aberrant branched-chain amino acid accumulation, developmental defects, poor mobile behavior and disrupted L-glutamate homeostasis. The DBT mutation causes neuronal apoptosis during the developmental progression of larval brains and severe impairment of retinal rhabdomeres. The DBT mutant shows elevated oxidative stress and higher lipid peroxidation accumulation in the larval brain. When the DBT mutants are administrated with antidiabetic drug metformin, the aberrances in branched-chain amino acid levels and motor behavior are ameliorated 2.3.1.176 propanoyl-CoA C-acyltransferase medicine SCP2 is a binding protein for endocannbinoids N-arachidonylethanolamine and 2-arachidonoylglycerol. N-arachidonylethanolamine and 2-arachidonoylglycerol associate with SCP2 at a putative cholesterol binding pocket with DeltaG values of ?3.6 and ?4.6 kcal per mol, respectively. SCP2-mediated transfer of cholesterol in vitro is inhibited by micromolar concentrations of N-arachidonylethanolamine, and heterologous expression of SCP2 in HEK-293 cells increases time-related accumulation of N-arachidonylethanolamine in a temperature-dependent fashion 2.3.1.176 propanoyl-CoA C-acyltransferase medicine SCP2 is a critical host factor for dengue virus production in mosquito Aag2 cells. Treatment with inhibitor SCPI-1, or knockdown of SCP2 dramatically represses the virus production in mosquito but not mammalian cells.The intracellular cholesterol distribution in mosquito cells is altered by SCP2 inhibitor treatment, suggesting that SCP2-mediates cholesterol trafficking pathway that is important for dengue virus viral production. SCPI-1 treatment decreases cholesterol in both mammalian and mosquito cell lines, but this decrease in cholesterol only leads to a decline in viral titer in mosquito host cells 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III medicine the enzyme is a target of antibacterial treatment of the pathogen Staphylococcus aureus 2.3.1.181 lipoyl(octanoyl) transferase medicine enzyme is considerably upregulated in patients with multiple-drug-resistant Mycobacterium tuberculosis 2.3.1.184 acyl-homoserine-lactone synthase medicine Acinetobacter baumannii is an important nosocomial pathogen and can cause a variety of infections including wound infection, bloodstrem infection, ventilator-acquired pneumonia, and urinary tract infections 2.3.1.194 acetoacetyl-CoA synthase medicine histological changes, decreased steroid hormone concentrations and decreased cholesterol supply are observed in nicotine-treated fetal adrenals. The expression of genes regulating ketone metabolic process decreases in nicotine-treated fetal adrenals. Acetoacetyl-CoA synthetase (AACS), the enzyme utilizing ketones for cholesterol supply, displays decreased expression and increased DNA methylation in the proximal promoter of AACS 2.3.1.199 very-long-chain 3-oxoacyl-CoA synthase medicine human cytomegalovirus HMCV induces isoform ELOVL7 by more than 150fold. The induction is dependent on mTOR and SREBP-1. ELOVL7 knockdown or mTOR inhibition impairs HCMV-induced fatty acid elongation, HCMV particle release, and infectivity per particle. ELOVL7 overexpression enhances HCMV replication. During HCMV infection, mTOR activity is maintained by the viral protein pUL38. Expression of pUL38 is sufficient to induce ELOVL7, and pUL38-deficient virus is partially defective in ELOVL7 induction and fatty acid elongation 2.3.1.225 protein S-acyltransferase medicine DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlates with diminished patient survival in breast cancer and six other human cancer types. DHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduces the sizes of both the primary tumor and metastatic lung colonies. Increased oxidative stress and senescence is observed in DHHC3-ablated cells. DHHC3-ablated tumors also show enhanced recruitment of innate immune cells associated with clearance of senescent tumors. Concomitant ablation of the upregulated oxidative stress protein TXNIP substantially negates the effects of DHHC3 depletion on oxidative stress and senescence 2.3.1.226 carboxymethylproline synthase medicine carboxymethylproline synthases is a biocatalysts for preparing functionalised N-heterocycles in a diastereoselective fashion. The products can be converted into the respective bicyclic beta-lactams of potential application in the semisynthesis of stable beta-lactam antibiotics 2.3.1.251 lipid IVA palmitoyltransferase medicine PagP is not required for the initial colonization of the mouse respiratory tract by Bordetella bronchiseptica, but is required for persistence of the organism within this organ 2.3.1.255 N-terminal amino-acid Nalpha-acetyltransferase NatA medicine the enzyme is associated with Ogden syndrome 2.3.1.257 N-terminal L-serine Nalpha-acetyltransferase NatD medicine the enzyme is a therapeutic target in colorectal cancers 2.3.1.258 N-terminal methionine Nalpha-acetyltransferase NatE medicine Naa50p is a therapeutic anti-cancer target, the structure of the ternary Naa50p complex also provides a molecular scaffold for the design of NAT-specific small molecule inhibitors with possible therapeutic applications 2.3.1.286 protein acetyllysine N-acetyltransferase medicine 3-((2-methoxynaphthalen-1-yl)methyl)-7-((pyridin-3-ylmethyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one (ICL-SIRT078) has a significant neuroprotective effect in a lactacystin-induced model of Parkinsonian neuronal cell death in the N27 cell line and an optimised derivative thereof, is a candidate neuroprotective agent in in vivo models of Parkinson's disease 2.3.1.286 protein acetyllysine N-acetyltransferase medicine down-regulation of intratumoral and peritumoral Sirt3 are both associated with poor outcome in hepatocellular carcinoma. Intratumoral Sirt3 is a favorable prognostic predictor in early stage patients 2.3.1.286 protein acetyllysine N-acetyltransferase medicine inhibitors of sirtuin-2 deacetylase are protective in various models of Huntington’s disease by decreasing polyglutamine aggregation, a hallmark of pathology of Huntington’s disease 2.3.1.286 protein acetyllysine N-acetyltransferase medicine the enzyme is a promising drug target in the treatment of age-related diseases, such as neurodegenerative diseases and cancer 2.3.1.291 sphingoid base N-palmitoyltransferase medicine both isoforms CerS4 and CerS5 are up-regulated in endometrial and colon cancer cells. Apoptosis induction by anastrozole or 5-FU results in down-regulation of CerS4 and CerS5 in endometrial and colon cancer cells 2.3.1.291 sphingoid base N-palmitoyltransferase medicine CerS1 and CerS5 mRNA expression is reduced in muscle biopsies from patients in advanced stage of chronic heart failure suffering from muscle wasting and frailty 2.3.1.291 sphingoid base N-palmitoyltransferase medicine CerS5-dependent ceramide synthesis has a strong impact in white adipose tissue after high fat diet feeding 2.3.1.291 sphingoid base N-palmitoyltransferase medicine in human breast cancer tissue, a significant increase in CerS4 and CerS6 mRNA is observed in estrogen receptor positive cancer tissue. The activities of CerS4 and CerS5 promoter constructs increase after estradiol treatment in MCF-7 cells. Estradiol and GPER1 mediate their effects on CerS4 and Cers5 promoter by activating AP-1, most likely through dimerization of c-Jun and c-Fos 2.3.1.291 sphingoid base N-palmitoyltransferase medicine in human breast cancer tissue, a significant increase in CerS4 and CerS6 mRNA isobserved in estrogen receptor positive cancer tissue. The activities of CerS4 and CerS5 promoter constructs increase after estradiol treatment in MCF-7 cells. Estradiol and GPER1 mediate their effects on CerS4 and Cers5 promoter by activating AP-1, most likely through dimerization of c-Jun and c-Fos 2.3.1.291 sphingoid base N-palmitoyltransferase medicine in human wild-type p53 HCT-116 colon cancer cells, treatment with oxaliplatin or 5-fluorouracil leads to a strong increase in ceramide synthase CerS5 expression and C16:0-ceramide levels, which is not seen in HCT-116 cells lacking p53 expression. The increase in CerS5 expression occurs by stabilizing CerS5 mRNA at the 3'-UTR 2.3.1.291 sphingoid base N-palmitoyltransferase medicine long-chain ceramides are upregulated whereas very long-chain ceramides are downregulated in cell lines, mouse animal model, and patients with cystic fibrosis, compared with their controls. Treatment with fenretinide decreases the levels of long-chain ceramides and increases the levels of very long-chain ceramides 2.3.1.299 sphingoid base N-stearoyltransferase medicine the combined therapy of enzyme and teniposide VM-26 is a therapeutic strategy for the treatment of human glioma 2.3.1.299 sphingoid base N-stearoyltransferase medicine the enzyme is a molecular target for controlling resistance to photodynamic therapy 2.3.1.303 alpha-L-Rha-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Gal-PP-Und 2IV-O-acetyltransferase medicine construction of bivalent vaccines for preventing both Salmonella typhimurium and Salmonella newport infections by using the aspartate semialdehyde dehydrogenase-based balanced-lethal vector-host system. The constructed plasmid pCZ11 carrying a subset of the Salmonella newport O-antigen gene cluster including the wzx-wbaR-wbaL-wbaQ-wzy-wbaW-wbaZ genes is introduced into Salmonella typhimurium. Upon deletion of the crp gene for attenuation purposes, BALB/c mice are orally immunized with the strains. Compared with a mock immunization, immunization with the vaccine strains induces significant serum IgG responses against both Salmonella typhimurium and Salmonella newport lipopolysaccharide 2.3.2.2 gamma-glutamyltransferase medicine bioconversion of cytotoxic and mutagenic agents to inactive 5-L-glutamyl-derivatives 2.3.2.2 gamma-glutamyltransferase medicine a longitudinal increase in GGT, independently of baseline GGT and even within its normal range, significantly increases risk of fatal cardiovascular disease 2.3.2.2 gamma-glutamyltransferase medicine elevated gamma-glutamyltransferase is associated with significantly increased risk of stroke, fatal coronary heart disease events and cardiovascular disease mortality independent of established cardiovascular disease risk factors and may be a useful additional marker for long-term cardiovascular disease 2.3.2.2 gamma-glutamyltransferase medicine elevated GGT is significantly associated with increased cancer risk in men 2.3.2.2 gamma-glutamyltransferase medicine gamma-glutamyltransferase is a strong predictor of metabolic syndrome. Lipid peroxide measured by tert-butyl hydroperoxide-initiated chemiluminescence and gamma-glutamyltransferase activity are reliable markers of oxidative stress in this syndrome 2.3.2.2 gamma-glutamyltransferase medicine gamma-glutamyltransferase is a useful as an indirect marker of liver disease 2.3.2.2 gamma-glutamyltransferase medicine gamma-glutamyltransferase is associated with mortality in both men and women, especially in patients younger than 30 years. Even high-normal gamma-glutamyltransferase is a risk factor for all-cause mortality 2.3.2.2 gamma-glutamyltransferase medicine gamma-glutamyltransferase is confirmed as independent risk factor in patients with established coronary artery disease. gamma-Glutamyltransferase, C-reactive protein, fasting glucose show an additive prognostic value, whereas low values of these biomarkers identify a subset of patients with the lowest risk of cardiac death 2.3.2.2 gamma-glutamyltransferase medicine gamma-glutamyltransferase is positively associated with incident coronary heart disease and stroke in both women and men in European populations and among self-reported nondrinkers. Therefore, gamma-glutamyltransferase levels probably also reflect other biological processes or indeed lifestyle or dietary behaviors that are linked to cardiovascular disease 2.3.2.2 gamma-glutamyltransferase medicine gamma-glutamyltransferase levels may be a surrogate marker of insulin resistance, inflammation and metabolic syndrome 2.3.2.2 gamma-glutamyltransferase medicine gamma-glutamyltransferase might be an additional marker of arterial stiffness, especially in men, though the relationship with arterial stiffness is very weak 2.3.2.2 gamma-glutamyltransferase medicine gender-specific clusters including mean corpuscular erythrocyte volume, carbohydrate-deficient transferrin, gamma-glutamyltransferase, homocysteine and folate led to an increase in sensitivity compared to single laboratory markers. This is a reliable help to identify patients with regular heavy drinking in clinical practice which might prevent further complications 2.3.2.2 gamma-glutamyltransferase medicine GGT, a predictor of type 2 diabetes, is associated with a risk of incident metabolic syndrome 2.3.2.2 gamma-glutamyltransferase medicine given the involvement of GGT in bone and joint diseases characterized by accelerated osteoclast development, GGT may be a novel target for the development of diagnostics and therapeutics 2.3.2.2 gamma-glutamyltransferase medicine GSTM1- and GSTM1-/GSTT1- genotypes may be a genetic risk factor for the increase of GGT in Japanese epileptic patients treated with valproic acid patients. It is not possible to clarify whether the GGT increase is caused by valproic acid-induced hepatotoxicity or not 2.3.2.2 gamma-glutamyltransferase medicine habitual coffee consumption is associated with lower incidence of type II diabetes particularly in those with higher baseline serum GGT levels 2.3.2.2 gamma-glutamyltransferase medicine high gamma-glutamyltransferase levels significantly increased cancer risk in women 2.3.2.2 gamma-glutamyltransferase medicine high serum gamma-glutamyltransferase is associated with an increased risk of liver cancer 2.3.2.2 gamma-glutamyltransferase medicine level of GGT may be a useful marker to determine appropriate amounts of drinking for individuals 2.3.2.2 gamma-glutamyltransferase medicine retreatment with PegIFN-alpha-2b and ribavirin for a minimum of 48 weeks should be considered in all patients with chronic hepatitis C unresponsive to previous IFN-based therapies. Baseline gamma-glutamyltransferase values and rapid virological response are highly predictive for retreatment outcome 2.3.2.2 gamma-glutamyltransferase medicine serum GGT is specifically associated with the visceral fat area, but not with the subcutaneous fat area, suggests that the serum GGT may be useful as a convenient indicator of visceral fat area in the clinical treatment of obesity 2.3.2.2 gamma-glutamyltransferase medicine serum GGT within its normal range can predict cardiovascular diseases mortality in those aged less than 70 years, but may have limited usefulness for risk assessment in older adults 2.3.2.2 gamma-glutamyltransferase medicine the early detection of alcohol consumption (EDAC) test shows better performance than gamma-glutamyltransferase to detect heavy drinking in a large population of males and females 2.3.2.2 gamma-glutamyltransferase medicine the modest elevation of GGT in overweight children may be of pathophysiological importance in the long term 2.3.2.2 gamma-glutamyltransferase medicine the use short, simple questionnaires, combined with that of low-cost biochemical markers, such as gamma-glutamyltransferase, can serve as an initial screening for alcohol-related problems, especially for employees in hazardous occupations 2.3.2.2 gamma-glutamyltransferase medicine GGT levels are higher in patients with coronary artery disease than in control. GGT activity and c-reactive protein levels are higher, left ventricular ejection fraction is lower in patients with acute coronary syndrome compared with stable coronary artery disease group. The increased GGT activity is related to left ventricular function, clinical stability, and inflammatory activity rather than the severity of coronary artery disease. Measurement of GGT activity may be useful in predicting cardiovascular risk 2.3.2.2 gamma-glutamyltransferase medicine study on the association between gamma-GT and disability pension in a cohort of construction workers. gamma-GT is a strong risk indicator of all-cause occupational disability even at levels of gamma-GT in the normal range and is in particular associated with disability pension due to diseases of the digestive system, musculoskeletal disorders, cardiovascular, and mental diseases 2.3.2.2 gamma-glutamyltransferase medicine the enzyme level in the serum is a marker for liver function 2.3.2.2 gamma-glutamyltransferase medicine development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors 2.3.2.2 gamma-glutamyltransferase medicine direct detection of GGT activity can provide critical information for the diagnosis of several pathologies. GGT may serve as a tumor biomarker and its presence on the cell surface is particularly attractive for imaging applications 2.3.2.3 lysyltransferase medicine MprF could be a target for new anti-virulence drugs 2.3.2.5 glutaminyl-peptide cyclotransferase medicine inhibition of glutaminyl cyclase offers a new therapeutic option for the treatment of Alzheimer’s disease and provides implications for other amyloidoses, such as familial Danish dementia 2.3.2.5 glutaminyl-peptide cyclotransferase medicine the enzyme is a pharmacological target for Alzheimer’s disease therapy 2.3.2.5 glutaminyl-peptide cyclotransferase medicine hQC isozymes, sQC and gQC, inhibition is considered to be an attractive strategy to prevent the formation of pGlu-Abeta and to reduce neuroinflammation and provides an opportunity for the treatment of Alzheimer disease 2.3.2.5 glutaminyl-peptide cyclotransferase medicine the development of hQC enzyme inhibitors can prevent the self-aggregation of Abeta peptides, resulting in impeding Alzheimer's disease 2.3.2.8 arginyltransferase medicine arginyltransferase inversely correlates with metastases in human cancers and patient survival 2.3.2.8 arginyltransferase medicine the inhibition of ATE1 activity may provide an approach for the treatment of cardiac hypertrophy in humans 2.3.2.10 UDP-N-acetylmuramoylpentapeptide-lysine N6-alanyltransferase medicine potential target for antimicrobial drugs 2.3.2.10 UDP-N-acetylmuramoylpentapeptide-lysine N6-alanyltransferase medicine Fem transferases are considered as attractive targets for the development of novel antibiotics active against multi-resistant bacteria 2.3.2.10 UDP-N-acetylmuramoylpentapeptide-lysine N6-alanyltransferase medicine Fem transferases are considered attractive targets for the development of novel antibiotics active against multiply resistant bacteria 2.3.2.12 peptidyltransferase medicine antibiotic target 2.3.2.B12 ubiquitin transferase U-box E4 medicine DELTANp63alpha, dominant negative isoform of the p63 family and essential survival factor in head and neck squamous cell carcinoma, physically interacts with U-box-type E4 ubiquitin ligase UFD2a. UFD2a stabilizes DELTANp63alpha, and ubiquitylation of DELTANp63?alpha is attenuated by UFD2a both in the presence and absence of cisplatin. Ectopic expression of UFD2a increases the half-life of DELTANp63alpha in association with a significant enhancement of the repressive transcriptional activity of DELTANp63alpha. Downregulation of endogenous UFD2a by RNAi results in degradation of DELTANp63alpha 2.3.2.B12 ubiquitin transferase U-box E4 medicine low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression is associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels are associated with high-risk features. UBE4B protein levels are also associated with levels of phosphorylated ERK 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine enzyme activity is implicated in the pathogenesis of diseases related to wound healing and neovascularization. Enzyme deficient cells display normal attachment but delayed spreading on extracellular matrix substrates and defects in motility unrelated to crosslinking. Enzyme deficient fibroblasts have defects in focal adhesion turnover and stress fibre formation, show changes in focal adhesion kinase phosphorylation and fail to activate protein kinase C alpha 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine enzyme activity is significantly lower in the plasma of patients with active ulcerative colitis than in those with inactive ulcerative colitis and controls. In the damaged colon, enzyme is needed in response to chronic injury 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine enzyme is the major autoantigen in coeliac disease. Enzyme contains at least four major antigenic molecules. Human antibodies recognize enzyme but do not inhibit 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine involvement of enzyme in age-related cataractogenesis 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine plant produced enzyme recognizes autoantibodies in the serum of coeliac patients, use in diagnosis of coeliac disease 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine colocalization of isoform TG2 and fibronectin in glioblastoma extracellular matrix and secretion of high levels of enzyme and fibronectin by small clusters of invading human glioblastoma cells present in non-neoplastic brain. Downregulation of enzyme by RNAi in U87MG glioblastoma cells demonstrates decreases assembly of fibronectin in the extracellular matrix. KCC009 inhibits the enzyme and subsequently blocks fibronectin assembly in the extracellular matrix of glioblastoma cells 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine epithelial distribution of tissue transglutaminase is specific for coeliac disease rather than due to a non-specific mucosal inflammation. Epithelial distribution of enzyme is gluten dependent 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine isoform tTG at the placental syncytial mircovillus membrane is a plausible target of maternal autoantibody action 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine KCC009 treatment in mice harboring orthotopic glioblastomas sensitizes the tumors to N,N’-bis(2-chloroethyl)-N-nitrosourea chemotherapy 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine no expression of isoform TGase II in normal mammary tissue and that showing benign hyperplasia, but 44% of mammary carcinomas strongly express isoform TGase II in either a stromal, cellular or combined pattern 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine no expression of isoform TGase II in normal mammary tissue and that showing benign hyperplasia, but 83% of mammary carcinomasstrongly express isoform TGase II in either a stromal, cellular or combined pattern 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine use of enzyme as a drug target for treatment of human lymohatic filariasis 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine Celiac disease is mediated by IgA antibodies to wheat gliadins and tissue transglutaminase (tTG). As tTG is homologous to microbial transglutaminase (mTG) used to improve foodstuff quality, it could elicit the immune response of celiac patients. Sera pool IgA titers are higher against prolamins of mTG-treated wheat or gluten-free breads than against mTG-untreated, mainly due to two individual patients’ sera. The electrophoretic pattern of gluten-free bread prolamins is changed by the mTG treatment, and a new 31000 band originates in maize is recognized by three CD patients’ IgA. It is suggested that IgA immunoreactivity can be used as a preliminary test of the safeness of a food product for celiac disease patients 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine central role of TG2 in the mechanistic pathway of CF inflammation, opening a possible new wave of therapies for sufferers of chronic inflammatory diseases 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine cystamine delays the onset of the neurological symptoms associated with Huntington’s disease when applied to the R6/2 Huntington’s mouse model, and dihydroisoxazoles, when used in tandem with BCNU, are able to decrease tumor size and extend survival in a mouse model of glioblastoma 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine glucosamine, as a TGase 2 inhibitor, might be an attractive novel target for treatment of malignant cancers 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine inhibition of TG2 may provide a new and important therapeutic target against the progression of renal fibrosis 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine patients with low FXIII plasma levels, which occur naturally after myocardial infarction, may potentially benefit from transient and local augmentation of FXIII activity in the infarct 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine TGase can contribute to Alzheimer disease by initiating amyloid beta-protein oligomerization and aggregation at physiological levels, by reducing the clearance of amyloid beta-protein due to the generation of protease-resistant amyloid beta-protein species, and by forming amyloid beta-protein assemblies that inhibit processes involved in memory and learning. TGase might constitute a specific therapeutic target for slowing or blocking the progression of Alzheimer disease 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine therapeutic potential of the transglutaminase 2 inhibitor cystamine in systemic lupus erythematosus 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine transglutaminase 2 is involved in the pathogenesis of a number of diseases, such as celiac sprue, neurodegenerative disorders, diabetes, liver cirrhosis and fibrosis, renal scarring, and certain types of cancer. It is the enzymatic function of TG2 that is thought to contribute to the pathology or etiology of most of the aforementioned diseases. Therefore, inhibition of the TG2 active site offers a potential strategy to therapeutically treat these disease 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine TG2 is the major autoantigen in celiac disease, and testing the reactivity of mutants with autoantibodies from celiac disease patients reveals that calcium binding site S4, i.e. residues Y149 to Y159, strongly determines antigenicity 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine developments in mTGase engineering together with its role in biomedical applications including biomaterial fabrication for tissue engineering and biotherapeutics, biomedical engineering, overview 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine microbial transglutaminase (mTG) is used as a crosslinking agent in the preparation of gelatin sponges. The physical properties of the materials are evaluated by measuring their material porosity, water absorption, and elastic modulus. The stability of the sponges are assessed via hydrolysis and enzymolysis, overview. To evaluate the cell compatibility of them TG crosslinked gelatin sponges (mTG sponges), adipose-derived stromal stem cells are cultured and inoculated into the scaffold. Cell proliferation and viability are measured using alamarBlue assay and LIVE/DEAD fluorescence staining, respectively. Cell adhesion on the sponges is observed by scanning electron microscopy. mTG sponges have uniform pore size, high porosity and water absorption, and good mechanical properties. In subcutaneous implantation (in Spraguex15Dawley rats), the material is partially degraded in the first month and completely absorbed in the third month. Cell experiments show evident cell proliferation and high viability. The cells grow vigorously and adhered tightly to the sponge. In conclusion, mTG sponge has good biocompatibility and can be used in tissue engineering and regenerative medicine 2.3.2.13 protein-glutamine gamma-glutamyltransferase medicine the microbial transglutaminase is used for biotechnological and biomedical engineering, protein engineering by post-translational modification towards the generation of multifunctional conjugates. Biotechnological applications, detailed overview. Construction of protein-polymer and of antibody-drug conjugations for pharmaceutical applications 2.3.2.17 N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-glycyl)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase medicine expression levels of femA in methicillin-sensitive, low-level methicillin-resistant and high-level methicillin-resistant Staphylococcus aureus are 0.035%-29.91%, 0.055%-310% and 13.88-5500%, respectively. EMSA detects a signal shift in 57 high-level methicillin-resistant isolates but not in four low-level methicillin-resistant and four methicillin-sensitive strains. Expression of femA in high-level methicillin-resistant non-beta-lactamase-producing strains is higher than in low-level methicilln-resistant and methicillin-sensitive strains 2.3.2.17 N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-(N6-glycyl)-D-alanyl-D-alanine-diphosphoundecaprenyl-N-acetylglucosamine:glycine glycyltransferase medicine in 40 methicillin-susceptible and 6 resistant clinical isolates of Staphylococcus aureus, the FemA content or its affinity to the antibodies is reduced compared to laboratory parent strains. In susceptible strains, an additional protein of higher molecular weight, present in large quantities, is also able to bind the FemA antibodies. Such a protein is also present in methicillin-resistant isolates, although it is not as pronounced as in the susceptible strains 2.3.2.23 E2 ubiquitin-conjugating enzyme medicine UBE2L3 might be a potential therapeutic target to treat SLE and B-cell lymphomas that are characterized by LUBAC hyperactivation and constitutive NF-kappaB signalling 2.3.2.26 HECT-type E3 ubiquitin transferase medicine functional interaction of NEDD4-like ubiquitin protein ligase NEDL1 with p53 might contribute to the induction of apoptosis in cancerous cells bearing wild-type p53 2.3.2.26 HECT-type E3 ubiquitin transferase medicine high-risk human papilloma virus E6 oncoproteins interact with the ubiquitin ligase E6AP and target several cellular proteins, including p53 and proteins of the MAGI family, towards ubiquitin-mediated degradation. E6 oncoproteins from major high-risk risk human papilloma virus types 16, 18, 33 and 58 bind to a 15-mer peptide containing the LxxphiLsh motif of E6AP, where L indicates conserved leucine residues, phi is a hydrophobic residue, h is an amino acid residue with a side-chain capable of accepting hydrogen bonds, s represents a small amino acid residue and xx is a dipeptide where one of the residues is Asp, Asn, Glu or Gln. The equilibrium dissociation constants are in the low micromolar range. Low-risk risk human papilloma virus 11 E6 does not interact with E6AP. The two zinc-binding domains of E6 are required for E6AP recognition 2.3.2.26 HECT-type E3 ubiquitin transferase medicine antidepressant drug clomipramine specifically blocks ITCH auto-ubiquitylation, as well as p73 ubiquitylation. Treating a panel of breast, prostate and bladder cancer cell lines with clomipramine, or its homologs, leads to reduced cancer cell growth, and synergize with gemcitabine or mitomycin in killing cancer cells by blocking autophagy 2.3.2.27 RING-type E3 ubiquitin transferase medicine mutation D76E has been identified in Thai familial breast cancer patients. The mutation is located in the vicinity of Zn2+ binding site II. The D67E BRCA1 RING protein assumes a preformed structure in the absence of Zn2+. The Zn2+-bound mutant protein is more folded than wild-type, resulting in enhanced proteolytic resistance and dimerization. The mutation retains Zn2+ binding, and barely perturbs the native global structure of the BRCA1 RING domain. The D67E mutation might be a neutral or mild cancer-risk modifier of other defective mechanisms underlying BRCA1-mutation-related breast cancer 2.3.2.27 RING-type E3 ubiquitin transferase medicine the gene encoding RNF43 is upregulated in colon adenocarcinoma as well as in colon adenoma 2.3.2.27 RING-type E3 ubiquitin transferase medicine human T lymphotropic virus type 1 trans-activator/oncoprotein, Tax, stimulates ring finger protein RNF8, and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, for TGFbeta-activated kinase TAK1 and i-kappaB kinase IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulates TAK1, IKK, I-kappaBalpha and JNK phosphorylation. In vivo, RNF8 over-expression augments while RNF8 ablation drastically reduces canonical NF-kappaB activation by Tax. Activation of the non-canonical NF-kappaB pathway by Tax, however, is unaffected by the loss of RNF8. Tax greatly stimulates RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-polyubiquitin chains. Co-transfection of Tax with increasing amounts of RNF8 greatly induces K63-polyubiquitin assembly in a dose-dependent manner 2.3.2.27 RING-type E3 ubiquitin transferase medicine human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation 2.3.2.27 RING-type E3 ubiquitin transferase medicine hyperactive mutations L51W and K65R are capable of rescuing the ligase activity of two cancer-associated variants, C61G and C64G. BRCA1 that contains both a cancer variation and the hyperactive substitutions activates the E2 Ube2d to build polyubiquitin chains as well as wild-type BRCA1. Both activating substitutions L51W and K65R are necessary to restore activity of the cancer variants to the level seen in wild-type 2.3.2.27 RING-type E3 ubiquitin transferase medicine low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression is associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels are associated with high-risk features. UBE4B protein levels are also associated with levels of phosphorylated ERK 2.3.2.27 RING-type E3 ubiquitin transferase medicine successive pruning of the RING structure network of cancer-associated E3 enzymes BRCA1, MDM2, and cIAP2 leads to a core for each RING domain. Substitutions of core residues are associated with cancers according to COSMIC catalog. 80% of the residues located in the core RING subnetworks are nonconserved within E3 RING domains. Core residues for BRCA1 are Thr37, Lys38, Ile68 and Leu73 2.3.2.27 RING-type E3 ubiquitin transferase medicine successive pruning of the RING structure network of cancer-associated E3 enzymes BRCA1, MDM2, and cIAP2 leads to a core for each RING domain. Substitutions of core residues are associated with cancers according to COSMIC catalog. 80% of the residues located in the core RING subnetworks are nonconserved within E3 RING domains. Core residues for cIAP2 are Ser566, I567, Val568, Arg600 and Thr601 2.3.2.27 RING-type E3 ubiquitin transferase medicine successive pruning of the RING structure network of cancer-associated E3 enzymes BRCA1, MDM2, and cIAP2 leads to a core for each RING domain. Substitutions of core residues are associated with cancers according to COSMIC catalog. 80% of the residues located in the core RING subnetworks are nonconserved within E3 RING domains. Core residues for MDM2 are Pro437, Asn447, Gly448, Ala460, Cys461, Ile485 2.3.2.31 RBR-type E3 ubiquitin transferase medicine isoform RNF144A interacts with poly(ADP-ribose) polymerase PARP1 through its carboxy-terminal region containing the transmembrane domain, and targets PARP1 for ubiquitination and subsequent proteasomal degradation. Induced expression of RNF144A decreases PARP1 protein levels and renders breast cancer cells resistant to the clinical-grade PARP inhibitor olaparib. Knockdown of endogenous RNF144A increases PARP1 protein levels and enhances cellular sensitivity to olaparib 2.3.2.31 RBR-type E3 ubiquitin transferase medicine parkin patient disease-associated mutation largely mediate their effect by altering transthiolation activity 2.3.2.31 RBR-type E3 ubiquitin transferase medicine upon infection, Trichinella spiralis secretes E2 Ub-conjugating protein UBE2L3, located in the secretory organ of the parasite during the muscle stages of infection. UBE2L3 but specifically binds to a panel of human RING E3 ligases, including the RBR E3 ARIH2 with which it interacts with a higher affinity than the mammalian ortholog UbcH7/UBE2L3. Expression of UBE2L3 in skeletal muscle cells causes a global downregulation in protein ubiquitination, most predominantly affecting motor, sarcomeric and extracellular matrix proteins, thus mediating their stabilization with regards to proteasomal degradation 2.3.3.5 2-methylcitrate synthase medicine invasive aspergillosis is a life-threatening disease mainly caused by the fungus Aspergillus fumigatus, blocking of methylcitrate synthase abrogates fungal growth and provides a suitable target for new antifungals 2.3.3.8 ATP citrate synthase medicine renal stone patients have low urinary citrate excretion with high leukocyte ATP citrate (pro-3S)-lyase activity. In Northeast Thailand, low potassium status and a high carbohydrate and low fat diet may cause the increased enzyme activity. Hypokaliuria and high leukocyte ATP citrate (pro-3S)-lyase activity can be corrected by potassium-sodium citrate salt therapy 2.3.3.8 ATP citrate synthase medicine diabetic patients in resting conditions and after activation with thrombin, show higher enzyme activity than controls, accompanied by increased pyruvate dehydrogenase activity, acetyl-CoA content, and thrombin-evoked malonyl dialdehyde synthesis. Activation of diabetic platelets causes 2 times greater release of acetyl-CoA from their mitochondria than in controls 2.3.3.8 ATP citrate synthase medicine supplementary diet with potassium-magnesium citrate for male renal stone patients results in significant decrease in enzyme and m-aconitase activity in urinary leukocytes, inversely correlated with an increase in urinary excretion of both potassium and citrate 2.3.3.8 ATP citrate synthase medicine 3,5-dichloro-2-hydroxy-N-(4-methoxybiphenyl-3-yl)benzenesulfonamide is a cell-permeable inhibitor with modest potency. It shows an oral availability of 55%, but a half-life of only 2.1 h. After 20 days of treatment, there is a modest lowering of both plasma cholesterol and triglycerides in high-fat fed mice 2.3.3.8 ATP citrate synthase medicine ATP citrate synthase inhibition by RNAi or the chemical SB-204990 limits in vitro proliferation and survival of tumor cells displaying aerobic glycolysis 2.3.3.8 ATP citrate synthase medicine ATP citrate synthase inhibition by RNAi or the chemical SB-204990 limits in vitro proliferation and survival of tumor cells displaying aerobic glycolysis. The same treatments also reduce in vivo tumor growth and induce differentiation 2.3.3.8 ATP citrate synthase medicine stable knockdown of ATP citrate synthase significantly impairs Akt-mediated tumorigenesis in vivo 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine - 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine target of a potent antisteroidogenic drug 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine potential of the mevalonate pathway enzymes of enterococci as targets for antibiotics 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine enzyme is of growing medical interest as it is highly regulated 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine deficiency of the mitochondrial isoform correlates with human metabolic disease, cytosolic isoform is potentially useful target for drugs aimed at lowering cholesterol levels 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine expression of isoform HMGCS2 is down-regulated in 90% of Myc-dependent colon and rectum tumors. Protein expression is down-regulated preferentially in moderately and poorly differentiated carcinomas. In addition, it is also down-regulated in 80% of small intestine Myc-independent tumors 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine acetaminophen, APAP, is a leading cause of drug-induced liver failure 2.3.3.10 hydroxymethylglutaryl-CoA synthase medicine the ketogenic HMG-CoA synthase 1/HMG-CoA lyase-acetoacetate axis may represent a promising therapeutic target for managing BRAFV600E-positive human cancers 2.3.3.13 2-isopropylmalate synthase medicine potential target for drugs against microbial pathogens due to the absence of this enzyme in mammals 2.3.3.13 2-isopropylmalate synthase medicine alpha-isopropylmalate synthase is a target for the design of new antitubercular therapeutics 2.3.3.14 homocitrate synthase medicine homocitrate synthase is a potential target for antifungal drugs 2.3.3.21 (R)-citramalate synthase medicine catalyses the first reaction of the pathway which converts pyruvate and acetyl-CoA into citramalate, thus making it an attractive target for the development of antibacterial agents 2.3.3.21 (R)-citramalate synthase medicine Leptospira interrogans is the causative agent for leptospirosis, LiCMS is an atttractive target for the development of antibacterial agents 2.4.1.1 glycogen phosphorylase medicine presubiculum, but not subiculum, of entorhinal cortex, is strongly reactive for glycogen phosphorylase. Glycogenolytic demand in Layers I and II is organized in a modular fashion and demand can be modified by brief exposure of animals to a novel holeboard 2.4.1.1 glycogen phosphorylase medicine use of commercially available glycogen phosphorylase BB ELISA assay for diagnosis of myocardial damage and comparison with established cardiac markers such as troponin T, creatine kinase isoenzyme MB mass, and myoglobin. Glycogen phosphorylase BB is a promising marker for the early diagnosis of acute coronary syndrome and could probably act as a marker of ischemia 2.4.1.1 glycogen phosphorylase medicine false negative histochemical reaction for myophosphorylase activity in fulminant sepsis due to methicillin resistant Staphylococcus aureus 2.4.1.1 glycogen phosphorylase medicine glycogen phosphorylase inhibitory flavonoids have potential to contribute to the protection or improvement of control of diabetes type II 2.4.1.1 glycogen phosphorylase medicine inhibition of the liver glycogen targeting subunit/glycogen phosphorylase interaction may provide an attractive approach for rebalancing the disturbed glycogen metabolism in diabetic patients (prevention of the GL–GP interaction increases the glycogen synthesis rate) 2.4.1.5 dextransucrase medicine industrial production of dextrans, that have important medical application in the production of fine chemicals such as plasma substitutes and Sephadex 2.4.1.5 dextransucrase medicine the effects of sodium ions on dextran succrase activity are specific, thus it can be useful to block its catalytic activity, and reducing the cariogenic potential of Streptococcus mutans 2.4.1.5 dextransucrase medicine the enzyme synthesizes dextran and oligosaccharides, which act as prebiotics and are popularly used in such industries as food and medicine 2.4.1.7 sucrose phosphorylase medicine specific determination of phosphate 2.4.1.B7 ursodeoxycholate N-acetylglucosaminyltransferase medicine important role in therapies for ameliorating the symptoms of cholestasis or for dissolving gallstones 2.4.1.11 glycogen(starch) synthase medicine glycogen synthase activity correlates inversely with phosphorylation of glycogen synthase sites 2 + 2a and 3a. Insulin significantly decreases 2 + 2a phosphorylation in lean subjects only and induces a larger dephosphorylation at site 3 in lean compared with obese subjects. The exaggerated insulin resistance in type 2 diabetes mellitus compared with obese subjects is not reflected by differences in site 3 phosphorylation but is accompanied by a significantly higher site 1b phosphorylation during insulin stimulation. Hyperphosphorylation of another Ca2/calmodulin-dependent kinase-II target, phospholamban-Thr17, is also evident in type 2 diabetes mellitus. Dephosphorylation of glycogen synthase by phosphatase treatment fully restores glycogen synthase activity in all groups 2.4.1.11 glycogen(starch) synthase medicine in patients with polycystic ovary syndrome, reduced insulin-mediated glucose disposal is associated with a lower insulin-stimulated glycogen synthase activity, explained by absent insulin-mediated dephosphorylation of glycogen synthase at the NH2-terminal sites 2 + 2a, whereas dephosphorylation at the COOH-terminal sites 3a + 3b is intact in polycystic ovary syndrome subjects. Insulin activation of glycogen synthase is dependent on dephosphorylation of sites 3a + 3b in women with polycystic ovary syndrome. No significant abnormalities in glycogen synthaseK-3 or -3 are found. Pioglitazone treatment improves insulin-stimulated glucose metabolism and glycogen synthase activity in polycystic ovary syndrome and restores the ability of insulin to dephosphorylate glycogen synthase at sites 2 and 2a 2.4.1.11 glycogen(starch) synthase medicine insulin, insiulin-like growth factor 1 and relaxin stimulate the enzymatic activity. In patients with type 1 diabetes glycogen synthase activity remains unchanged versus control, and insulin does not stimulate the enzyme activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1 > relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1 increase thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions 2.4.1.11 glycogen(starch) synthase medicine mutation R243X has been identified in a patient with glycogen storage disease type 0, together with frameshift mutation 966_967delGA/insC introducing a stop codon 21 amino acids downstream from the site of the mutation and leading to loss of 51% of the C-terminal portion of the protein. Patient is heterozygous for the mutations and presents with fasting hypoglycemia and postprandial hyperglycemia 2.4.1.11 glycogen(starch) synthase medicine old compared to young rats maintained ad libitum on a standard diet have reduced glycogen synthase activity, lower muscle glycogen synthase protein levels, increased phosphorylation of glycogen synthase at site 3a with less activation in soleus muscle. Age-associated impairments in glycogen synthase protein and activation-phosphorylation are also shown in tibialis anterior muscle. There is an age-associated reduction in glycogen phosphorylase activity level in soleus, while brain/muscle isoforms of glycogen phosphorylase protein levels are higher. Calorie restriciton does not alter glycogen synthase or glycogen phosphatase activity/protein levels in young rats. Calorie restriction hinders age-related decreases in glycogen synthase activity/protein, unrelated to glycogen synthase mRNA levels, and glycogen synthase inactivation-phosphorylation 2.4.1.11 glycogen(starch) synthase medicine patient with muscle-specific glycogen synthase deficiency due to homozygous two base pair deletion in exon 2, c.162-163delAG. Mutation is predicted to result in a protein frameshift that alters the amino acid sequence after the mutation and terminates prematurely. Patient presents with abnormal mitochondrial ultrastructure and pre-ragged red fibres, predominance of type I oxidative fibres in the muscle and depletion of glycogen stores 2.4.1.15 alpha,alpha-trehalose-phosphate synthase (UDP-forming) medicine the enzyme should be a valuable target for chemotherapeutic intervention in tuberculosis 2.4.1.17 glucuronosyltransferase medicine some drugs frequently coadministered with morphine (tamoxifen, tacrolimus, diclofenac, carbamazepine, imipramine, clomipramine, amitriptyline, diazepam, lorazepam and oxazepam) extensively inhibit the morphine 3- and 6-glucuronosyltransferase activities of UGT2B7. If patients receive morphine and these drugs simultaneously, the drug-drug interaction may change the levels of morphine and these glucuronides, resulting in altered analgesic efficacy and the risk of side effects 2.4.1.17 glucuronosyltransferase medicine UGT1A10 codon 139 polymorphism may be an important determinant in risk for tobacco-related cancers 2.4.1.17 glucuronosyltransferase medicine some male athletes have testosterone to epitestosterone values greater than the accepted threshold value 4.0, even without testosterone abuse. The main reason for such false-positive results in doping tests is a low epitestosterone glucuronide concentration but not a high level of testosterone glucuronide 2.4.1.17 glucuronosyltransferase medicine the UGT1A6 splice variant isoform 2, detected in the liver and kidney, has no transferase activity for deferiprone. When UGT1A6_i2 is coexpressed with the classic UGT1A6_i1 isoform, velocity is reduced for deferiprone but remains similar for 4-nitrophenol or serotonin glucuronidation 2.4.1.17 glucuronosyltransferase medicine imidazoacridinone and triazoloacridinone drugs are glucuronidated in human liver 2.4.1.17 glucuronosyltransferase medicine isoform UGT2A1 is an important detoxification enzyme in the metabolism of polycyclic aromatic hydrocarbons within target tissues for tobacco carcinogens, and functional polymorphisms in UGT2A1 may play a role in tobacco-related cancer risk 2.4.1.18 1,4-alpha-glucan branching enzyme medicine defining the molecular basis of equine glycogen storage disease IV will allow for accurate DNA testing and the ability to prevent occurence of this disease affecting American Quarter Horses and related breeds. A C to A substitution at base 102 results in a tyrosine (Y) to stop (X) mutation in codon 34 of exon of exon 1. All 11 affected foals are homozygous for the X34 allele, all 16 control horses are homozygous for the Y34 allele 2.4.1.25 4-alpha-glucanotransferase medicine understanding of the molecular basis of Cori's disease 2.4.1.25 4-alpha-glucanotransferase medicine lyme disease 2.4.1.27 DNA beta-glucosyltransferase medicine a comparison between cancer and healthy tissue genomes suggests a lower percentage of 5-hydroxymethyl cytosine in cancer 2.4.1.34 1,3-beta-glucan synthase medicine exposure of strain RG101 to caspofungin during growth yields a modified enzyme that is drug insensitive (4 log orders) in kinetic inhibition assays, and this insensitivity is also observed for enzymes isolated from clinical isolates. The lipid microenvironment of the enzyme with resistance induced by caspofungin reveals a prominent increase in the abundances of dihydrosphingosine and phytosphingosine. Exogenous addition of dihydrosphingosine and phytosphingosine to the sensitive enzyme recapitulates the drug insensitivity of the caspofungin-derived enzyme. Caspofungin induces mitochondrion-derived reactive oxygen species, and dampening reactive oxygen species formation by antimycin A or thiourea eliminates drug-induced resistance 2.4.1.38 beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase medicine GalT V might represent a target in glioma therapy 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase medicine cancer cells compared to normal cells exhibit altered glycosyltransferase activities, enzyme is a new tool for the investigation of motif peptide O-glycosylation alterations in pathological situations 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase medicine isoform GalNAc-T3 expression is an indicator of tumor differentiation in thyroid carcinoma 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase medicine isoform GALNT3 expression significantly correlates with shorter progression-free survival intervals in epithelial ovarian cancer patients with advanced disease 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase medicine the enzyme serves as targets for intervention in cryptosporidiosis 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase medicine isoform GalNAc-T1 is largely required for the Ebola virus surface glycoprotein-mediated adhesion defects. Despite its profound effect on surface glycoprotein function, the absence of GalNAc-T1 only modestly reduces the O-glycan mass of surface glycoprotein. A small segment of the mucin-like domain of the surface glycoprotein is critical for function and mutation of five glycan acceptor sites within this segment are sufficient to abrogate surface glycoprotein function 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase medicine isoform GalNAc-T4 shows a stage-dependent expression at the different stages of colorectal cancer in 62 pair-matched tumor/normal tissues. GalNAc-T4 expression is significantly induced at stage I and II but not at stage III and IV. Overexpression of GalNAc-T4 in colorectal cancer cells enhances colony formation and sphere formation. Knockdown of GalNAc-T4 in colorectal cancer cells increases the cell migration and invasion, and leads to an epithelial-mesenchymal transition-like transition. Loss of GalNAc-T4 contributes to the dedifferentiation of colorectal cancer cells and high expression of GalNAc-T4 correlates to a good prognosis of patients 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase medicine isoform Galnt3-deficient mice serve as a model for the disease hyperphosphatemic familial tumoral calcinosis 2.4.1.47 N-acylsphingosine galactosyltransferase medicine study of CGT expression and polymorphism may provide a clue for the understanding of neuropathological diseases involving myelin and myelination 2.4.1.47 N-acylsphingosine galactosyltransferase medicine study on UGT8 expression in tissue specimens of primary and corresponding metastatic lung tumors in 19 non-small cell lung carcinoma patients undergoing surgery. The majority of both lung primary and metastatic tumor tissues are positive in UGT8 signals. The cytoplasmic expression of UGT8 is found in 68.4% of cases of primary tumors and 82.2% of metastases, with a positive correlation between the UGT8 expression in both tumor tissues. The normal tissue adjacent to tumors shows no positive UGT8 staining. There is no appreciable difference in UGT8 expression depending on the clinical stage of non-small cell lung carcinoma or lymph node involvement found nor is there any association between UGT8 expression in tumor tissues and patients' survival time. UGT8, although enhanced in non-small cell lung carcinoma tissues, does not meet the criteria of a lung tumor marker 2.4.1.50 procollagen galactosyltransferase medicine high enzyme expression in breast cancer biopsies is associated with increased risk of mortality 2.4.1.B62 small GTPase glucosyltransferase medicine evaluation of comercially available rapid membrane enzyme immunoassays that use either glutamate dehydrogenase antigen or toxin A and B detection or a combination of both. Sensitivity, specificity, positive predictive values, and negative predictive values are 63.6%, 98.0%, 76.1%, and 96.4%, respectively, for the CD COMPLETE-toxin assay and 75.5%, 97.4%, 72.5%, and 97.8%, respectively, for the VIDAS CDAB assay. In comparison to the enriched Clostridium difficile cultures, the sensitivity, specificity, positive predictive values, and negative predictive values for the CD COMPLETE-GDH assay are 91.0%, 92.4%, 70.5%, and 98.1%, respectively. The CD COMPLETE assay is a reliable method for the diagnosis of Costridium difficile infection and provides greater sensitivity than toxin enzyme immunoassay alone 2.4.1.B62 small GTPase glucosyltransferase medicine Peptoclostridium difficile toxins A and B are S-nitrosylated by the infected host and S-nitrosylation attenuates virulence by inhibiting toxin self-cleavage and cell entry. InsP(6)- and inositol diphosphate InsP(7)-induced conformational changes in the toxin enable host S-nitrosothiols to transnitrosylate the toxin catalytic cysteine, which forms part of a structurally conserved nitrosylation motif. Treatment with exogenous InsP(6) enhances the therapeutic actions of oral S-nitrosothiols in mouse models of Peptoclostridium difficile infection 2.4.1.B62 small GTPase glucosyltransferase medicine phosphorylated mitogen-activated protein kinase MK-2 is activated by toxins TcdA and TcdB and regulates the expression of proinflammatory cytokines. Activation of p38-MK2 in infected animals and humans suggests that this pathway is a key driver of intestinal inflammation in patients with Clostridium difficile infection 2.4.1.B62 small GTPase glucosyltransferase medicine toxin A-positive, toxin B-positive strains representing 12 variant toxinotypes all express considerably lower levels of toxin A and are less cytotoxic in vitro than non-variant strain VPI 10463. Truncated forms of toxin occur in toxinotype VI and VII strains and these toxins are differentiated from each other and from toxin A of the non-variant strain. Toxin A-positive, toxin B-positive strains of toxinotypes IX, XIV and XV are able to exhibit an alternative Clostridium sordellii-like cytopathic effect on Vero cells, characterized by marked cell clumping. The abnormal cytotoxicity observed for these strains is due to an altered toxin B 2.4.1.B62 small GTPase glucosyltransferase medicine construction of highly optimized plasmids encoding the receptor-binding domains from TcdA and TcdB in which any putative N-linked glycosylation sites are altered to test the potential of DNA vaccination against Clostridium difficile-associated disease. In mice and nonhuman primates, vaccination induces significant levels of both anti-receptor-binding domain antibodies (blood and stool) and receptor-binding domain-specific antibody-secreting cells. Sera from immunized mice and nonhuman primates can detect receptor-binding domain protein from transfected cells, as well as neutralize purified toxins in an in vitro cytotoxicity assay. Mice that are immunized with plasmids or given nonhuman-primate sera are protected from a lethal challenge with purified TcdA and/or TcdB. Immunized mice are significantly protected when challenged with Clostridium difficile spores from homologous (VPI 10463) and heterologous, epidemic (UK1) strains 2.4.1.B62 small GTPase glucosyltransferase medicine in a batch release potency test, 3 out of 52 strains show gene TcsH expression. The vast majority of the toxicity (more than 97%) of the crude toxin prepared from a isoforms TcsL+ TcsH+ isolate is due toTcsL 2.4.1.B62 small GTPase glucosyltransferase medicine the vast majority of the toxicity (more than 97%) of the crude toxin prepared from a isoforms TcsL+ TcsH+ isolate is due toTcsL 2.4.1.B65 4-hydroxy-3-methoxybenzyl alcohol alpha-D-glucosyltransferase medicine reaction product vanillyl alcohol alpha-D-glucoside shows good antioxidant activity as well as stability in gastrointestinal tract. It is hydrolyzed on brush border membrane of enterocytes, so it can serve in protecting the gastrointestinal system from oxidation 2.4.1.68 glycoprotein 6-alpha-L-fucosyltransferase medicine serum alpha1-6-fucosylated alpha-fetoprotein is employed for an early diagnosis of patients with hepatoma and hepatic disease 2.4.1.68 glycoprotein 6-alpha-L-fucosyltransferase medicine enzyme of blood platelets is a diagnostic marker for the ploidy level of megakaryocytes in thrombocytopenia 2.4.1.68 glycoprotein 6-alpha-L-fucosyltransferase medicine the enzyme is a candidate for the earliest marker of megakaryocyte-commitment in cultured hematopoietic stem cells. Such a marker should allow an earlier detection and earlier transplantation of patients own, ex vivo expanded, megakaryocyte progenitors 2.4.1.68 glycoprotein 6-alpha-L-fucosyltransferase medicine the enzymatic product of core alpha1,6-fucosyltransferase plays a major role in a plethora of pathological conditions, e.g. in prognosis of hepatocellular carcinoma and in colon cancer 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine alpha-galactosidase and alpha-1,2-fucosyltransferase can inhibit the expression of Gal-alpha-1,3-Gal synergistically, leading to stronger resistance of xenograft against cytolysis mediated by natural antibodies and complements. It implies a practical significance of combined transgenic strategy with alpha galactosidase and alpha-1,2-fucosyltransferase 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine FUT1 can efficiently prevent the synthesis of slex antigens in hepatocarcinoma and colon carcinoma cells and their interaction with activated endothelia. The FUT-EGFP gene transfer approach would be expected to decrease or even suppress the initial vascular arrest of tumor cells and may provide a basis for the development of antimetastatic gene therapy 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine tumor marker for human gastric cancer, down regulation of alpha1,2-fucosyltransferase activity is associated with human gastric tumorigenesis 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine involvement of alpha 1-2-fucosyltransferase I (FUT1) and surface-expressed Lewis(y) (CD174) in first endothelial cell-cell contacts during angiogenesis is shown 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine it is shown that human alpha(1,2)-fucosyltransferase activity is remarkably decreased (40-90%) in human gastric cancer and may serve as a potential tumor marker 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine sequence variations in the proximal promoter region of FUT2 in several human populations is studied. In African populations, two SNPs (17606C>T and 17721T>G) with intermediate frequency that affected the promoter activity in vitro with a cell type-specific pattern are found 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine systematic sequence analysis of the human FUT2 gene in healthy chinese and caucasian subjects identifies 18 sequence variations in the FUT2 gene, and 6 are novel 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine using nude mice subcutaneously xenotransplanted with parental or FUT1-transduced hepatocarcinoma cells HepG2 it is shown that FUT1 displays a strong antitumorigenicity due to a defect in tumor vascularization 2.4.1.69 type 1 galactoside alpha-(1,2)-fucosyltransferase medicine co-expression of the enzyme with 1,3-galactosyltransferase leads to a considerable reduction of the alpha-Gal antigen level on the surface of cells and a decrease of xenotransplant immunogenicity 2.4.1.B74 GlcAGroAc2:mannosyltransferase medicine infection of human macrophages by a PimB gene disruption mutant leads to an alteration in macrophage phenotype concomitant with a significant increase in the rate of macrophage death 2.4.1.B79 triptophenolide beta-glucosyltransferase medicine product triptophenolide 14-O-beta-D-glucopyranoside exhibits significant inhibitory effects on U87-MG, U251, C6, MCF-7, HeLa, K562, and RBL-2H3 cells 2.4.1.80 ceramide glucosyltransferase medicine - 2.4.1.80 ceramide glucosyltransferase medicine potential therapeutic target for inherited sphingolipidoses such as Gaucher, Fabry, and Tay-Sachs disease 2.4.1.80 ceramide glucosyltransferase medicine enzyme inhibition is a possible target for chemotherapeutic agents for a number of diseases, including cancer 2.4.1.80 ceramide glucosyltransferase medicine GCS expression is significantly down-regulated in Alzheimer brain 2.4.1.80 ceramide glucosyltransferase medicine it is shown that pharmacological lowering of glycosphingolipids, without significant reduction of ceramide, dramatically reverses insulin resistance in in vitro and in vivo models and may present a novel approach to the therapy of type 2 diabetes 2.4.1.80 ceramide glucosyltransferase medicine results show that high level of GCS in leukemia cells is associated with multidrug resistance of these cells 2.4.1.80 ceramide glucosyltransferase medicine substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher disease 2.4.1.83 dolichyl-phosphate beta-D-mannosyltransferase medicine increased DPMS activity through protein phosphorylation is a driving force for angiogenesis 2.4.1.83 dolichyl-phosphate beta-D-mannosyltransferase medicine D-P-M enzyme activity represents a potentially useful approach to address the problem of porcine endogenous retrovirus infections in clinical xenotransplantations 2.4.1.83 dolichyl-phosphate beta-D-mannosyltransferase medicine subunits Dpm1 and Dpm3 function as host dependency factors for Dengue virus and other related flaviviruses such as Zika virus. Mutation in the DXD motif of Dpm1, which is essential for its catalytic activity, abolishes DPMS-mediated Dengue virus infection. Genetic ablation of mannosyltransferase ALG3 renders cells poorly susceptible to Dengue virus. In cells deficient for DPMS activity, viral RNA amplification is hampered and truncated oligosaccharides are transferred to the viral precursor of the M protein and E glycoproteins, affecting their proper folding 2.4.1.87 N-acetyllactosaminide 3-alpha-galactosyltransferase medicine Galalpha(1,3)Gal synthesized by iGb3S is immunogenic and elicits antibodies in GGTA1-/- mice. Galalpha(1,3)Gal synthesized by iGb3S may affect survival of pig transplants in humans 2.4.1.87 N-acetyllactosaminide 3-alpha-galactosyltransferase medicine protection against tumors by immunization with AdaGT-transduced tumor cells (replication deficient adenovirus containing the alpha1,3GT gene) is studied in alpha1,3GT knockout (KO) mice, challenged with the highly tumorigenic BL6 melanoma cells. These mice lack alpha-gal epitopes and can produce anti-Gal. Immunization of KO mice with AdaGT-transduced BL6 cells protects many of the mice against challenge with live BL6 cells lacking alpha-gal epitopes. Immunization with AdalphaGT transduced autologous tumor cells may serve as adjuvant immunotherapy delivered after completion of standard therapy 2.4.1.87 N-acetyllactosaminide 3-alpha-galactosyltransferase medicine the Bacillus thuringiensis phosphatidylinositol-specific phospholipase C and the alpha(1,3)GT genes are engineered to be delivered to cells in two separate retroviral vectors. Activity of phosphatidylinositol-specific phospholipase C, secreted from transduced A549 human lung tumor cells shows a synergistic increase in alphagal mediated complement killing in an in vitro assay. When applied to in vivo therapy of solid tumors, this approach may enhance anti-tumor immune responses 2.4.1.87 N-acetyllactosaminide 3-alpha-galactosyltransferase medicine application of pig liver for extracorporeal blood circulation in conditions of acute liver failure. GalT knockout hepatocytes and wild-type cells diplay no tumorigenicity. GalT knockout cells show less apoptosis and more viability than wild-type cells when exposed to complement and xenogeneic serum 2.4.1.87 N-acetyllactosaminide 3-alpha-galactosyltransferase medicine development of alpha-1,3-galactosyltransferase (GGTA1) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) double-knockout piglets as donor animals for xenotransplantation. Compared to cells from GGTA1-knockout pigs, human antibody binding and antibody-mediated complement-dependent cytotoxicity are significantly reduced in cells from GGTA1/CMAH double-knockout pigs 2.4.1.87 N-acetyllactosaminide 3-alpha-galactosyltransferase medicine in patients with pretreated metastatic renal cell carcinoma, HyperAcute Renal immunotherapy, i.e. treatment with two allogeneic renal cancer cell lines genetically modified to express alpha(1,3)Gal, is well tolerated and demonstrates antitumor activity 2.4.1.90 N-acetyllactosamine synthase medicine an UDP-galactose: N-acetylglucosamine beta 1-4 galactosyltransferase expressing attenuated Leishmania donovani clonal population is able to confer protection against the experimental challenge with the virulent Leishmania donovani AG83 parasite 2.4.1.90 N-acetyllactosamine synthase medicine enzyme expression is an independent prognostic factor for poor survival of neuroblastoma patients 2.4.1.90 N-acetyllactosamine synthase medicine the enzyme serves as a diagnostic and therapeutic biomarker for the progression of human colorectal cancer 2.4.1.92 (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase medicine GD2 synthase is a surface marker for the identification of mesenchymal stromal cells 2.4.1.92 (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase medicine GD2/GM2 synthase mRNA is not a reliable biomarker for small cell lung cancer 2.4.1.101 alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase medicine mutant enzyme does not show any activity in an HPLC analysis. In the case of pig cell transfectants with pigGnT-I(320), cell surface carbohydrate structures are significantly altered and its antigenicity to human serum is reduced. pigGnT-I(320) appears to be potentially useful in xenotransplantation by remodeling the carbohydrate structures on pig cells 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine C2GnT-1 may be a candidate of therapeutic target for the inhibition of infiltration of leukemia cells 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine core2GnT is an extremely useful prognostic marker for prostate cancer progression 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine good drug targets for the treatment of inflammatory disorders and other pathologies involving selectins 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine the results reveal a rationale towards a specific treatment of diabetic retinopathy, based on the inhibition of core 2 GlcNAc-T activity and/or the blockage of cognate glycans 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine biomarker for aggressive potential of testicular germ cell tumor 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine clinical relevance of the differential expression of the glycosyltransferase gene GCNT3 in colon cancer, clinicopathological parameters, overview 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine GCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient 2.4.1.102 beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine GCNT3 is a potential molecular target in melanoma therapeutics through abrogation of the S100A8/A9-MCAM axis 2.4.1.109 dolichyl-phosphate-mannose-protein mannosyltransferase medicine Pmt proteins may be suitable targets for future novel classes of antifungal agents 2.4.1.109 dolichyl-phosphate-mannose-protein mannosyltransferase medicine protein O-mannosyltransferase isoforms regulate biofilm formation in Candida albicans. Inhibition may prevent surface anchoring and biofilm-dependent resistance of fungal pathogens 2.4.1.109 dolichyl-phosphate-mannose-protein mannosyltransferase medicine POMT1 mutations in patients with congenital muscular dystrophy (Italian population) 2.4.1.109 dolichyl-phosphate-mannose-protein mannosyltransferase medicine POMT2 mutations in patients with congenital muscular dystrophy (Italian population) 2.4.1.109 dolichyl-phosphate-mannose-protein mannosyltransferase medicine using Drosophila as model for investigating the mechanisms of human congenital muscular dystrophies (dystroglycanopathies) resulting from the abnormal glycosylation of alpha-dystroglycan 2.4.1.122 N-acetylgalactosaminide beta-1,3-galactosyltransferase medicine polymorphisms of the C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy in Chinese population 2.4.1.122 N-acetylgalactosaminide beta-1,3-galactosyltransferase medicine C1GALT1 predicts poor prognosis and is a potential therapeutic target in head and neck cancer 2.4.1.129 peptidoglycan glycosyltransferase medicine PGT activity can be a useful target for antibiotic therapies because the enzymatic site of the enzyme is highly conserved and inhibition of PGT activity results in the inhibition of bacterial growth 2.4.1.132 GDP-Man:Man1GlcNAc2-PP-dolichol alpha-1,3-mannosyltransferase medicine hALG2 is the cause of a new type of congenital disorders of glycosylation designated CDG-Ii 2.4.1.144 beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine enzyme activity in extrahepatic bile duct carcinoma is increased 3fold compared to mean enzyme activity values, resulting in increased bisecting-GlcNAc on the glycans of glycoproteins in cancer tissues and a 201 kDa bile glycoprotein 2.4.1.144 beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine enzyme activity is elevated in serum of 60 out of 86 patients with liver cirrhosis, and of 86 out of 91 patients with chronic hepatitis 2.4.1.144 beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine enzyme activity is elevated in three choriocarcinoma cell lines compared to normal placenta. Activity in JEG-3 cells is 27 times higher than normal 2.4.1.144 beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine apart from GnT-III overexpression, engineering of GnT-III localization is a versatile tool to modulate the biological activities of antibodies relevant for their therapeutic application 2.4.1.144 beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine the majority of N-glycans of a recombinant antibody produced in Nicotiana tabacum expressing GnT-III is bisected and devoid of paucimannosidic structures. This might improve the efficacy of therapeutic antibodies produced in the transgenic plants 2.4.1.144 beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine therapeutic potential of inhibiting GnT-III as a treatment for controlling epithelial ovarian carcinoma (EOC) growth and recurrence 2.4.1.145 alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine enzyme activity in tissue from patients with extrahepatic bile duct carcinoma remains unchanged 2.4.1.145 alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase medicine enzyme activity is elevated in three choriocarcinoma cell lines compared to normal placenta. Activity in JEG-3 cells is 29 times higher than normal 2.4.1.147 acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase medicine the enzyme would be a useful marker for distinguishing between benign adenomas and premalignant lesions 2.4.1.148 acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase medicine the expression of the enzyme in bladder tumors positively correlates with tumor progression 2.4.1.149 N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase medicine enzyme may be used as diagnostic marker of human cancer or as target molecule for the development of a new therapy 2.4.1.150 N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase medicine GCNT2 is overexpressed in highly metastatic breast cancer and its expression correlates with adverse pathologic phenotypes. Blocking TGF-beta/GCNT2 signaling is a promising approach for targeting metastatic breast cancer 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase medicine FT-IV and FT-VII are both important contributors to selectin-dependent eosinophil recruitment to the skin and may represent therapeutic targets in which eosinophil recruitment contributes to pathophysiology 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase medicine FucT-VII is critical for the recruitment of Th1 cells in inflamed brain microcirculation 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase medicine FUT7 mRNA is highly over-expressed at the site of inflammation and in tumorigenesis 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase medicine granzyme B-induced caspase 3-activation leads to up-regulation of FUT4 and FUT9 mRNA expression, which increases the surface expression of Lewis X and Y antigens 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase medicine fucosyltransferase IV overexpression promotes cell proliferation, increases the expression of proliferating cell nuclear antigen and augments Lewis Y expression to trigger neoplastic cell proliferation, fucosyltransferase IV may serve as a potential therapeutic target for the treatment of Lewis Y-positive epithelial cancers 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase medicine isoform FUT4 is a regulator of epithelial-mesenchymal transition in breast cancer cells and a target for cancer therapy 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine link between elevated expression of enzyme and malignant transformation, macrophage fusion hybrids with Cloudman S91 mouse melanoma cells are highly metastatic in vivo, motile in vitro and express macrophage-associated traits of increased enzyme activity, beta1,6-branching and polylactosamine content 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine a selective inhibitor for this GnT-V secretion, a gamma-secretase inhibitor, could provide a useful strategy for the inhibition of tumor angiogenesis and progression 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine GnT-V is a potential target for tumor treatment 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine higher expression of GnT-V is correlated with a favorable prognosis for neuroblastoma patients. GnT-V may cause these tumors to regress by increasing their susceptibility to apoptosis 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine prognosis of thyroid carcinoma after surgery is not correlated with the expression GnT-V because the levels of expression is quite low in anaplastic (undifferentiated) carcinomas 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine a simple glycoproteomic strategy to identify the glycoproteins from breast tissue that bind to the lectin L-phytohemagglutinin is developed 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine conditional expression of beta1,6GlcNAc-branched N-glycans in postnatal tissues promotes anabolic metabolism and tissue renewal by adapting cellular sensitivities to growth and arrest cues 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine GnT-III transfection into highly pigmented, highly metastatic macrophage-melanoma fusion hybrids resulted in the suppression of both melanogenesis and motility 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine GnT-V and beta1-6 branching N-linked oligosaccharide expressions are downregulated during carcinogenesis and progression of human testicular germ cell tumors, GnT-V may be a promising recurrence predictor for stage I non-seminomatous germ cell tumors 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine high GnT-V expression is correlated with impaired clinical outcome in endometrial cancer patients, GnT-V is an independent prognostic factor for progression-free survival 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine knowledge of the biological behavior of metalloproteinases and tissue inhibitor of metalloproteinases and the roles in various diseases have an eventual goal of therapeutic uses and clinical trials of anti-cancer agents 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine MGAT5 is important in the metastasis of prostate cancer 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine the study demonstrates the effect of down-regulating GnT-V on glucose uptake and provides a new mechanistic link between GnT-V and GLUT1, since ER stress may cause apoptosis of tumor cells, selective modulation of GLUT1 may be a useful pro-apoptotic strategy for liver or other cancers 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine GnT-V expression correlated with a poor prognosis in gastric cancer patients due to metastases 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine possible decrease of human hepatoma SMMC-7721 cell adhesion 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine enzyme expression is positively related with malignancy in HCC. The enzyme is both a differentiation marker and a potential target for the treatment of hepatocellular carcinoma 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine the enzyme is a potential therapeutic target for vascular inflammatory conditions 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase medicine radiotherapy combining GnT-V down-regulation and cetuximab decelerates tumor growth 2.4.1.165 N-acetylneuraminylgalactosylglucosylceramide beta-1,4-N-acetylgalactosaminyltransferase medicine the enzyme can alter alpha dystroglycan glycosylation, either directly or indirectly, in ways that may be therapeutic even in congenital muscular dystrophies where the glycosylation of dystroglycan is abnormal 2.4.1.165 N-acetylneuraminylgalactosylglucosylceramide beta-1,4-N-acetylgalactosaminyltransferase medicine Galgt2 overexpression inhibits muscular dystrophy in old dystrophic muscles and may have therapeutic impact in many types of muscle injury 2.4.1.175 glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase medicine antimicrobial approach, understanding microbial capsule biosynthesis may assist the uncloaking of bacterial camouflage without disrupting host GAG synthesis 2.4.1.175 glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase medicine CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance 2.4.1.175 glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase medicine gene ChGn-2 may serve as a plausible target to treat atherosclerotic-related diseases in humans 2.4.1.206 lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase medicine adhesion of Helicobacter pylori to epithelial cells is mediated by bacterial adhesins that bind carbohydrate ligands expressed by the epithelial gastric cells, bea3GnT5 transferase induction is specific to infection with highly pathogenic strains 2.4.1.210 limonoid glucosyltransferase medicine pharmacological application of limonoid GTase gene 2.4.1.210 limonoid glucosyltransferase medicine Citxadrus limonoid metabolic engineering, and extraction as well as utilization of bioactive limonoids for health promoting and disease-preventing benefits. Limonoids are present in a very high amount in Citrus seeds and peel and thus their extractions can have commercial value. Limonoid aglycones and a mixture of limonoid glucosides are administered in human breast cancer cell lines. It has been demonstrated that limonoids are more potent than tamoxifen for estrogen-independent breast cancer cells and equally potent as tamoxifen for estrogen-dependent breast cancer cells. Effects and mechanisms of limonoids on cancer cells, overview. The Citrus limonoids such as obacunone, limonin, nomilxadin and their glucosides and some aglycones are found to have cytotoxic effects against lung, oral and skin cancers in animal test system and human breast cancer cells 2.4.1.210 limonoid glucosyltransferase medicine overexpression of the LGT gene can enhance the accumulation of specific glucosides that have anticancer effects. Citrus limoxadnoids, specifically limonoid glucosides, which are the prodxaduct of glucosyltransferase enzyme, are water-soluble and have good bioavailability and non-toxic effects in animals and huxadmans. Thus, they can easily be used as nutraceuticals and health fortifiers in many functional foods 2.4.1.211 1,3-beta-galactosyl-N-acetylhexosamine phosphorylase medicine galactosyl-N-acetylhexosamine phosphorylase has a predominant role in the digestive tract of human and in the metabolism of galactose 2.4.1.212 hyaluronan synthase medicine expression of HAS1Vb, an intronic splice variant, correlates with poor survival in multiple myeloma patients 2.4.1.212 hyaluronan synthase medicine an in vitro model is developed to study the biomechanical effects of excess hyaluronan, which is relevant to many cardiovascular events 2.4.1.212 hyaluronan synthase medicine heregulin activation of ErbB2-ERK signaling modulates HAS phosphorylation/activation and hyaluronan production leading to CD-44-mediated oncogenic events and ovarian cancer progression 2.4.1.212 hyaluronan synthase medicine hyaluronan synthase 3 is the most dramatically up-regulated isozyme in metastatic prostate tumor cells 2.4.1.212 hyaluronan synthase medicine the overproduction of hyaluronan in soft connective tissues can transform their biological and biomechanical functionality, the results demonstrate the feasibility of using a tissue-engineering approach with genetically modified cells to study the role of individual extracellular matrix components 2.4.1.212 hyaluronan synthase medicine HAS 2 appears to be a major contributor to the baseline levels of hyaluronan. Reduced HAS 2 gene expression and increased excreted urinary hyaluronidase activity during dehydration contribute to the reduced amount of hyaluronan and to antidiuretic response. In hydrated animals, the diuretic response is followed by a 58% elevation in papillary hyaluronan and a 45% reduction in the excreted urinary hyaluronidase activity. No difference is determined in HAS 1–3 mRNA or HYAL 1, 3–4 mRNA expression. In dehydrated animals, antidiuresis is followed by a 22% reduction in papillary hyaluronan and a 62% elevation in excreted urinary hyaluronidase activity. Plasma vasopressin is 2.8-fold higher in dehydrated versus hydrated rats 2.4.1.212 hyaluronan synthase medicine HAS1 variant Vc is transforming in vitro and tumorigenic in vivo when introduced as a single oncogene to untransformed cells. In co-transfected cells, full length HAS1 and HAS1 variants interact with themselves and with each other to form heteromeric multiprotein assemblies 2.4.1.212 hyaluronan synthase medicine in hydrated animals, the diuretic response is followed by a 58% elevation in papillary hyaluronan and a 45% reduction in the excreted urinary hyaluronidase activity. No difference is determined in HAS 1–3 mRNA or HYAL 1, 3–4 mRNA expression. In dehydrated animals, antidiuresis is followed by a 22% reduction in papillary hyaluronan and a 62% elevation in excreted urinary hyaluronidase activity. Plasma vasopressin is 2.8-fold higher in dehydrated versus hydrated rats 2.4.1.212 hyaluronan synthase medicine in serous epithelial ovarian tumors, expression of HAS1 is low or absent. The levels of HAS2 and HAS3 mRNA are not consistently increased in the carcinomas, and are not significantly correlated with HAS protein or hyaluronan accumulation in individual samples 2.4.1.212 hyaluronan synthase medicine somatic HAS1 genetic variations occur in all hematopoietic cells tested, including normal CD34 hematopoietic progenitor cells and T cells, or as tumor-specific genretic variations restricted to malignant B and plasma cells. HAS1 genetic variations direct aberrant HAS1 intronic splicing. Nearly all newly identified inherited and somatic genetic variations in multiple myeloma and/or Waldenstrom macroglobulinemia are absent from B chronic lymphocytic leukemia, nonmalignant disease, and healthy donors 2.4.1.212 hyaluronan synthase medicine targeting HAS2 to induce fibroblast senescence can be an attractive approach to resolve tissue fibrosis 2.4.1.212 hyaluronan synthase medicine the role of HAS1 as a poor predictor in breast cancer, and is correlated with high relapse rate and short overall survival 2.4.1.221 peptide-O-fucosyltransferase medicine an aberrant activated Pofut1-Notch pathway is involved in hepatocellular carcinoma progression, and blockage of this pathway can be a promising strategy for the therapy of hepatocellular carcinomas 2.4.1.222 O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase medicine the Notch signaling pathway is involved in numerous developmental cascades in mammals, mutations in the pathway have been implicated in a variety of Human diseases, like CADASIL, spondylocostal dysostosis, alagille syndrome, cancer and multiple sclerosis 2.4.1.224 glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase medicine analysis of enzyme mutations in patients with hereditary multiple exostoses, mutation spectrum 2.4.1.225 N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase medicine analysis of enzyme mutations in patients with hereditary multiple exostoses, mutation spectrum 2.4.1.225 N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase medicine there is deficiency of heparan sulfate and perlecan, together with accumulation of collagens in the matrix of EXT1-associated osteosarcomas 2.4.1.226 N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase medicine CSGalNAcT-1 plays a critical role in chondroitin sulfate biosynthesis in cartilage 2.4.1.226 N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase medicine CSGalNAcT-1 plays a critical role in chondroitin sulphate biosynthesis in cartilage 2.4.1.226 N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase medicine CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance 2.4.1.226 N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase medicine gene ChGn-2 may serve as a plausible target to treat atherosclerotic-related diseases in humans 2.4.1.228 lactosylceramide 4-alpha-galactosyltransferase medicine infections caused by Shiga toxin-producing Escherichia coli result in diarrhea, bloody diarrhea, and the hemolytic uremic syndrom, thus, it is important to better understand the pathways of intracellular transport of the toxin and to develop preventive and therapeutic measures for Shiga toxin-mediated diseases 2.4.1.228 lactosylceramide 4-alpha-galactosyltransferase medicine verotoxin induces endothelial cell death via the verotoxin receptor globotriaosylceramide, Gb3/CD77, leading to hemolytic uremic syndrome 2.4.1.255 protein O-GlcNAc transferase medicine pharmacological inhibition of OGT in breast cancer cells has similar anti-growth and anti-invasion effects. OGT may represent novel therapeutic targets for breast cancer 2.4.1.255 protein O-GlcNAc transferase medicine the neurodegenerative disease protein ataxin-10 (Atx-10) is associated with cytoplasmic OGT p110 in the brain 2.4.1.258 dolichyl-P-Man:Man5GlcNAc2-PP-dolichol alpha-1,3-mannosyltransferase medicine two Vietnamese siblings with confirmed ALG3-Congenital disorders of glycosylation, 15 and 21 years old, show clinical features with previously reported patients including facial dysmorphism, severe psychomotor retardation, microcephaly, seizures, and gastrointestinal symptoms. Both patients show mutations c.206T > C (p.169 T) and c.626T > C (p.M209T) 2.4.1.258 dolichyl-P-Man:Man5GlcNAc2-PP-dolichol alpha-1,3-mannosyltransferase medicine identification of an additional open-reading frame of 141 bp (AAGRP) in the coding region of ALG3 in a patient with congenital disorder of glycosylation. Expression of this hybrid protein is significantly increased due to the homozygous variant c.160_196del. Patient shows secondary microcephaly, significantly decreased head control and axial muscular hypotonia associated with increased limb stiffness. Frequent episodes of hyperextension are observed 2.4.1.259 dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine T-lymphocytes from adult patients suffering classical galactosaemia identified systemic dysregulation of numerous gene pathways, including the glycosylation, inflammatory and inositol pathways. The glycosylation gene alpha-1,2-mannosyltransferase (ALG9) and the inflammatory gene annexin A1 (ANXA1) are susceptible to increased galactose concentrations. The expression of ALG9 is increased by 4.3fold in Galactosaemia versus healthy controls. Expression of Alg9 grown in galactose-free media is decreased significantly Galactosaemia dermal fibroblasts cell-lines at 30 min, compared with normal dermal fibroblast cells 2.4.1.259 dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine ALG9 homozygous splice variant NM_024740.2: c.1173+2T4A causes skipping of exon 10, leading to shorter RNA and resulting in an increase in monoglycosylated transferrin. Patients show a lethal skeletal dysplasia with visceral malformations as the most severe phenotype, i.e. Gillessen-Kaesbach-Nishimura skeletal dysplasia 2.4.1.259 dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine in a patient with homozygous mutation in ALG9, c.860A > G, i.e. Y287C, prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Postnatally, dysmorphic features include shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata 2.4.1.259 dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine inactivation of Alg9 results in impaired maturation and defective glycosylation of polycystin-1. Seven of eight (88%) cases selected have at least four kidney cysts, compared with none in matched controls 2.4.1.259 dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine patients with ALG9-congenital disorder of glycosylation present with drug-resistant infantile epilepsy, hypotonia, dysmorphic features, failure to thrive, global developmental disability, and skeletal dysplasia. One patient presented with nonimmune hydrops fetalis, showing global atrophy with delayed myelination caused by homozygous mutation c.1075G>A, i.e. E359K 2.4.1.260 dolichyl-P-Man:Man7GlcNAc2-PP-dolichol alpha-1,6-mannosyltransferase medicine a patient with heterozygous variants in the ALG12 gene, c.367 G>A (G123R) and c.1439 T>C (L480P), shows serum transferrin with underoccupancy of N-glycosylation sites. Total serum proteins and IgG N-glycans show accumulating amounts of definite high-mannose and hybrid structures. ALG12-congenital disorder of glycosylation displays CDG-I and II defects and it is associated with distinct, abnormal glycosylation of total serum and IgG N-glycans 2.4.1.261 dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine homozygous splice variant NM_024740.2: c.1173+2T4A in the ALG9 gene causes rare lethal autosomal recessive Gillessen-Kaesbach-Nishimura skeletal dysplasia. Skipping of exon 10 leads to shorter RNA and results in an increase in monoglycosylated transferrin 2.4.1.261 dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine ALG9 homozygous splice variant NM_024740.2: c.1173+2T4A causes skipping of exon 10, leading to shorter RNA and resulting in an increase in monoglycosylated transferrin. Patients show a lethal skeletal dysplasia with visceral malformations as the most severe phenotype, i.e. Gillessen-Kaesbach-Nishimura skeletal dysplasia 2.4.1.261 dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine in a patient with homozygous mutation in ALG9, c.860A > G, i.e. Y287C, prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Postnatally, dysmorphic features include shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata 2.4.1.261 dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine inactivation of Alg9 results in impaired maturation and defective glycosylation of polycystin-1. Seven of eight (88%) cases selected have at least four kidney cysts, compared with none in matched controls 2.4.1.261 dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase medicine patients with ALG9-congenital disorder of glycosylation present with drug-resistant infantile epilepsy, hypotonia, dysmorphic features, failure to thrive, global developmental disability, and skeletal dysplasia. One patient presented with nonimmune hydrops fetalis, showing global atrophy with delayed myelination caused by homozygous mutation c.1075G>A, i.e. E359K 2.4.1.267 dolichyl-P-Glc:Man9GlcNAc2-PP-dolichol alpha-1,3-glucosyltransferase medicine single nucleotide polymorphisms ALG6 rs10889417 G>A and GALNTL4 rs12270446 G>C independently predict cutaneous melanoma disease-specific survival. The low death-risk-associated rs10889417 A allele is associated with increase in ALG6 mRNA expression levels in cultured skin fibroblasts and whole blood cells and the rs12270446 G allele is associated with decrease in GALNTL4 mRNA expression levels in skin tissues 2.4.1.274 glucosylceramide beta-1,4-galactosyltransferase medicine the amounts of Lac-Cer synthesized by isoform beta4GalT5 correlate with the tumorigenic potentials of malignantly transformed cells 2.4.1.274 glucosylceramide beta-1,4-galactosyltransferase medicine B4GALT5 expression is upregulated in porcine reproductive and respiratory syndrome virus (PRRSV) infected porcine alveolar macrophage. The PRRSV proliferation is slightly inhibited by overexpression of B4GALT5. B4GALT5 and PRRSV protein GP5 colocalize in Golgi membrane. mRNA transcription, including inflammatory cytokines IFN-alpha, IL-6, IL-18, IL-1beta, TNF-alpha and some cell surface glycosylated proteins involved in antigen presentation (MHC-I/II), cell adhesion and migration (chemokine MCP-1 and receptor CCR2; LFA-1, ICAM-1) are upregulated in B4GALT5 overexpressing PRRSV infected cells 2.4.1.274 glucosylceramide beta-1,4-galactosyltransferase medicine B4GALT5 gene/protein expression is specifically increased in human colorectal cancer tumors, with a concomitant increase in its enzymatic activity, and product lactosylceramide, and increased dihydrosphingolipid metabolites. Inhibition of glycosphingolipid synthesis by the synthetic ceramide analog, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, concurrently inhibits colorectal cancer cell proliferation, as well as B4GALT5 mass and several glycosphingolipid levels 2.4.1.277 10-deoxymethynolide desosaminyltransferase medicine the catalytic flexibility of the glycosyltransferase DesVII offers an means for creating new macrolide antibiotics. The substrate flexibility of DesVII/DesVIII is apparently extended to a wide range of linear as well as cyclic substrates. Although the yield of products is notably reduced when unnatural substrates are used, once a desired activity is identified, the catalytic efficiency of these enzymes may be fine-tuned by protein engineering. The substrate flexibility of glycosyltransferases expands the opportunities for glycodiversification to generate new glycoforms of synthetic compounds and macrolide analogues 2.4.1.277 10-deoxymethynolide desosaminyltransferase medicine the requirement for an additional protein component, DesVIII, for activity must be taken into consideration in the design of combinatorial biosynthetic experiments with new glycosylated macrolides 2.4.1.278 3-alpha-mycarosylerythronolide B desosaminyl transferase medicine potential use to make unnatural macrolides for use as antibacterial 2.4.1.278 3-alpha-mycarosylerythronolide B desosaminyl transferase medicine the activated enzyme is capable of transferring an alternative unnatural sugar donor. Because the desosamine sugar contacts the 50S subunit of ribosome, the discovery that an unnatural sugar can be transferred has implications for the synthesis of new erythromycin derivatives with improved properties. Reconstitute of the activity of EryCIII in vitro for the synthesis of unnatural macrolides 2.4.1.291 N-acetylgalactosamine-N,N'-diacetylbacillosaminyl-diphospho-undecaprenol 4-alpha-N-acetylgalactosaminyltransferase medicine among FabG, HydB, CJJ81176_0876 or MscS, CetB, FlhF, PurH, LpxC, Icd, enzyme PglJ is linked to bacterial adaptation in the poultry host 2.4.1.303 UDP-Gal:alpha-D-GlcNAc-diphosphoundecaprenol beta-1,3-galactosyltransferase medicine differences between mammalian and bacterial enzymes could be exploited in the design of specific glycosyltransferase inhibitors that block the synthesis of O-antigens 2.4.1.312 protein O-mannose beta-1,4-N-acetylglucosaminyltransferase medicine mutations in GTDC2, beta-1,3-N-acetylgalactosaminyltransferase 2B3GALNT2, and kinase SGK196 disrupt dystroglycan receptor function and lead to congenital muscular dystrophy 2.4.1.313 protein O-mannose beta-1,3-N-acetylgalactosaminyltransferase medicine a 5-year-old patient heterozygous for a one-base duplication and a missense mutation in the gene B3GALNT2 patient shows psychomotor retardation, ataxia, spasticity, muscle weakness and increased serum creatine kinase levels. The skeletal muscle displays reduced glycosylated alpha-dystroglycan. The brain at 3.5 years of age shows increased T2 signal from supratentorial and infratentorial white matter, a hypoplastic pons and subcortical cerebellar cysts. The patient shows a milder phenotype than previously described patients with mutations in the B3GALNT2 gene 2.4.1.313 protein O-mannose beta-1,3-N-acetylgalactosaminyltransferase medicine mutations in GTDC2, beta-1,3-N-acetylgalactosaminyltransferase 2B3GALNT2, and kinase SGK196 disrupt dystroglycan receptor function and lead to congenital muscular dystrophy 2.4.1.331 8-demethyltetracenomycin C L-rhamnosyltransferase medicine generation of L- and D-stereoisomers of amicetose by combining sugar biosynthesis genes from four different antibiotic gene clusters and transfer of both sugars to the elloramycin aglycone by the sugar flexible ElmGT glycosyltransferase to yield antitumor tetracenomycins 2.4.1.344 type 2 galactoside alpha-(1,2)-fucosyltransferase medicine FUT1 transcript is expressed in some of tumor cell lines. The FUT1 transcript has several forms generated by two distinct transcription start sites and alternative splicing. Two transcription initiation sites of the FUT1 have been identified in gastric cancer cells and in ovarian cancer cells. Only exon 1A is a transcription start site in one more gastric cancer cell line, two colonic cancer cell lines, and in K562 cells, whereas only exon 2A has been identified in HEL cells and in bone marrow cells 2.4.1.344 type 2 galactoside alpha-(1,2)-fucosyltransferase medicine transcript level for beta-D-galactoside alpha-2-L-fucosyltransferase is 40- and 340fold increased in all adenocarcinomas and tumor cell lines, respectively, compared to normal colon mucosa where a low level of mRNA transcript is detected. A variable increase in mRNA transcript levels is observed in 50% of adenomatous polyps. There are no tumor-associated allelic variations found within the H beta-D-galactoside alpha-2-Lfucosyltransferase cDNA 2.4.1.344 type 2 galactoside alpha-(1,2)-fucosyltransferase medicine FUT2 SNPs rs601338 and rs602662 are associated with the risks of respiratory and diarrheal illnesses, as well as vomiting and nocturnal cough, from birth to 24 months of age in infants. The risk of diarrheal infections is significantly higher among infants possessing the G allele as compared to those with the A alleles in FUT2 SNPs. Longer breastfeeding duration predicted a lower risk of diarrhea, independent of infant FUT2 genotype 2.4.1.345 phosphatidyl-myo-inositol alpha-mannosyltransferase medicine PimA is required for viability during macrophage infection. In two different mouse models of infection a dramatic decrease in viable counts is observed upon silencing of the gene. Depletion of PimA results in complete clearance of the mouse lungs during both the acute and chronic phases of infection 2.4.1.355 poly(ribitol-phosphate) beta-N-acetylglucosaminyltransferase medicine methicillin-resistant Staphylococcus aureus is sensitized to beta-lactams upon tarS deletion. Strains lacking tarS have no growth or cell division defects 2.4.1.379 GDP-Man:alpha-D-Gal-diphosphoundecaprenol alpha-1,3-mannosyltransferase medicine construction of bivalent vaccines for preventing both Salmonella typhimurium and Salmonella newport infections by using the aspartate semialdehyde dehydrogenase-based balanced-lethal vector-host system. The constructed plasmid pCZ11 carrying a subset of the Salmonella newport O-antigen gene cluster including the wzx-wbaR-wbaL-wbaQ-wzy-wbaW-wbaZ genes is introduced into Salmonella typhimurium. Upon deletion of the crp gene for attenuation purposes, BALB/c mice are orally immunized with the strains. Compared with a mock immunization, immunization with the vaccine strains induces significant serum IgG responses against both Salmonella typhimurium and Salmonella newport lipopolysaccharide 2.4.1.381 dTDP-Rha:alpha-D-Man-(1->3)-alpha-D-Gal diphosphoundecaprenol alpha-1,2-rahmnosyltransferase medicine construction of bivalent vaccines for preventing both Salmonella typhimurium and Salmonella newport infections by using the aspartate semialdehyde dehydrogenase-based balanced-lethal vector-host system. The constructed plasmid pCZ11 carrying a subset of the Salmonella newport O-antigen gene cluster including the wzx-wbaR-wbaL-wbaQ-wzy-wbaW-wbaZ genes is introduced into Salmonella typhimurium. Upon deletion of the crp gene for attenuation purposes, BALB/c mice are orally immunized with the strains. Compared with a mock immunization, immunization with the vaccine strains induces significant serum IgG responses against both Salmonella typhimurium and Salmonella newport lipopolysaccharide 2.4.1.382 CDP-abequose:alpha-L-Rha2OAc-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Gal-PP-Und alpha-1,3-abequosyltransferase medicine construction of bivalent vaccines for preventing both Salmonella typhimurium and Salmonella newport infections by using the aspartate semialdehyde dehydrogenase-based balanced-lethal vector-host system. The constructed plasmid pCZ11 carrying a subset of the Salmonella newport O-antigen gene cluster including the wzx-wbaR-wbaL-wbaQ-wzy-wbaW-wbaZ genes is introduced into Salmonella typhimurium. Upon deletion of the crp gene for attenuation purposes, BALB/c mice are orally immunized with the strains. Compared with a mock immunization, immunization with the vaccine strains induces significant serum IgG responses against both Salmonella typhimurium and Salmonella newport lipopolysaccharide 2.4.2.1 purine-nucleoside phosphorylase medicine - 2.4.2.1 purine-nucleoside phosphorylase medicine the purine nucleoside phosphorylases may play a role in chemotherapy in two ways: 1. by catalyzing the breakdown of nucleosides that contain purine analogs and by promoting the incorporation of purine and pyrimidine analogs into the nucleotides and nucleic acids of the cell by increasing the intracellular pool of ribose 1-phosphate and deoxyribose 1-phosphate 2.4.2.1 purine-nucleoside phosphorylase medicine the enzyme constitutes a target for antitrichomonial chemotherapy 2.4.2.1 purine-nucleoside phosphorylase medicine overview of clinical aspects 2.4.2.1 purine-nucleoside phosphorylase medicine since PNP inhibitors block the catabolism of purine nucleosides to hypoxanthine and guanine, precursors of uric acid, they should be useful in the treatment of goat and other hyperuricemic conditions. A number of parasites, including the malaria parasite, lacking the ability to synthesize purine nucleotides de novo, must utilize host purines, formed by PBP, for DNA synthesis. Thus inhibition of PNP could prevent the spread of parasitic infection 2.4.2.1 purine-nucleoside phosphorylase medicine structural data from crystal structure may be useful in designing prodrugs that can be activated by E. coli enzyme but not the human enzyme 2.4.2.1 purine-nucleoside phosphorylase medicine high-resolution structure may serve for design of inhibitors with potential pharmacological application 2.4.2.1 purine-nucleoside phosphorylase medicine the enzyme inhibitors 8-amino-5'-deoxy-5'-chloroguanosine and 8-amino-9-benzylguanine may have some antimalarial potential by limiting hypoxanthine production in the parasite-infected erythrocyte 2.4.2.1 purine-nucleoside phosphorylase medicine delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts. Replication-competent retroviral vectors are a potentially efficient gene delivery method and replication-competent retroviral vector mediated PNP gene transfer and fludarabine phosphate treatment might be a novel and potentially therapeutic modality for bladder cancer 2.4.2.1 purine-nucleoside phosphorylase medicine trans-activator of transcription-mediated long-term intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice 2.4.2.1 purine-nucleoside phosphorylase medicine endogenous PNP deficiency leads to specific T-cell immunodeficiency, a genetic disease. PNP inhibition leads to the elevation of 2'-deoxyguanosine levels and accumulation of intracellular deoxyguanosine 5'-triphosphate, inducing cellular apoptosis. Forodesine is a highly potent, orally active, rationally designed PNP inhibitor that is active in preclinical studies with malignant cells and clinical utility against T-cell acute lymphoblastic leukemia and cutaneous T-cell lymphoma 2.4.2.1 purine-nucleoside phosphorylase medicine purine nucleoside phosphorylase inhibition is a novel therapeutic approach for B-cell lymphoid malignancies 2.4.2.1 purine-nucleoside phosphorylase medicine construction of lentiviral vectors containing the human purine-nucleoside phosphorylase gene and transduction of lymphocytes from a purine nucelotide phosphorylase-deficient patient as well as lymphocytes, fibroblasts and bone marrow from purine nucelotide phosphorylase-deficient mice. Transduction significantly increases purine nucelotide phosphorylase expression in purine nucelotide phosphorylase-deficient human lymphocytes, murine lymphocytes, fibroblasts and bone marrow cells. Lenti-purine nucelotide phosphorylase transduction also significantly improves the proliferation of PNP-/- murine lymphocyte and survival of irradiated purine nucelotide phosphorylase-/- fibroblasts. Transduced purine nucelotide phosphorylase-/- bone marrow cells transplanted into purine nucelotide phosphorylase-/- mice express purine nucelotide phosphorylase in vivo, partially restore urinary uric acid secretion, show improved thymocytes maturation, increased weight gain and extended survival of the mice. 12 weeks after transplant, the benefit of lenti-purine nucelotide phosphorylase transduced cells and normal bone marrow diminishes and the percentage of engrafted donor cells decrease 2.4.2.1 purine-nucleoside phosphorylase medicine expression of the Escherichia coli purine nucleoside phosphorylase/9-(2-deoxy-beta-dribofuranosyl)-6-methylpurine suicide gene system in human hepatocarcinoma cells together with a chimeric human alpha-fetoprotein promoter. In the presence of hypoxia, the Escherichia coli purine nucleoside phosphorylase gene directed by the human promoter is specifically expressed in two human hepatocarcinoma cell lines and, the therapy yields significant and selective cytotoxicity in both alpha-fetoprotein-positive and low-alpha-fetoprotein-generating hepatocarcinoma cells 2.4.2.1 purine-nucleoside phosphorylase medicine mutation A117 leads to purine-nucleoside phosphorylase deficiency. Mutation occured in two sisters with a fatal course due to delay in diagnosis. The first patient developed a liver abscess by Aspergillus fumigatus and the second patient developed Mycobacterium tuberculosis complex lymphadenitis and probable pulmonary tuberculosis due to disseminated BCG infection. The patients also suffered from sclerosing cholangitis 2.4.2.1 purine-nucleoside phosphorylase medicine use of mutant E201Q/N243D in Antibody Dependent Enzyme Prodrug Therapy ADEPT by fusion to the human anti-HER2/neu single chain Fv. In vitro the construct binds specifically to HER2/neu expressing tumor cells and localizes the enzyme to tumor cells, where the enzymatic activity of the mutant, but not the wild type enzyme, results in phosphorolysis of the prodrug, 2-fluoro-2'-deoxyadenosine to the cytotoxic drug 2-fluoroadenine causing inhibition of tumor cell proliferation 2.4.2.1 purine-nucleoside phosphorylase medicine for inhibitor (S)-3-(guanin-9-yl)pyrrolidin-N-ylcarbonylphosphonic acid, Ki values widely vary from 16 to 100 nM for enzyme from cancer cell lines. For inhibitor (3S,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N-ylcarbonylphosphonic acid, Ki values are around 10 to 24 nM for enzyme from cancer cell lines 2.4.2.2 pyrimidine-nucleoside phosphorylase medicine the cytostatic and antiviral activity of pyrimidine nucleoside analogues is markedly decreased by a Mycoplasma hyorhinis infection and the phosphorolytic activity of the mycoplasmas is responsible for this 2.4.2.3 uridine phosphorylase medicine uridine phosphorylase plays an important role in the antineoplastic activity of 5-fluorouracil and in the anabolism of its oral prodrug, capecitabine, through the conversion of 5'-deoxy-5-fluorouridineinto 5-fluorouracil. TNF-alpha efficiently induces UPase gene expression through a NF-kappaB subunit p65-dependent pathway enhancing cell sensitivity to 5'-deoxy-5-fluorouridine. The elucidation of this regulation mechanism may aid in the clinical use of 5-fluorouracil-based chemotherapy 2.4.2.3 uridine phosphorylase medicine the paired expression level of the uridine phosphorylase gene in gastric cancer is a possible prognostic marker for patients with 5-fluorouracil treatment 2.4.2.4 thymidine phosphorylase medicine structural insight into the binding mode of the inhibitor to this important drug target forms the basis for designing novel inhibitors for use in anticancer therapy 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase activity might be useful in diagnostic characterization of ovarian cancer 2.4.2.4 thymidine phosphorylase medicine tumor-associated macrophages that express thymidine phosphorylase may be a good target for chermotherapy of thymidine phosphorylase positive solid tumors 2.4.2.4 thymidine phosphorylase medicine because pancreatic cancer is sensitive to 5-fluorouracil, thymidine phosphorylase-activated oral drug capecitabine in tumoral and endothelial cells and tumor infiltrating thymidine phosphorylase-positive macrophages could increase the concentration of 5-fluorouracil at tumor site, thus resulting in an enhanced antitumor activity 2.4.2.4 thymidine phosphorylase medicine expression of PD-ECGF/TP may play an important role in the progression of solid tumors, and inhibitors of thymidine phosphorylase and analogs of the degradation products of thymidine may suppress the growth of tumors by promoting apoptosis 2.4.2.4 thymidine phosphorylase medicine important target enzyme for cancer chemotherapy 2.4.2.4 thymidine phosphorylase medicine mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder characterized by ptosis and progressive external ophthalmoplegia, peripheral neuropathy, severe gastrointestinal dysmotility, cachexia and leukoencephalopathy, morphologically abnormal mitochondria and defects of respiratory chain enzymes. Patients harbor depletion, multiple deletions, and point mutations of mitochondrial DNA. This disorder is caused by loss-offunction mutations in the gene encoding thymidine phosphorylase. In patients with mitochondrial neurogastrointestinal encephalomyopathy, thymidine phosphorylase activity is very low or absent resulting in dramatically elevated levels of plasma thymidine and deoxyuridine. It is hypothesized that the increased levels of thymidine and deoxyuridine cause mitochondrial nucleotide pool imbalances that, in turn, generate mtDNA alterations 2.4.2.4 thymidine phosphorylase medicine there is no tumour-selective depletion of thymidine and there does not appear to be any potential benefit of combining antibody-targeted thymidine phosphorylase with the thymidylate synthase inhibitor raltitrexed 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase activity in normal liver tissue adjacent to hepatocellular carcinoma is related to tumor occurrence and may predict postoperative tumor recurrence. Patients who have a high thymidine phosphorylase level in normal liver tissue have significantly earlier recurrence compared with patients who have a low thymidine phosphorylase level. Patients who have a low thymidine phosphorylase level in adjacent liver tissue have a 0.387fold higher risk of postoperative recurrence compared with patients who have a high TP level 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase expression seems to be an important prognostic indicator in gastric cancer patients only when the enzyme is located in tumor cells 2.4.2.4 thymidine phosphorylase medicine a high level of thymidine phosphorylase gene expression is significantly associated with favorable diagnosis of patients treated with 5-fluorouracil-based chemotherapy 2.4.2.4 thymidine phosphorylase medicine dThdPase plays an important role in tumor angiogenesis in ductal adenocarcinoma of the pancreas 2.4.2.4 thymidine phosphorylase medicine expression of thymidine phosphorylase mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy 2.4.2.4 thymidine phosphorylase medicine gliostatin and vascular endothelial growth factor have synergistic effects on angiogenesis in rheumatoid synovitis 2.4.2.4 thymidine phosphorylase medicine immunhistochemical evaluation of thymidine phosphorylase expression is a promising predictor of therapeutic benefit from docetaxel-modulated capecitabine for metastatic breast cancer 2.4.2.4 thymidine phosphorylase medicine in gastric cancer, thymidine phosphorylase expression of the cancer cells, not stromal cells may play an important role in tumor growth by microvessel formation 2.4.2.4 thymidine phosphorylase medicine low tumour expression level of thymidine phosphorylase is linked with improved outcome for colorectal cancer patients treated with 5-fluorouracil, low thymidine phosphorylase protein expression is predictive of good response to 5-fluorouracil chemotherapy 2.4.2.4 thymidine phosphorylase medicine the ThdPase expression in tumors may be a predictive marker for the effectiveness in response to chemotherapy with irinotecan and 5'-deoxy-5-fluoridine 2.4.2.4 thymidine phosphorylase medicine the thymidine phosphorylase/dihydropyrimidine dehydrogenase ratio may be useful as prognostic factor in patients with pancreatic cancer 2.4.2.4 thymidine phosphorylase medicine there is no significant association between the occurrence of palmar-plantar erythrodysesthesia after capecitabine treatment and higher tumor thymidine phosphorylase levels 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase delivers information about endometrial cancer progression 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase enzymatic activity may be associated with lymph node metastasis 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase expression at the invasive front of tumor may be an important prognostic factor for T3 rectal cancer 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase expression correlates well with tumor grade, metastasis and shorter patient survival in colorectal, pancreatic, renal, ovarian, cervical, bladder and non-small cell lung cancer, loss of function mutants of thymidine phosphorylase case the disease mitochondrial neurogastrointestinal encephalomyopathy 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase expression in breast cancer can represent a biomarker of sensitivity to capecitabine treatment 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase expression in cancer-infiltrating inflammatory cells can affect lymph node metastasis and patients' survival in gastric cancer 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is a predictive biomarker in breast cancer 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is a predictive factor of therapeutic efficacy of capecitabine chemotherapy for breast cancer 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is a predictor of response to capecitabine-based chemotherapy in gastric cancer patients 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is an independent prognostic and therapeutic marker for nasopharyngeal carcinoma 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is associated with tumor angiogenesis 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase may be involved in up-regulating P-selectin expression in breast cancer cells, tumor cell thymidine phosphorylase correlates with tumor cell P-selectin but not with endothelial cell P-selectin in vascular endothelial cells 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase plays a role in oropharyngeal tumourigenesis and 5-fluorouracil activation in the adjuvant setting of oropharyngeal squamous cell carcinoma patients 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase serum levels reflect the prognosis of patients with colorectal cancer, particularly the risk of liver metastasis 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is a promising target for the treatment of vascular obstructive diseases, effect on cancer cells, detailed overview 2.4.2.4 thymidine phosphorylase medicine use of thymidine phosphorylase inhibitors might offer a promising strategy for cancer treatment 2.4.2.4 thymidine phosphorylase medicine methods to measure thymidine and deoxyuridine concentrations and thymidine phosphorylase activity in biological samples. Thymidine phosphorylase activity can be measured by an endpoint determination of the thymine formed after 1 h incubation of the buffy coat homogenate in the presence of a large excess of its substrate thymidine, either spectrophotometrically or by HPLC-UV. The protocols allow the detection of thymidine phosphorylase dysfunction in patients with mitochondrial neurogastrointestinal encephalomyopathy, MNGIE 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is identified as a prime target for developing anticancer therapies 2.4.2.4 thymidine phosphorylase medicine thymidine phosphorylase is involved regulation of intra- or extracellular thymidine concentration, angiogenesis, cancer chemotherapy, radiotherapy, as well as tumor imaging 2.4.2.6 nucleoside deoxyribosyltransferase medicine the low substrate specificity of the enzyme is used advantageously for synthesis of nucleoside analogs, some of them of medical interest 2.4.2.7 adenine phosphoribosyltransferase medicine expression of both Escherichia coli purine nucleoside phosphorylase and human adenine phosphoribosyl transferase in tumor cell lines. Purine nucleoside phosphorylase cleaves purine nucleoside analogs to generate toxic adenine analogs, which are activated by adenine phosphoribosyl transferase to metabolites that inhibit RNA and protein synthesis. In vivo studies with 6-methylpurine-2'-deoxyriboside, 2-fluoro-2'-deoxyadenosine or 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-phosphate indicate that increased adenine phosphoribosyl transferase in human tumor cells coexpressing Escherichia coli purine nucleoside phosphorylase does not enhance either the activation or the anti-tumor activity of any of the three prodrugs. Expression of excess adenine phosphoribosyl transferase in bystander cells improves the activity of 6-methylpurine-2'-deoxyriboside, but diminishes the activity of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-phosphate. In vitro studies indicate that increasing the expression of adenine phosphoribosyl in the cells does not significantly increase the activation of 6-methylpurine 2.4.2.8 hypoxanthine phosphoribosyltransferase medicine target for antiparasite drug design 2.4.2.8 hypoxanthine phosphoribosyltransferase medicine target for anti-trichomonial therapy 2.4.2.8 hypoxanthine phosphoribosyltransferase medicine potential target for antiparasitic chemotherapy 2.4.2.8 hypoxanthine phosphoribosyltransferase medicine prospective pharmacodynamic study to determine the effect of combination therapy for treatment of inflammatory bowel disease on the activity of hypoxanthine-guanine phosphoribosyltransferase, which activates of thiopurine prodrugs to thioguanine nucleotides. The activity of hypoxanthine-guanine phosphoribosyltransferase and thioguanine nucleotides concentrations was measured in red blood cells during thiopurine monotherapy and after 4 weeks of combination therapy. The activity of hypoxanthine-guanine phosphoribosyltransferase was also measured after 12 weeks of combination therapy. Combination therapy increases the activity of hypoxanthine-guanine phosphoribosyltransferase and subsequently thioguanine nucleotides concentrations 2.4.2.8 hypoxanthine phosphoribosyltransferase medicine the enzyme is an anti-malarial drug target 2.4.2.8 hypoxanthine phosphoribosyltransferase medicine the enzyme is an efficient antischistosomal chemotherapy target 2.4.2.9 uracil phosphoribosyltransferase medicine enzyme is a possible therapeutic target 2.4.2.9 uracil phosphoribosyltransferase medicine combination of 5-flurocytosine/cytosine deaminase-uracil phosphoribosyltransferase with curcumin can be a potential chemosensitization strategy for cancer treatment 2.4.2.9 uracil phosphoribosyltransferase medicine increased expression of UPRT may improve the antitumoral effect of 5-fluorouracil and 5-fluorocytosine, and thereby enhance the potential gene-directed enzyme prodrug therapy 2.4.2.9 uracil phosphoribosyltransferase medicine the CD/UPRT construct confers 5-fluorocytosine sensitivity to some pancreatic cell lines 2.4.2.9 uracil phosphoribosyltransferase medicine the efficiacy of 5-fluorouracil-based chemotherapy in prostate cancers can be significantly improved by targeted expression of the suicide gene UPRT under the control of the human prostate-specific membrane antigen promotor/enhancer 2.4.2.9 uracil phosphoribosyltransferase medicine in presence of 5-fluorocytosine, rat glioblastoma cells C6 and C6r5-FU are sensitive to the cytotoxic effect of human adipose tissue-derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase. The stem cells migrate to glioblastoma cells in vivo and mediate inhibition of glioblastoma growth 2.4.2.9 uracil phosphoribosyltransferase medicine the enzyme augments the cancer treatment efficacy of 5-fluorouracil in vitro 2.4.2.9 uracil phosphoribosyltransferase medicine the enzyme increases the sensitivity to 5-fluorouracil in HaP-T1 cells in vitro 2.4.2.10 orotate phosphoribosyltransferase medicine enzyme activity is 7.5fold enhanced in bladder carcinoma compared to normal. Bladder carcinoma subtypes show distinct levels of enzyme activity and there is positive association between the activity levels of enzyme and thymidylate synthase/thymidine kinase. Enzyme activity in bladder carcinoma cells also correlates positively with their sensitivity to 5-fluorouracil 2.4.2.10 orotate phosphoribosyltransferase medicine immunochemical detection of tumoral enzyme expression by antibody, method for predicting the clinical response to 5-fluorouracil-based chemotherapy 2.4.2.10 orotate phosphoribosyltransferase medicine OPRT activity is significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis, thus OPRT activity level in tumor tissue may be an important prognostic factor for survival in Dukes B and C colorectal carcinoma cells with radical resection and adjuvant chemotherapy with orally administered tegafur/uracil 2.4.2.10 orotate phosphoribosyltransferase medicine OPRT expression is negatively associated with colorectal cancer progression 2.4.2.10 orotate phosphoribosyltransferase medicine the expression of OPRT may be useful to predict the response to adjuvant chemotherapy with 5-fluorouracil in human pancreatic cancer 2.4.2.10 orotate phosphoribosyltransferase medicine the OPRT mRNA level is positively correlated with the 5-fluorouracil efficacy in antitumor therapy 2.4.2.10 orotate phosphoribosyltransferase medicine the enzyme is used as a predictor of benefit from S-1 adjuvant chemotherapy for cholangiocarcinoma patients. Cholangiocarcinoma patients with high enzyme expression can benefit from postoperative adjuvant S-1 therapy, which increases the disease-free survival 2.4.2.10 orotate phosphoribosyltransferase medicine the expression of the enzyme shows no association with the overall survival or diseasex1efree survival, even in the patients who receive Sx1e1 adjuvant chemotherapy 2.4.2.12 nicotinamide phosphoribosyltransferase medicine longevity enzyme for human SMCs 2.4.2.12 nicotinamide phosphoribosyltransferase medicine a dose of 75 mg/kg GMX1777, i.e. 1-[2-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)-ethoxy-carbonyloxymethyl]-4-[N'-cyano-N''-(6-(4-chlorophenyl)-hexyl)-N-guanidino]pyridinium chloride, prodrug of GMX1778, administered over a 24 h intravenous infusion causes tumor regression in the IM-9 model, the SHP-77 model, and HCT-116 model. A 72 h continuous intravenous infusion is also effective in the IM-9 model, but is associated with smaller therapeutic index 2.4.2.12 nicotinamide phosphoribosyltransferase medicine a dose of 75 mg/kg GMX1777, i.e. 1-[2-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)-ethoxy-carbonyloxymethyl]-4-[N'-cyano-N''-(6-(4-chlorophenyl)-hexyl)-N-guanidino]pyridinium chloride, prodrug of GMX1778, administered over a 24 h intravenous infusion produces GMX1778 steady-state plasma levels of about 1 microg/ml and causes nicotinamide dinucleotide levels to decrease significnantly in tumors. Nicotinic acid protects mice treated with a lethal dose of GMX1777 2.4.2.12 nicotinamide phosphoribosyltransferase medicine specific inhibition of enzyme transport into the nucleus might be a potential avenue for managing cancer 2.4.2.12 nicotinamide phosphoribosyltransferase medicine the enzyme is a therapeutic target in metastatic melanoma 2.4.2.22 xanthine phosphoribosyltransferase medicine the enzyme lacks a mammalian counterpart and is, therefore, a potential target for antiparasitic therapy 2.4.2.26 protein xylosyltransferase medicine monitoring of the seminal plasma for enzyme activity is proposed to be an advantegeous additional biochemical parameter to improve in vitro fertilization methods, because the activity is reduced in seminal plasma of infertile men 2.4.2.26 protein xylosyltransferase medicine serum xylosyltransferase activity is a biochemical marker for the assessment of disease activity in systemic sclerosis and for the diagnosis of fibrotic remodeling processes. Sequence variations in the XT-I and XT-II coding genes are identified as risk factors for diabetic nephropathy, osteoarthritis or pseudoxanthoma elasticum. Important role of the xylosyltransferases as disease modifiers in pathologies which are characterized by an altered proteoglycan metabolism 2.4.2.26 protein xylosyltransferase medicine serum xylosyltransferase I, the novel fibrosis marker, may be useful for the assessment of extracellular matrix alterations and disease activity in Pseudoxanthoma elasticum 2.4.2.26 protein xylosyltransferase medicine xylosyltransferase I is a fibrosis marker 2.4.2.26 protein xylosyltransferase medicine serum xylosyltransferase activity is a biochemical marker for the assessment of disease activity in systemic sclerosis and for the diagnosis of fibrotic remodeling processes, sequence variations in the XT-I coding gene are identified as risk factors for diabetic nephropathy, osteoarthritis or pseudoxanthoma elasticum 2.4.2.26 protein xylosyltransferase medicine serum xylosyltransferase activity is a biochemical marker for the assessment of disease activity in systemic sclerosis and for the diagnosis of fibrotic remodeling processes, sequence variations in the XT-II coding gene are identified as risk factors for diabetic nephropathy, osteoarthritis or pseudoxanthoma elasticum 2.4.2.26 protein xylosyltransferase medicine serum XylT levels may be an informative biomarker in patients who suffer from diseases affecting platelet and/or liver homeostasis 2.4.2.26 protein xylosyltransferase medicine ways of modulating the XYLT1 gene expression, especially in the development of therapeutic strategies for the treatment of fibrotic remodeling processes or cartilage repair 2.4.2.28 S-methyl-5'-thioadenosine phosphorylase medicine gene is linked to the important tumor suppressor gene p16INK4A, enzyme is of key importance in defining the chromosomal area homozygously deleted in a large number of human tumors, absence of enzyme activity only in malignant cells is of great value in developing selective antitumor therapeutic strategies 2.4.2.28 S-methyl-5'-thioadenosine phosphorylase medicine possibility of targeting the enzyme in the design of an enzyme-selective therapy for patients with T-cell acute lymphoblastic leukemia and other enzyme-deficient malignancies 2.4.2.28 S-methyl-5'-thioadenosine phosphorylase medicine enzyme is a potential chemotherapeutic target 2.4.2.29 tRNA-guanosine34 preQ1 transglycosylase medicine the enzyme is a target for the design of potent drugs against Shigellosis 2.4.2.31 NAD+-protein-arginine ADP-ribosyltransferase medicine isolation of ADP-ribosyltransferase toxin CDT producing strains of Peptoclostridium difficile from Equidae with gastro-intestinal disease. Out of 17 strains isolated from Equidae, 11 are positive for the genes tcdA and tcdB encoding ToxA and ToxB. In addition four of these 11 isolates are positive for the cdtA gene encoding the catalytic subunit of the ADP-ribosyltransferase CDT 2.4.2.31 NAD+-protein-arginine ADP-ribosyltransferase medicine Peptoclostridium difficile can be divided into at least five diffent toxin-producing groups: large clostridial cytotoxins producers, large clostridial cytotoxins and binary toxin producers, toxin B-only producers, toxin B and binary toxin producers and binary toxin-only producers. These groupings add further support to the theory Peptoclostridium difficile is divided into stable subpopulations that have evolved from common ancestors 2.4.2.36 NAD+-diphthamide ADP-ribosyltransferase medicine therapy for autoimmune diabetes with glutamic acid decarboxylase 65 as autoantigen combined with cholera toxin B subunit as adjuvans lowering the number of antigens needed for autoimmune suppression, oral application for 5 weeks reduces insulitis of pancreas in mouse model 2.4.2.38 glycoprotein 2-beta-D-xylosyltransferase medicine development of diagnostic and therapeutic strategies due to importance of xylose transfer in cryptococcal biology, pathogenesis and virulence 2.4.2.38 glycoprotein 2-beta-D-xylosyltransferase medicine xylose residues within the capsule polysaccharide are important for normal host-pathogen interaction, loss of CXT1p attenuates virulence 2.4.2.38 glycoprotein 2-beta-D-xylosyltransferase medicine loss of XT1 leads to attenuation of virulence 2.4.2.38 glycoprotein 2-beta-D-xylosyltransferase medicine the enzyme is a biomarker for myofibroblast differentiation and fibrotic development 2.4.2.45 decaprenyl-phosphate phosphoribosyltransferase medicine the enzyme is a good target for the development of tuberculosis drugs 2.4.2.61 alpha-dystroglycan beta1,4-xylosyltransferase medicine gene defects of TMEM5 are involved in severe cobblestone lissencephaly type A 2.4.2.64 tRNA-guanosine34 queuine transglycosylase medicine the enzyme is required for pathogenicity in Shigella flexneri and therefor is a potentially novel antibacterial target 2.4.3.1 beta-galactoside alpha-(2,6)-sialyltransferase medicine protein sialylation might be a target to overcome radioresistance in radiation therapie 2.4.3.1 beta-galactoside alpha-(2,6)-sialyltransferase medicine two kinds of sandwich enzyme-linked immunosorbent assay (ELISA) systems are very useful tools for measuring plasma ST6Gal I, which represents a potential biomarker for diagnosing hepatic diseases 2.4.3.1 beta-galactoside alpha-(2,6)-sialyltransferase medicine patients with pancreatic ductal adenocarcinoma expressing higher enzyme levels present poorer prognosis compared to other groups 2.4.3.1 beta-galactoside alpha-(2,6)-sialyltransferase medicine the enzyme is associated with reduced recurrence-free intervals and a poorer overall survival in ovarian, prostate and pancreatic cancer 2.4.3.1 beta-galactoside alpha-(2,6)-sialyltransferase medicine increased enzyme expression in hepatocellular carcinoma tissues correlates with poor prognosis 2.4.3.3 alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase medicine St6GalNAc-II expression provides a prognostic factor for patient survival in human colorectal carcinomas, overexpression is related to poor patient survival 2.4.3.3 alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase medicine patients with IgA nephropathy display an aberrant glycosylation of IgA. EBV-immortalized IgA1-producing cells from these patients indicate a decrease in beta1,3-glucosyltransferase activity and an increase in N-acetylgalactosamine-specific alpha2,6-sialyltransferase activity, with concomitant increase in alpha2,6-sialyltransferase gene expression. EBV-immortalized cells from patients with lupus nephritis and healthy individuals do not produce IgA with the defective galactosylation pattern 2.4.3.3 alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase medicine sialylated histo-blood group carbohydrate CD175 is present in all hematopoietic cell lines and native lymphocytes examined. CD175 and sialylated CD175 are preferentially expressed on erythroblastic leukemia cell lines. Presence of sialylated CD175 is consistent with the expression of the gene encoding alpha2,6-sialyltransferase ST6GalNAc-1 2.4.3.4 beta-galactoside alpha-2,3-sialyltransferase medicine the enzyme is a prognostic factor for migration and peritoneal dissemination of human ovarian cancer cells. High enzyme expression is associated with advanced stage epithelial ovarian cancer 2.4.3.6 N-acetyllactosaminide alpha-2,3-sialyltransferase medicine the enzyme is a drug target for modulating leukocyte trafficking in human disorders, including autoimmune diseases and cancer 2.4.3.7 alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3-N-acetylgalactosaminide 6-alpha-sialyltransferase medicine the expression profiles of isoform ST6GalNAc VI among 20 renal cancer cell lines correlates clearly with those of disialylgalactosylgloboside, suggesting that the sialyltransferase involved in the synthesis of disialylgalactosylgloboside in the kidney is ST6GalNAc-VI. ST6GalNAc-VI and disialylgalactosylgloboside are found in proximal tubule epithelial cells in normal kidney tissues, while they are downregulated in renal cancer cell lines and cancer tissues 2.4.3.8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase medicine enhancing effects of enzyme on proliferation or mobility are differential depending on the cell type 2.4.3.8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase medicine enzyme has an apoptotic effect on ECV304 cells through downregulation of B-cll/CLL lymphoma 2 expression via dephosphorylation of AKT and cyclic-AMP responsive element binding protein 2.4.3.8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase medicine examination of amyloid beta-ganglioside interactions in neural tissue from mice lacking the gene coding for GD3 synthase, St8sia1, and in a double-transgenic mouse model of Alzheimer’s disease mutated in amyloid precursor protein APP and presenilin PSEN1 cross-bred with GD3 synthase deficient mice. In primary neurons and astrocytes lacking GD3 synthase, amyloid beta-induced cell death and amyloid beta aggregation are inhibited. Like GD3 synthase eficient and APP/PSEN1 double-transgenic mice, APP/PSEN1/GD3 synthase deficient triple-mutant mice are indistinguishable from wild-type mice on casual examination. APP/PSEN1 double-transgenics exhibit robust impairments on a number of reference-memory tasks. In contrast, APP/PSEN1/GD3 synthase deficient triple-mutant mice perform as well as wild-type control and GD3-synthase deficient mice. Consistent with the behavioral improvements, both aggregated and unaggregated amyloid beta and associated neuropathology are almost completely eliminated in triple-mutant mice 2.4.3.8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase medicine plasma membrane associated gangliosides GD3 play important roles in apoB secretion, and an enhancement in GD3 levels might be a risk factor for the development of atherosclerosis by increasing the secretion of triglyceride-enriched apoB containing lipoproteins 2.4.3.8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase medicine adenoviral enzyme can slow the growth of ganglioside GD3 expressing tumors in patients 2.4.3.9 lactosylceramide alpha-2,3-sialyltransferase medicine GM3 synthase may be of value as a therapeutic target in breast cancer 2.4.3.9 lactosylceramide alpha-2,3-sialyltransferase medicine the enzyme is a marker of hereditary inclusion body myopathy 2.4.99.18 dolichyl-diphosphooligosaccharide-protein glycotransferase medicine PglB-mediated transfer of poylsaccharides might be valuable for in vivo production of O-polysaccharides-protein congugates for use as antibacterial vaccines 2.4.99.18 dolichyl-diphosphooligosaccharide-protein glycotransferase medicine the development of powerful inhibitors of this enzyme would be valuable in the quest for antibiotics for Campylobacter jejuni-induced gastrointestinal disorders 2.4.99.18 dolichyl-diphosphooligosaccharide-protein glycotransferase medicine mutation in OTase subunits are responsible for isolated cognitive deficit 2.4.99.18 dolichyl-diphosphooligosaccharide-protein glycotransferase medicine enzyme inhibition could have therapeutic potential against trypanosomiasis 2.4.99.18 dolichyl-diphosphooligosaccharide-protein glycotransferase medicine the relaxed specificity of the PglB oligosaccharyltransferase toward the glycan structure is exploited to create novel N-glycan structures containing two distinct Escherichia coli or Pseudomonas aeruginosa O antigens. PglB-mediated transfer of polysaccharides might be valuable for in vivo production of O polysaccharides-protein conjugates for use as antibacterial vaccines 2.4.99.19 undecaprenyl-diphosphooligosaccharide-protein glycotransferase medicine application for protein glycosylation in recombinant bacteria in the production of potent conjugate vaccines where polysaccharide antigens of pathogenic bacteria are covalently bound to immunogenic carrier proteins 2.4.99.23 lipopolysaccharide heptosyltransferase I medicine absence of the enzyme results in a truncated lipopolysaccharide associated with the deeprough phenotype causing a greater susceptibility to antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria. Thus, the enzyme represents a promising target in antibacterial drug design 2.4.99.23 lipopolysaccharide heptosyltransferase I medicine the enzyme represent a promising and attractive target for the discovery of new Gram-negative antibacterial drugs based on antivirulence mechanisms 2.5.1.2 thiamine pyridinylase medicine - 2.5.1.2 thiamine pyridinylase medicine ferns that have thiaminase produce thiamine deficiency in rat, cattle and horse 2.5.1.2 thiamine pyridinylase medicine plant extracts that have thiaminase activity can be toxic to animals or humans 2.5.1.2 thiamine pyridinylase medicine bacteria can infect organisms and produce thiaminase disease 2.5.1.2 thiamine pyridinylase medicine thiamine transporter THTR2 downregulation in breast tumors may present a nutritional vulnerability that can be exploited by thiaminase I enzyme therapy 2.5.1.2 thiamine pyridinylase medicine modification of thiaminase with linear chain methox polyethylene glycol of 5 kDa eliminates cytotoxic activity in all cell lines tested. Both native thiaminase and 5k-PEGylated thiaminase efficiently depletes thiamine from cell culture medium, and both can use intracellular phosphorylated thiamine as substrates. Native enzyme more effectively depletes thiamine and thiamine diphosphate in RS4 leukemia cell cytosol, and native thiaminase depresses cellular respiration, whereas PEGylated thiaminase does not. Despite the lack of in vitro cytotoxicity, PEGylation markedly increases the in vivo toxicity of the enzyme. The half-life of native thiaminase is 1.5 h compared with 34.4 h for the 5k-PEGylated enzyme. Serum thiamine levels are depleted by both native and 5k-PEGylated enzyme. Despite superior pharmacokinetics, 5k-PEGylated thiaminase shows no antitumor effect against an RS4 leukemia xenograft, in contrast to native thiaminase 2.5.1.6 methionine adenosyltransferase medicine animals fed ethanol intragastrically for 9 weeks switch hepatic MAT expression from MAT1A to MAT2A followed by decrease in S-adenosylmethionine levels, hypomethylation of c-myc, increase in c-myc expression and increased DNA strand break accumulation 2.5.1.6 methionine adenosyltransferase medicine MAT1A knockout mice, spontaneous steatohepatitis develops by 8 months, hepatocellular carcinoma develops by 18 months 2.5.1.6 methionine adenosyltransferase medicine patients with acoholic liver disease, decrease in hepatic enzyme activity due to decreased MAT1A expression and inactivation of MAT1A-encoded isoenzymes 2.5.1.6 methionine adenosyltransferase medicine S-adenosyl-L-methionine is applied to patients with alcoholic liver disease 2.5.1.7 UDP-N-acetylglucosamine 1-carboxyvinyltransferase medicine enzyme is a target for the antibiotic fosfomycin 2.5.1.7 UDP-N-acetylglucosamine 1-carboxyvinyltransferase medicine target for development of antibacterial agents 2.5.1.9 riboflavin synthase medicine enzyme is an attractive target for antimicrobial agents, since it is nonexistent in humans 2.5.1.10 (2E,6E)-farnesyl diphosphate synthase medicine chronic treatment with an FPPS inhibitor attenuates the development of cardiac hypertrophy and fibrosis 2.5.1.10 (2E,6E)-farnesyl diphosphate synthase medicine shRNA-mediated knock-down of expression results in conversion of hematopoietic and nonhematopoietic tumor cell lines into Vgamma9Vdelta2 T-cell activators. Knock-down cells activate Vgamma9Vdelta2 cells. Vgamma9Vdelta2 cells act as sensors of a dysregulated isoprenoid metabolism, therapeutic down-modulation of FPPS expression may be used as a tool to target tumor cells to Vgamma9Vdelta2 T-cell mediated immunosurveillance 2.5.1.10 (2E,6E)-farnesyl diphosphate synthase medicine the enzyme is a target for Chagas’ disease chemotherapy 2.5.1.15 dihydropteroate synthase medicine sulfonamide resistance in Pneumocystis jirovecii, determination of gene mutations in South African strain of Pneumocystis jirovecii, one of 53 DHPS genes sequenced contains the double mutation T55A/P57S 2.5.1.15 dihydropteroate synthase medicine DHPS is an antimicrobial therapeutic target by chemical and genetic means 2.5.1.15 dihydropteroate synthase medicine the enzyme is important in predicting the emergence of drug resistance to sulphadoxine-pyrimethamine 2.5.1.16 spermidine synthase medicine pharmacologic inhibition of spermidine ssynthase, and perhaps all components of the polyamine biosynthetic pathway, is a valid therapeutic strategy for the treatment of visceral and, potentially, other forms of leishmaniasis 2.5.1.17 corrinoid adenosyltransferase medicine ACA-mediated catalysis provides insights in molecular basis for dysfunction in methylmalonic aciduria 2.5.1.17 corrinoid adenosyltransferase medicine insight in molecular mechanism of methylmalonic aciduria 2.5.1.18 glutathione transferase medicine the enzyme is a promising vaccine candidate against schistosomiasis 2.5.1.18 glutathione transferase medicine isozyme GST-1 is a vaccine target 2.5.1.18 glutathione transferase medicine GSTs catalyzing inactivation of anticancer drugs may find clinical use in protecting sensitive normal tissues to toxic side effects in treated patients, and as selectable markers in gene therapy 2.5.1.18 glutathione transferase medicine the GST isozymes are useful as vaccine against hookworm infection 2.5.1.18 glutathione transferase medicine dichloroacetate, a degradation product of chloral hydrate, is further metabolized by glutathione transferase zeta 1, and inhibits its own metabolism through depletion/inactivation of GSTZ1/MAAI with repeated exposure, resulting in lower plasma clearance of the drug and the accumulation of the urinary biomarker maleylacetone. The amount of dichloroacetate produced from clinically relevant doses of chloral hydrate, although insufficient to alter dichloroacetate kinetics, is sufficient to inhibit MAAI and tyrosine catabolism 2.5.1.21 squalene synthase medicine induction of enzyme by a diet containing fluvastatin and cholestyramine 2.5.1.21 squalene synthase medicine enzyme may be important during response to infection and inflammation 2.5.1.21 squalene synthase medicine 1-allyl-2-[3-(benzylamino)propoxy]-9H-carbazole shows 50% inhibition of enzyme at 63 nM, significant reduction of both plasma cholesterol and plasma triglyceride levels following oral dosing 2.5.1.21 squalene synthase medicine potential target for antineoplastic intervention 2.5.1.21 squalene synthase medicine single nuceotide polymorphism K45R, i.e. rs11549147:A>G is associated with increased total cholesterol and non-high-density lipoprotein cholesterol. Mutation also influences low-density lipolrotein cholesterol and triglycerides 2.5.1.21 squalene synthase medicine aim of inhibitors in treatment of hypercholesterolemia 2.5.1.21 squalene synthase medicine attractive target for pharmaceutical discovery in treatment of hypercholestermiae 2.5.1.21 squalene synthase medicine squalene synthase is a potential target for antilipogenic and antiinfective therapies 2.5.1.22 spermine synthase medicine specific and marked decrease in spermine after diet containing N-(3-aminopropyl)cyclohexylamine 2.5.1.22 spermine synthase medicine enzyme null mutant, lack of spermine increases sensitivity of cells to anti-tumor agents 2.5.1.22 spermine synthase medicine mutation p.G56S in the N-terminal region of spermine synthase greatly reduces spermine synthase activity and leads to severe epilepsy and cognitive impairment related to Snyder-Robinson X-linked recessive mental retardation syndrome 2.5.1.22 spermine synthase medicine Snyder-Robinson syndrome (SRS) mutations drastically reduce spermine synthase activity and cause mild-to-moderate mental retardation, and may lead to a variety of other characteristics including a marfanoid habitus, skeletal defects, osteoporosis, and facial asymmetry, as well as hypotonia and movement disorders 2.5.1.26 alkylglycerone-phosphate synthase medicine enzyme levels are strongly reduced in fibroblasts derived from Zellweger syndrome and rhizomelic chondrodysplasia punctata patients 2.5.1.26 alkylglycerone-phosphate synthase medicine in fibroblast cell lines derived from Zellweger syndrome and rhizomelic chondrodysplasia punctata patients enzyme is mainly present as precursor form 2.5.1.26 alkylglycerone-phosphate synthase medicine enzyme AGPS may be a potential glioma and hepatic carcinoma therapeutic target 2.5.1.29 geranylgeranyl diphosphate synthase medicine this enzyme is an attractive target for drug development, because the order of inhibition of the enzyme by a number of bisphosphonates is the same as that for inhibition of parasite growth. This enzyme as a valid target for the chemotherapy of toxoplasmosis 2.5.1.29 geranylgeranyl diphosphate synthase medicine women with 2 deletion alleles of GGPS1 -8188A ins/del (rs3840452) have significantly higher femoral neck bone marrow densitiy at baseline compared with those with one or no deletion allele. The response rate of women with 2 deletion alleles of GGPS1 -8188A ins/del (28.6%) is significantly lower than the rate of women with one or no deletion allele. Women with 2 deletion alleles of GGPS1 -8188A ins/del have 7fold higher risk of non-response to bisphosphonate therapy compared with women with other genotypes in GGPS1 -8188. Other polymorphisms in or GGPS1 are not associated with lumbar spine bone marrow density or femoral neck bon marrow density 2.5.1.29 geranylgeranyl diphosphate synthase medicine validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism 2.5.1.29 geranylgeranyl diphosphate synthase medicine enzyme expression is significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of geranylgeranyl diphosphate synthase is correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients 2.5.1.31 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] medicine enzyme represents a potential target for developing new antibiotics 2.5.1.39 4-hydroxybenzoate polyprenyltransferase medicine in patients with encephalomyopathy, nephropathy and severe CoQ10 deficiency, a homozygous mutation was identified in the CoQ10 biosynthesis gene COQ2. mRNA levels of this gene are significantly increased in patients fibroblast, and its activity is significantly lower in fibroblasts of patients with mutation c.890A.G relative to controls and CoQ10-deficient fibroblasts from ataxic patient 2.5.1.46 deoxyhypusine synthase medicine elevated mRNA levels of the target enzymes deoxyhypusine synthase (DHPS) and ornithine decarboxylase (ODC) correlate with poor prognosis in a large cohort of neuroblastoma tumors. The DHPS inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) and the ODC inhibitor alpha-difluoromethylornithine (DFMO) are target-specific and in combination induce synergistic effects in neuroblastomas at concentrations that are not individually cytotoxic. The drug combination induces caspase 3/7/9, but not caspase 8-mediated apoptosis, in neuroblastoma cells. Hypusinated eIF5A levels and intracellular spermidine levels correlate directly with drug treatments 2.5.1.46 deoxyhypusine synthase medicine in a transgenic mouse model of type 1 diabetes, in which human GAD65 is expressed in pancreatic beta-cells, and human MHC-II is expressed on antigen presenting cells, deoxyhypusine synthase inhibitor N''-guanyl-1,7-diaminoheptane, i.e. GC7, alters the pathophysiology by catalyzing the crucial hypusination and the rate-limiting step of elF5A activation. Inhibition of eIF5A resets the proinflammatory bias in the pancreatic microenvironment. There is reduction of Th1/Th17 response, an increase in Treg numbers, debase in IL17 and IL21 cytokines levels in serum, lowering of anti-GAD65 antibodies, and ablation of the ER stress that improves functionality of the beta-cells, but minimal effect on the cytotoxic CD8 T-cell mediated response 2.5.1.46 deoxyhypusine synthase medicine recurrent missense variant p.Asn173Ser is identified with likely gene disrupting variant (c.1014+1G>A, c.912_917delTTACAT [p.Tyr305_Ile306del]), or c.1A>G [p.Met1?] in unrelated individuals having similar neurodevelopmental features that include global developmental delay and seizures. Two of four affected females have short stature. The c.1014+1G>A variant causes aberrant splicing. Recombinant p.Asn173Ser or p.Tyr305_Ile306del protein show reduced (20%) or absent in vitro activity, respectively. The p.Tyr305_Ile306del and p.Asn173Ser variants result in reduced hypusination of eIF5A compared to wild-type DHPS enzyme 2.5.1.47 cysteine synthase medicine humans lack cysteine synthase. Therefore, this parasite enzyme could be an exploitable drug target 2.5.1.47 cysteine synthase medicine target for novel peptidomimetic antibiotics based on the C-terminal pentapeptide of serine acetyltransferase 2.5.1.47 cysteine synthase medicine purified recombinant CysK is usefula as vaccine against Brucella in BALB/c mice, maximum protection by usage of rCysK-Al with aluminium hydroxide gel formulation followed by Freund's adjuvant formulation 2.5.1.49 O-acetylhomoserine aminocarboxypropyltransferase medicine no association of the polymorphisms A2756G in methionine synthase gene, C677T and A1298C in methylenetetrahydrofolate reductase gene, and 2R-3R in thymidylate synthase gene with increased risk for multiple myeloma 2.5.1.49 O-acetylhomoserine aminocarboxypropyltransferase medicine no significant difference in polymorphism A2756G distribution is observed between controls and patients with esophageal squamous cell carcinoma. There is no association between methionine synthase A2756G polymorphism and the cystathionine beta-synthase 844ins68 insertion polymorphism and cancer of the upper gastrointestinal tract 2.5.1.55 3-deoxy-8-phosphooctulonate synthase medicine enzyme absent in mammals, therefore potential target for the development of new antibiotics 2.5.1.58 protein farnesyltransferase medicine - 2.5.1.58 protein farnesyltransferase medicine evidence that inhibitors of enzyme could be effective therapeutic agents in treatment of many human cancers 2.5.1.58 protein farnesyltransferase medicine enzyme a target in developing drug therapy for malaria 2.5.1.58 protein farnesyltransferase medicine prime target for development of anticancer therapeutics 2.5.1.58 protein farnesyltransferase medicine enzyme from trypanosomatid parasites are target of anti-trypanosomatid agents because inhibitors of this enzyme are highly toxic to these parasites compared to mammalian cells 2.5.1.58 protein farnesyltransferase medicine possibility of development of specific inhibitors for parasitic protozoa 2.5.1.58 protein farnesyltransferase medicine farnesyltransferase inhibitors as potential cancer therapeutics 2.5.1.58 protein farnesyltransferase medicine inhibition of protein farnesyltransferase with influence for oncogenesis, potential target for treatment of cancer 2.5.1.58 protein farnesyltransferase medicine possible target of therapy of Hutchinson-Gilford progeria syndrome by inhibiting protein farnesylation 2.5.1.58 protein farnesyltransferase medicine analysis of reaction mechanism using catalytically active crystals and comparison with the human enzyme. In the CAAX binding site, a single residue substitution at the a2 site from tyrosine to asparagine results in a deeper cavity in this region compared with the human enzyme. The prenylated product exit groove is wider in the Cryptococcus neoformans enzyme relative to human enzyme and varies in amino acid composition. A substrate-induced conformational change observed for the 4alpha-5alpha loop of results in a molecular surface in the active site with two distinct states that can be individually exploited for inhibitor design 2.5.1.58 protein farnesyltransferase medicine design of a protein farnesyltransferase-driven plasma membrane-targeted chimeric peptide, PpIX-C6-PEG8-KKKKKKSKTKC-OMe, for plasma membrane-targeted photodynamic therapy and enhanced immunotherapy. The plasma membrane targeting ability of the peptide originates from the cellular K-Ras signaling, which occurs exclusively to drive the corresponding proteins to plasma membrane by protein farnesyltransferase 2.5.1.59 protein geranylgeranyltransferase type I medicine S-prenylated enzymes are interesting targets for noncytotoxic anticancer agents 2.5.1.59 protein geranylgeranyltransferase type I medicine potential target in anticancer drug research 2.5.1.59 protein geranylgeranyltransferase type I medicine target for anti-cancer drugs 2.5.1.59 protein geranylgeranyltransferase type I medicine inhibitor GGTI-298 induces apoptosis and augments tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. GGTI-298 induces DR4 and DR5 expression and reduces c-FLIP levels. Enforced c-FLIP expression or DR5 knockdown attenuates apoptosis induced by GGTI-298 and TRAIL combination. DR4 knockdown sensitizes cancer cells to GGTI298/TRAIL-induced apoptosis. The combination of GGTI-298 and TRAIL is more effective than each single agent in decreasing the levels of IkappaBalpha and p-Akt 2.5.1.59 protein geranylgeranyltransferase type I medicine enzyme GGTase-I is abundantly expressed in human primary glioma tissues. Inhibition or downregulation of GGTase-I markedly decreases the proliferation of glioma cells and induces their apoptosis, while overexpression of GGTase-I promotes cell growth in vitro. Inactivation of GGTase-I eliminates geranylgeranylation of RhoA and Rac1, prevents them from targeting to the plasma membrane, and inhibits Rac1 activity. Overexpressing wild type or constitutively active Rac1 stimulates glioma cell growth, similar to the effect of GGTase-I overexpression. Overexpressing dominant-negative Rac1 or Rac1 with the prenylation site deleted or mutated abrogates GGTase-I-induced proliferation in glioma cells 2.5.1.60 protein geranylgeranyltransferase type II medicine RabGGT is a therapeutically relevant target for modulation of apoptosis 2.5.1.60 protein geranylgeranyltransferase type II medicine siRNA-mediated knockdown of alpha- or beta-subunits of the enzyme and Rab escort protein-1 markedley attenuates glucose-stimulated insulin secretion in INS-1 832/13 cells 2.5.1.61 hydroxymethylbilane synthase medicine a HPLC method for simultaneous determination of porphobilinogen deaminase and uroporphobilinogen III synthase activity. The estimation of porphobilinogen deaminase activity is widely used for the diagnosis of acute intermittent porphyria where the abnormality of the enzyme is the primary genetic defect 2.5.1.61 hydroxymethylbilane synthase medicine acute intermittent porphyria is caused by partial deficiency of hydroxymethylbilane synthase affecting heme biosynthesis 2.5.1.61 hydroxymethylbilane synthase medicine cats with naturally occurring mutant enzymes can be used as animal model for acute intermittent porphyria 2.5.1.61 hydroxymethylbilane synthase medicine enzyme over-expression in hepatocytes reduces precursor accumulation, liver-directed gene therapy might offer an alternative to liver transplantation 2.5.1.61 hydroxymethylbilane synthase medicine network analysis of residues involved in acute intermittent porphyria. Residues R150, R26 and Q217 are critical for the catalytic activity as they facilitate the interaction between the structural clusters and the active site 2.5.1.75 tRNA dimethylallyltransferase medicine expression of full-length transcript is downregulated 6-14fold in lung adenocarcinomas compared to normal tissue. A549-cells transfected to express the functional enzyme form significantly smaller colonies with reduced scattering on the edges and have only limited ability to induce tumors in nude mice 2.5.1.75 tRNA dimethylallyltransferase medicine identification of compound heterozygous missense mutations, i.e. c.244A>G p.(Met82Val) in exon 2 in the maternally derived allele, and c.1034A>G p.(Tyr345Cys) in exon 9 in the paternally derived allele, in Trit1 in a girl with a developmental delay, frequent episodes of seizures induced by febrile illness, and myoclonic epilepsy. In peripheral blood and urine, a marked decrease in both i6A and ms2i6A modifications is observed. The mitochondrial disorder is caused by defective tRNA isopentenylation arising from a loss-of-function mutation in Trit1 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine Brucella lumazine synthase can be used as both an antigen-carrier and as an adjuvant in the design of new oral subunit vaccines 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine certain purinetriones bearing phosphate side chains can inhibit both lumazine synthase as well as riboflavin synthase, and molecular modeling with 3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate suggests possible binding modes to each enzyme. Antibiotics that would inhibit both lumazine synthase and riboflavin synthase would be less likely to suffer from the development of antibiotic resistance by the organisms that they are supposed to treat, since pathogenic microorganisms would have to simultaneously select for mutations in both enzymes in order to escape the cytotoxic effects of the antibiotics 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine feasibility of using Brucella spp. lumazine synthase as a novel and effective delivery system to induce a protective immune response against rotavirus disease. In particular, previous results showing the plasticity of the Brucella spp. lumazine synthase scaffold for the production of polyvalent chimeras suggest that VP8 from different strains can be coupled to Brucella spp. lumazine synthase in order to elicit wide-protecting neutralizing antibodies against different field strains of rotavirus 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine lumazine synthase is a potent delivery system for the improvement of subunit vaccines 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine the fact that the enzymes of the riboflavin biosynthesis pathway are not present in the human or animal host makes them potential targets for anti-infective agents 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine this protein constitutes an interesting candidate for serological diagnosis and for the design of specific chemotherapeutic agents, and its polymeric characteristics could provide the basis for the development of an acellular vaccine 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine Brucella suis lumazine synthase (BLS) molecule is a favorable transport vector for antigenic protein, e.g. rL7/L12-BLS fusion protein, in vaccination, e.g. for antibody production in Oryctolagus cuniculus. The BLS molecule also has adjuvant property for improving immunity stimulation effects, when a foreign protein antigen is covalently attached to it 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine partially protective effect of enzyme BLS against B16 melanoma in mice generating a protective response at the first stages of tumor growth but not at later stages, therapeutic effect of BLS vaccination 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine the BLS scaffold is assessed for in plants for recombinant vaccine development by N-terminally fusing BLS to bovine rotavirus VP8d and expressing the resulting fusion (BLS-VP8d) in Nicotiana tabacum chloroplasts. BLS-VP8d remains soluble and stable during all stages of plant development and even in lyophilized leaves stored at room temperature 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine the striking feature of enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome. Immunization with a chimera consisting of the B subunit of Shiga toxin type 2 and Brucella sp. lumazine synthase confers total protection against Shiga toxins in mice, analysis of antibody efficacy against EHEC challenge. The enzyme can be used as transport vehhicle and antigen in vaccination against EHEC infections 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine evalutation of the immunogenicity and protection ability of a recombinant adenovirus and plasmid DNA vaccine coexpressing P39 and lumazine synthase proteins. The immunization strategy of DNA priming followed by adenovirus boosting induces robust humoral and cellular immune responses, and it significantly reduces the numbers of Brucella abortus in a mouse model 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine generation of a chimeric protein (BLS-FliC131) by fusing flagellin from Salmonella typhimurium in the N-termini of BLS. The fusion protein is recognized by anti-flagellin and anti-BLS antibodies, keeps the oligomerization capacity of BLS, without affecting the folding of the monomeric protein components. The thermal stability of each fusion partner is conserved. BLS-FliC131 retains the capacity of triggering TLR5. The humoral response against BLS elicited by BLS-FliC131 is stronger than the one elicited by equimolar amounts of BLS1FliC 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase medicine use of lumazine synthase as a scaffold to present 60 copies of a linear B cell epitope (PB10) from the ricin toxin fused to the C-terminus of lumazine synthase via four different linkers. Fusion of the PB10 peptide onto lumazine synthase does not affect protein assembly, thermal stability or exposure of the epitope, but has a minor impact on protein conformation. Formaldehyde crosslinking considerably improves protein thermal stability with only minor impact on protein conformation. All lumazine synthase-PB10 constructs, when administered to mice by injection without adjuvant, elicites measurable anti-ricin serum IgG titers, although the titers are not sufficient to confer protection against a 10x lethal dose ricin challenge 2.5.1.106 tryprostatin B synthase medicine enzyme converts tryptophan-containing cyclic dipeptides to their C2-regularly prenylated derivatives. In human leukemia K562 and ovarian cancer A2780 sens and A2780 CisR cell lines, prenylation at C2 leads to a significant increase of the cytotoxicity of the tested cyclic dipeptides in all the 14 cases 2.6.1.1 aspartate transaminase medicine the inhibitor of C-S lyase, aminooxyacetic acid hemihydrochloride, reduces renal injuries due to cisplatin in rats. On day 5 following a bolus cisplatin injection, in vivo nephrotoxic potentials are in the decreasing order of species rats > mice, rabbits, based on body surface. The levels of renal Pt residue at the nephrotoxic dose are in order of rabbits > rats > mice. The activity of endogenous basal mitochondrial aspartate aminotransferase, one of the C-S lyases, in the renal cortex of naive animals is rats > mice, rabbits. Expression of mitochondrial C-S lyase in the kidney is observed at approximately 37 kDa in all five species used. In in vitro studies, the cytotoxicity of cisplatin is dependent on the expression level of C-S lyase mRNA in the respective renal cells 2.6.1.1 aspartate transaminase medicine following doxorubicin administration, triple-negative breast cancer cells, which do not express the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor, acquire metabolic alteration, causing increased glutamine flux for the synthesis of aspartate which can be converted into oxaloacetate by GOT1. Subsequently, this oxaloacetate is converted into malate and then pyruvate, maintaining the NADP+/NADPH ratio which neutralizes doxorubicin-induced oxidative stress. Repression of GOT1 results in doxorubicin-induced formation of reactive oxygen species, thereby increasing doxorubicin sensitivity 2.6.1.2 alanine transaminase medicine enzyme is an effective neuroprotectant against glutamate excitotoxicity. When exposure is limited to endogenously released glutamate, neuroprotection by enzyme is not dependent on added pyruvate 2.6.1.2 alanine transaminase medicine patients with hepatitis C treated with NS3-4A protease inhibitor telaprevir and/or peginterferon alpha-2a. Patients receiving telaprevir alone show a decrease in mean neopterin and alanine aminotransferase levels. Patients receiving peginterferon alpha-2a plus telaprevir or peginterferon alpha-2a plus placebo show an ioncrease in neopterin levels and decrease in alanine aminotransferase level, suggesting that treatment of chronic hepatitis C patients with an NS3-4A protease inhibitor ameliorates inflammation. Interferon-mediated immunomodulatory effects remain intact when interferon is combined with telaprevir 2.6.1.2 alanine transaminase medicine treatment of HIV/HCV co-infected patients with pegylated interferon and ribavirin. At week 1, serum HCV RNA levels and changes in alanine aminotransferase levels relative to baseline can identify likely responders better than plasma ribavirin levels. During the first four weeks of treatment, median plasma ribavirin levels and area under the ribavirin curve are significantly lower in sustained responders compared with nonresponders 2.6.1.5 tyrosine transaminase medicine tyrosine aminotransferase is not directly associated with resistance to benznidazole, but may act as a general secondary compensatory mechanism or stress response factor. In Trypanosoma cruzi strains resistant o benznidazole, no amplification of the tyrosine aminotransferase gene is observed, and all strain show similar levels of tyrosine aminotransferase mRNA 2.6.1.7 kynurenine-oxoglutarate transaminase medicine isoforms KAT I and KAT II, no change of enzyme activity 24 and 72 h after transient global ischemia episode 2.6.1.7 kynurenine-oxoglutarate transaminase medicine isoform KAT2 is a therapeutic target for the management of schizophrenia 2.6.1.13 ornithine aminotransferase medicine patient with gyrate atrophy of the choroid and retina, mutation G237D, responds to vitamin B6 medication 2.6.1.13 ornithine aminotransferase medicine pharmacological doses of testosterone down-regulate level of enzyme protein. Variations of levels of enzyme are strongly correlated with testosteronemia. Orchidectomy increases renal level of enzyme protein. Effects are reversed by injecting physiological doses of testosterone into castrated male animals 2.6.1.13 ornithine aminotransferase medicine role in mitotic cell division and target for chemotherapeutic drug development 2.6.1.13 ornithine aminotransferase medicine before puberty, ornithine aminotransferase expression is similar between female and male kidneys whereas from puberty until adulthood ornithine aminotransferase expression increases in the female kidney, becoming 2.5fold higher than in the male kidney. This sex-differential expression of ornithine aminotransferase is associated with a sex-specific distribution of enzyme along the corticopapillary axis and within the nephron. Ornithine aminotransferase is three- to fourfold more expressed in the female than the male cortex. In males, enzyme is highly expressed in the medulla, mainly in the thick ascending limbs. Renal enzyme distribution in orchidectomized mice resembles that in the females. Ovariectomy does not influence enzyme expression. Ornithine aminotransferase is naturally downregulated in the presence of testosterone 2.6.1.13 ornithine aminotransferase medicine transgenic mice that specifically overexpress human ornithine aminotransferase in the liver, kidneys and intestine exhibit higher enzyme activity in the liver than wild-type, but there are no differences in kinetic parameters between wild-type and transgenic animal. Ornithine aminotransferase overexpression decreases plasma and liver ornithine concentrations but does not affect glutamine or arginine homeostasis. There is an inverse relationship between ornithine levels and enzyme activity 2.6.1.13 ornithine aminotransferase medicine in rats, a liver portacaval shunt causes a marked decrease in glutamine synthetase activity and an increase in ornithine aminotransferase activity. The glutamine synthetase and ornithine aminotransferase proteins maintain their location in the perivenous cells, indicating that there is no generalized loss of perivenous hepatocytes, but rather, there is a significant alteration in the expression of these proteins and hence metabolism in this cell population 2.6.1.13 ornithine aminotransferase medicine inhibition of OAT may represent a therapeutic strategy in treatment of non-small cell lung cancer (NSCLC) 2.6.1.13 ornithine aminotransferase medicine potential utility of OAT inhibitors for the treatment of cancer 2.6.1.16 glutamine-fructose-6-phosphate transaminase (isomerizing) medicine target for antifungal agents 2.6.1.16 glutamine-fructose-6-phosphate transaminase (isomerizing) medicine hypoxia induces gene expression in phagocyte 2.6.1.16 glutamine-fructose-6-phosphate transaminase (isomerizing) medicine mean glutamine:fructose 6-phosphate amidotransferase activity is significantly higher in diabetic compared to control subjects. Plasma levels of diabetic patients also exhibit increased lipid peroxidation and protein carbonylation. Glutamine:fructose 6-phosphate amidotransferase activity is positively correlated with glutamine:fructose 6-phosphate amidotransferase mRNA, HbA1c, insulin resistance, postprandial plasma glucose and levels of thiobarbituric acid reactive substances and protein carbonyl content 2.6.1.16 glutamine-fructose-6-phosphate transaminase (isomerizing) medicine GFPT1 mutations in congenital myasthenic syndrome patients do not appear to compromise global N-glycosylation in muscle cells. The N-glycomes of myoblasts and myotubes derived from healthy controls, GFPT1 patients, and patients with other muscular diesease exhibit broadly similar levels of branching and relative abundances of bi-, tri-, and tetra-antennary N-glycans. Although some differences are observed in the relative abundances of some of the N-glycan constituents, these variations are modest and are not confined to the GFPT1 samples 2.6.1.19 4-aminobutyrate-2-oxoglutarate transaminase medicine chronical administration of vigabatrin with drinking water completely and reversibly eliminates the psychophysical evidence of tinnitus 2.6.1.19 4-aminobutyrate-2-oxoglutarate transaminase medicine in a family with encephalomyopathic mitochondrial DNA depletion syndrome, the homozygous missense mutation L211F in ABAT results in elevated GABA in subjects' brains as well as decreased mtDNA levels in subjects' fibroblasts 2.6.1.19 4-aminobutyrate-2-oxoglutarate transaminase medicine attenuating GABAT activity and enhancing GABA expression are a promising way to relieve spasticity following stroke. The modulation of GABA and its metabolism by acupuncture, particularly waggle needling, might attenuate GABAT and enhance GABA, alleviating post-stroke spasticity. Waggle needling decreases cerebral infarction and alleviates neurological deficits, overview. No significant difference is found between waggle needling group and baclofen group 2.6.1.39 2-aminoadipate transaminase medicine L-2-aminoadipate, the substrate for AadAT, is a well known astroglial-specific toxin, knowledge of the cerebral disposition of this compound is instrumental for the elucidation of its mechanism of toxicity and possible relevance in pathology 2.6.1.42 branched-chain-amino-acid transaminase medicine a fusion protein of AGT with the membrane-penetrating Tat peptide shows subtle active site conformational changes as compared with untagged AGT, but retains a significant transaminase activity. Active Tat-AGT can be successfully delivered to a mammalian cellular model of primary hyperoxaluria type I consisting of chinese hamster ovary cells expressing glycolate oxidase. The intracellular transduced Tat-AGT makes the cells able to detoxify endogenously produced glyoxylate to an extent similar to that of cells stably expressing AGT 2.6.1.42 branched-chain-amino-acid transaminase medicine heterogeneous BCAT2 gene mutations R170Q and E264K, found in a 25-year-old patient presenting with headache complaints and mild memory impairment for about six years. The two BCAT2 gene mutations result in decreased BCAT2 enzyme activity. After treatment with vitamin B6, the levels of branched chain amino acids, especially valine are remarkably decreased and brain symmetric white matter abnormal signals are improved 2.6.1.42 branched-chain-amino-acid transaminase medicine levels of branched-chain aminotransferase-1 transcripts are significantly decreased on the polysomes of lymphoblastoid cell lines derived from Diamond-Blackfan anemia patients and translation of BCAT1 protein is especially impaired in cells with small ribosomal protein gene mutations. This effect may be due in part to the unusually long 5'UTR of the BCAT1 transcript 2.6.1.43 aminolevulinate transaminase medicine target for chemotherapy against Chagas disease or American trypanosomiasis 2.6.1.43 aminolevulinate transaminase medicine immunological difference between the enzyme from mammalian source and this enzyme presents a potential target for chemotherapy, development of treatment for Leishmaniasis, a major parasitic disease in humans and opportunistic infections in patients with AIDS, an inhibitor specific for the leishmanial enzyme may be used as a therapeutic agent 2.6.1.43 aminolevulinate transaminase medicine in streptozotocininduced diabetic mice, treatment with Bauhinia forficata Link subsp. pruinosa tea does not not normalize delta-aminolevulinate dehydratase activity 2.6.1.44 alanine-glyoxylate transaminase medicine - 2.6.1.44 alanine-glyoxylate transaminase medicine hereditary disease primary hyperoxaluria type 1 is caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase, diagnosis with selective inhibitors and enzyme assays 2.6.1.44 alanine-glyoxylate transaminase medicine after 4 weeks of vitamin B6-deficient diet, hepatic enzyme activity and mRNA level are significantly lower than in control animals. Urinary oxalate-to-creatinine and glycolate-to-creatinine ratios are higher than in controls, but urinary glycine-to-creatinine and citrate-to-creatinine ratios are significantly lower 2.6.1.44 alanine-glyoxylate transaminase medicine primary hyperoxaluria type I is a severe kidney stone disease caused by mutations in the protein alanine:glyoxylate aminotransferase 2.6.1.44 alanine-glyoxylate transaminase medicine infusion of asymmetric dimethylarginines causes a 3- to 4fold increase in plasma and urine asymmetric dimethylarginine levels and a 2- to 3fold increase in plasma and urine levels of the asymmetric dimethylarginine-specific metabolite of AGXT2, alpha-keto-delTA-(N,N-dimethylguanidino)valeric acid. Plasma levels of alpha-keto-delTA-(N,N-dimethylguanidino)valeric acid are elevated 32fold in the mice, which underwent bilateral nephrectomy. Neither bilateral nephrectomy nor asymmetric dimethylarginine infusion causes upregulation of AGXT2 expression or activity 2.6.1.44 alanine-glyoxylate transaminase medicine mutations in conserved residue Gly161 to Arg, Cys or Ser are associated with Primary Hyperoxaluria Type I, a severe rare disorder of metabolism. Mutations of Gly161 strongly reduce the expression levels and the intracellular half-life of AGT, and make the protein in the apo-form prone to an electrostatically-driven aggregation in the cell cytosol. The coenzyme pyridoxal 5'-phospahte, by shifting the equilibrium from the apo- to the holo-form, is able to reduce the aggregation propensity of the variants, thus partly decreasing the effect of the mutations 2.6.1.44 alanine-glyoxylate transaminase medicine the effectiveness of pharmacological doses of pyridoxine results froman improved metabolic effectiveness of AGT. In cells expressing glycolate oxidase the great majority of glycolate is converted to oxalate and glyoxylate, with the latter causing the greater decrease in cell survival. Co-expression of normal AGTs and some, but not all, mutant AGT variants partially counteracts this cytotoxicity and leads to decreased synthesis of oxalate and glyoxylate. Increasing the extracellular pyridoxine up to 0.3 microM leads to an increased metabolic effectiveness of normal AGTs and the G170R variant. The increased survival seen with G170R is paralleled by a 40% decrease in oxalate and glyoxylate levels 2.6.1.51 serine-pyruvate transaminase medicine absence of human SPT/AGT or mistargeting of this enzyme causes primary hyperoxaluria type 1, an inborn error of glyoxylate metabolism characterized by increased oxalate production 2.6.1.52 phosphoserine transaminase medicine useful for creating a new concept or target for the diagnosis and therapy of human serine metabolism-related disorders and cancer 2.6.1.52 phosphoserine transaminase medicine promoter hypermethylation and mRNA expression of PSAT1 are indicators of response to tamoxifen-based endocrine therapy in steroid hormone receptor–positive patients with recurrent breast cancer 2.6.1.52 phosphoserine transaminase medicine PSAT1 represents a target for colorectal cancer therapy 2.6.1.52 phosphoserine transaminase medicine hepatic PSAT1 expression and liver serine levels are reduced in genetically engineered leptin receptor-deficient (db/db) mice and high-fat diet (HFD)-induced diabetic mice. Overexpression of PSAT1 by adenovirus expressing PSAT1 improves insulin signaling and insulin sensitivity in vitro and in vivo under normal conditions. Opposite effects are observed when PSAT1 is knocked down by small hairpin RNA specific for PSAT1. Overexpression of PSAT1 also significantly ameliorates insulin resistance in diabetic mice. PSAT1 inhibits the expression of hepatic tribbles homolog TRB3 in vitro and in vivo. Serine mediates PSAT1 regulation of TRB3 expression and insulin signaling in vitro 2.6.1.52 phosphoserine transaminase medicine isoform PSAT1 expression is elevated in esophageal squamous cell carcinoma tissues compared to normal esophageal tissues. Increased PSAT1 expression is significantly associated with stage of disease, lymph node metastasis, distant metastasis and poor prognosis. In vitro, PSAT1 overexpression promotes esophageal squamous cell carcinoma cell proliferation and matrigel invasion. In vivo, injection of mice with esophageal squamous cell carcinoma cells overexpressing PSAT1 enhances tumor formation. PSAT1 upregulatesthe expression and/or activity of GSK3beta/Snail 2.6.1.76 diaminobutyrate-2-oxoglutarate transaminase medicine - 2.6.1.76 diaminobutyrate-2-oxoglutarate transaminase medicine responsible for many human infections including otitis media, meningitis, epiglottis and pneumonia 2.6.1.76 diaminobutyrate-2-oxoglutarate transaminase medicine drug development, Acinetobacter sp. can be part of the normal flora of human skin but also of opportunistic infections like septicemia, pneumonia, endocarditis, meningitis, skin and wound sepsis or urinary tract infections, clinically important isolates show widespread and increasing resistance to many commonly used antibiotics 2.6.1.77 taurine-pyruvate aminotransferase medicine identification of Bilophila wadsworthia by specific PCR which targets the taurine:pyruvate aminotransferase gene 2.6.1.92 UDP-4-amino-4,6-dideoxy-N-acetyl-beta-L-altrosamine transaminase medicine the enzyme is involved biosynthesis of 5,7-bis(acetylamino)-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-2-nonulopyranosonic acid (pseudaminic acid). Helicobacter pylori flagellin is heavily glycosylated with pseudaminic acid. The glycosylation process is essential for assembly of functional flagellar filaments and consequent bacterial motility. Because motility is a key virulence factor for this and other important pathogens, the pseudaminic acid biosynthetic pathway offers potential for novel therapeutic targets 2.6.1.120 beta-alanine—2-oxoglutarate transaminase medicine both beta-AlaAT I and beta-AlaAT II activities in the liver are increased with the level of protein in the diet in accordance with changes in their mRNA levels. The beta-AlaAT I activity in the kidney is increased by protein-free and low-protein diets in relation to changes in its mRNA level. The level of beta-AlaAT II activity in the kidney is slightly decreased by a protein-free diet. Neither beta-AlaAT I nor beta-AlaAT II activities in the kidney are affected by a high-protein diet 2.7.1.1 hexokinase medicine given the combined prominent role of glucokinase on insulin secretion and hepatic glucose metabolism where the GK-GKRP mechanism is involved, activation of glucokinase has a new therapeutic potential in the treatment of type 2 diabetes 2.7.1.1 hexokinase medicine glucokinase mutations are found only in medically responsive children with congenital hyperinsulinism who are negative for ABCC8 and KCNJ11 mutations 2.7.1.1 hexokinase medicine HK II gene can act as a crucial therapeutic target for slowing colon cancer growth 2.7.1.1 hexokinase medicine HK II inhibitors may be therapeutically useful for the treatment of advanced infiltrative hypovascular hepatocellular carcinomas, which are growing in a hypoxic environment 2.7.1.1 hexokinase medicine TbHK1 is a valid therapeutic target while identifying a potential molecular target of the anti-trypanosomal agent lonidamine 2.7.1.1 hexokinase medicine activation of glucokinase as glucose lowering therapy for type 2 diabetes 2.7.1.1 hexokinase medicine glucokinase is a potential therapeutic target for treating maturity-onset diabetes of the young and persistent hyperinsulinemic hypoglycemia of infancy 2.7.1.1 hexokinase medicine 28-homobrassinolide is able to protect or restore the native structure of hexokinase when exposed to diabetic levels of glucose 2.7.1.1 hexokinase medicine endogenous glucokinase expression correlates with O-GlcNAc levels in the pathophysiological model of type II diabetes, ob/ob mice. In response to the pharmacological inhibition of O-GlcNAcase, contents of glucokinase increase. Glucokinase is modified by O-GlcNAcylation. siRNA-mediated O-linked N-acetylglucosamine transferase knock-down not only decreases O-GlcNAc content but also glucokinase protein level 2.7.1.1 hexokinase medicine hexokinase is distributed in the worm extensively as well as in liver tissue and serum from infected rats. High-level specific IgG1 and IgG2a are induced in rats by immunization with recombinant enzyme. The enzymatic activity of hexokinase is suppressed by the antibodies in vitro, and the survival of Clonorchis sinensis is inhibited by the antibodies in vivo and in vitro 2.7.1.1 hexokinase medicine hexokinase-II binds to the voltage-dependent anion channel located on the mitochondrial outer membrane. When bound, hexokinase-II is blocking a major cell death pathway. A series of truncations and point mutations to the N-terminal end of hexokinase-II identify the binding site to the channel within the first 10 amino acids 2.7.1.1 hexokinase medicine HIV-1 induces a robust increase in hexokinase-1 expression. Hexokinase enzymatic activity is significantly inhibited in HIV-1 infected peripheral blood mononuclear cells and in phorbol 12-myristate 13-acetate differentiated U1 cells. Increased levels of mitochondria-bound hexokinase -1are observed in phorbol 12-myristate 13-acetate-induced U1 cells and in the HIV-1 accessory protein, viral protein R transduced U937 cell derived macrophages. Dissociation of hexokinase-1 from mitochondria in U1 cells using clotrimazole induces mitochondrial membrane depolarization and caspase-3/7 mediated apoptosis. Dissociation of hexokinase-1 from mitochondria in viral protein R transduced U937 also activates caspase-3/7 activity 2.7.1.1 hexokinase medicine in cancer cells, elevated hexokinase-2 expression is induced by activated PI3K/Akt signaling. Hexokinase-2 is overexpressed in 83.3% of specimens detected and is closely correlated with Ki67, a cell proliferation index. Silencing of endogenous hexokinase-2 results in decreased aerobic glycolysis. Inhibition of PI3K/Akt signaling also suppresses aerobic glycolysis and this effect can be reversed by reintroduction of hexokinase-2. Knockdown of HK2 leads to increased cell apoptosis and reduced ability of colony formation 2.7.1.1 hexokinase medicine mutations A379S, D400Y, E300A, E395A, E395G, H380N, I348N, L301M, M298I, M381G, M402R, R308K, R394P, R397S, and S398R are observed in 12 different patients with type 2 diabetic condition. The structural analysis of these mutated GKs shows a variable number of beta-alpha-beta units, hairpins, beta-bulges, strands, helices, helix-helix interactions, beta-turns, and gamma-turns along with the RMSD variations when compared to wild-type GK. The substrate shows variable binding orientations and cannot fit into the active site of these mutated structures, it is expelled out of the conformations 2.7.1.1 hexokinase medicine the peptidoglycan of Lactobacillus casei shows cytotoxic activity against various tumour cells. A synthetic peptide derived from the peptidoglycan impairs the entire metabolism of cultured tumour cells and restores the apoptotic process. Normal cells appear to be stimulated rather than inhibited by the peptide. The pentapeptide binds with the hexokinase and exerts a weak inhibitory effect on hexokinase enzymatic specific activity. in tumour cells, a percentage of peptide is partially blocked by the cytosolic hexokinase and the remaining is available to bind with the mitochondrial-bound hexokinase. This binding triggers the Bax-induced proapoptotic process including a decrease in succinate dehydrogenase activity, cellular ATP and mitochondrial membrane potential, as well as changes in the voltage dependent anion channel structure on the outer mitochondrial membrane and cytochrome C release. As the final stage, the antiapoptotic process is suppressed, the cellular functions are altered and the cell is destroyed 2.7.1.3 ketohexokinase medicine compared with normal hepatocytes, hepatocellular carcinoma cells markedly reduce the rate of fructose metabolism and the level of reactive oxygen species, as a result of a c-Myc-dependent and heterogeneous nuclear ribonucleoprotein H1- and H2-mediated switch from expression of the high-activity fructokinase KHK-C to the low-activity KHK-A isoform. KHK-A acts as a protein kinase, phosphorylating and activating phosphoribosyl pyrophosphate synthetase PRPS1. c-Myc, hnRNPH1/2 and KHK-A expression levels and PRPS1 Thr225 phosphorylation levels correlate with each other in hepatocellular carcinoma specimens and are associated with poor prognosis for hepatocellular carcinoma 2.7.1.3 ketohexokinase medicine mutually exclusive splicing of adjacent exons 3A and 3C in ketohexokinase precursor RNA results in expression of ketohexokinase isoform KHK-A or KHK-C. KHK-A but not KHK-C interacts with phosphoribosyl diphosphate synthetase PRPS1. KHK-A functions as a protein kinase and directly phosphorylates PRPS1 at T225. This phosphorylation blocks the binding of the allosteric inhibitor ADP to PRPS1, thereby abrogating the feedback inhibition by ADP and leading to elevated de novo nucleic acid synthesis by constitutively activating PRPS1 in hepytocellular carcinoma cells 2.7.1.4 fructokinase medicine wild-type mice that receive delayed hydration develop renal injury, with elevated serum creatinine, increased urinary neutrophil gelatinase-associated lipocalin, proximal tubular injury, and renal inflammation and fibrosis. This is associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration are protected from renal injury. Access to sufficient water during the dehydration period can protect mice from developing renal injury. Studies provide a potential mechanism for Mesoamerican nephropathy 2.7.1.6 galactokinase medicine analysis of residues involved in type II galactosemia within three-dimensional architecture of enzyme 2.7.1.6 galactokinase medicine identification of five mutations of GALK1 gene in five unrelated Korean patients with GALK deficiency and investigaion of their biochemical characteristics using mammalian cell expression studies. Four missense mutations (p.G137R, p.R256W, p.R277Q, and p.V281M) and one small insertion (c.850_851insG) are identified. Among four patients with severely reduced GALK activity, two are found to be homozygotes for p.R256W and the other two are compound heterozygotes for different molecular defects (p.G137R/p.R277Q and p.V281M/c.850_851insG). One patient with moderately decreased GALK activity is heterozygous for p.R256W. Expression analysis in Cos7 cells confirms that each of the mutations results in reduction of GALK activity and causes GALK deficiency 2.7.1.6 galactokinase medicine in primary fibroblasts of patients suffering Classic Galactosemia, inhibitor 2-(1,3-benzoxazol-2-ylamino)-4-(4-chloro-1H-pyrazol-3-yl)-4,6,7,8-tetrahydroquinazolin-5(1H)-one is able to lower galactose 1-phosphate levels without significant effect on viability of cells 2.7.1.6 galactokinase medicine the enzyme has biotechnological potential in enzyme replacement therapy for type II galactosaemia 2.7.1.11 6-phosphofructokinase medicine somatic PFK1 mutations identified in human cancers have distinct effects on allosteric regulation of enzymic activity and lactate production 2.7.1.11 6-phosphofructokinase medicine total PFK1 levels are higher in human breast cancer tissues than in paracancer tissues. The human breast cancer and paracancer tissues mainly express PFK-P and PFK-L isoforms, respectively. Depending on the pathological stage of breast cancer, the expression of PFK1 is significantly positively correlated with the activity of PFK1 2.7.1.14 sedoheptulokinase medicine sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose 2.7.1.14 sedoheptulokinase medicine patient with an isolated sedoheptulokinase deficiency presents with neonatal cholestasis, hypoglycemia, and anemia, while a second patient presents with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients have elevated excretion of erythritol and sedoheptulose, and each has a homozygous nonsense mutation in sedoheptulokinase. In fibroblasts from patient 1, strongly reduced formation of sedoheptulose 7-phosphate is detected, but no mature enzyme. It is questionable whether enzyme deficiency is a causal factor for the clinical phenotypes of the patients 2.7.1.20 adenosine kinase medicine the enzyme is an excellent target for chemotherapy with 6-substituted purine nucleosides being potential selective antitoxoplasmic agents 2.7.1.20 adenosine kinase medicine adenosine kinase represents a potential chemotherapeutic target for the treatment of Toxoplasma gondii infections 2.7.1.20 adenosine kinase medicine the enzyme is a rational therapeutic target to enhance neuroprotection in ischemia 2.7.1.20 adenosine kinase medicine ADK has emerged as a novel target to predict and to prevent epileptogenesis. High levels of ADK expression (e.g. as a long-term consequence of traumatic brain injury) are expected to be predictive for subsequent epileptogenesis. This means that the determination of ADK expression levels in brain, e.g. by using ADK-selective PET or SPECT ligands, has high diagnostic value. On the other hand, prevention of epileptogenesis by focal reconstitution of the adenosine system is an important therapeutic goal 2.7.1.20 adenosine kinase medicine astrocyte-based ADK provides a critical link between astrogliosis and neuronal dysfunction in epilepsy 2.7.1.20 adenosine kinase medicine lentiviral expression of anti-adenosine kinase miRNA constitutes a versatile tool to generate therapeutically effective adenosine releasing mesenchymal stem cells, thus representing a model system to generate patient identical autologous adult stem cell grafts 2.7.1.20 adenosine kinase medicine pathologic overexpression of ADK as in epilepsy may also render the brain more susceptible to injury from ischemia. Consequently, ADK emerges as a rational therapeutic target to enhance neuroprotection 2.7.1.20 adenosine kinase medicine siRNAs transfected into cells can work efficiently to regulate gene expression in Toxoplasma gondii. The application of siRNA in interrupting gene expression in Toxoplasma gondii would be useful for elucidating gene function as a step toward development of antitoxoplasmasis vaccines and therapeutic reagents 2.7.1.20 adenosine kinase medicine Toxoplasma gondii adenosine kinase is an excellent target for chemotherapy and 7-deaza-6-benzylthioinosines are potential antitoxoplasmic agents 2.7.1.20 adenosine kinase medicine transfection of dsRNAs into cells can efficiently regulate gene expression in Toxoplasma gondii. Application of dsRNA to disrupt gene expression in Toxoplasma gondii would be useful for elucidating gene function as a step towards the development of therapeutic reagents 2.7.1.20 adenosine kinase medicine upregulation of adenosine kinase is a common pathologic hallmark of Rasmussen encephalitis. Focal astrogliosis and marked expression of adenosine kinase are observed in the lesions of Rasmussen encephalitis. Significantly greater adenosine kinase expression in Rasmussen encephalitis versus controls and greater enzymatic activity for adenosine kinase are found 2.7.1.21 thymidine kinase medicine enzyme can be useful in gene therapy 2.7.1.21 thymidine kinase medicine enzyme is a target for antiviral therapy and treatment of EBV-associated malignancies 2.7.1.21 thymidine kinase medicine Hsv1-tk mutants are present in multiple ganglia of an immunocompromised patient with a history of chronic Acv(r) skin lesions. Mutations in the thymidine kinase gene of herpes simplex virus type 1 explain in most cases of the virus resistance to acyclvir treatment. Mutants arise independently under drug selection and establish latency in human sensory ganglia alone or together with the wild-type virus 2.7.1.21 thymidine kinase medicine the serum levels of thymidine kinase do not correlate with prognosis in a group of patients during the time of the initial diagnosis of acute leukemia. The entry levels of thymidine kinase are not suitable for stratification of child patients with acute leukemia into risk categories 2.7.1.21 thymidine kinase medicine potential efficacy of the adenovirus-thymidine kinase/ganciclovir gene therapy approach as a viable nonsurgical alternative treatment for uterine leiomyomas 2.7.1.21 thymidine kinase medicine the thymidine kinase 1 gene from tomato in combination with azidothymidine is a powerful suicide gene for anticancer gene therapy 2.7.1.21 thymidine kinase medicine mean serum TK1 activities in sera from myelodysplastic syndrome, breast and prostate cancer patients are 11, 6.7 and 1.8 pmol/min/ml, differing significantly from blood donors (mean value 1.1 pmol/min/ml). Serum TK1 protein levels are also significantly higher in myelodysplastic syndrome, breast, prostate cancer patients compared to blood donors. The detected active TK1 is primarily a high molecular weight complex, similar to the forms found in sera from myelodysplastic syndrome patients and blood donors. High TK1 25 kDa protein levels are found in fractions lacking TK1 activity in sera from cases with breast and prostate cancer 2.7.1.21 thymidine kinase medicine serum TK1 activity displays a statistically significant decline from young (18-35 years) to middle-aged (36-60 years) and further on to elderly (60-86 years) healthy individuals. Age-related reference range is: <30 U/l for young, <25 U/l for middle-aged and <19 U/l for elderly. There is no difference in TK1 activity between the studied healthy men and women. In chronic lymphocytic leukemia patients, TK1 activity is the highest in the advanced Rai stages. TK1 is significantly elevated in CD38+/Zap70+ chronic lymphocytic leukemia patients, and shows significant correlation with white blood cell and absolute B-cell count 2.7.1.21 thymidine kinase medicine serum TK1 protein and activity levels are significantly higher in canine mammary tumor than in healthy dogs. Major differences are found in the molecular forms of TK1 in acute lymphocytic leukemia, healthy, and in canine mammary tumor dogs, with a large fraction of inactive TK1 protein in in canine mammary tumor dogs. The serum TK1 protein assay can differentiate benign tumors (early stage tumors) from healthy more efficiently than the serum TK1 activity assay 2.7.1.32 choline kinase medicine in intact lenses, choline and ethanolamine are phosphorylated independently, during galactosemic cataractogenesis choline and ethanolamine become competing substrates of a single enzyme 2.7.1.32 choline kinase medicine new enzyme inhibitors with in vivo antitumor activity, mechanism 2.7.1.32 choline kinase medicine potential target for anti-tumor drugs, potential use of the enzyme level as tumor marker 2.7.1.32 choline kinase medicine target in anti-cancer therapy 2.7.1.32 choline kinase medicine the enzyme is implicated in tumorigenesis and an attractive target for anticancer chemotherapy 2.7.1.32 choline kinase medicine enzyme downregulation is a cancer-specific treatment 2.7.1.33 pantothenate kinase medicine a young girl with early onset pantothenate kinase-associated neurodegeneration whose initial clinical manifestation is ataxia at the age of 2.5 years and refractory severe dystonia resulting in essentially complete loss of motor control. She has a mutation in PANK2 gene consisting of an amino acid change of alanine to valine in exon 5 (A382V). After Globus Pallidus deep brain stimulation at the age of 11 years, the patient regains useful motor function and speech with a marked decrease in the severity of the dystonia 2.7.1.33 pantothenate kinase medicine neurodegeneration with brain iron accumulation is a heterogenous group of disorder. One group of patiens bears mutations in the gene encoding pantothenate kinase 2 2.7.1.33 pantothenate kinase medicine pallidal stimulation for dystonia in pantothenate kinase associated neurodegeneration 2.7.1.33 pantothenate kinase medicine pantothenate kinase associated neurodegeneration is an autosomal recessive disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. Many patients have a mutation in the gene encoding pantothenate kinase 2 which is a key regulator enzyme in the biosynthesis of coenzyme A 2.7.1.33 pantothenate kinase medicine pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome), the most prevalent form of neurodegeneration with brain iron accumulation, is a rare degenerative brain disease characterised by predominantly extrapyramidal dysfunction resulting from mutations in the PANK2 (pantothenate kinase 2) gene. A novel missense mutation (P354L) in exon 4 of the PANK2 gene is identified in an adolescent with classic pantothenate kinase-associated neurodegeneration. DNA-based diagnosis of pantothenate kinase-associated neurodegeneration plays a key role in determination, and can make the diagnosis more simply, directly, and economically because it obviates the need for unnecessary biochemical tests. Once pantothenate kinase-associated neurodegeneration-like symptoms are identified, mutation analysis and target screening for the family of the proband can provide efficient and accurate evidence of pantothenate kinase-associated neurodegeneration inheritance 2.7.1.33 pantothenate kinase medicine pantothenate kinase-associated neurodegeneration is a neurodegenerative condition with a broad phenotypic spectrum 2.7.1.33 pantothenate kinase medicine pantothenate kinase-associated neurodegeneration is a progressive neurodegenerative disorder with autosomal recessive inheritance. The major symptoms of PKAN include the onset before the age of 20 years, progressive pyramidal and extrapyramidal signs, retinitis pigmentosa, optic atrophy, dementia, and iron depositions in the globus pallidus. Identification of mutations of PANK2 gene in patients with proven molecular diagnosis of pantothenate kinase-associated neurodegeneration 2.7.1.33 pantothenate kinase medicine pantothenate kinase-associated neurodegeneration is an autosomal-recessive disorder associated with the accumulation of iron in the basal ganglia. The disease presents with dystonia, rigidity, and gait impairment, leading to restriction of activities and loss of ambulation. The disorder is caused by defective iron metabolism associated with mutations in the PANK2 gene, which codes for the pantothenate kinase enzyme. A mutation screen conducted in two siblings to establish a molecular diagnosis of the disease and a genetic test for the family is reported 2.7.1.33 pantothenate kinase medicine pantothenate-kinase-associated neurodegeneration (PKAN) is caused by mutations of the pantothenate kinase (PANK2) on chromosome 20p13. PKAN is characterized clinically by extrapyramidal symptoms (in 98% of cases), in particular, generalized dystonia with oromandibular involvement, and parkinsonism-spasticity (25%), behavioral changes followed by dementia (29%), and pigmentary retinal degeneration. The mean age at onset is between 3 and 4 years 2.7.1.33 pantothenate kinase medicine pantothenate-kinase-associated neurodegeneration is caused by mutations of the pantothenate kinase gene. Pantothenate-kinase-associated neurodegeneration is characterized clinically by extrapyramidal symptoms (in 98% of cases), in particular, generalized dystonia with oromandibular involvement, and parkinsonism-spasticity (25%), behavioral changes followed by dementia (29%), and pigmentary retinal degeneration. The mean age at onset is between 3 and 4 years 2.7.1.33 pantothenate kinase medicine pantothenic acid deprivation provides a useful phenocopy for pantothenate kinase associated neurodegeneration (formerly called Hallervorden-Spatz syndrome) and allows us to test pharmacological and other interventional strategies in the treatment of this devastating disease 2.7.1.33 pantothenate kinase medicine patient with pantothenate kinase-associated neurodegeneration whose dystonia and freezing of gait respond dramatically to anticholinergic treatment 2.7.1.33 pantothenate kinase medicine the cognitive deterioration in pantothenate kinase-associated neurodegeneration dystonia has been overemphasised and many of the apparent disabilities are more a consequence of the dystonia 2.7.1.33 pantothenate kinase medicine the enzyme is a suitable target for therapeutic intervention in metabolic disorders that feature hyperglycemia and hypertriglyceridemia 2.7.1.35 pyridoxal kinase medicine potential target for drugs 2.7.1.35 pyridoxal kinase medicine ingestion of 4'-O-methylpyridoxine, i.e. ginkgotoxin, triggers epileptic convulsions and other neuronal symptoms. 4'-O-Methylpyridoxine is an competitive inhibitor of pyridoxal kinase and leads to temporarily reduced pyridoxal phosphate formation in vitro and possibly in vivo 2.7.1.36 mevalonate kinase medicine potential target for drugs 2.7.1.36 mevalonate kinase medicine case study of patients with mevalonic aciduria. Patients display high urinary excretion of mevalonic acid. After the second year of life they developed mental retardation, ataxia and hypotonia as well as cerebellar atrophy of both hemispheres and vermis 2.7.1.36 mevalonate kinase medicine clinical relevance of the measurement of IgD for diagnosis of mevalonate kinase deficiency is poor 2.7.1.36 mevalonate kinase medicine inhibition of HMG-CoA reductase by simvastatin treatment of LPS-stimulated peripheral blood mononuclear cells mimicks mevalonate kinase deficiency and results in increased interleukin-1beta secretion in Rac1/phosphatidylinositol-3 kinase-dependent manner. Results suggest that in mevalonate kinase deficiency, dysregulated isoprenoid biosynthesis activates Rac1/phosphatidylinositol-3 kinase/PKB resulting in caspase-1 activation with increased interleukin-1beta processing and release. Inhibition of Rac1 in LPS-stimulated peripheral blood mononuclear cells from patients with mevalonate kinase deficiency results in dramatic reduction in interleukin-1beta release 2.7.1.36 mevalonate kinase medicine inhibition of the isoprenoid pathway results in a dose-dependent reduction of amyloid formed. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibits amyloidogenesis 2.7.1.36 mevalonate kinase medicine luteinizing hormone receptor mRNA is up-regulated due to increased stability when estrogen negatively controls mevalonate kinase 2.7.1.36 mevalonate kinase medicine mouse model for typical mevalonate kinase deficiency can be obtained by treatment of BALB/c mice with aminobisphosphonate alendronate and bacterial muramyldipeptide. Exogenous isoprenoids geraniol, farnesol and geranylgeraniol are effective in prevention of the inflammation induced by alendronate/muramyldipeptide 2.7.1.36 mevalonate kinase medicine no significant correlation between mutations in the mevalonate kinase gene and Behcet's disease. Of 97 patients, two had paired mutations in the mevalonate kinase gene and displayed typical features of Behcet's disease and mevalonate kinase deficiency 2.7.1.36 mevalonate kinase medicine patient with hyperimmunoglobulinemia D due to mutations of the gene coding for mevalonatekinase, and periodic fever syndrome. Treatment with etanercept with a dose of 0.8 mg/kg per week results in great improvement of both attacks and acute-phase response but with still persistent massive hepatosplenomegaly 2.7.1.36 mevalonate kinase medicine patient with mevalonate kinase deficiency due to mutation Q390P and a four-base deletion c.475-478 delACTG. Patient shows high serum immunoglobulin D, elevated mevalonaciduria and low mevalonate kinase activity in lymphocytes. Patient was treated with subcutaneous doses of anakinra. Most disease manifestations regressed dramatically and no new flares have occurred 2.7.1.36 mevalonate kinase medicine patients with hyperimmunoglobulinemia D and periodic fever syndrome due to mutations V377I/I268T. Patients developed significant B cell cytopenia with hypogammaglobulinemia. Therapy of prednisone, azathioprine, and intravenous immunoglobulins resulted in reduced incidence and severity of febrile attacks 2.7.1.36 mevalonate kinase medicine severe case of mevalonate kinase deficiency associated with nephritis. Patient is homozygous for mutation G336S, catalytic activity of the mutant enzyme is less than 1% of wild-type activity. Laboratory data obtained in a period of well-being show increased values of markers of inflammation, severe anemia, and high serum IgA values. Serum autoantibodies are undetectable. Treatment with interleukin 1 receptor antagonist anakinra resulted in normalization of the C-reactive protein, a rise in the hemoglobin value, and disappearance of proteinuria. Hematuria disappeared after 2 months of treatment 2.7.1.39 homoserine kinase medicine potential target for antibiotics due to the fact, that the pathway is not found in mammals 2.7.1.40 pyruvate kinase medicine mutation R510Q causes nonspherocytic hemolytic anemia 2.7.1.40 pyruvate kinase medicine target for cancer therapy 2.7.1.40 pyruvate kinase medicine acute pharmacological inhibiton of mitochondrial fatty acid oxidation using 2-tetradecylglcidic acid has no effect on endogenous glucose production and only a marginal effect on de novo glucose 6-phosphate synthesis 2.7.1.40 pyruvate kinase medicine correlation betwen severity of pyruvate kinase-deficiency and extent of protection against malaria 2.7.1.40 pyruvate kinase medicine determination of the performance characteristics of the tumour M2 pyruvate kinase test with respect to colorectal adenomas in the target population. Median tumour M2 pyruvate kinase level in the whole study population was 1.3 U/ml. At a cutoff of 4 U/ml. sensitivity is 22% and 23% for detection of advanced and other adenomas, respectively, whereas specificity is 82%. In conclusion, the tumour M2 pyruvate kinase test has only very limited potential to distinguish between people bearing precursors to colorectal cancer and people with no finding at colonoscopy 2.7.1.40 pyruvate kinase medicine during ageing, 69 proteins exhibit a drastically changed expression in skeletal muscle. Levels of pyruvate kinase, enolase and phosphofructokinase decrease, while mitochondrial ATP synthase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and adenylate kinase are increased in senescent fibres 2.7.1.40 pyruvate kinase medicine overexpression of promyelocytic leukemia tumor suppressor protein mutant PML-2KA in the cytoplasm suppresses M2-type pyruvate kinase activity and the accumulation of lactate. PML-2KA suppresses the activity of the high-affinity terameric form of M2-type pyruvate kinase, but not of the low-affinity dimeric form 2.7.1.40 pyruvate kinase medicine specific downregulation of M2-type pyruvate kinase by shRNA inhibits the replication of hepatitis C virus in hepatitis C virus replicon 9B cells 2.7.1.40 pyruvate kinase medicine type 1 diabetic patients with nephropathy show increases in the gene expression of hexokinase, phosphoglucomutase, phosphofructokinase, aldolase and triosephosphate isomerase and alterations in protein levels of pyruvate kinase, triosephosphate isomerase, and enolase. Pyruvate kinase activity in fibroblasts from type 1 diabetic patients with nephropathy is lower than in type 1 diabetic patients without nephropathy and in controls 2.7.1.40 pyruvate kinase medicine vitamin E-deficient diets decrease serum alpha-tocopherol and increase pyruvate kinase activity in a time-dependent manner. The vitamin E-deficient diet increases plasma protein carbonyls but does not affect malondialdehyde. Dietary quercetin supplementation increases quercetin and its metabolites in plasma and liver but does not affect vitamin E deficiency-induced changes in plasma alpha-tocopherol, pyruvate kinase or protein carbonyls. Plasma isorhamnetin and its disposition in muscle are enhanced by the vitamin E deficient diet, as compared to the vitamin E-replete diet. Tamarixetin disposition in muscle is decreased by the vitamin E-deficient diet 2.7.1.40 pyruvate kinase medicine faecal M2-PK is a sensitive, noninvasive marker of ileal pouch inflammation (pouchitis) 2.7.1.40 pyruvate kinase medicine faecal tumour M2-PK is a highly sensitive marker for colorectal cancer and larger polyps 2.7.1.40 pyruvate kinase medicine PK-M2 is a predictive marker of response in patients with oxaliplatin-treated colorectal cancer 2.7.1.40 pyruvate kinase medicine tumor pyruvate kinase isoenzyme M2 is not of diagnostic relevance as a marker for oral cancer 2.7.1.40 pyruvate kinase medicine human pyruvate kinase muscle isoform 2 is considered an attractive therapeutic target for modulating tumor metabolism 2.7.1.48 uridine/cytidine kinase medicine target for antitumor and antiviral drug design 2.7.1.48 uridine/cytidine kinase medicine liver-specific targeting of ribavirin by conjugation with asialoglycoprotein to enhance its antiviral activity. Conjugation reaction starts with ribavirin phosphorylation by uridine kinase followed by direct conjugation to asioloosomucoid 2.7.1.48 uridine/cytidine kinase medicine role of UCK2-dependant nucleoside analogues in cancer therapy, overview. Nucleoside antimetabolites are amongst the most important chemotherapeutic agents currently used or under clinical trials against several cancers. This included the important clinically used nucleoside analogue, 5-fluorouracil. UCK2 is also involved in the phosphorylation of ribonucleoside analogues, 5-azacytidine, cyclopentenyl cytosine/uracil, 5-fluorocytidine, 6-azauridine, 3-deazauridine, 5-fluorouridine as well as ethynyl cytidine and uridine. To exert their pharmacological actions, these cytotoxic drugs depend on the action of the UCK2 enzyme to sequentially transform them into nucleoside 5'-triphosphate, thereby interfering with gene synthesis vital for metabolic processes required for cancer cell growth and maintenance 2.7.1.60 N-acylmannosamine kinase medicine clinical relevance of the enzyme in the basic defect in sialuria 2.7.1.60 N-acylmannosamine kinase medicine no siginificant difference in the binding kinetics of alpha-activin 1 with either wild-type or mutant UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase involved in hereditary inclusion body myopathy 2.7.1.67 1-phosphatidylinositol 4-kinase medicine PI4Ks are panviral host therapeutic targets 2.7.1.74 deoxycytidine kinase medicine direct inhibition of DNA polymerases by aphidicolin stimulated enzyme in normal, acute myeloid leukaemic and HL60 promyelocytic cells 2.7.1.74 deoxycytidine kinase medicine recombinant enzyme in human A-549 lung carcinoma cells or murine NIH3T3 fibroblast cells, increase in cytotoxicity of cytosine arabinoside, 5'-aza-2'-deoxycytidine, decrease in toxicity of 2',2'-difluorodeoxycytidine 2.7.1.74 deoxycytidine kinase medicine enzyme is active and important in anticancer and antiviral therapy due to high phosphorylation activity of prodrugs, overview 2.7.1.74 deoxycytidine kinase medicine deoxycytidine kinase overexpression substantially increases both the toxic and radiosensitizing effects of gemcitabine. Enhancement is mild in murine GI261 cells and much stronger in rat C6 and human U373 cells. Combination of enzyme overexpression, gemcitabine treatment and irradiation improves the survival rate of C6 cell bearing rats significantly 2.7.1.74 deoxycytidine kinase medicine in gemcitabine-resistant pancreatic cancer cells, expression of deoxycytidine kinase is significantly reduced compared with that of parental cells. Treatment with siRNA targeted to deoxycytidine kinase reduces gemcitabine sensitivity without affecting cell proliferation. Downregulation of gemcitabine-related genes RRM1 and RRM2 by siRNA increases gemcitabine sensitivity and reduces cell proliferation even without gemcitabine treatment 2.7.1.74 deoxycytidine kinase medicine interindividual variability in deoxycytidine kinase activity is related to its phosphorylation level on residue Ser74 2.7.1.74 deoxycytidine kinase medicine sequencing of gene from European and African individuals reveals 64 genetic polymorphisms. In general, African ancestry subjects show higher mRNA expression compared with subjects with European ancestry. In both groups, single nucleotide polymorphism 35708 C>T of a 3'-untranslated region is significantly associated with lower mRNA expression and with lower blast 1-beta-D-arabinofuranosylcytosine 5'-triphosphate levels in acute myeloid leukemia patients 2.7.1.74 deoxycytidine kinase medicine thymocytes lacking adenosine deaminase activity accumulate intracellular dATP and undergo apoptosis. Inhibition of deoxycytidine kinase prevents the accumulation of dATP and induction of apoptosis to a large degree, inhibition of both deoxycytidine kinase and adenosine kinase completely abrogates accumulation of dATP and significantly reduces the induction of apoptosis 2.7.1.74 deoxycytidine kinase medicine ability of the designer enzymes to activate 5-substitued pyrimidines makes it possible to utilize such nucleoside analogs in suicide gene therapy or protein therapy applications that target cancer cells 2.7.1.76 2'-deoxyadenosine kinase medicine thymocytes lacking adenosine deaminase activity accumulate intracellular dATP and undergo apoptosis. Inhibition of both deoxycytidine kinase and adenosine kinase completely abrogates accumulation of dATP and significantly reduces the induction of apoptosis 2.7.1.78 polynucleotide 5'-hydroxyl-kinase medicine A12B4C3 enhances the radiosensitivity of human A549 lung carcinoma and MDA-MB-231 breast adenocarcinoma cells by a factor of two 2.7.1.78 polynucleotide 5'-hydroxyl-kinase medicine human Machado-Joseph disease patients' brain samples show a significant accumulation of DNA strand breaks. PNKP stably associates with ataxin-3, a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3, i.e. Machado-Joseph disease 2.7.1.82 ethanolamine kinase medicine galactosemic cataractogenesis changes substrate specificity of enzyme 2.7.1.82 ethanolamine kinase medicine ethanolamine kinase could be a target for antimalerial therapy 2.7.1.91 sphingosine kinase medicine involved in signal transduction by TRAF2, tumor necrosis factor-alpha receptor-associated factor 2 2.7.1.91 sphingosine kinase medicine isozyme SPHK1 is a potential therapeutic target in the treatment of inflammatory and autoimmune diseases 2.7.1.91 sphingosine kinase medicine anti-tumor therapy 2.7.1.91 sphingosine kinase medicine potential therapeutic target in anti-cancer therapy 2.7.1.91 sphingosine kinase medicine targeting SPHK may provide a novel therapeutic tool to treat bronchial asthma 2.7.1.91 sphingosine kinase medicine 89% of human colon cancer samples tested stain positively for SphK1, whereas normal colon mucosa has negative or weak staining. Adenomas have higher expression of SphK1 versus normal mucosa, and colon cancers with metastasis have higher expression of SphK1 than those without metastasis 2.7.1.91 sphingosine kinase medicine adenovirus-mediated SPK1 gene transfer promotes recovery of the surgically damaged mesothelial cell layer and prevents postoperative peritoneal adhesion formation 2.7.1.91 sphingosine kinase medicine after 4 weeks of systemic ovalbumin sensitization and local airway challenge, airway responsiveness increases less in SphK1-/- compared with wild-type mice, whereas pulmonary vascular responsiveness is greatly increased and does not differ between strains. Acute lung inflammation leads to an increase in eosinophils and mRNA expression for sphingosine 1-phosphate phosphatase 2 and sphingosine 1-phosphate lyase in lungs of wild-type but not SphK1-/- mice. After repetitive allergen exposure for 8 weeks, airway responsiveness is not augmented in SphK1-/- or wild-type mice, but pulmonary vascular responsiveness is increased in both strains, with significantly higher vascular responsiveness in SphK1-/- mice compared with that seen in wild-type mice 2.7.1.91 sphingosine kinase medicine chronic activation of SPHK1-S1P signalling results in both pathological cardiac remodelling through reactive oxygen species mediated by S1P3 and favourable cardioprotective effects 2.7.1.91 sphingosine kinase medicine in a mouse model of streptozotocin-induced diabetic nephropathy, isoform Sk1 and connective tisuue grwoth factor CTGF are upregulated in podocytes. In Sk1 deficient mice, exacerbation of diesease is detected by increased albuminuria and CTGF expression when compared to wild-type 2.7.1.91 sphingosine kinase medicine in a murine collagen-induced arthritis model, prophylactic i.p. administration of SphK1 siRNA significantly reduces the incidence, disease severity, and articular inflammation compared with control siRNA recipients. Treatment of SphK1 siRNA also down-regulates serum levels of sphingosine 1-phosphate, IL-6, TNF-alpha, IFN-gamma, and IgG2a anticollagen Ab. Ex vivo analysis demonstrates significant suppression of collagen-specific proinflammatory/Th1 cytokine IL-6, TNF-alpha, IFN-gamma release in SphK siRNA-treated mice. Mice received with SphK2 siRNA develop more aggressive disease, higher serum levels of IL-6, TNF-alpha, and IFN-gamma, and proinflammatory cytokine production to collagen in vitro when compared with control siRNA recipients 2.7.1.91 sphingosine kinase medicine In the azoxymethane murine model of colon cancer, SphK1 and sphingosine 1-phosphate are significantly elevated in colon cancer tissues compared to normal mucosa. Blood levels of sphingosine 1-phosphate are higher in mice with colon cancers than in those without cancers. SphK1-/- mice subjected to azoxymethane have significantly less aberrant crypt foci formation and significantly reduced colon cancer development 2.7.1.91 sphingosine kinase medicine isoform Sk1 expression is increased in the podocytes of kidney sections of patients with diabetic nephropathy 2.7.1.91 sphingosine kinase medicine isoform SphK1 protein and mRNA levels are higher in clinical tissue samples of patients with non-Hodgkin lymphomas than in reactive lymphoid hyperplasias, with a clear trend towards increasng levels with increasing clinicla grade 2.7.1.91 sphingosine kinase medicine levels of SPHK1mRNA and protein are higher in gastric cancer cell lines than in normal gastric epithelial cells. SPHK1 protein level is up-regulated in gastric cancer lesions compared with that in the paired adjacent noncancerous tissues. Gastric cancer tissues from 65.7% of patients reveals high level of SPHK1protein expression in contrast to the undetectable or marginally detectable expression of SPHK1 in the adjacent noncancerous gastric tissues. Significantly different expression levels of SPHK1 are found in patients at different clinical stages. Patients with higher SPHK1expression have shorter overall survival time, whereas those with lower SPHK1 expression survive longer 2.7.1.91 sphingosine kinase medicine patients with breast cancer that express higher CerS2 or 4 mRNA levels tend to show no changes in sphingosine kinase 1 levels, and likewise patients that express no change in CerS2 or CerS4 mRNA levels tend to express higher levels of sphingosine kinase 1. Results suggest an important role for the CerS genes in breast cancer etiology or diagnosis 2.7.1.91 sphingosine kinase medicine pharmacologic SphK1 inhibition with B-5354c sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to sphingosine 1-phosphate sphingolipid ratio 2.7.1.91 sphingosine kinase medicine sphingosine analogue FTY720, which is activated by phosphorylation specifically by SPHK2, mediates apoptotic signaling of cultured synovial fibroblasts 2.7.1.91 sphingosine kinase medicine SphK1 inhibition by docetaxel is a two-step process involving an initial loss of enzyme activity followed by a decrease in SphK1 gene expression. Both pharmacological and siRNA-mediated SphK1 inhibition leads to a four-fold decrease in the docetaxel IC50 dose 2.7.1.91 sphingosine kinase medicine SPHK1in astrocytoma cell lines is elevated at both mRNA and protein levels, and the SPHK1 mRNA and protein are significantly up-regulated by up to 6.8- and 40fold, respectively, in primary astrocytomas compared with those in the adjacent noncancerous brain tissues. 41.2% of paraffin-embedded archival astrocytoma biopsies exhibit high expression of SPHK1. The up-regulation of SPHK1 is significantly correlated with the histologic grade of astrocytoma and patients with high SPHK1 level exhibit shorter survival time 2.7.1.91 sphingosine kinase medicine synthesis of shingosine kinase substrates as sphingosine 1-phosphate receptor prodrugs, with varying activities at the five sphingosine 1-phosphate receptors 2.7.1.91 sphingosine kinase medicine synthesis of shingosine kinase substrates as sphingosine 1-phosphate receptor prodrugs, with varying activities at the five sphingosine 1-phosphate receptors. Substrate (2R)-2-amino-2-[5-(4-octylphenyl)-1H-imidazol-2-yl]propan-1-ol causes lymphopenia for more than 20h 2.7.1.91 sphingosine kinase medicine the growth of SphK2-deficient MCF-7 breast tumor xenografts is markedly delayed when compared with controls. Infiltration of macrophages in SphK2-deficient and control tumors is comparable. Tumor-associated macrophages from SphK2-deficient tumors display a pronounced anti-tumor phenotype, showing an increased expression of pro-inflammatory markers/mediators such as NO, TNF-alpha, IL-12 and MHCII and a low expression of anti-inflammatory IL-10 and CD206 2.7.1.91 sphingosine kinase medicine the synovial fluid levels of sphingosine 1-phosphate are significantly higher in patients with rheumatoid arthritis than in those with osteoarthritis. Small chronic increases in SK1 activity in the endothelial cells enhance the ability of the cells to support inflammation and undergo angiogenesis, and sensitize the cells to inflammatory cytokines. The SK1 signaling pathway is activated in rheumatoid arthritis 2.7.1.91 sphingosine kinase medicine treatment of wild-type and Sphk1 null mouse hearts by ischaemic postconditioning. Postconditioning consisting of 5 s of ischaemia and 5 s of reperfusion for three cycles after the index ischaemia, protects hearts against ischaemia/reperfusion injury, recovery of left ventricular developed pressure and maximum velocity of increase or decrease of left ventricular pressure are elevated and left ventricular end-diastolicpressure is decreased, infarction size is reduced from 40% in the control group to 29% of the risk area in the postconditioning group. Phosphorylation of Akt and extracellular signal-regulated kinases is increased at 10 min of reperfusion. The protection induced by postconditioning is abolished in Sphk1 null mouse hearts 2.7.1.91 sphingosine kinase medicine when sphingosine kinase 1 is deleted in Sandhoff disease mice, a prototypical neuronopathic lysosomal storage disorder, a milder disease course occurs, with decreased proliferation of glial cells and less-pronounced astrogliosis. A similar result of milder disease course and reduced astroglial proliferation is obtained by deletion of the gene for the S1P(3) receptor, a G protein-coupled receptor enriched in astrocytes 2.7.1.91 sphingosine kinase medicine the expression level and properties of N-terminal 86 amino-acid isoform variant of sphingosine kinase 1, SK1b, in prostate cancer cells reduce its sensitivity to proteasomal degradation induced by 2-(4-hydroxyanilino)-4-(4-chlorophenyl)thiazole in comparison to isoform SK1a. The reduced sensitivity of SK1b to proteasomal degradation in response to 2-(4-hydroxyanilino)-4-(4-chlorophenyl)thiazole results in specific changes in ceramide and S1P levels that lead to apoptosis of androgen-sensitive but not androgen-independent LNCaP prostate cancer cells 2.7.1.91 sphingosine kinase medicine sphingosine kinase-1 expression inversely correlates with survival after immune checkpoint inhibitor (ICI) therapy in melanoma tumors. Downregulation of sphingosine kinase-1 improves the efficacy of ICI therapy in various cancer models 2.7.1.94 acylglycerol kinase medicine homozygous mutation c.3G>A, p.M1I in the gene encoding acylglycerol kinase has been identified in two brothers who presented with vascular strokes, lactic acidosis, cardiomyopathy and cataracts, abnormal muscle cell histopathology and mitochondrial function. One proband had very abnormal mitochondria with citrate synthase crystals visible in electron micrographs, associated with markedly high citrate synthase activity. Homozygous c.979A>T, p.K327* mutation has been identified in a family with four affected members, of which two have been examined. They presented with similar clinical symptoms, but no strokes. Postmortem heart and skeletal muscle tissues showed low complex I, III and IV activities in the heart, but normal in the muscle. Skin fibroblasts showed elevated lactate/pyruvate ratios and low complex I+III activity 2.7.1.94 acylglycerol kinase medicine identification of a novel autosomal recessive cataract locus on 7q33-q36.1 in a multiplex consanguineous family with isolated congenital cataractl. Mutation is a splice-site mutation in AGK, encoding acylglycerol kinase, which leads to aberrant splicing and predicted premature truncation 2.7.1.94 acylglycerol kinase medicine in membranes from patients with proliferative diabetic retinopathy, vascular endothelial cells express autotaxin and acylglycerol kinase in 16 and 19 out of 22 membranes, respectively. Stromal cells express autotaxin and acylglycerol kinase in 19 and 22 out of membranes, respectively. There are significant correlations between number of blood vessels expressing the panendothelial cell marker CD34 and number of blood vessels and stromal cells expressing autotaxin and acylglycerol kinase. In proliferative diabetic retinopathy membranes, spindle-shaped myofibroblasts expressing alpha-smooth muscle actin co-express autotaxin, acylglycerol kinase and LPA1 receptor 2.7.1.94 acylglycerol kinase medicine high enzyme expression is significantly associated with the grade of malignancy and poor prognosis in glioma patients. The enzyme is a therapeutic target for treatment of glioma 2.7.1.95 kanamycin kinase medicine the enzyme can be used in immunoliposome-mediated delivery for the lineage-specific selection of differentiated/committed stem cell progenies for transplantation, method development and evaluation, potential advantages over transfection with marker genes, fluorescence-activated and magnetic affinity cell-sorting, overview 2.7.1.100 S-methyl-5-thioribose kinase medicine 5-methylthioribose kinase is a key enzyme in methionine salvage in bacteria and the absence of a mammalian homolog suggests that it is a good target for the design of novel antibiotics 2.7.1.103 viomycin kinase medicine antibiotic-inactivating enzyme 2.7.1.105 6-phosphofructo-2-kinase medicine a molecule in which EDTA is covalently linked to ADP is a good starting molecule for the development of new cancer-therapeutic molecules 2.7.1.105 6-phosphofructo-2-kinase medicine the key role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in neoplastic transformation provides a rational for the development of agents that selectively inhibit the PFKFB3 enzyme as antineoplastic agents 2.7.1.105 6-phosphofructo-2-kinase medicine the pharmacologic inhibition of this enzyme may effect the survival and growth of neoplastic cells 2.7.1.105 6-phosphofructo-2-kinase medicine analysis of increase in cardiac glycolysis during ischemia and heart failure 2.7.1.105 6-phosphofructo-2-kinase medicine clinical development of PFKFB3 inhibitors as chemotherapeutic agents 2.7.1.105 6-phosphofructo-2-kinase medicine bifunctional 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 mRNA expression is greater in metastatic prostate cancer compared with primary tumors 2.7.1.105 6-phosphofructo-2-kinase medicine pharmacological disruption of the PFKFB4 kinase domain may have clinical utility for the treatment of human cancers 2.7.1.105 6-phosphofructo-2-kinase medicine PFK-2/FBPase-2 enzymes is attractive targets for cancer treatment 2.7.1.105 6-phosphofructo-2-kinase medicine in colonic and bladder cancer cells, additive growth inhibitory effects are seen with phenformin and with an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3. The increased acidification of the culture medium and glucose uptake caused by phenformin is blocked by combined treatment with PFKFB3 inhibitors 2.7.1.105 6-phosphofructo-2-kinase medicine tumor suppressor p53 regulates the expression of PFKFB4 and p53-deficient cancer cells are highly dependent on the function of the enzyme. Depletion of PFKFB4 from p53-deficient cancer cells increases levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 is also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Depletion of PFKFB4-attenuated cellular biosynthetic activity and results in the accumulation of reactive oxygen species and cell death in the absence of p53. Silencing of PFKFB4-induces apoptosis in p53-deficient cancer cells in vivo and interferes with tumor growth 2.7.1.105 6-phosphofructo-2-kinase medicine chemical enzyme PFKFB3 inhibition synergizes with erlotinib in increasing erlotinib s antiproliferative activity in NSCLC cells 2.7.1.105 6-phosphofructo-2-kinase medicine enzyme inhibition can enhance the effect of paclitaxel-based primary chemotherapy upon ovarian and breast cancers retaining wild type TP53 2.7.1.105 6-phosphofructo-2-kinase medicine high PFKFB3 protein and gene expression may be associated with the occurrence, development, and prognosis of esophageal squamous cell carcinoma 2.7.1.107 diacylglycerol kinase (ATP) medicine DGKzeta may be a therapeutic target to prevent cardiac hypertrophy and progression to heart failure 2.7.1.107 diacylglycerol kinase (ATP) medicine comparison of transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice in streptozotocin-induced diabetic and non-diabetic conditions. After 8 weeks, decreases in heart weight and heart weight/body weight ratio in diabetic wild-type mice are inhibited in transgenic mice. Decreases in left ventricular end-diastolic diameter and fractional shortening observed in wild-type mice are attenuated in transgenic mice. Thinning of the interventricular septum and the posterior wall in diabetic wild-type hearts are blocked in transgenic mice. Reduction of transverse diameter of cardiomyocytes isolated from the left ventricle in diabetic wild-type mice is attenuated in transgenic mice. Cardiac fibrosis was much less in diabetic transgenic than in diabetic wild-type mice 2.7.1.107 diacylglycerol kinase (ATP) medicine creation of thoracic transverse aortic constriction in transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice. Increases in heart weight at 4 weeks after thoracic transverse aortic constriction are attenuated in diacylglycerol kinase zeta transgenic mice compared with wild-type mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in wild-type mice are observed at 4 weeks after surgery and are attenuated in diacylglycerol kinase zetatransgenic mice. Contrary to wild-type, cardiac fibrosis and gene induction of type I and type III collagens, but not transforming growth factor are blocked in diacylglycerol kinase zeta transgenic mice 2.7.1.107 diacylglycerol kinase (ATP) medicine deficiency for diacylglycerol kinase zeta results in impaired interleukin 12 and tumor necrosis factor alpha production following toll-like receptor stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection 2.7.1.107 diacylglycerol kinase (ATP) medicine diacylglycerol kinase delta haploinsufficiency increases diacylglycerol content, reduces peripheral insulin sensitivity, insulin signaling, and glucose transport, and leads to age-dependent obesity. Metabolic flexibility is impaired 2.7.1.107 diacylglycerol kinase (ATP) medicine diacylglycerol kinase delta knock-down mice reveal abnormal epiletic discharges and electrographic seizures in three out of six homozygotes 2.7.1.107 diacylglycerol kinase (ATP) medicine diacylglycerol kinase zeta blocks cardiac dysfunction and progression to lethal heart failure by activated G-protein subunit alphaq protein without detectable adverse effects in the in-vivo heart 2.7.1.107 diacylglycerol kinase (ATP) medicine diacylglycerol kinases are required for anchorage-independent growth in MDA-MB-231 cells. Activity is induced by hepatocyte growth factor 2.7.1.107 diacylglycerol kinase (ATP) medicine in a female patient with a de novo balanced translocation, 46,X,t(X,2)(p11.2,q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity, diacylglycerol kinase delta is disrupted at 2q37.Diacylglycerol kinase delta is involved in the etiology of seizures 2.7.1.107 diacylglycerol kinase (ATP) medicine overexpression of wild-type diacylglycerol kinase alpha, but not of its kinase-dead mutant, markedly suppresses tumor necrosis factor alpha-induced apoptosis of AKI human melanoma cells and enhances the tumor necrosis factor alpha-stimulated transcriptional activity of transcription factor NF-kappaB. siRNA-mediated knock-down of diacylglycerol kinase alpha enhances the apoptosis. Overexpression of isoforms beta and gamma has no detectable effect on apoptosis 2.7.1.107 diacylglycerol kinase (ATP) medicine patients with certain forms of systematic vasculitis, such as Wegener’s granulomatosis, have circulating antineutrophil cytoplasmic antibodies. Diacylglycerol kinase is selectively activated by circulating antineutrophil cytoplasmic antibodies and the generated phosphatidic acid is responsible for promoting neutrophil adhesion, in part through integrin activation 2.7.1.107 diacylglycerol kinase (ATP) medicine patients with type 2 diabetes mellitus display reduced diacylglycerol kinase delta expression and activity in skeletal muscle 2.7.1.107 diacylglycerol kinase (ATP) medicine study on genetic basis of bipolar disorder. Of 37 single nucleotide polymorphisms selected for individual genotyping, the strongest association signal is detected at a marker within the diacylglycerol kinase eta. Several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease 2.7.1.107 diacylglycerol kinase (ATP) medicine transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta. Left ventricular chamber dilatation, reduction of left ventricular systolic function and increases in left ventricular weight and lung weight at 4 weeks after myocardial infarction are attenuated in transgenic mice compared with wild-type mice. In the noninfarct area, fibrosis fraction and upregulation of profibrotic genes, such as transforming growth factor-1, collagen type I, and collagen type III, are blocked in transgenic mice. Survival rate at 4 weeks after myocardial infarction is higher in transgenic mice than in wild-type 2.7.1.107 diacylglycerol kinase (ATP) medicine DGKepsilon is a therapeutic target to prevent cardiac hypertrophy and progression to heart failure 2.7.1.107 diacylglycerol kinase (ATP) medicine diaclyglycerol kinase activity is reduced by oxidative stress in glomerular mesangial cells cultured under high glucose conditions. Antioxidants, including D-alpha-tocopherol and probucol may improve hyperglycemia-induced diacylglycerol-protein kinase C activation by enhancing diacylglycerol kinase activity 2.7.1.107 diacylglycerol kinase (ATP) medicine enzyme is able to remove 1-stearoyl-2-arachidonoylglycerol, the precursor of the endocannabinoid 2-arachidonoyl glycerol 2.7.1.107 diacylglycerol kinase (ATP) medicine the isozyme DGKdelta may be a target for cancer chemotherapy 2.7.1.107 diacylglycerol kinase (ATP) medicine isoform DGKalpha can be used as strategy for treating diabetic nephropathy 2.7.1.113 deoxyguanosine kinase medicine enzyme is useful in anticancer therapy due to activation of anticancer drugs through phosphorylation 2.7.1.113 deoxyguanosine kinase medicine the enzyme activates a number of medically important nucleoside analogues 2.7.1.127 inositol-trisphosphate 3-kinase medicine the actin bundling enzyme inositol-trisphosphate 3-kinase A (ITPKA) is a target in tumor therapy, because it is upregulated in tumor but not in corresponding normal cells. Downregulation of ITPKA in lung adenocarcinoma cancers reduced both, tumor growth and metastasis 2.7.1.137 phosphatidylinositol 3-kinase medicine p110a is a target for cancer therapies 2.7.1.137 phosphatidylinositol 3-kinase medicine selective enhancement of the PI3K activity in the nuclear accumbens shell may be one of key alterations underlying the long-term cocaine sensitization. To the extent cocaine sensitization is an important factor in human cocaine abuse, pharmacological interventions targeted toward the NAc shell PI3K alteration may be useful in cocaine abuse treatment 2.7.1.137 phosphatidylinositol 3-kinase medicine dual inhibition of the mTORC1 complex and the IGF-1/IGF-1R/PI3K/Akt pathway in acute myeloid leukemia may enhance the efficacy of mTOR inhibitors in treatment of this disease 2.7.1.137 phosphatidylinositol 3-kinase medicine inhibition of PI 3-K enhances the susceptibility of oral squamous cell carcinoma cells to anticancer drug-mediated apoptosis through regulation of expression and post-translational modification of both pro- and antiapoptotic proteins. These findings could potentially lead to new strategies for improving the efficacy of anticancer drugs in oral squamous cell carcinoma cells 2.7.1.137 phosphatidylinositol 3-kinase medicine inhibition of the class I PI3K signaling pathway is a potential strategy for managing gastric cancers 2.7.1.137 phosphatidylinositol 3-kinase medicine inhibitors of PI3K/Akt may prove to be useful novel therapies in the treatment of asthma and chronic obstructive pulmonary disease 2.7.1.137 phosphatidylinositol 3-kinase medicine PI 3-K inhibitors may represent a novel strategy for overcoming resistance to TRAIL-mediated apoptosis in oral squamous cell carcinoma cell 2.7.1.137 phosphatidylinositol 3-kinase medicine PI3K inhibitors might have therapeutic potential when combined with cycloheximide in the treatment of hepatoma 2.7.1.137 phosphatidylinositol 3-kinase medicine preclinical evidence for the in vivo efficacy for the phosphatidylinositol 3-kinase inhibitor LY294002 in the treatment of follicular thyroid cancer 2.7.1.137 phosphatidylinositol 3-kinase medicine PI3K lipid kinase is an attractive target for the development of therapeutic agents to treat cancer and other related diseases 2.7.1.138 ceramide kinase medicine ceramide kinase is important for neutrophil homeostasis, ceramide kinase is important for the defense against Streptococcus pneumoniae infections 2.7.1.138 ceramide kinase medicine potential target for anti-allergic therapeutics 2.7.1.138 ceramide kinase medicine potentially important therapeutic target in oncology and inflammation 2.7.1.138 ceramide kinase medicine therapeutic agent 2.7.1.138 ceramide kinase medicine CerK inhibition has potential for treating mesangioproliferative kidney diseases in humans 2.7.1.138 ceramide kinase medicine the enzyme is a therapeutical target in breast cancer treatment due to its functional role in breast cancer recurrence 2.7.1.145 deoxynucleoside kinase medicine enzyme with increased specificity towards certain analogues can be used as a suicide gene in combined gene/chemotherapy treatment of cancer 2.7.1.145 deoxynucleoside kinase medicine the enzyme activates a number of medically important nucleoside analogues 2.7.1.145 deoxynucleoside kinase medicine the enzyme can be used as a suicide gene in combined gene/chemotherapy treatment of cancer 2.7.1.145 deoxynucleoside kinase medicine deoxynucleoside kinase gene is introduced into HeLa cells with cationic lipids, to allow its transient expression. Cytotoxicities of 1-beta-D-arabinofuranosylcytosine, 5-fluorodeoxyuridine, and 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine are increased by the deoxynucleoside kinase gene. The combination of the transient expression of the Drosophila deoxynucleoside kinase gene and these nucleoside analogs is a candidate for suicide gene therapy 2.7.1.145 deoxynucleoside kinase medicine mitochondrial targeting of Dm-dNK facilitates nucleoside and nucleoside analog phosphorylation and could be used as a strategy to enhance the efficacy of nucleoside analog phosphorylation and concomitantly their cytostatic potential 2.7.1.145 deoxynucleoside kinase medicine transduced deoxyribonucleoside kinases can be used to kill recipient cells in combination with nucleoside prodrugs 2.7.1.145 deoxynucleoside kinase medicine mitochondrial targeting of multisubstrate nucleoside kinase facilitates nucleoside and nucleoside analog phosphorylation and could be used as a strategy to enhance the efficacy of nucleoside analog phosphorylation and concomitantly their cytostatic potential 2.7.1.145 deoxynucleoside kinase medicine possible use of this enzyme as a suicide gene in vitro and in vivo 2.7.1.145 deoxynucleoside kinase medicine suicide gene dmdnk in several cancer cell lines, overview. In vivo testing in a xenograft model for breast cancer, both wild-type DmdNK and mutants of DmdNK are combined with gemcitabine (dFdC, 2',2'-difluoro-deoxycytidine) as the NA prodrug and a positive effect of decreasing tumor volume and increased survival time 2.7.1.145 deoxynucleoside kinase medicine lentivirusx1emediated Drosophila melanogaster deoxyribonucleoside kinase combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine or 1-beta-D-arabinofuranosylthymine therapy may be effective in treating keloid fibroblasts 2.7.1.145 deoxynucleoside kinase medicine the enzyme is a potential candidate for reversing acquired gemcitabine resistance in triplex1enegative breast cancer cells, which may form the basis of strategies for the treatment of patients with drugx1eresistant triplex1enegative breast cancer 2.7.1.145 deoxynucleoside kinase medicine the recombinant enzyme is used to sensitize human cancer cell lines to gemcitabine 2.7.1.148 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase medicine potential target for antimalarial therapy 2.7.1.149 1-phosphatidylinositol-5-phosphate 4-kinase medicine phosphatidylinositol-5-phosphate 4-kinase type II beta might be an effective therapeutic target for preventing of colon cancer progression 2.7.1.151 inositol-polyphosphate multikinase medicine putative treatment of cancer 2.7.1.151 inositol-polyphosphate multikinase medicine delivery of IPMK in a transgenic Huntington's disease model improves pathological changes and motor performance. The Ctip2-IPMK-Akt signaling pathway provides a previously unidentified therapeutic target for Huntington's disease 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine reduction of regulatory subunit p85alpha as a therapeutic target for enhancing insulin-like growth factor 1/insulin signaling, prolongation of cell survival, and protection against apoptosis 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine p110delta may be a good target for pharmaceutical intervention of T cell-dependent autoimmune pathologies 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine therapeutic target for Th2-mediated airway disease 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine genetic deletion or selective inhibition of isoform PI3Kdelta diminishes joint erosion to a level comparable to its PI3Kgamma counterpart. The induction and progression of joint destruction is profoundly reduced in the absence of both PI3K isoforms and correlates with a limited ability of neutrophils to migrate into tissue in response to leukotriene B4. fMLP-induced neutrophil extravasation is primarily reliant on PI3Kgamma 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine in human leukemic cell lines and in primary blast cells from acute myelogenous leukemia patients, inhibitor 4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol/PI-103 inhibits constitutive and growth factor-induced PI3K/Akt and mTORC1 activation. PI-103 is essentially cytostatic for cell lines and induces cell cycle arrest in the G1 phase. In blast cells, PI-103 inhibits leukemic proliferation, the clonogenicity of leukemic progenitors and induces mitochondrial apoptosis. PI-103 has additive proapoptotic effects with etoposide in blast cells and in immature leukemic cells. PI-103 does not induce apoptosis in normal CD34þ cells and has moderate effects on their clonogenic and proliferative properties 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine inhibitor 4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol, i.e. PI103 is inhibitory to phosphatidylinositol 3-kinases, TORC1 and DNA protein kinase. PI103 potently inhibits proliferation and invasion of a wide variety of human cancer cells in vitro and shows biomarker modulation consistent with inhibition of phosphatidylinositide 3-kinase signaling. PI103 is extensively metabolized, but distributed rapidly to tissues and tumors. This results in tumor growth delay in eight different human cancer xenograft models with various phosphatidylinositide 3-kinase pathway abnormalities. Decreased phosphorylation of AKT is observed in U87MG gliomas, consistent with drug levels achieved 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine transition of CD4-/CD8- double-negative to CD4+/CD8+ double-positive thymocytes triggered by anti-CD3 monoclonal antibodies is significantly impaired in mice lacking both major reglulatory subunit p85alpha of phosphatidylinositol 3-kinases and Rag-2 compared with p85alpha+/- Rag-2-/- mice. Inhibition by IC87114 of the major class IA phosphatidylinositol 3-kinase catalytic subunit expressed in lymphocytes, p110, blocks transition of CD4-/CD8- double-negative to CD4+/CD8+ double-positive cells in embryonic day 14.5 fetal thymic organ culture without affecting cell viability 2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase medicine application of PI3K/Akt/mTOR inhibitors in T-cell acute lymphoblastic leukemia, T-ALL 2.7.1.171 protein-fructosamine 3-kinase medicine inhibition of fructoseamine-3-kinase is a promising new therapeutic target for diabetic complications, as well as other 3-deoxyglucosone-dependent pathologies 2.7.1.171 protein-fructosamine 3-kinase medicine FN3K may be a potential predictor of the risk of diabetes complications. Pharmacological modifications of its activity may provide an approach to their prevention 2.7.2.3 phosphoglycerate kinase medicine enzyme of parasite is target for vaccine and drug development, enzyme elicits antibodies and can therefore be utilized as immunoreagent in serodiagnostics for clonorchiasis 2.7.2.3 phosphoglycerate kinase medicine inhibition of the enzyme can provide a method of treatment for cardiovascular and respiratory disorders, construction of possible specific fluoro-phosphonate inhibitors 2.7.2.3 phosphoglycerate kinase medicine overexpression or down-regulation of PGK affects the cytotoxicity of beta-L-dioxolane-cytidine, which is under clinical trials for treating cancer, but not that of beta-D-2',2'-difluorodeoxycytidine under normoxic conditions, overexpression of PGK does not further increase the cytotoxicity of beta-L-dioxolane-cytidine under hypoxic conditions 2.7.2.3 phosphoglycerate kinase medicine PGK deficiency (D164V mutation) is a rare X-linked disease that is characterised by mild to severe haemolytic anaemia, rhabdomyolysis, and variable defects in the central nervous system, it is a recurrent mutation 2.7.2.3 phosphoglycerate kinase medicine PGK1 is a potential biomarker and/or therapeutic target for pancreatic ductal adenocarcinoma 2.7.2.3 phosphoglycerate kinase medicine two missense mutations in patients of Spanish origin with a severe life-long chronic haemolytic anaemia associated with progressive neurological impairment. One patient with an amino acid change of Ile to Asn at 46th position from the NH2-terminal serine residue, the second patient with a Ser319Asn amino acid substitution. In both cases, the mutations do not modify any of the PGK binding sites for ATP or 3-phospho-D-glycerate, so their consequence is related to a loss of enzyme stability rather than a decrease of enzyme catalytic function 2.7.2.3 phosphoglycerate kinase medicine PGK-1 may be an important therapeutic target for pharmacological or gene therapy intervention in non-small cell lung carcinoma 2.7.2.3 phosphoglycerate kinase medicine the gene encoding the erythrocyte enzyme PGK1, is X-linked. Mutations of this gene may cause chronic haemolysis with or without mental retardation and they may cause myopathies, often with episodes of myoglobinuria, or a combination of these clinical manifestations 2.7.2.3 phosphoglycerate kinase medicine the X-linked recessive disease phosphoglycerate kinase deficiency is caused by altered expression of the PGK1 enzyme, which causes muscle stiffness, hemolytic anemia, and mental retardation. The PGK1 gene is charaterized in a family of two brothers, two sisters, and their parents. A single mutation in exon 6, which is associated with the pattern of inheritance of PGK1 deficiency, is observed. This silent G213G mutation is localized to the conserved exon-intron boundary. A method for quantification of PGK1 mRNA is developed. A marked reduction in PGK1 mRNA is demonstrated in both brothers with the disease. A smaller decrease in PGK1 expression is observed in one sister with symptoms of PGK deficiency and in her mother. Only the normal PGK1 allele is expressed in the two heterozygous women. Whereas most known PGK1 mutations cause amino acid alterations, this study indicates that inhibition of the transcription mechanism is the cause of PGK deficiency 2.7.2.3 phosphoglycerate kinase medicine PGK1 may serve as prognostic marker and/or be a potential therapeutic target to prevent dissemination of gastric carcinoma cells into the peritoneum 2.7.2.3 phosphoglycerate kinase medicine transgenic mice ubiquitously expressing enhanced green fluorescent protein (EGFP) under the control of the phosphoglycerate kinase 1 promoter by allotransplantation of transgenic mice ovaries may be useful for studies assessing the use of gene therapy of bone marrow or nerve cells, as well as for tumorigenesis and organ transplantation studies 2.7.2.4 aspartate kinase medicine L-lysine, one of the essential amino acids required for nutrition in animals and humans, is widely used in the food industry, medical industry, etc. L-lysine has been mainly produced by microbial fermentation employing mutant strains of bacteria. An L-lysine high-yielding strain is developed by modification of aspartokinase III and dihydrodipicolinate synthetase 2.7.3.2 creatine kinase medicine possible roles in pathology 2.7.3.2 creatine kinase medicine transgenic mice lacking mitochondrial enzyme or both mitochondrial and cytoplasmic enzyme, myocardial energy-recruiting mechanims 2.7.3.2 creatine kinase medicine enzyme properties relevant for analysis 2.7.3.2 creatine kinase medicine role of enzyme in severe left ventricular hypertrophy 2.7.3.2 creatine kinase medicine ethylmalonic acid accumulates in patients affected by short-chain acyl-CoA dehydrogenase deficiency and other diseases. Ethylmalonic acid inhibits the activity of respiratory chain complexes and also inhibits creatine kinase at concentrations o 1 mM and 5 mM and may therefore compromise energy metabolism in skeletal muscle 2.7.3.2 creatine kinase medicine levels of both free and protein-bound 4-hydroxy-2-nonenal are increased in alzheimer’s disease brain. 4-Hydroxy-2-nonenal inhibitis creatine kinase dose-dependently and forms adducts with specific amino acids including the active site residues H66, H191, C283, and H296 2.7.3.2 creatine kinase medicine neurotoxicitiy of L-arginine in hyperargininemia may in part be due to inhibition of creatine kinase 2.7.3.2 creatine kinase medicine study on the effect of antipsychotics haloperidol, clozapine, olanzapine or aripiprazole chronic administration on creatine kinase in rat brain 2.7.3.2 creatine kinase medicine increased troponin I levels in the presence of rest pain and normal creatine kinase is not a spurious finding, but may actually be a marker of advanced coronary artery disease. However, some of these patients may also have nonsignificant coronary artery disease 2.7.3.2 creatine kinase medicine mutations in the dysferlin gene cause several muscular dystrophy phenotypes including limb girdle 2B, Miyoshi myopathy, and distal anterior compartment myopathy. These disorders are characterized by autosomal recessive inheritance, early adult onset, and elevated levels of serum creatine kinase 2.7.3.2 creatine kinase medicine strategies aimed at increasing isozyme CKB expression might lead to the development of therapeutic treatments for Huntington's disease 2.7.3.2 creatine kinase medicine changes in the kinetics of the creatine kinase shuttle are sensitive markers of cardiac energetics 2.7.3.2 creatine kinase medicine the enzyme is one of the most preferred biomarkers used for the diagnosis of acute coronary syndrome 2.7.3.3 arginine kinase medicine arginine kinase is a possible chemotherapy target for Chagas‘ disease 2.7.3.3 arginine kinase medicine the enzyme is a possible target for chemotherapy 2.7.3.3 arginine kinase medicine the recombinant enzyme may be used to identify a group of polysensitized indoor allergic patients and for immunotheraphy of theses individuals 2.7.3.3 arginine kinase medicine this enzyme as a possible novel chemotherapy target for VLM syndrome in humans 2.7.3.3 arginine kinase medicine the enzyme HcAK is a potential vaccine candidate because of the strong antigenicity of invertebrate phosphagens and kinases and presence in metabolically active parts of the worm 2.7.3.3 arginine kinase medicine the enzyme TcAK is a potential vaccine candidate because of the strong antigenicity of invertebrate phosphagens and kinases and presence in metabolically active parts of the worm 2.7.3.9 phosphoenolpyruvate-protein phosphotransferase medicine virulence of enzyme deletion mutants 2.7.3.9 phosphoenolpyruvate-protein phosphotransferase medicine the enzyme can function as an adhesin, evaluation of its potential as a vaccine. Immunization with rPtsA protects mice against a sublethal intranasal and a lethal intravenous pneumococcal challenge. PtsA binding peptides derived from its putative target molecules can be considered for development of therapeutics, and rPtsA is a candidate for vaccine development 2.7.3.9 phosphoenolpyruvate-protein phosphotransferase medicine recombinant enzyme and anti-enzyme antiserum inhibit adhesion of Streptococcus pneumoniae to cultured human lung adenocarcinoma A-549 cells 2.7.4.1 ATP-polyphosphate phosphotransferase medicine PPK1 is necessary for survival under anaerobic conditions or oxidative stress 2.7.4.1 ATP-polyphosphate phosphotransferase medicine PPK1 exhibits potential as a target for chemotherapy 2.7.4.2 phosphomevalonate kinase medicine the enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis represent potential for addressing a pressing human health concern, the development of antibiotics against resistent strains of the Gram-positive streptococci 2.7.4.3 adenylate kinase medicine secreted enzyme as virulence factor, involved in macrophage cell death by producing a pool of toxic mixtures of AMP, ADP, ATP 2.7.4.3 adenylate kinase medicine enzyme has an increased contribution to cellular phosphotransfer in heart failure 2.7.4.3 adenylate kinase medicine adenylate kinase participates in the regulation of ADP-dependent endocytosis of high-density lipoprotein by consuming the ADP generated by the ecto-F1-ATPase 2.7.4.3 adenylate kinase medicine characterization of enzyme mutations from patients deficient in red cell adenylate kinase, suffering from chronic hemolytic anemia 2.7.4.3 adenylate kinase medicine in contrast to decreased levels of pyruvate kinase, enolase and phosphofructokinase, the mitochondrial ATP synthase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and adenylate kinase are increased in senescent fibres 2.7.4.3 adenylate kinase medicine knock out of the major isoform adenylate kinase 1 disrupts the synchrony between inorganic phosphate turnover at ATP-consuming sites and gamma-ATP exchange at ATP synthesis sites. This reduces energetic signal communication in the post-ischemic heart. Adenylate kinase 1 gene deletion blunts vascular adenylate kinase phosphotransfer, compromises the contractility-coronary flow relationship, and precipitates inadequate coronary reflow following ischemiareperfusion. Deficit in adenylate kinase activity abrogates AMP signal generation and reduces the vascular adenylate kinase/creatine kinase activity ratio essential for the response of metabolic sensors. The sarcolemma-associated splice variant adenylate kinase 1beta facilitates adenosine production. Adenosine treatment bypasseds adenylate kinase 1 deficiency and restores post-ischemic flow to wild-type levels 2.7.4.3 adenylate kinase medicine study on patients with limbic encephalitis refractory to corticosteroids, IVIg and plasma exchange. Both patients have serum/cerebrospinal fluid antibodies recognizing brain autoantigen adenylate kinase 5 2.7.4.3 adenylate kinase medicine adenylate kinase immunization provides protection against Mycobacterium tuberculosis infection 2.7.4.6 nucleoside-diphosphate kinase medicine kinetic parameters of nucleotide analogues for use as anti-HIV nucleosides 2.7.4.6 nucleoside-diphosphate kinase medicine no effect of diabetes on enzymic activity 2.7.4.6 nucleoside-diphosphate kinase medicine low affinity of enzyme for L-dideoxynucleoside triphosphates, implications for antiviral therapies and treatment of AIDS 2.7.4.6 nucleoside-diphosphate kinase medicine crystallization data of mutant S120G identified in aggressive neuroblastomas, no significant changes between wild-type and mutant even in the surroundings of the catalytic His residue, suggesting that the mutation might affect an other protein property than enzyme activity 2.7.4.6 nucleoside-diphosphate kinase medicine NME1 expression is associated with reduced overall and event-free survival of neuroblastoma patients and with the strongest associations of any of the NME family member genes. NME1 expression is also higher in tumors with MYCN oncogene amplification and in tumors from patients with stage 4 disease. Isoforms NME1/NMe2 and multiple phosphorylated His-containing proteins are found in all tested neuroblastoma cell lines and in xenograft neuroblastoma tumors. NME1 expression is asssociated with neuroblastoma cell migration and differentiation 2.7.4.8 guanylate kinase medicine GMPK from bacterial pathogens, in which this enzyme is essential, are potential targets for therapeutic inhibition. 2.7.4.9 dTMP kinase medicine the enzyme is a promising target for developing drugs against tuberculosis because the configuration of its active site is unique in the TMPK family 2.7.4.9 dTMP kinase medicine enzyme/prodrug combination for selectively inducing apoptosis in lentiviral vector-transduced cells, based on designed variants of human thymidylate kinase that effectively phosphorylate 3'-azido-3'-deoxythymidine. Mechanism involves apoptosis induction via disruption of the inner membrane potential and activation of caspase-3. Low-dose 3'-azido-3'-deoxythymidine administration to non-obese diabetic/severe combined immunodeficiency mice injected with the engineered cells suppresses tumor growth 2.7.4.9 dTMP kinase medicine introduction of an engineered, highly active dTMP kinase into T cells for more efficient conversion of the 3'-azido-3'-deoxythymidine prodrug to its diphosphorylated form and blocking replication of formerly 3'-azido-3'-deoxythymidine resistant HIV. Combined treatment of HIV-infected T-cells with 3'-azido-3'-deoxythymidine and the engineered thymidylate kinases restores 3'-azido-3'-deoxythymidine-induced repression of viral production 2.7.4.9 dTMP kinase medicine silencing of expression in p53-/- and in p53+/+ colon cancer cells by lentiviral-based small hairpin RNA results in decrease of the dTTP pool without affecting p53 expression and generating cytotoxicity. Thymidylate kinase knock-down increases doxorubicin sensitivity dramatically in p53-proficient, p53-null HCT-116,and LoVo colon cancer cells. The decrease in the dTTP pool augments the DNA damage response and enhances apoptotic induction after exposure to low-dose doxorubicin, leading to cell death 2.7.4.9 dTMP kinase medicine bystander cell killing contributes to tumor regression in a xenograft model relying on the delivery of expression of the thymidylate kinase suicide gene into tumors via direct intratumoral injection of recombinant therapeutic lentivirus. The thymidylate kinase/azidothymidine enzyme-prodrug axis can be effectively utilized in suicide gene therapy of solid tumors 2.7.4.14 UMP/CMP kinase medicine screening of acyclic phosphonate analogs to find antimetabolites for antivirus and anticancer therapies 2.7.4.14 UMP/CMP kinase medicine lipopolysaccharide-induced human chorionic trophoblast HTR8/SVneo cell model to mimic missed abortion in vitro. CMPK2 expression and NLRP3 inflammasome activation, downstream pro-IL-18 and pro-IL-1beta expression, and IL-18 and IL-1beta release, are all significantly increased in missed abortion tissues or LPS-induced HTR8/SVneo cells. Pigment epithelium-derived factor reverses the increase in CMPK2 expression and activation of the NLRP3 inflammasome axis and downregulates the production of mitochondrial reactive oxygen species and mitochondrial DNA release 2.7.4.21 inositol-hexakisphosphate 5-kinase medicine selectively blocking HSP90-IP6K2 binding could provide effective and safer modes of chemotherapy to block apoptosis 2.7.4.21 inositol-hexakisphosphate 5-kinase medicine enzyme IP6K1 is a target in obesity and type-2 diabetes 2.7.4.21 inositol-hexakisphosphate 5-kinase medicine transition variant R837H segregates with DFNB100-associated hearing loss 2.7.4.22 UMP kinase medicine interest in new therapies against anthrax has arisen from its potential for bioterrorism. The allosteric pocket of the enzyme, with its atypical configuration of side chains, may provide a particularly suitable site for pharmacological intervention 2.7.4.24 diphosphoinositol-pentakisphosphate 1-kinase medicine transition variant R837H segregates with DFNB100-associated hearing loss 2.7.6.1 ribose-phosphate diphosphokinase medicine mutations Q165P and R228W mimick missense mutations identified in neurological disorders such as Arts syndrome. Mutant flies are able to develop normally, but have a shortened lifespan and locomotive defects. Patient-derived PRPS mutations result in profound defects in lipolysis, macroautophagy, and lysosome function. The nervous system of these mutant flies is affected by these defects 2.7.6.2 thiamine diphosphokinase medicine Malaria is a devastating and quite often deadly parasitic disease, resulting in significant public health problems in the tropics. The inevitable emergence of drug-resistant forms requires the continuous discovery and development of new antimalarials. These drugs should only target the parasite, with only harmless or no effects on the human host. Thus, ideal drug targets would be peculiarities in the parasite metabolism, such as vitamin B1 and B6 biosyntheses that are absent in its host. 2.7.6.2 thiamine diphosphokinase medicine TPK1 is post-transcriptionally upregulated in cancer cells following hypoxic exposure. TPK1 expression is also adaptively upregulated following alterations of redox status by chemotherapeutic and antioxidant treatments. Despite upregulation by hypoxia, intracellular TPP levels are reduced. This loss was reversed by treatment with cell-permeable antioxidants and corresponds with reduced ROS production and enhanced cellular proliferation during supplemental thiamine conditions. siRNA-mediated knockdown of TPK1 directly enhances basal ROS levels and reduces tumor cell proliferation 2.7.6.3 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase medicine because the enzyme is essential for microorganisms but is absent from human and animals, the enzyme is an excellent target for developing antimicrobial agent 2.7.7.1 nicotinamide-nucleotide adenylyltransferase medicine the mitochondrial localization of NMNAT activity plays an important role in NMNAT expression-mediated axonal protection 2.7.7.1 nicotinamide-nucleotide adenylyltransferase medicine given its vital role in cell life, the enzyme represents a possible target for the development of new antibacterial agents 2.7.7.1 nicotinamide-nucleotide adenylyltransferase medicine NMNAT1 is a potential therapeutic target for stroke 2.7.7.1 nicotinamide-nucleotide adenylyltransferase medicine loss of function mutations in two stillborn siblings lead to fetal akinesia deformation sequence, severely reduced skeletal muscle mass and hydrops fetalis. Both protein variants are incapable of supporting axon survival in mouse primary neuron cultures when overexpressed. Variants display altered protein stability and/or defects in NAD+ synthesis and chaperone functions 2.7.7.3 pantetheine-phosphate adenylyltransferase medicine PPAT is a target for antibacterial drug discovery 2.7.7.3 pantetheine-phosphate adenylyltransferase medicine the enzyme is a therapeutical target in treatment of Helicobacter induced gastritis 2.7.7.6 DNA-directed RNA polymerase medicine the enzyme is a promising target for the discovery of new antimicrobial agents 2.7.7.7 DNA-directed DNA polymerase medicine clinically, POLG mutations can present from early neonatal life to late middle age, with a spectrum of phenotypes that includes common neurological disorders such as migraine, epilepsy and Parkinsonism 2.7.7.7 DNA-directed DNA polymerase medicine mitochondrial toxicity is a limiting factor in the use of some nucleoside reverse transcriptase inhibitors of HIV. DNA polymerase gamma incorporates chain-terminating dioxolane guanosine and 2',3'-dideoxy-2',3'-didehydroguanosine more than 3000fold efficiently than the carboxylic analog carbovir triphosphate 2.7.7.7 DNA-directed DNA polymerase medicine mutation R964C is identified in a patient with lactic acidosis. Recombinant R964C Pol gamma shows only 14% activity of wild-type enzyme. The mutation could be associated with the severe lactic acidosis induced by long-term use of nucleoside reverse-transcriptase inhibitors 2.7.7.7 DNA-directed DNA polymerase medicine adenovirus DNA polymerase is a target for immunotherapy of adenovirus disease 2.7.7.8 polyribonucleotide nucleotidyltransferase medicine depletion of enzyme by RNAi approach or overexpression of c-myc protects melanoma cells from interferon-beta mediated grwoth inhibition. Targeted overexpression of enzyme as a therapeutic strategy for c-myc overexpressing and interferon-beta resistant tumors 2.7.7.8 polyribonucleotide nucleotidyltransferase medicine the apoptosis-inducing activity of polynucleotide phosphorylase is mediated by activation of double-stranded RNA-dependent protein kinase. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase precedes phosphorylation of eukaryotic initiation factor-2A and induction of growth arrest and DNA damage-inducible gene 153, GADD153, that culminates in the shutdown of protein synthesis and apoptosis. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase also instigates down-regulation of the antiapoptotic protein Bcl-xL. A dominant-negative inhibitor of RNA-dependent protein kinase, as well as GADD153 antisense or bcl-xL overexpression, effectively inhibits apoptosis induction by polynucleotide phosphorylase 2.7.7.8 polyribonucleotide nucleotidyltransferase medicine the promoter of Progression Elevated Gene-3 functions selectively in a diverse array of human cancer cells. An adenovirus constructed with the Progression Elevated Gene-3 promoter driving expression of polyribonucleotide phosphorylase containing a C-terminal hemaglutinin-tag induces robust transgene expression, growth suppression, apoptosis, and cell-cycle arrest in a broad panel of pancreatic cancer cells, with minimal effects in normal immortalized pancreatic cells. Expression correlates with arrest in the G2/M phase of the cell cycle and up-regulation of the cyclin-dependent kinase inhibitors p21CIP1/WAF-1/MDA-6 and p27KIP1. In a nude mouse xenograft model,construct injections effectively inhibit growth of human pancreatic cancer cells in vivo 2.7.7.8 polyribonucleotide nucleotidyltransferase medicine targeted overexpression of hPNPaseold-35 might provide an effective therapeutic strategy for miR-221-overexpressing and IFN-resistant tumors, such as melanoma 2.7.7.9 UTP-glucose-1-phosphate uridylyltransferase medicine UDP glucose diphosphorylase is an allergen in natural rubber latex and able to cause latex-fruit allergy syndroms. It may act as a potential pan-allergen in vegetable foods 2.7.7.12 UDP-glucose-hexose-1-phosphate uridylyltransferase medicine characterization of a large deletion spanning 8489 bp in the GALT gene accounting for the majority of disease alleles in Cypriot patients with classic galactosemia. The deletion eliminates all GALT exons as well as the non-translated sequences of the adjacent interleukin 11 receptor IL11RA gene. It is flanked by a 6 bp block of homologous sequence on either side. Patients homozygous for the deletion show a lack of IL11RA transcripts 2.7.7.12 UDP-glucose-hexose-1-phosphate uridylyltransferase medicine identification of six likely pathogenic variations including three missense (Ala101Asp, Tyr165His, and Pro257Thr), one small deletion/insertion [c.826_827delinsAA (Ala276Asn)], one frameshift (Asn96Serfs*5), and one splicing (c.378-1G > C) in patients with classic galactosemia. The most frequent variation is the Duarte variant (c.940A > G, 35.3%), followed by c.507G > C (p.Gln169His, 9.6%), among 34 Korean patients 2.7.7.12 UDP-glucose-hexose-1-phosphate uridylyltransferase medicine not all pathogenic GALT mutations are inherited and GALT may have a higher new mutation rate than previously believed. The variant Q188P is found in the compound heterozygous state in a child with classic galactosemia, but not in either of her parents. The patient inherited a common Q188R GALT mutation from the mother 2.7.7.12 UDP-glucose-hexose-1-phosphate uridylyltransferase medicine Q188R, the most commonly detected disease-associated variant, increases the rate of aggregation in the absence of zinc likely due to its reduced ability to form the uridylylated intermediate 2.7.7.13 mannose-1-phosphate guanylyltransferase medicine mutations in guanosine diphosphate mannose diphosphorylase GMPPB can result in muscular dystrophy variants with hypoglycosylated alpha-dystroglycan. Produkt GDP-mannose is required for O-mannosylation of proteins, including alpha-dystroglycan, and it is the substrate of cytosolic mannosyltransferases. In the muscle biopsies of affected individuals and in available fibroblasts, reduced alpha-dystroglycan glycosylation is found. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restores glycosylation of alpha-dystroglycan. Whereas wild-type GMPPB localizes to the cytoplasm, five of the identified missense mutations cause formation of aggregates in the cytoplasm or near membrane protrusions 2.7.7.13 mannose-1-phosphate guanylyltransferase medicine mutations in guanosine diphosphate mannose diphosphorylase B (GMPPB) can result in muscular dystrophy variants with hypoglycosylated alpha-dystroglycan. Reduced alpha-dystroglycan glycosylation is found in the muscle biopsies of individuals suffering from congenital and limb-girdle muscular dystrophies and in available fibroblasts. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restored glycosylation of alpha-dystroglycan. Wild-type GMPPB localizes to the cytoplasm, but five of the identified missense mutations cause formation of aggregates in the cytoplasm or near membrane protrusions 2.7.7.13 mannose-1-phosphate guanylyltransferase medicine mutations in GMPPB can result in muscular dystrophy variants with hypoglycosylated alpha--dystroglycan. Muscle biopsies of affected individuals and available fibroblasts display reduced alpha-dystroglycan glycosylation. Five of the identified missense mutations cause formation of aggregates in the cytoplasm or near membrane protrusions 2.7.7.15 choline-phosphate cytidylyltransferase medicine possible role for macrophage CCTalpha in Gaucher disease pathology 2.7.7.18 nicotinate-nucleotide adenylyltransferase medicine the enzyme is a target for developing antimycobacterial therapies 2.7.7.18 nicotinate-nucleotide adenylyltransferase medicine loss of function mutations in two stillborn siblings lead to fetal akinesia deformation sequence, severely reduced skeletal muscle mass and hydrops fetalis. Both protein variants are incapable of supporting axon survival in mouse primary neuron cultures when overexpressed. Variants display altered protein stability and/or defects in NAD+ synthesis and chaperone functions 2.7.7.19 polynucleotide adenylyltransferase medicine use as prognostic factor for early recurrence and death in breast cancer patients 2.7.7.19 polynucleotide adenylyltransferase medicine enzyme is overexpressed in cancers 2.7.7.19 polynucleotide adenylyltransferase medicine PAP activity is used to measure the effects of anticancer drugs etoposide and cordycepin in two epithelial cancer cell lines, HeLa (human epithelioid cervix carcinoma) and MCF-7 (human breast cancer). MCF-7 is found to express significantly more PAP than the cervical cancer cell line, HeLa. Treatment of HeLa cells with etoposide (0.034 mM) leads to a continuous increase in PAP activity levels during the 2 h of exposure. Important differential modulations in both PAP enzyme activity and isoforms are observed, occurring earlier than chromatin condensation and cleavage, in both epithelial cancer cell lines tested. Treatment of HeLa cells with cordycepin (0.067 mM) leads to a continuous increase in PAP activity and isoform levels after 4 h of exposure. In the case of MCF-7 cells, treatment with 0.067 mM cordycepin leads to a decrease in both PAP II enzyme activity and phosphorylated PAP isoforms after 4 h of exposure. Thus high PAP activity levels in breast cancer cells may be an independent unfavorable prognostic factor contributing to the malignant phenotype of cells. The differentiated modulations of PAP in the two epithelial cancer cell lines correlate to changes in the cell cycle, suggesting that in this case PAP II follows the cell cycle despite the course of apoptosis. Thus in these two epithelial cell lines PAP modulations follow cell cycle progression rather than apoptosis 2.7.7.19 polynucleotide adenylyltransferase medicine the enzyme possesses tumor-suppressing activity and sensitizes breast cancer cells to chemotherapy drugs. In breast cancer patients, high levels of enzyme correlate with an improved prognosis 2.7.7.B22 transposase medicine Sleeping Beauty (SB) transposon is a nonviral gene transfer vector, already used in clinical trials. Full-length dysferlin transfer by the hyperactive sleeping beauty transposase restores dysferlin-deficient muscle, which can be used for nonviral gene delivery of full-length human dysferlin into muscle cells, along with a successful and efficient transplantation into skeletal muscle, important advances towards successful gene therapy of dysferlin-deficient muscular dystrophy 2.7.7.B22 transposase medicine an hyperactive variant with enhanced solubility and stability can be delivered with transposon DNA to genetically modify cell lines and embryonic, hematopoietic and induced pluripotent stem cells. The variant is used to generate chimeric antigen receptor T-cells, which exhibit potent anti-tumor activity in vitro and in xenograft mice. The variant spontaneously penetrates cells, enabling modification of induced pluripotent stem cells and generation of generate chimeric antigen receptor T-cells without the use of transfection reagents 2.7.7.B22 transposase medicine plasmid based delivery of the sleeping beauty transposase SB100X system reveals significantly increased integration efficiencies compared with the hyperactive sleeping beauty transposase HSB5. Up to eightfold and 100fold increased integration efficiencies are observed compared with the hyperactive SB transposase HSB5 and the inactive transposase mSB, respectively. Transposon copy numbers per cell are doubled with SB100X compared with HSB5. This hybrid vector system represents a tool for achieving stabilized transgene expression in cycling cells and for treatment of numerous genetic disorders 2.7.7.B22 transposase medicine strategy to genetically engineer cancer patient T cells with cell receptors (TCRs) using the clinical Sleeping Beauty transposon/transposase system. Patient-specific TCRs are assembled with murine constant chains and cloned into Sleeping Beauty transposons. Patient peripheral blood lymphocytes are coelectroporated with SB11 transposase and Sleeping Beauty transposon, and transposed T cells are enriched by sorting on murine TCRbeta expression. Transposed T cells specifically mount a polyfunctional response against cognate mutated neoantigens and tumor cell lines 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase medicine potential target for antibacterial agents 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase medicine GlmUMtb is a strong candidate for intervention measures against established tuberculosis infections 2.7.7.24 glucose-1-phosphate thymidylyltransferase medicine RmlA is a potential target for the development of new antituberculosis drugs 2.7.7.31 DNA nucleotidylexotransferase medicine little reliability of enzyme as marker of lymphoblastic lymphoma and leukemia 2.7.7.31 DNA nucleotidylexotransferase medicine mechanism for inhibition of viral proliferation by L-nucleosides 2.7.7.31 DNA nucleotidylexotransferase medicine use of enzyme in staining of apoptotic cells of leukemia cell lines 2.7.7.33 glucose-1-phosphate cytidylyltransferase medicine ebosin is an exopolysaccharide with antagonist activity for interleukin-1 receptor in vitro and remarkable anti-rheumatic arthritis activity in vivo 2.7.7.38 3-deoxy-manno-octulosonate cytidylyltransferase medicine - 2.7.7.38 3-deoxy-manno-octulosonate cytidylyltransferase medicine exclusive pathogen of humans, cause of epidemic bacterial meningitis and sepsis, potential target for develpoment of antibiotic tools 2.7.7.38 3-deoxy-manno-octulosonate cytidylyltransferase medicine KDO is not present in animals but is vital for gram-negative bacteria, suggests the possibility of using selective inhibition of its synthesis as antibacterial tool 2.7.7.38 3-deoxy-manno-octulosonate cytidylyltransferase medicine essential for the biosynthesis of lipopolysaccharides in gram-negative bacteria, potential target for the discovery of antibacterial agents 2.7.7.38 3-deoxy-manno-octulosonate cytidylyltransferase medicine kanamycin and fosfomycin show no inhibitory effect on the production and release of Vero toxins by Escherichia coli O157, both kanamycin and fosfomycin show the remarkable inhibition of Vero toxin 2 release through synergistic collaboration with CMP:KDO synthase inhibitor (1R,4S,5R)-3-[2-[(S)-1-((S)-1-carboxy-ethylcarbamoyl)-ethylamino]-ethyl]-4,5-dihydroxy-cyclohexanecarboxylic acid 2.7.7.38 3-deoxy-manno-octulosonate cytidylyltransferase medicine the structure of 3-deoxy-manno-octulosonate cytidylyltransferase from Haemophilus influenzae in complex with 3-deoxy-manno-octulosonate will be useful in structure-based inhibitor design 2.7.7.43 N-acylneuraminate cytidylyltransferase medicine the enzyme is involved in the production of activated sialic acids. Sialic acids are virulence factors in a variety of bacterial species, e.g. Neisseria menigitidis. As such, the identification of the bacterial CMP-NeuAc synthetase active site can serve as a starting point for rational drug design strategies 2.7.7.46 gentamicin 2''-nucleotidyltransferase medicine application of alternative substrate diagnostic 2.7.7.46 gentamicin 2''-nucleotidyltransferase medicine gentamicin resistance, mediated by multiple resistance plasmids in different species of Enterobacteriaceae, can be a problem in hospitals 2.7.7.46 gentamicin 2''-nucleotidyltransferase medicine studies should aid in the design of effective inhibitors possessing a broad range of aminoglycoside-modifying enzymes as targets 2.7.7.47 streptomycin 3''-adenylyltransferase medicine streptomycin continues to be an important drug for synergistic therapy of serious enterococcal infections 2.7.7.47 streptomycin 3''-adenylyltransferase medicine common community-acquired human drug-resistant infections are caused by bacterial strains that harbor mobile drug resistance determinants of identical sequences that are found in diverse bacterial species from varied animal sources worldwide 2.7.7.47 streptomycin 3''-adenylyltransferase medicine Klebsiella pneumoniae strains carrying the enzyme gene and a dihydrofolate reductase gene confering resistance to trimethoprim were found in eight out of 44 different diabetic foot ulcer patients 2.7.7.48 RNA-directed RNA polymerase medicine the enzyme is a key target for developing specific antiviral therapy 2.7.7.48 RNA-directed RNA polymerase medicine NS5B RdRp is a prime target for therapeutic intervention of hepatitis C virus infection 2.7.7.48 RNA-directed RNA polymerase medicine NS5B is strictly required for viral replication and thus represents an attractive therapeutic target 2.7.7.48 RNA-directed RNA polymerase medicine NS5B RNA-dependent RNA polymerase is essential for replication of hepatitis C virus and is a prime target for therapeutic intervention 2.7.7.49 RNA-directed DNA polymerase medicine the recombinant group O enzyme should be useful for studies aimed at discovering and designing drugs directed towards group O isolates of HIV-1 2.7.7.49 RNA-directed DNA polymerase medicine the modified vector system harboring the viral DNA polymerase mutant with reduced dNTP binding affinity can be a potential gene delivery system for the specific transduction of cells with high dNTP concentrations, such as tumor cells.The identification and use of unique cellular and virological factors essential for the specificity of viral based vectors can contribute to the development of safe and effective gene delivery tools 2.7.7.49 RNA-directed DNA polymerase medicine combination therapy consisting of nucleoside reverse-transcriptase together with non-nucleoside reverse-transcriptase inhibitors or protease inhibitors leads to a suppression of viral replication 2.7.7.49 RNA-directed DNA polymerase medicine gene inhibition causing reduction of telomerase reverse transcriptase activity may provide a basis for cancer therapeutics 2.7.7.49 RNA-directed DNA polymerase medicine target in HIV therapy 2.7.7.49 RNA-directed DNA polymerase medicine telomerase activity in exfoliated/disseminated epithelial cells can be used as a reliable marker for gastrointestinal cancers 2.7.7.49 RNA-directed DNA polymerase medicine telomerase is a universal tumor antigen 2.7.7.49 RNA-directed DNA polymerase medicine HIV-1 reverse transcriptase is a major target of antiviral therapy 2.7.7.52 RNA uridylyltransferase medicine a single C2H2-type zinc finger domain of Zcchc11 is responsible for the functional interaction with pluripotency factor Lin28. Lin28 uses terminal uridylyltransferases Zcchc11 and Zcchc6 to control let-7 expression and has important implications for stem cell biology as well as cancer 2.7.7.52 RNA uridylyltransferase medicine pluripotency factor Lin28 uses terminal uridylyltransferases Zcchc11 and Zcchc6 to control let-7 expression and has important implications for stem cell biology as well as cancer 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase medicine the structure of CMS of Mycobacterium tuberculosis could be a starting point for structure-based design of new antituberculosis drugs 2.7.7.65 diguanylate cyclase medicine diguanylate cyclases are interesting targets for new antimicrobial agents with biofilm activity 2.7.7.72 CCA tRNA nucleotidyltransferase medicine congenital sideroblastic anemia causing mutations in patient-derived fibroblasts do not affect subcellular localization of TRNT1 and show no gross morphological differences when compared to control cells. Both basal and maximal respiration rates are decreased in patient cells 2.7.7.72 CCA tRNA nucleotidyltransferase medicine the clinical phenotypes associated with TRNT1 mutations are largely due to impaired mitochondrial translation, resulting from defective CCA addition to mitochondrial tRNASer(AGY), and the severity of this biochemical phenotype determines the severity and tissue distribution of clinical features. TRNT1 mutations A148V and.D128G/Y173F are identified in two unrelated subjects with different clinical features. The first presented with acute lactic acidosis at 3 weeks of age and developed severe developmental delay, hypotonia, microcephaly, seizures, progressive cortical atrophy, neurosensorial deafness, sideroblastic anemia and renal Fanconi syndrome, dying at 21 months. The second presented at 3.5 years with gait ataxia, dysarthria, gross motor regression, hypotonia, ptosis and ophthalmoplegia and had abnormal signals in brainstem and dentate nucleus. In subject 1, muscle biopsy showed combined oxidative phosphorylation defects, but there was no oxidative phosphorylation deficiency in fibroblasts from either subject, despite a 10fold reduction in TRNT1 protein levels in fibroblasts of the first subject. In normal controls, TRNT1 protein levels are 10fold lower in muscle than in fibroblasts 2.7.7.79 tRNAHis guanylyltransferase medicine homozygosity for the V55A mutation in THG1L is the cause of an abnormal mitochondrial network in the patient fibroblasts, likely by interfering with THG1L activity towards MFN2 2.7.7.81 pseudaminic acid cytidylyltransferase medicine Helicobacter pylori, heavily modifies its flagellin with pseudaminic acid. Because this sugar is unique to bacteria, its biosynthetic pathway offers potential as a novel therapeutic target 2.7.7.84 2'-5' oligoadenylate synthase medicine in lymphoid cell of thymus, expression increases during inflammatory processes under ulcerogenic conditions caused by stress factors. Omeprazole treatment leads to increase in enzymic activity in thymocytes under stress, but not in the absence of stress. Omeprazole treatment does not increase enzymic activity in lymphoid cells of spleen 2.7.7.84 2'-5' oligoadenylate synthase medicine isoforms OAS1 p46 and OAS3 p100 mediate the RNase L-dependent antiviral activity against hepatitis C virus. The expression of isoform p46 shows a notable inhibition for the protein expression from HCV JFH-1 in an RNase L-dependent manner, whereas no inhibitory effect is produced by the p42, p48 or p52 isoforms of OAS1 2.7.7.84 2'-5' oligoadenylate synthase medicine secreted OAS2 is capable of regulating T-cell receptor CD3-zeta chain expression. Incubation of T-cells with cell-free supernatants of oral tumours or recombinant human OAS2 induces caspase-3 activation, which results in CD3-zeta chain down-regulation 2.7.7.86 cyclic GMP-AMP synthase medicine cGAS activates the AKT and ERK pathways to promote the inflammatory response of rheumatoid arthritis fibroblast-like synoviocytes 2.7.7.86 cyclic GMP-AMP synthase medicine cGAS and Ifi204 cooperate to sense cytosolic dsDNA and rancisella. novicida infection to produce a strong type I IFN response 2.7.7.86 cyclic GMP-AMP synthase medicine complete interferon IFN-beta induction by live Neisseria gonorrhoeae depends on both cGAS and toll-like receptor TLR4. Type I IFN is detrimental to the host, and dysregulation of iron homeostasis genes may explain lower bacteria survival in cGAS-/- and TLR4-/- cells 2.7.7.86 cyclic GMP-AMP synthase medicine Mycobacterium tuberculosis activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase cGAS in macrophages to produce cGAMP, that activates the adaptor protein stimulator of interferon genes STING to induce type I interferons and other cytokines 2.7.7.86 cyclic GMP-AMP synthase medicine the enzyme is a target for treatment of Huntigton disease 2.7.8.1 ethanolaminephosphotransferase medicine exposure of cortical neurons to neurotoxic concentrations of N-methyl-D-aspartate strongly reduces enzymic activity 2.7.8.2 diacylglycerol cholinephosphotransferase medicine exposure of cortical neurons to neurotoxic concentrations of N-methyl-D-aspartate strongly reduces enzymic activity 2.7.8.2 diacylglycerol cholinephosphotransferase medicine above 50 mM, ethanol is inhibitory 2.7.8.2 diacylglycerol cholinephosphotransferase medicine cholinephosphotransferase can be used as a biomarker for breast cancer in an animal model 2.7.8.5 CDP-diacylglycerol-glycerol-3-phosphate 1-phosphatidyltransferase medicine treatment of animals for 5 consecutive days with thyroxine at 250 mg per kg of body weight results in enzyme stimulation up to 3.5fold 2.7.8.7 holo-[acyl-carrier-protein] synthase medicine producer of the hybrid peptide-polyketide antitumor drug bleomycin 2.7.8.7 holo-[acyl-carrier-protein] synthase medicine enzyme plays an important role in bacterial fatty acid and lipid biosynthesis, making it an attractive target for therapeutic intervention, drug design by identifying inhibitors with potential antibacterial activity 2.7.8.7 holo-[acyl-carrier-protein] synthase medicine isoform PptT is a target for anti-tuberculosis drugs 2.7.8.11 CDP-diacylglycerol-inositol 3-phosphatidyltransferase medicine one of the major human fungal pathogens, expanded knowledge about essential metabloic processes and enzymes in this pathogenic fungus can pave the way for the development of more effective treatments 2.7.8.11 CDP-diacylglycerol-inositol 3-phosphatidyltransferase medicine enzymes involved in the PI biosynthetic pathway are potential antimycobacterial agents 2.7.8.11 CDP-diacylglycerol-inositol 3-phosphatidyltransferase medicine causative agent of toxoplasmosis, screening of drugs against the parasite enzyme 2.7.8.13 phospho-N-acetylmuramoyl-pentapeptide-transferase medicine opportunistic pathogen causing infections in patients with burns or neutropenia and involved in respiratory tract infections of cystic fibrosis patients, pathway of peptidoglycan biosynthesis is both essential and unique to bacteria, making it an attractive target for antibiotic research 2.7.8.13 phospho-N-acetylmuramoyl-pentapeptide-transferase medicine target for antimicrobial therapeutic intervention, novel antibiotic chemotypes must be developed to deter the alarming rate of antibiotic resistance growth 2.7.8.13 phospho-N-acetylmuramoyl-pentapeptide-transferase medicine the enzyme is a potential target for antibacterial compounds 2.7.8.13 phospho-N-acetylmuramoyl-pentapeptide-transferase medicine translocase I is a target of antibiotics 2.7.8.15 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase medicine selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions. Inhibition of DPAGT1 may be the Achilles' heel of the biosynthesis of essential N-glycan in solid tumors 2.7.8.17 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase medicine AAV-mediated expression of gene GNPTAB in mucolipidosis II, ML II, mice can attenuate bone loss via inhibition of IL-6 production 2.7.8.17 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase medicine mucolipidosis II in cats is caused by a deficiency of N-acetylglucosamine-1-phosphotransferase. All affected cats tested are homozygous for a single base substitution (c.2644C > T) in exon 13 of GNPTAB. The variant results in a premature stop codon (p.Gln882*) which predicts severe truncation and complete dysfunction of the GNPTAB enzyme. About 140 GNPTAB variants have been described in human ML II patients, with 41.3% nonsense/missense mutations, nine occurring in the same gene region as in this feline model 2.7.8.17 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase medicine mucolipidosis patient mutations within the N-terminal transmembrane domain of the alpha subunit of GlcNAc-1-phosphotransferase, i.e. V27D, V28D, A34P, F24V, G26D, E36P, cause either mucolipidosis II or mucolipidosis III alphabeta.Mutations impair endoplasmicreticulum translocation or Golgi retention 2.7.8.17 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase medicine mutations in the GNPTAB and GNPTG genes cause mucolipidosis type II, type III alpha/beta, and type III gamma. Report on 200 published and 58 novel GNPTAB mutations, including frameshift mutations (39%), missense mutations (26%), nonsense mutations (23%), splice defects (9%), and deletions/duplications/insertions/deletion-insertions (3%). The variants are spread throughout the gene, although 25% of the mutations are located in the 1112 bp exon 13 2.7.8.27 sphingomyelin synthase medicine adenovirus-mediated SMS1 overexpression increases lipoprotein atherogenic potential. Such an effect may contribute to the increased plasma sphingomyelin levels observed in animal models of atherosclerosis and in human patients with coronary artery disease 2.7.8.27 sphingomyelin synthase medicine adenovirus-mediated SMS2 overexpression increases lipoprotein atherogenic potential. Such an effect may contribute to the increased plasma sphingomyelin levels observed in animal models of atherosclerosis and in human patients with coronary artery disease 2.7.8.27 sphingomyelin synthase medicine sphingomyelin synthase is a potential target for tricyclodecan-9-yl-xanthogenate (D609) and inhibition of sphingomyelin synthase may contribute to D609-induced cell death via modulation of the cellular levels of ceramide and diacylglycerol 2.7.8.27 sphingomyelin synthase medicine regulation of liver SMS2 may be used as treatment for atherosclerosis 2.7.8.27 sphingomyelin synthase medicine SMS2 is a potential therapeutic target for treatment of atherosclerosis 2.7.8.27 sphingomyelin synthase medicine SMS inhibitors might be useful for the treatment of atherosclerosis or coronary artery disease 2.7.8.29 L-serine-phosphatidylethanolamine phosphatidyltransferase medicine the phosphatidylserine biosynthetic activity of brain, especially for 18:0, 22:6-phosphatidylserine production, is hampered significantly by maternal exposure to ethanol. Phosphatidylserine levels are consistently reduced significantly in brain cortices of the pups from ethanol-exposed dams, due mainly to the depletion of 18:0, 22:6-phosphatidylserine. The mRNA expression of phosphatidylserine synthase 1, EC 2.7.8.8, and PSS2 is not reduced by ethanol 2.7.8.41 cardiolipin synthase (CMP-forming) medicine cardiolipin synthase as a therapeutic target to attenuate mitochondrial dysfunction in diabetic myocardium 2.7.8.41 cardiolipin synthase (CMP-forming) medicine CRLS1 expression is significantly downregulated in genetically obese and diet-induced mice models 2.7.8.41 cardiolipin synthase (CMP-forming) medicine expression of Crls1 mRNA is significantly reduced in subcutaneous fat from diabetic subjects. The Crls1 mRNA levels in human subcutaneous white adipose tissue negatively correlate with HOMA2 measures of insulin resistance and positively correlate with HOMA2 measures of insulin sensitivity. Increased CRLS1 expression in human white adipocytes stimulates UCP1 expression and increases inducible uncoupled respiration 2.7.9.3 selenide, water dikinase medicine Sps1 and its reaction product selenophosphate might play a role in cancer prevention and therapy when a modulation of the enzyme activity is combined with cancer therapies 2.7.10.1 receptor protein-tyrosine kinase medicine may serve as a new target for the development of new antibiotics 2.7.10.1 receptor protein-tyrosine kinase medicine therapeutic targets for chronic lung diseases 2.7.10.1 receptor protein-tyrosine kinase medicine a potential mechanism of action of Src kinase inhibitors on 5-fluorouracil chemosensitivity may be linked to the inhibition of 5-fluorouracil-induced EGFR-AKT activation 2.7.10.1 receptor protein-tyrosine kinase medicine Axl gene expression in cancer cells is constitutively driven by Sp1/Sp3 bound to five core promoter motifs, and is restricted by methylation within/around Sp-binding sites 2.7.10.1 receptor protein-tyrosine kinase medicine AXL is overexpressed in leukemia cells isolated from acute myeloid leukemia patients who develop drug resistance after chemotherapy. Upregulation of AXL by chemotherapy may induce drug resistance in acute myeloid leukemia in the presence of Gas6 stimulation 2.7.10.1 receptor protein-tyrosine kinase medicine c-kit receptor is mainly expressed in peptidergic small-sized dorsal root ganglia neurons and may be involved in pain regulation both peripherally and centrally 2.7.10.1 receptor protein-tyrosine kinase medicine differential sFlt-1 expression in placentas from discordant twins. sFlt-1 expression is increased in severe intrauterine growth restriction placentas with abnormal umbilical artery Doppler of singletons and also in discordant intrauterine growth restriction twins. Reduced placental perfusion may contribute to the increased expression of sFlt-1 in intrauterine growth restriction pregnancies 2.7.10.1 receptor protein-tyrosine kinase medicine during apoptotic cell uptake by murine macrophages, scavenger receptor A is essential for optimal phosphorylation of Mertk and subsequent signaling is required for apoptotic cell ingestion. The Mertk/SR-A complex may be a potential target to manipulate apoptotic cell clearance and hence, resolution of inflammation and infections 2.7.10.1 receptor protein-tyrosine kinase medicine EGF-R may be a more useful marker than TGF-alpha in epithelial ovarian tumors. Increased EGF-R immunoreactivtiy in tumors with greater malignant potential, indicating that EGF-R may be a suitable target for more effective therapeutic approaches to ovarian carcinoma 2.7.10.1 receptor protein-tyrosine kinase medicine EGFR protein is overexpressed in 65% of cases recurrent glioblastoma multiformes. EGFR protein overexpression is associated with EGFR gene amplification in 35% of cases, and with high polysomy in 15% of cases. Mutations in the kinase domain are absent in recurrent glioblastoma multiforme, and this may be a preponderant factor in the lack of major clinical responses of tyrosine kinase inhibitors in glioblastoma multiforme. Responsiveness to EGFR kinase inhibitors is strongly associated with coexpression of EGFRvIII and PTEN 2.7.10.1 receptor protein-tyrosine kinase medicine EphA2 cooperates with ErbB2 to promote tumor progression and may provide a novel therapeutic target for ErbB2-dependent tumors. EphA2 function in tumor progression appears to depend on oncogene context, an important consideration for the application of therapies targeting EphA2 2.7.10.1 receptor protein-tyrosine kinase medicine heregulin-induced activation of ErbB3 via EGFR (EGFR is a possible heterodimeric counterpart of ErbB3) promotes tumor growth and metastasis of melanoma cells 2.7.10.1 receptor protein-tyrosine kinase medicine human ether-a-go-go-related gene channels are regulated by EGFR kinase and Src-family kinases. EGFR kinase likely works on residue Y611. Regulation of human ether-a-go-go-related gene channels by protein tyrosine kinases likely modifies the channel activity and thus alters electrophysiological properties including action potential duration and cell excitability in human heart and neurons 2.7.10.1 receptor protein-tyrosine kinase medicine in wound-healing, Ror2 plays critical roles in Wnt5a-induced cell migration by regulating formation of lamellipodia and reorientation of microtubule-organizing center. Wnt5a/Ror2 activates c-Jun N-terminal kinase JNK, through a process involving filamin A and PKCsigma, to regulate polarized cell migration 2.7.10.1 receptor protein-tyrosine kinase medicine intact Ron receptor protein enhances survival following cecal ligation and puncture-induced bacterial peritonitis in mice. Ron signaling negatively regulates the response to polymicrobial infection by regulating the activation and recruitment of inflammatory cells necessary for clearing a systemic bacterial burden. This effect may be regulated in part through the Ron-dependent, macrophage-mediated production of cytokines and chemokines, namely monocyte chemoattractant protein-1, interleukin-6, and macrophage inflammatory protein-2, important for neutrophil mobilization 2.7.10.1 receptor protein-tyrosine kinase medicine internatlization and retrograde trafficking of TrkA is required for neuronal survial 2.7.10.1 receptor protein-tyrosine kinase medicine no exonic mutation in the tyrosine kinase domain of ErbB2 in Asian hepatocellular carcinoma patients. Alternative mechanisms may be responsible for the observed efficacy of ErB1 and ErbB2 tyrosine kinase inhibitors 2.7.10.1 receptor protein-tyrosine kinase medicine non-oncogenic role for HER2 in the process of adipose differentiation and HER2 may represent a previously unrecognized target to manage obesity via the lipogenic enzyme FASN 2.7.10.1 receptor protein-tyrosine kinase medicine patients with PDGFRbeta rearrangement reveal common clinical features resembling chronic myelogenous leukemia or chronic myelomonocytic leukemia. FGFR3 is involved peripheral T cell lymphoma 2.7.10.1 receptor protein-tyrosine kinase medicine Ret is expressed in primary breast tumors and is functional in a panel of breast tumor cell lines, in particular, cell lines characterized for their dependence on endocrine signaling. Ret signaling stimulates anchorage-independent proliferation of breast cancer cells. Functional interaction with estrogen receptor alpha signaling in vitro strengthens the potential of Ret pathway inhibition in a combination approach with endocrine therapy 2.7.10.1 receptor protein-tyrosine kinase medicine role of drug-induced autocrine events leading to the activation of alternative HER receptors in maintaining HER2 phosphorylation and in mediating resistance to EGFR tyrosine kinase inhibitors in breast cancer cells, and hence specify treatment opportunities to overcome resistance in patients 2.7.10.1 receptor protein-tyrosine kinase medicine RON has two alternative modes of signaling that can contribute to oncogenic behavior in normal breast epithelial cells. RON-mediated proliferation requires MSP. RON-mediated cell spreading or RON-mediated evasion of cell death are MSP independent 2.7.10.1 receptor protein-tyrosine kinase medicine Ron is a critical factor in tumorigenesis 2.7.10.1 receptor protein-tyrosine kinase medicine Ron is a critical factor in tumorigenesis and its inhibition, alone or in combination with current therapies, may prove beneficial in the treatment of cancer patients 2.7.10.1 receptor protein-tyrosine kinase medicine RON receptor regulates both the production of and response to IFN-gamma, resulting in enhanced susceptibility to endotoxin challenge 2.7.10.1 receptor protein-tyrosine kinase medicine RON represses HIV transcription at multiple transcriptional check points including initiation, elongation and chromatin organization. RON expression decreases basal levels of NF-kappaB and RNA polymerase II binding to the HIV provirus long terminal repeat but does not prevent the induction of these complexes following treatment with cytokines. RON decreases efficient transcription elongation because reduced RNA polymerase II is associated with HIV-1 genomic sequences downstream of the transcriptional start site. There is a correlation between RON expression and increased binding of factors that negatively regulate transcription elongation, NELF, Spt5, and Pcf11. The ability of RON to inhibit HIV-1 transcription is associated with nucleosome remodeling 2.7.10.1 receptor protein-tyrosine kinase medicine RTKs mediate diverse processes within the developing and adult brain. Trafficking of RTKs is required for the specificity and fidelity of signal transduction and consequent biological responses within neural cells. Segregation of signaling complexes and the appropriate delivery of RTKs to these complexes is highly regulated through mechanisms including receptor-sorting sequences, adaptor proteins, specific ligand-receptor interactions, and lipid raft microdomains 2.7.10.1 receptor protein-tyrosine kinase medicine the constitutively active immature mutant FLT3 receptor protein with an internal tandem duplication is aberrantly accumulating intracellularly in an unidentified compartment of the secretory pathway. From its intracellular location, it may be able to recruit additional or different signaling pathways compared to the predominantly surface-localized wild-type FLT3 receptor protein enabling transformation of the cell 2.7.10.1 receptor protein-tyrosine kinase medicine TrkA and TrkB are the major players in neuroblastoma biology. High expression of TrkA is associated with favorable prognosis, but also with a lack of structural chromosomal changes, whereas TrkB is mainly expressed on neuroblastoma demonstrating high genomic instability. TrkB is associated with a favorable biology and good prognosis in medullary thyroid carcinoma 2.7.10.1 receptor protein-tyrosine kinase medicine tyrosine phosphorylation events mediated by aberrant activation of RTK pathways are proven to be involved in the development of several diseases including cancer. 70% of tyrosine phosphorylation events are conserved in human orthologs and paralogs 2.7.10.1 receptor protein-tyrosine kinase medicine failure of EGFR antibody therapy in patients with wild type KRAS colorectal cancer may result from activating BRAF or PIK3CA mutations and false-negative sequencing results caused by intratumoral heterogeneity 2.7.10.1 receptor protein-tyrosine kinase medicine small stature is not associated with growth hormone receptor mutations 2.7.10.1 receptor protein-tyrosine kinase medicine aldehyde dehydrogenase ALDH1A1-positive lung cancer cells display resistance to gefitinib, compared to ALDH1A1-negative lung cancer cells. Lung cancer cells with resistance to EGFR tyyrosine kinase inhibitors and chemotherapy drugs contain significantly increased proportions of ALDH1A1-positive cells. ALDH1A1 positivity in cancer stem cells may confer resistance to EGFR tyrosine kinase inhibitors in lung cancer 2.7.10.1 receptor protein-tyrosine kinase medicine effects of Src kinase inhibitor saracatinib and multiple receptor tyrosine kinase inhibitor sunitinib on renal cell carcinoma cell line ACHN and Caki-1. Saracatinib alone or in combination with sunitinib inhibits the migration of ACHN and Caki-1 cells in vitro. Combined treatment results in improved growth inhibition, greater loss of the S phase cell population and decreased clonogenic colony formation compared to sunitinib alone in the metastatic Caki-1 line. Saracatinib alone and in combination with sunitinib inhibits phosphorylation of the cell progression regulator c-Myc in a dose-dependent manner. Sunitinib alone or in combination suppresses cyclin-D1 expression with the combination showing greater dose-dependent effect. Sunitinib inhibits vascular endothelial growth factor secretion through the inhibition of STAT3 signaling and VEGF biosynthesis. HIF1-alpha expression in normoxic and hypoxic conditions in Caki-1 cells is inhibited by either saracatinib or sunitinib when administered alone, however, a greater reduction occurrs when these compounds are given in combination. Targeting Src kinase and RTK simultaneously with saracatinib and sunitinib results in 70-80% blockade of renal cell carcinoma cell migration, synergistic inhibition of cell growth and reduction of acquired drug resistance in Caki-1 cells 2.7.10.1 receptor protein-tyrosine kinase medicine hepatocyte growth factor expression leads to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the acute myeloid leukemia cell lines and clinical samples studied. Genetic depletion of hepatocyte growth factor or MET potently inhibits the growth and survival of hepatocyte growth factor-expressing acute myeloid leukemia cells. Leukemic cells treated with the specific MET kinase inhibitor crizotinib develop resistance due to compensatory upregulation of hepatocyte growth factor expression, leading to restoration of MET signaling. In cases of acute myeloid leukemia where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1, concomitant inhibition of FGFR1 and MET blocks compensatory hepatocyte growth factor upregulation, resulting in sustained logarithmic cell kill both in vitro and in xenograft models in vivo 2.7.10.1 receptor protein-tyrosine kinase medicine large-scale proteomic approach to identify over 200 substrates of the receptor tyrosine kinases kinase family in cancer cell lines driven by the c-Met, epidermal growth factor receptor, or platelet-derived growth factor receptor alpha receptor tyrosine kinases. For a subset of proteins with RxRxxS/T sites, phosphorylation is decreased by receptor tyrosine kinase inhibitors as well as by inhibitors of the PI3K, mTOR, and MAPK pathways. Phosphorylation of the protein chaperone small glutamine-rich tetratricopeptide repeat-containing protein alpha at Ser305 is essential for PDGFRalpha stabilization and cell survival in PDGFRalpha-dependent cancer cells 2.7.10.1 receptor protein-tyrosine kinase medicine phosphorylated insulinlike growth factor 1 receptor/insulin receptor expression in nonsmall cell lung cancer specimens is associated with a history of tobacco smoking, squamous cell carcinoma histology, mutant K-Ras, and wild-type EGFR, all of which have been strongly associated with poor response to EGFR tyrosine kinase inhibitors. Insulinlike growth factor 1 receptor tyrosine kinase inhibitors exhibit significant antitumor activity in nonsmall cell lung cancer cells with wild-type EGFR and wild-type K-Ras but not in those with mutations in these genes. Introduction of mutant K-Ras attenuates the effects of insulinlike growth factor 1 receptor tyrosine kinase inhibitors on nonsmall cell lung cancer cells expressing wild-type K-Ras. Conversely, inactivation of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase restores sensitivity to IGF-tyrosine kinase inhibitors in cells carrying mutant K-Ras 2.7.10.2 non-specific protein-tyrosine kinase medicine the Brk kinase is a potential therapeutic target in lymphomas 2.7.10.2 non-specific protein-tyrosine kinase medicine aberrant Src kinase activity is associated with the invasive phenotype in both early and advanced solid tumors 2.7.10.2 non-specific protein-tyrosine kinase medicine Abl1 and Abl2 have a role in axonogenesis and cancer 2.7.10.2 non-specific protein-tyrosine kinase medicine Btk is a potential therapeutic target for bone diseases 2.7.10.2 non-specific protein-tyrosine kinase medicine Btk plays a critical role in osteoclast multinucleation by modulating the activity of the nuclear factor of activated T cells c1, NFATc1 2.7.10.2 non-specific protein-tyrosine kinase medicine due to their involvement in various forms of cancer, PTK have become prominent targets for therapeutic intervention 2.7.10.2 non-specific protein-tyrosine kinase medicine Lyn is a key kinase in the molecular machineries mediating the P2X4R upregulation in microglia, and thereby, in neuropathic pain 2.7.10.2 non-specific protein-tyrosine kinase medicine Lyn kinase inhibitors are becoming an increasingly important class of chemotherapeutic agents 2.7.10.2 non-specific protein-tyrosine kinase medicine mutations in the gene encoding for Bruton's tyrosine kinase are responsible for most of the agammaglobulinemia 2.7.10.2 non-specific protein-tyrosine kinase medicine over-expression of Eph receptors on cancer cells is able to confer tumourigenic phenotypes such as proliferation and invasion, EphB4 could be a target for therapeutic intervention 2.7.10.2 non-specific protein-tyrosine kinase medicine overexpressed or activated Src is present in a high percentage of tumours, Src has therefore been an target for the development of anti-cancer therapies 2.7.10.2 non-specific protein-tyrosine kinase medicine protein tyrosine kinase inhibitors represent emerging therapeutics for cancer chemoprevention 2.7.10.2 non-specific protein-tyrosine kinase medicine PTK6 may serve as a future target for the development of novel treatments in breast cancer 2.7.10.2 non-specific protein-tyrosine kinase medicine Pyk2 may represent a novel target for the development of innovative therapeutic strategies against inflammatory conditions 2.7.10.2 non-specific protein-tyrosine kinase medicine spleen tyrosine kinase is involved in the activation of cells implicated in allergic or autoimmune diseases and certain cancers, inhibitors may prove to be effective in treating diseases where Syk activity is increased or deregulated 2.7.10.2 non-specific protein-tyrosine kinase medicine Src-family protein tyrosine kinases are involved in the regulation of the long-term depression, LTD, induction 2.7.10.2 non-specific protein-tyrosine kinase medicine SYK is a good target for therapeutic intervention in allergic diseases such as asthma, roles in the development of cancer are reported 2.7.10.2 non-specific protein-tyrosine kinase medicine Syk may be a potential target for the development of potent anti-inflammatory drugs 2.7.10.2 non-specific protein-tyrosine kinase medicine Tec kinase is a potential therapeutic target for bone diseases 2.7.10.2 non-specific protein-tyrosine kinase medicine the activated c-Abl tyrosine kinase plays an important role in malignant solid tumors of lung and breast, mutant forms are involved in hematopoietic malignancies such as chronic myeloid leukemia, CML 2.7.10.2 non-specific protein-tyrosine kinase medicine the importance of de-regulated c-Abl cytoplasmic signalling in solid tumours is discussed 2.7.10.2 non-specific protein-tyrosine kinase medicine the results have important implications for the design of therapeutics targeted against specific cytokines and their regulators in inflammatory disease 2.7.10.2 non-specific protein-tyrosine kinase medicine X-linked agammaglobulinaemia is a primary immune deficiency characterized by lack of circulating mature B cells, hypogammaglobulinaemia and recurrent infections because of a mutations in the Btk gene 2.7.10.2 non-specific protein-tyrosine kinase medicine high levels of protein tyrosine kinase focal adhesion kinase and Src combined are predictive for recurrence of colorectal cancer 2.7.10.2 non-specific protein-tyrosine kinase medicine in HT29 colon carcinoma cells, silencing of tyrosine kinase c-Yes, but not of kinase c-Src, selectively leads to an increase of cell clustering associated with a localisation of beta-catenin at cell membranes and a reduction of expression of beta-catenin target genes. c-Yes silencing induces an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Reintroduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. c-Yes kinase activity is required for its role in beta-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that are not shared with c-Src 2.7.10.2 non-specific protein-tyrosine kinase medicine in isoform Btk-deficient patients with X-linked agammaglobulinemia, reduced toll-like receptor TLR3-triggered activation of human natural killer cells is observed, as evidenced by the reduced IFN-gamma, CD69, and CD107a expression and cytotoxic activity 2.7.10.2 non-specific protein-tyrosine kinase medicine isoform c-Abl kinase activity is required for regulation of the estrogen receptor alpha function, and a Y52F/Y219F mutant estrogen receptor, unable to be phosphorylated by c-Abl, leads to reduced breast cancer cell growth and invasion 2.7.10.2 non-specific protein-tyrosine kinase medicine lymphocyte-specific protein tyrosine kinase LCK is involved in the fractionated radiation-induced expansion of the glioma-initiating cell population and acquisition of resistance to anticancer treatments. Fractionated radiation causes a selective increase in the activity of LCK. The activities of other Src family kinases Src, Fyn, and Lyn are not significantly increased. Knockdown of LCK expression with siRNA effectively block fractionated radiation-induced expansion of the CD133+ cell population. siRNA targeting of LCK also suppresses fractionated radiation-induced expression of the glioma stem cell marker proteins CD133, Nestin, and Musashi. Expression of the proteins Notch2 and Sox2 in glioma cells treated with fractionated radiation is also downregulated by LCK inhibition. siRNA-mediated knockdown of LCK effectively restores the sensitivity of glioma cells to cisplatin and etoposide 2.7.10.2 non-specific protein-tyrosine kinase medicine nonreceptor tyrosine kinase c-Abl phosphorylates tyrosine 143 of parkin, which encodes a ubiquitin E3 ligase, related to autosomal recessive Parkinson disease. Phosphorylation inhibits parkin’s ubiquitin E3 ligase activity and protective function. Tyrosine phosphorylation of parkin by c-Abl is a major posttranslational modification that inhibits parkin function, possibly contributing to pathogenesis of sporadic Parkinson's disease 2.7.11.1 non-specific serine/threonine protein kinase medicine GSK-3 is a target for the therapeutic treatment of Alzheimer's disease and other tauopathies 2.7.11.1 non-specific serine/threonine protein kinase medicine a phase II trial of enzastaurin is conducted to determine the 6-month progression-free survival rate in advanced non-small-cell lung cancer using Enzaustaurin: 13% of the patients have a progression-free survival for more than 6 months 2.7.11.1 non-specific serine/threonine protein kinase medicine GSK3 is an important therapeutic target for gliomas 2.7.11.1 non-specific serine/threonine protein kinase medicine high-tidal-volume ventilation induced microvascular permeability, lung fibrosis, and chemokine production are dependent, in part, on activation of the Akt and ERK1/2 pathways 2.7.11.1 non-specific serine/threonine protein kinase medicine increased pancreatic islet mass induced by dexamethasone is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D2 protein levels in insulin-resistant rats 2.7.11.1 non-specific serine/threonine protein kinase medicine the results show the spectrum of mutations of the STK11 gene by identifying a novel de novo mutation in a Peutz-Jeghers syndrome patient and further support the hypothesis that STK11 mutations are disease-causing mutations for Peutz-Jeghers syndrome with or without a positive family history 2.7.11.1 non-specific serine/threonine protein kinase medicine Pim-2 is a target for mutiple myeloma treatment 2.7.11.1 non-specific serine/threonine protein kinase medicine the CK1 family of serine/threonine kinases appears to be a viable therapeutic target for the treatment of a number of human malignancies like jet-lag and cancer, overview 2.7.11.1 non-specific serine/threonine protein kinase medicine enzyme expression is inversely correlated with patient prognosis in mesenchymal, but not proneural high-grade gliomas 2.7.11.1 non-specific serine/threonine protein kinase medicine serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal cancer 2.7.11.1 non-specific serine/threonine protein kinase medicine regulating CK2 activity may be useful to provide a safe and efficient way of activating brown adipose tissue in humans so that the beneficial effects of having ample amounts of brown fat can be made available to all that suffer from obesity and obesity-linked maladies such as type 2 diabetes 2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase medicine increased glucose oxidation by inhibition of PDHK activity may be effective for increasing glucose utilization in diabetes treatment 2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase medicine PDHK inhibition provides a route for therapeutic intervention in diabetes and cardiovascular disorders 2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase medicine the results implicate the invariant C-terminal DW-motif anchoring site as a drug target for the inhibition of aberrant PDK activity in cancer and diabetes 2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase medicine blocking enzyme activity has therapeutic benefits against hepatitis C virus replication 2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase medicine the enzyme is a therapeutic target for vascular calcification 2.7.11.8 Fas-activated serine/threonine kinase medicine the increased enzyme expression of is significantly associated with poor survival outcome in astrocytoma patients 2.7.11.10 IkappaB kinase medicine IKK activates TNFalpha-dependent signaling pathways inducing drug resistance, e.g. increasing cell survival in anti-cancer treatment with 5-fluoro-2'-deoxyuridine, overview 2.7.11.10 IkappaB kinase medicine inhibition of IKK-driven NF-kappaB activation offers a strategy for treatment of different malignancies and can convert inflammation-induced tumor growth to inflammation-induced tumor regression 2.7.11.10 IkappaB kinase medicine IKKlapha may represent a specific target for treatment of ErbB2-positive breast cancer 2.7.11.10 IkappaB kinase medicine 17-acetoxyjolkinolide B is a novel type NF-kappaB pathway inhibitor. Its unique interaction mechanism with IKK may render it a strong apoptosis inducer of tumor cells and a novel type anticancer drug candidate 2.7.11.10 IkappaB kinase medicine Helicobacter pylori-mediated gastric inflammation critically depends on the efficient recruitment and activation of macrophages, with sufficient NF-kappaB activation 2.7.11.10 IkappaB kinase medicine IKKalpha is responsible for the development of acantholytic squamous cell carcinoma (ASCC), a human SCC variant 2.7.11.10 IkappaB kinase medicine results reveal a novel function of the two IkappaB kinases in cooperatively regulating liver immune homeostasis and bile duct integrity and suggest that IKK signaling may be implicated in human biliary diseases 2.7.11.10 IkappaB kinase medicine TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells 2.7.11.10 IkappaB kinase medicine the IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy 2.7.11.10 IkappaB kinase medicine IKK is thought to be a focal target of drug development 2.7.11.10 IkappaB kinase medicine IKK2 inhibition represents a promising strategy for the treatment of advanced stages of cutaneous T-cell lymphomas 2.7.11.10 IkappaB kinase medicine IKKbeta inhibitors are utilized for the treatment of cancer and immunological disorders 2.7.11.10 IkappaB kinase medicine IKKbeta-targeted NF-kappaB blockade is an attractive therapeutic approach for the prevention of colitis-associated tumors 2.7.11.10 IkappaB kinase medicine inhibition of IkappaB kinase beta induces growth suppression and death in cells expressing wild-type, Imatinib-resistant, or the T315I Imatinib/Dasatinib-resistant forms of BCR-ABL 2.7.11.10 IkappaB kinase medicine inhibition of IkappaB kinase beta restrains oncogenic proliferation of pancreatic cancer cells 2.7.11.10 IkappaB kinase medicine inhibitors of IKK2 could be effective in the treatment of autoimmune and inflammatory disorders such as rheumatoid arrthritis, inflammatory bowel disease, lupus and multiple sclerosis 2.7.11.10 IkappaB kinase medicine N-tosyl-L-phenylalanine chloromethyl ketone has been shown to have therapeutic effects in hypoxic-ischemic brain injury and collagen-induced arthritis in experimental animals, without any obvious adverse side effects 2.7.11.10 IkappaB kinase medicine PHA-408 is efficacious in a chronic model of arthritis with no adverse effects 2.7.11.10 IkappaB kinase medicine since IKK2 is vital for translating pro-inflammatory stimuli into the activation of NF-kappaB, an inhibitor of IKK2 could be effective in the treatment of autoimmune and inflammatory disorders 2.7.11.10 IkappaB kinase medicine the IKKbeta/IKK2 inhibitor PHA-408 is a powerful anti-inflammatory agent against LPS- and cigarette smoke-mediated lung inflammation 2.7.11.10 IkappaB kinase medicine the role of IKK-2 in regulating NF-kappaB signaling in resonse to proinflammatory stimuli has made IKK-2 a primary anti-inflammation therapeutic target 2.7.11.10 IkappaB kinase medicine enzyme expression is negatively correlated with the invasiveness, migration, and angiogenesis of nasopharyngeal carcinoma cells 2.7.11.11 cAMP-dependent protein kinase medicine PKA is a target for the therapeutic treatment of Alzheimer's disease and other tauopathies 2.7.11.11 cAMP-dependent protein kinase medicine activation of protein kinase A by elevation of the intracellular cAMP level inhibits skeletal myogenesis 2.7.11.11 cAMP-dependent protein kinase medicine cAMP-dependent protein kinase acts synergistically with exchange protein directly activated by cAMP to promote adipogenesis 2.7.11.11 cAMP-dependent protein kinase medicine hepatitis C virus infection activates PKA in a cAMP-dependent manner to promote virus release and transmission 2.7.11.12 cGMP-dependent protein kinase medicine gene transfer of the catalytic domain of the enzyme might provide a new strategy for treatment of diabetic renal fibrosis 2.7.11.12 cGMP-dependent protein kinase medicine cGKII deficiency leads to dwarfism in mice as consequence of an elongated growth plate and impaired chondrocyte hypertrophy 2.7.11.12 cGMP-dependent protein kinase medicine downregulation of cyclic GMP-dependent protein kinase-1 alpha is linked to erectile dysfunction and diabetis mellitus 2.7.11.12 cGMP-dependent protein kinase medicine GMP-dependent protein kinase II gene is significantly related to gout disease independent of hyperuricemia 2.7.11.12 cGMP-dependent protein kinase medicine PKG exerts dual functional regulation of neuronal ATP-sensitive potassium channels in a sulfonylurea receptor subunit-dependent manner, which may provide new means of therapeutic intervention for manipulating neuronal excitability and/or survival 2.7.11.12 cGMP-dependent protein kinase medicine all-D-YGRKKRRQRRRPPLRKKKKKH may help our understanding of how blood vessels constrict and dilate and may also aid the development of new strategies and therapeutic agents targeted to the prevention and treatment of vascular disorders 2.7.11.13 protein kinase C medicine a phase II trial of enzastaurin is conducted to determine the 6-month progression-free survival rate in advanced non-small-cell lung cancer using Enzaustaurin: 13% of the patients have a progression-free survival for more than 6 months 2.7.11.14 rhodopsin kinase medicine mutations occuring in the variable region of RK C-terminus and catalytic domain cause Oguchi disease, an inherited form of stationary night blindness 2.7.11.14 rhodopsin kinase medicine Oguchi disease patients suffering from congenital stationary night blindness have defective RK or arrestin genes 2.7.11.14 rhodopsin kinase medicine mutation in RK is associated with the Oguchi disease 2.7.11.15 beta-adrenergic-receptor kinase medicine heart failure: therapeutic strategy by manipulating beta-AR signaling, specifically through the inhibition of beta-ARK 1, elevated levels of beta-ARK 1 are an early ubiquitous consequence of myocardial injury 2.7.11.15 beta-adrenergic-receptor kinase medicine effectiveness of in vivo applications of beta-ARK 1-targeted gene therapy at ameliorating heart failure, beta-ARK 1 upregulation often precedes the development of measurable heart failure and may represent an indicator for cardiac injury and potential therapeutic intervention prior to clinical dysfunction 2.7.11.16 G-protein-coupled receptor kinase medicine inhibition of GRK2 activity in osteoblasts as therapeutic strategy for increasing bone mass 2.7.11.16 G-protein-coupled receptor kinase medicine low expression levels of isoform GRK6 are correlated with poor survival prognosis in patients with lung adenocarcinoma 2.7.11.16 G-protein-coupled receptor kinase medicine reducing enzyme protein expression in HeLa cells increases its sensitivity to paclitaxel and docetaxel and increases apoptosis in response to paclitaxel treatment 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine CaM-kinases act as potential targets in cancer therapy, strategies, overview 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine arrhythmia is favored by CamKII activation during acidosis 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine Ca2+/calmodulin-dependent protein kinases may be involved in cancer, cardiac hypertrophy, heart failure, arrhythmia, cardiomyocyte apoptosis, the regulation of higher order neuronal functions such as memory, learning disorder, Angelman's syndrome, Parkinson's disease, Alzheimer's disease, delayed neuronal death, diabetes, and osteoporosis 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine CaMKII activity is significantly increased in heart failure 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine CaMKII is an essential component of intracellular signaling pathways regulating chondrocyte maturation 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine CaMKII is associated with diabetes-induced renal and vascular dysfunction 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine CaMKIIcelta expression and activation state are increased in heart failure 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine blocking CaMKII or CaMKII-mediated signaling may offer a novel therapeutic target for the treatment of neuropathic pain 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine enzyme-dependent alterations in Na+ channel gating may cause arrhythmogenesis in many millions of people carrying the clinical diagnosis of heart failure 2.7.11.17 Ca2+/calmodulin-dependent protein kinase medicine CaMKII inhibition may be a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction 2.7.11.18 myosin-light-chain kinase medicine therapeutic inhibition via specific chemical inhibitors of endothelial isozyme, i.e. 11-(3-chloro-6-immino-6H-pyridazin-1-yl)-undecanoic acid (6-phenyl-pyridazin-3-yl)-amide, represents an important new target for the treatment of inflammatory lung disease with less side effects than other therapies 2.7.11.18 myosin-light-chain kinase medicine long isozyme MLCK-210 is a potential therapeutic target in the treatment of burn edema 2.7.11.19 phosphorylase kinase medicine elevated expression of phosphorylase kinase beta is an independent prognostic factor in patients with colorectal cancer 2.7.11.19 phosphorylase kinase medicine the low expression of enzyme subunit PHKB can serve as an independent indicator for predicting poor prognosis in hepatocellular carcinoma 2.7.11.20 elongation factor 2 kinase medicine eEF-2 kinase plays a regulatory role in the autophagic process in tumor cells, is a downstream member of the mTOR signaling, may promote cancer cell survival under conditions of nutrient deprivation through regulating autophagy. Therefore, eEF-2 kinase may be a part of a survival mechanism in glioblastoma and targeting this kinase may represent a novel approach to cancer treatment 2.7.11.20 elongation factor 2 kinase medicine plays a regulatory role in the autophagic process in tumor cells and may promote cancer cell survival under conditions of nutrient deprivation, eEF-2 kinase activation may be a part of a survival mechanism in glioblastoma 2.7.11.20 elongation factor 2 kinase medicine suppressing autophagy and augmenting apoptosis via inhibition of eEF-2 kinase can modulate sensitivity of tumor cells to Akt inhibition, and suggest that eEF-2 kinase may be utilized as an effective target for reinforcing the anti-tumor efficacy of Akt inhibitors such as MK-2206 2.7.11.20 elongation factor 2 kinase medicine the enzyme a possible target for therapeutic intervention in solid tumours 2.7.11.20 elongation factor 2 kinase medicine high expression levels of the enzyme are associated with poor prognosis of hepatocellular carcinoma 2.7.11.20 elongation factor 2 kinase medicine high levels of enzyme expression are associated with invasive carcinoma and metastatic tumors. Inhibiting the enzyme may help prevent cancer cell mobility and metastasis. The enzyme is a potential therapeutic target for preventing tumor metastasis 2.7.11.20 elongation factor 2 kinase medicine the enzyme is a valuable target in treating epilepsy, depression and major neurodegenerative diseases 2.7.11.21 polo kinase medicine correlation between Plk1 overexpression in tumors and poor patient prognosis, Plk1 acts at multiple discrete steps throughout late G2 phase, mitosis, and cytokinesis, triggers activation of the Ect2-RhoA network 2.7.11.21 polo kinase medicine in the study Plk1 is detected in 63.6% of Non-Hodgkin's Lymphoma cases and overexpression is positively linked to systemic symptom, elevated LDH level and higher IDI scores, Plk1 may be a new target in NHL therapy 2.7.11.21 polo kinase medicine Plk1 is a target for the development of anticancer therapeutics 2.7.11.21 polo kinase medicine Plks are targets for the development of anticancer therapeutics 2.7.11.21 polo kinase medicine GSK461364A is broadly antiproliferative for tumor cell lines in vitro and efficacious in multiple in vivo tumor models 2.7.11.21 polo kinase medicine inhibition of PLK1 activity in cancer cells causes mitotic arrest and finally induces strong cell-killing effect 2.7.11.21 polo kinase medicine it is possible that targeting PLK1 will enhance host innate immune responsees, leading to a novel strategy of clearing paramyxovirus infections quickly 2.7.11.21 polo kinase medicine knockdown of plk1 results in sensitization of multidrug resistant cells to doxorubicin, and this combination of gene silencing and small drug delivery may prove useful to achieve potent therapeutic effects 2.7.11.21 polo kinase medicine Plk1 attracts great attention in the field of cancer therapy because it exhibits generally elevated activity in cancer cells and is a negative prognostic factor for cancer patients 2.7.11.21 polo kinase medicine PLK1 can be a potential therapeutic target for the treatment of osteosarcoma 2.7.11.21 polo kinase medicine PLK1 is a promising target for the molecular therapy of anaplastic thyroid carcinoma, ATC 2.7.11.21 polo kinase medicine Plk1 is a promising therapeutic target for the treatmment of cancer 2.7.11.21 polo kinase medicine Plk1 is recognized as an attractive therapeutic target in the treatment of proliferative diseases 2.7.11.21 polo kinase medicine Plk1 may be a useful target for cancer chemoprevention 2.7.11.21 polo kinase medicine Plk1 represents a target for anticancer therapy 2.7.11.21 polo kinase medicine polo-like kinase may represent a novel drug target in imatinib-sensitive and imatinib-resistant chronic myeloid leukemia 2.7.11.21 polo kinase medicine polo-like kinases represent an attractive target for cancer treatment through interference with the cell cycle 2.7.11.21 polo kinase medicine potential new target against schistosomiasis 2.7.11.21 polo kinase medicine targeting Plk1 might be a promising approach for cancer therapy 2.7.11.21 polo kinase medicine targeting Plk1 will cause mitotic catastrophe, with significant cytotoxicity both in vitro and in vivo, underscoring the important therapeutic opportunity of Plk1 in nasopharyngeal cancer 2.7.11.21 polo kinase medicine the data demonstrate the function of Plk1 as a regulator of interferon induction and provide the basis for the development of inhibitors preventing the PLK1/MAVS association to sustain innate immunity 2.7.11.21 polo kinase medicine the skin is an attractive tissue for Plk1 based cancer chemoprevention and chemotherapeutic applications 2.7.11.21 polo kinase medicine good target in tumor therapy 2.7.11.21 polo kinase medicine overexpression of Plk1 is strongly correlated with aggressiveness and prognosis of many cancers, so Plk1 is a potential target for anticancer therapy 2.7.11.21 polo kinase medicine therapeutic target for Parkinson's disease 2.7.11.22 cyclin-dependent kinase medicine the CDK-cyclins are targets for pharmacological and gene therapy strategies for the treatment of cardiovascular disease 2.7.11.22 cyclin-dependent kinase medicine cdk activity is required at multiple steps during human cytomegalovirus infection, including the expression, modification, and localization of virus-encoded proteins 2.7.11.22 cyclin-dependent kinase medicine Cdk dysregulation in the generation of genomic instability, increased Cdk activity may critically reduce licensing of origins of DNA replication, drive re-replication, or mediate overexpression of checkpoint proteins, inducing deleterious cell cycle delay. These effects may fuel tumorigenesis 2.7.11.22 cyclin-dependent kinase medicine Cdk5 is a regulator of the parkin ubiquitin-ligase activity and modulates its ability to accumulate into and modify inclusions. Phosphorylation by Cdk5 may contribute to the accumulation of toxic parkin substrates and decrease the ability of dopaminergic cells to cope with toxic insults in Parkinson disease 2.7.11.22 cyclin-dependent kinase medicine combined action of the two protein kinases cdk5 and GSK-3 may be involved in the abnormal hyperphosphorylation of microtubule associated tau protein in Alzheimer disease 2.7.11.22 cyclin-dependent kinase medicine cyclin A/Cdk2 has profound effects on progesterone receptor activity and may have clinical implications for patients receiving antiprogestin therapies, multifaceted role for Cdk2 in the regulation of progesterone receptor transcriptional activity 2.7.11.22 cyclin-dependent kinase medicine interactions among Cdk2, dynein light chain 1, and cip-interacting zinc finger protein 1 play a regulatory role in cell cycle progression of cancer cells presumably by influencing the levels of nuclear p21WAF1 2.7.11.22 cyclin-dependent kinase medicine plays an important role in prostate cancer motility and metastasis, is important for spontaneous metastasis in vivo 2.7.11.22 cyclin-dependent kinase medicine role for cdk5 and Rho-GDI in senescence, cdk5-dependent decrease in ezrin-bound Rho-GDI can lead to increased Rho-GDI/Rac1 complexes and consequent Rac1 inhibition 2.7.11.22 cyclin-dependent kinase medicine role for Cdk5/p35 activity in primary afferent nociceptive signaling, Cdk5/p35 may be a target for the development of analgesic drugs 2.7.11.22 cyclin-dependent kinase medicine causal role in Alzheimer's disease 2.7.11.22 cyclin-dependent kinase medicine Cdk2 signaling pathways are critical regulators of cardiac ischemia/reperfusion injury in vivo 2.7.11.22 cyclin-dependent kinase medicine cdk5 contributes to the pathobiology of focal cortical dysplasia 2.7.11.22 cyclin-dependent kinase medicine Cdk5 in combination with p25 is a proapoptotic factor that promotes endoplasmic reticulum stress-induced neuronal cell death in nuclei 2.7.11.22 cyclin-dependent kinase medicine CDK9 is a key transcriptional regulator and potential drug target in oncology, virology and cardiology 2.7.11.22 cyclin-dependent kinase medicine the p25/Cdk5 complex is an important mediator of dopamine and glutamate neurotoxicity associated to Huntigton's disease 2.7.11.22 cyclin-dependent kinase medicine CDK9 represents a novel therapeutic target in chronic inflammatory diseases such as Rheumatoid Arthritis 2.7.11.23 [RNA-polymerase]-subunit kinase medicine IE2 and multiple cellular factors needed for viral RNA synthesis accumulate within the first 8 h at the viral transcriptosome, functional cdk activity is required for the specific recruitment of cdk7 and cdk9 during this time interval 2.7.11.23 [RNA-polymerase]-subunit kinase medicine the bromodomain protein, BRD4, is a therapeutic target in acute myeloid leukemia, multiple myeloma, Burkitt’s lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease. Loss of the enzyme BRD4 is a prognostic signature for metastatic breast cancer 2.7.11.24 mitogen-activated protein kinase medicine MAPKs are a molecular targets for pharmacological treatment of inflammatory lung diseases 2.7.11.24 mitogen-activated protein kinase medicine MAPKs are therapeutic targets in cardiac pathology 2.7.11.24 mitogen-activated protein kinase medicine Echinococcus multilocularis metacestode is able to sense epidermal growth factor from the host which results in an activation of the parasite’s MAP kinase cascade. MPK1 contains all amino acid residues characteristic for MAP kinases, including a conserved TEY motif which identifies the protein as a member of the ERK subfamily of MAP kinases 2.7.11.24 mitogen-activated protein kinase medicine ERK signaling is involved in cell cycle progression, cellular transformation and differentation. Spatial distribution and temporal qualities of ERK can markedly alter the qualitative and quantitative features of downstream signaling to immediate early genes and the expression of immediate early genes-encoded protein products. Targeting of ERK/DEF domain signaling axis may be beneficial in many cancers 2.7.11.24 mitogen-activated protein kinase medicine role in immune response to the spirochete of Borrelia burgdorferi mediated by CD4+ T cells, p38 MAP kinase pathway mediates production of IFN-gamma in response to a specific antigen, IL-12 contributes to IFN-gamma production by Borrelia burgdorferi specific effector Th1 cells 2.7.11.24 mitogen-activated protein kinase medicine the inhibitors of Erk1 or antioxidants may be exploited for prevention of cadmium-induced neurodegenerative diseases 2.7.11.24 mitogen-activated protein kinase medicine the inhibitors of Erk2 or antioxidants may be exploited for prevention of cadmium-induced neurodegenerative diseases 2.7.11.24 mitogen-activated protein kinase medicine the inhibitors of Erk2, or antioxidants may be exploited for prevention of cadmium-induced neurodegenerative diseases 2.7.11.24 mitogen-activated protein kinase medicine the inhibitors of JNK or antioxidants may be exploited for prevention of cadmium-induced neurodegenerative diseases 2.7.11.24 mitogen-activated protein kinase medicine the inhibitors of JNK, or antioxidants may be exploited for prevention of cadmium-induced neurodegenerative diseases 2.7.11.24 mitogen-activated protein kinase medicine c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms 2.7.11.24 mitogen-activated protein kinase medicine inhibition of JNK by nobiletin may imply its usefulness for the treatment of cardiovascular diseases relevant to vascular smooth muscle cells growth 2.7.11.24 mitogen-activated protein kinase medicine inhibition of p38 alpha mitogen-activated protein kinase is a promising therapeutic strategy for the treatment of cytokine-driven disorders like inflammatory bowel disease or rheumatoid arthritis 2.7.11.24 mitogen-activated protein kinase medicine JNK inhibitors are expected to be effective therapeutic agents against a variety of diseases 2.7.11.24 mitogen-activated protein kinase medicine JNK1 has emerged as an attractive target for diabetes therapy, since JNK1 is believed to play a key role in linking obesity and insulin resistance 2.7.11.24 mitogen-activated protein kinase medicine JNK3 may be a promising target for the treatment of neurodegenerative diseases such as Parkinsons disease, Alzheimers disease and other CNS disorders 2.7.11.24 mitogen-activated protein kinase medicine MG132 may be used as a pharmacological inhibitor of cardiac hypertrophy 2.7.11.24 mitogen-activated protein kinase medicine p38 MAP kinase inhibition constitutes a promising therapeutic strategy for treatment of chronic inflammatory diseases, based upon its potential to inhibit key pathways driving the inflammatory and destructive processes in these debilitating diseases 2.7.11.24 mitogen-activated protein kinase medicine p38 mitogen-activated protein kinase is a promising target for the treatment of chronic inflammatory diseases such as rheumatoid arthritis 2.7.11.24 mitogen-activated protein kinase medicine p38alpha is an attractive target for small molecule drug discovery 2.7.11.24 mitogen-activated protein kinase medicine results indicate that AZD6244 can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an increase in mitotic catastrophe 2.7.11.24 mitogen-activated protein kinase medicine RO4927350 represents a novel therapeutic modality in cancers with aberrant MAPK pathway activation 2.7.11.24 mitogen-activated protein kinase medicine small-molecule inhibitors of JNK1 activity might be developed as therapeutics against diabetes 2.7.11.24 mitogen-activated protein kinase medicine targeting JNK inhibition in the CNS may prove to protect against neurodegenerative insults, by either inhibiting JNK activation in neurons associated with increased apoptosis or preventing the inflammatory response in glial cells 2.7.11.24 mitogen-activated protein kinase medicine the study provides evidence on the existence of unknown cyanobacterial toxic metabolites that affect in vitro biomarkers of tumor promotion, i.e. activation of MAPKs 2.7.11.24 mitogen-activated protein kinase medicine the study suggests the possible importance in pediatric myelodysplastic syndrome of p38MAPK signaling pathway which may be a future therapeutic target 2.7.11.24 mitogen-activated protein kinase medicine therapeutic inhibition of JNK1 may provide a potential solution in type-2 diabetes mellitus 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine cleavage of MEKK1 and caspase-3 is highly increased in adenovirus-mediated overexpression of melanoma differentiation-associated gene-7–treated H1299-dnIkappaBalpha tumors than in adenovirus-mediated overexpression of melanoma differentiation-associated gene-7–treated H1299-Neo tumors 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine GCKR facilitates both canonical and noncanonical Wnt signaling in B lymphocytes 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine gene amplification and corresponding increased Tpl-2 expression in some human breast cancers 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine IL-1beta through MEKK1 inhibits human insulin gene transcription and does so, at least in part, by decreasing MafA transcriptional activity at the RIPE3b control element. Since inappropriate insulin biosynthesis contributes to beta cell dysfunction, inhibition of MEKK1 may decelerate or prevent progression from a prediabetic state to diabetes mellitus 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine MEKK4 is a critical signaling molecule during cardiovascular development, plays an important role in cardiac cushion morphogenesis, kinase activity of MEKK4 is essential, but not sufficient, to support developmental epithelial to mesenchymal transformation 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine role in epithelial wound healing, transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine stress kinase MEKK1-induced MMP-1 expression in human arthritis-affected synovial cells is mediated, in large part, by c/EBPbeta (NF-kappaBp65) promoter transactivation 2.7.11.25 mitogen-activated protein kinase kinase kinase medicine ZPK/DLK can become a strategic therapeutic target in motor neuron diseases in which aberrant activation of the apoptogenic cascade is involved 2.7.11.26 tau-protein kinase medicine - 2.7.11.26 tau-protein kinase medicine TPKI/GSK-3beta plays a key role in the pathogenesis of Alzheimer disease, tau protein kinases I and II are candidate enzymes responsible for hyperphosphorylation of tau to induce formation of paired helical filaments 2.7.11.26 tau-protein kinase medicine brain pathology in investigation of Alzheimers's disease, human tau phosphorylated by the kinase carries an epitope of the paired helical filaments that accumulate in the brain 2.7.11.26 tau-protein kinase medicine PKA and GSK-3 are targets for the therapeutic treatment of Alzheimer's disease and other tauopathies 2.7.11.26 tau-protein kinase medicine disruption of regulation of GSK3 activity underlies tau hyperphosphorylation in neurodegenerative tauopathies. GSK3 may be a prime target for therapeutic intervention in tauopathies including Alzheimer disease 2.7.11.26 tau-protein kinase medicine involvement of tau and TPKI/GSK3beta phosphorylation in an early phase of memory formation in the hippocampus and amygdala, possibility that a dysregulation of tau phosphorylation may underlie memory impairment in incipient Alzheimer's disease 2.7.11.26 tau-protein kinase medicine TTBK1 is located on human chromosome 6p21.1. It is a neuron-specific dual kinase involved in tau phosphorylation at Alzheimer’s disease-related sites and is also associated with tau aggregation 2.7.11.26 tau-protein kinase medicine GSK3 is an important therapeutic target for gliomas 2.7.11.26 tau-protein kinase medicine a significant inverse correlation is observed between level of phospho-GSK-3beta at the time of reperfusion and the extent of myocardium infarction in heart, phospho-GSK-3beta is a determinant of myocardial tolerance against reperfusion-induced necrosis. Thus, GSK-3beta is a target of therapy for cardioprotection upon reperfusion. Inactivation of GSK-3beta by phosphorylation at Ser9 elevates the threshold for mitochondrial permeability transition pore opening, which reduces myocyte necrosis. 2.7.11.26 tau-protein kinase medicine controlling GSK-3beta signaling in bone cells is a strategy for preventing glucocorticoid-induced osteopenia 2.7.11.26 tau-protein kinase medicine GSK-3beta is a therapeutic target in cancer treatment 2.7.11.26 tau-protein kinase medicine GSK3 is a fundamental and central component of Fragile X syndrome pathology 2.7.11.26 tau-protein kinase medicine isoform TTBK1 is a target for the treatment of neurodegenerative diseases 2.7.11.27 [acetyl-CoA carboxylase] kinase medicine clinical application of the enzyme activator metformin to obese or early diabetic patients may be helpful in preventing obesity- or diabetes-related kidney disease 2.7.11.30 receptor protein serine/threonine kinase medicine potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease, inhibition of activin receptor-like kinase-5 signaling in vivo with the selective small-molecule inhibitor IN-1233 prevented pulmonary arterial hypertension, right ventricular hypertrophy, and vascular remodeling after monocrotaline injection and inhibited the progression of established pulmonary arterial hypertension in this model 2.7.11.30 receptor protein serine/threonine kinase medicine therapeutic potential of TBRI inhibitors in myelodysplastic syndrome, MDS. The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by cytologic dysplasia and ineffective hematopoiesis 2.7.11.30 receptor protein serine/threonine kinase medicine the RIPK2 rs16900627 minor allele is significantly associated with the susceptibility to gastric cancer 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase medicine compounds that would cause activation of enzyme in skeletal muscle promise to be attractive agents for therapeutic intervention 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase medicine decreasing the ischaemic-induced activation of AMPK may be a therapeutic approach to treating ischaemic heart disease, AMPK may be an important pharmacological target for improving cardiac efficiency following ischaemia 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase medicine defects or disuse of the AMPK signaling system would be predicted to result in many of the metabolic perturbations observed in type 2 diabetes mellitus 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase medicine implication of AMPK in the pathogenesis of chronic intestinal inflammatory conditions, such as inflammatory bowel disease 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase medicine enzyme inhibition is a viable therapeutic strategy to prevent ischemic brain injury following stroke 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase medicine the enzyme can be an alternative therapeutic approach to preventing and managing obesity 2.7.12.1 dual-specificity kinase medicine involvement of early onset tauopathy in individuals with Down syndrome, research and development of therapeutics for tauopathies 2.7.12.1 dual-specificity kinase medicine molecular mechanism by which neurofibrillary degeneration occurs in adults with Down syndrome 2.7.12.1 dual-specificity kinase medicine phosphorylation and regulation of the oncogene E7 of human papillomvirus HPV16 2.7.12.1 dual-specificity kinase medicine potential link between Down syndrome and Alzheimers disease by activity of DYRK1A, overexpression of DYRK1A in patients with Down syndrome may play a role in accelerating pathogenesis of Alzheimers disease through phosphorylation of the beta-amyloid (Ab) precursor protein APP, therapeutics that inhibit DYRK1A expression and/or kinase activity suggested as a possibility to suppress the early-onset of Alzheimers disease and mental retardation in Down syndrome patients 2.7.12.1 dual-specificity kinase medicine role of DYRK3 as an erythropoietic suppressor selectively during stress erythropoiesis, possible candidate for targeting by small molecule inhibitors as potentially important anti-anemia agents 2.7.12.1 dual-specificity kinase medicine expression of DYRK2 can be a favorable prognostic marker in pulmonary adenocarcinoma 2.7.12.1 dual-specificity kinase medicine Dyrk1B may serve as a target for therapy in human papillomavirus-associated cancers 2.7.12.1 dual-specificity kinase medicine DYRK1A controls cyclin L2 expression, leading to restriction of HIV replication in macrophages 2.7.12.1 dual-specificity kinase medicine DYRK2 phosphorylates Notch1-IC in response to chemotherapeutic agents and facilitates its proteasomal degradation by FBXW7 ubiquitin ligase through a Thr-2512 phosphorylation-dependent mechanism. DYRK2 regulation by chemotherapeutic agents has a relevant effect on the viability, motility and invasion capacity of cancer cells expressing NOTCH1 2.7.12.2 mitogen-activated protein kinase kinase medicine acts as tumor suppressor, but can also promote tumor growth, plays a role in liver formation, the immune system and cardiac hypertrophy, contributes to optimal c-Jun N-terminal kinase activation 2.7.12.2 mitogen-activated protein kinase kinase medicine important role for MKK4 pathways in controlling cancer development, has a tumor suppression function, the MKK4 gene is mutated at a frequency of 5% in a number of cancer types. In contrast, studies in other cell types suggest that MKK4 and c-Jun N-terminal kinase participate in tumor promotion 2.7.12.2 mitogen-activated protein kinase kinase medicine key activator of p38 MAPK in glioma, MKK3 activation is strongly correlated with p38 activation in vitro and in vivo, strong promoter of tumor invasion, progression, and poor patient survival, interference with MKK3 signaling through a novel treatment combination of p38 inhibitor plus temozolomide heightens the vulnerability of glioma to chemotherapy 2.7.12.2 mitogen-activated protein kinase kinase medicine MKK4 immunolabeling detects precursor lesions of gastric adenocarcinoma that are otherwise clinically, radiographically, and endoscopically inapparent, is useful in the diagnosis and therapeutic targeting of gastric adenocarcinoma precursor lesions 2.7.12.2 mitogen-activated protein kinase kinase medicine novel isoform of human MKK7, is expressed in various normal tissues, tumors, and in synoviocytes from rheumatoid and osteoarthritis patients. Recombinant MKK7gamma1 can be phosphorylated and activated by MEKK1 2.7.12.2 mitogen-activated protein kinase kinase medicine plays a role in acute myelogenous leukemia, Raf/MEK/ERK pathway regulates the subcellular localization of p53 and the relative contribution of transcription-dependent and transcription-independent pathways in p53-mediated apoptosis 2.7.12.2 mitogen-activated protein kinase kinase medicine Porphyromonas gingivalis-secreted factors may initiate MEK/ERK signal pathways and lead to myocardial cell hypertrophy and apoptosis 2.7.12.2 mitogen-activated protein kinase kinase medicine targets c-Jun N-terminal kinase but not p38 2.7.12.2 mitogen-activated protein kinase kinase medicine MKK inhibition by anthrax lethal toxin LeTx is a broadly effective strategy for targeting neovascularization in fibrosarcomas and other similar proliferative lesions 2.7.13.3 histidine kinase medicine significance in pathological virulence of Salmonella enterica, seductive target for anti-bacterial therapeutic development 2.7.13.3 histidine kinase medicine NME1 expression is associated with reduced overall and event-free survival of neuroblastoma patients and with the strongest associations of any of the NME family member genes. NME1 expression is also higher in tumors with MYCN oncogene amplification and in tumors from patients with stage 4 disease. Isoforms NME1/NMe2 and multiple phosphorylated His-containing proteins are found in all tested neuroblastoma cell lines and in xenograft neuroblastoma tumors. NME1 expression is asssociated with neuroblastoma cell migration and differentiation 2.8.1.1 thiosulfate sulfurtransferase medicine in advanced colon cancers, expression of both thiosulfate sulfurtransferase and mercaptopyruvate sulfurtransferase is markedly reduced, the disease progression correlating with decrease in expression. In human colon cancer cell line HT-29, enzyme activity and expression are significantly increased by butyrate and by histone deacetylaseinhibition. Use of decrease in enzyme expression as a tumor marker for colorectal cancer 2.8.1.1 thiosulfate sulfurtransferase medicine thiosulfate sulfurtransferase does not metabolize sulfide. The rate limiting step in sulfide detoxification is oxidation by a sulfide oxidase to thiosulfate, therefor the use of thiosulfate sulfurtransferase activity to determine the rate that colonic mucosa detoxifies sulfide is inappropriate 2.8.1.1 thiosulfate sulfurtransferase medicine low expression of thiosulfate sulfurtransferase predicts mortality in hemodialysis patients 2.8.1.1 thiosulfate sulfurtransferase medicine enzyme mRNA expression in adipose tissue correlates positively with insulin sensitivity in adipose tissue and negatively with fat mass. Genetic enzyme identification as a beneficial regulator of adipocyte mitochondrial function has therapeutic significance for individuals with type 2 diabetes 2.8.1.1 thiosulfate sulfurtransferase medicine adult rats on high fructose diet have 56% decrease in thiosulfate-dithiol sulfurtransferase activity, 35% decrease in cystathionine beta synthase and 48% decrease in cystathionine gamma synthase activity, compared to a standard diet group. Aged rats on high fructose diet have lower activities of all three enzymes versus aged rats on standard diet. Increased activities of all H2S-related enzymes are oberved during induction of acute water immersion restraint stress. In adult rats exposed to stress on high fructose diet and treatment by NaHS, 1.8 times increased activities of cystathionine beta synthase, 1.3 times increased activities of cystathionine gamma synthase, and 69% increased activities of thiosulfate-dithiol sulfurtransferase are seen over adult rats with vehicle. Rats fed by high fructose diet have higher levels of the oxidative index than animals fed by standard diet. The pretreatment by H2S donors NaHS and 4-carbamothioylphenyl 2-(acetyloxy)benzoate in aged rats reduces the oxidative index levels and correlate with thiosulfate-dithiol sulfurtransferase activity 2.8.1.1 thiosulfate sulfurtransferase medicine CysA2 interacts with pulmonary cells, and it is capable to activate macrophages and dendritic cells 2.8.1.2 3-mercaptopyruvate sulfurtransferase medicine a significantly higher level of 3-MST protein expression is observed in Down syndrome (trisomy of human chromosome 21) fibroblasts compared to cells from healthy control individuals. The excess 3-MST is mainly localized to the mitochondrial compartment. Pharmacological inhibition of 3-MST activity improves mitochondrial electron transport and oxidative phosphorylation parameters and enhances cell proliferation in Down syndrome cells but not in healthy control cells 2.8.1.2 3-mercaptopyruvate sulfurtransferase medicine after 24 h and 48 h incubation of MCF-7 cells with 2245 microM S-allyl-L-cysteine, induction of late apoptosis is observed. A decrease in cell viability is observed with increasing S-allyl-L-cysteine concentration and incubation time. S-allyl-L-cysteine has no significant cytotoxic effect on the MCF-7 cells upon all analyzed concentrations 2.8.1.2 3-mercaptopyruvate sulfurtransferase medicine colon cancer cells exposed to N-acetylcysteine for 24 h display increased expression and activity of MST and sulfide:quinone oxidoreductase. N-acetylcysteine persists at detectable levels inside the cells exposed to the drug for up to 24 h and sustains H2S synthesis by MST more effectively than cysteine 2.8.1.2 3-mercaptopyruvate sulfurtransferase medicine CysA2 interacts with pulmonary cells, and it is capable to activate macrophages and dendritic cells 2.8.2.1 aryl sulfotransferase medicine concomitant ingestion of beverages such as green tea and black tea may increase the bioavailability of orally administered ritodrine, and perhaps other beta-agonists 2.8.2.1 aryl sulfotransferase medicine SULT1A1 is a useful biomarker for the detection of early hepatocellular carcinoma cell and helps predict the clinical outcome of patients with hepatocellular carcinoma cell 2.8.2.1 aryl sulfotransferase medicine isoforms SULT1A1, 1A2, 1A3, 1B1, 1C4, 1E1 display significant sulfating activities toward rotigotine. Of the 6 human organ samples tested, small intestine and liver cytosols display considerably higher rotigotine-sulfating activity than brain, lung, and kidney. Sulfation of rotigotine occurs in HepG2 cells and Caco-2 cells under metabolic conditions 2.8.2.2 alcohol sulfotransferase medicine model studies on the carcinogenesis of benzylic and allylic alcohols 2.8.2.2 alcohol sulfotransferase medicine hEST1 involved in the production of stable precursors for local steroid biosynthesis or in activation of promutagenic estrogen metabolites into carcinogens 2.8.2.2 alcohol sulfotransferase medicine isoenzyme EST plays important roles in regulating the in situ production of estrogens in breast carcinoma tissue, immunoreactivity of the enzymes is a potent prognostic factor for cancer 2.8.2.2 alcohol sulfotransferase medicine diagnostic of liver diseases, in chronic hepatitis the immunopositive area of DHEA-ST is significantly increased compared to normal liver 2.8.2.2 alcohol sulfotransferase medicine the HNF4alpha-SULT2B1b-CS axis represents a key endogenous mechanism to prevent uncontrolled gluconeogenesis. Thiocholesterol may be used as a therapeutic agent to manage hyperglycemia 2.8.2.4 estrone sulfotransferase medicine diagnosis of atherosclerotic changes, enzymatic distribution and involvement in the development and pathogenesis of atherosclerosis is different between males and females 2.8.2.4 estrone sulfotransferase medicine development of flavonoid, isoflavonoid and phenolic inhibitors of the bioactivation of carcinogens by the enzyme 2.8.2.4 estrone sulfotransferase medicine potential clinical applications in breast cancer 2.8.2.4 estrone sulfotransferase medicine formation of inactive estrogen sulfates can cause a reduction in the estrogenic environment which confers a beneficial effect to Org OD14 reducing the risk of breast tumours in long-term hormone replacement treatment 2.8.2.4 estrone sulfotransferase medicine EST is an independent prognostic factor in human breast carcinoma 2.8.2.4 estrone sulfotransferase medicine the steroid sulfatase/estrogen sulfotransferase status of carcinoma tissue determines intratumoral estrogen levels and can be a significant prognostic factor in colon carcinoma 2.8.2.4 estrone sulfotransferase medicine enzyme immunoreactivity is inversely correlated with tumor size or lymph node status in the invasive breast carcinoma, and is also significantly associated with a decreased risk of recurrence or improved prognosis of the patients. Ovarian cancer patients with higher enzyme activity are significantly associated with shorter progression-free survival than those with lower enzyme activity 2.8.2.4 estrone sulfotransferase medicine inhibition of estrogen sulfotransferase, at least in females, represents an effective approach to manage hepatic ischemia and reperfusion injury 2.8.2.4 estrone sulfotransferase medicine there is a positive correlation between the enzyme expression and body mass index 2.8.2.4 estrone sulfotransferase medicine pharmacological inhibition of EST may represent an effective approach to manage hemorrhagic shock-induced acute lung injury (ALI) 2.8.2.5 chondroitin 4-sulfotransferase medicine gene-trap mutation in bone morphogenic protein-induced enzyme causes severe chondrodysplasia characterised by disorganised cartilage growth plate as well as specific alterations in the orientation of chondrocyte columns. Phenotype is associated with chondroitin sulfation imbalance, mislocalization of chondroitin sulfate and imbalance of apoptotic signals 2.8.2.5 chondroitin 4-sulfotransferase medicine translocations t(12,14)(q23,q32) in a patient with B-cell chronic lymphocytic leukemia result in expression of two truncated forms of enzyme protein, resulting in disturbance of the cellular distribution of enzyme, and further in deregulation of a chondroitin-sulfate dependent pathway specific to the hematopoietic lineage 2.8.2.5 chondroitin 4-sulfotransferase medicine the enzyme is an independent unfavorable prognostic factor for ovarian cancer progression 2.8.2.B6 [heparan sulfate]-iuronate 2-sulfotransferase medicine specific HS sulfotransferases may serve as molecular markers and targets for cancer treatment 2.8.2.8 [heparan sulfate]-glucosamine N-sulfotransferase medicine diabetes substantially suppresses hepatic N-deacetylase/N-sulfotransferase-1 mRNA, protein and enzymatic activity. Suppression of hepatic N-deacetylase/N-sulfotransferase-1 may contribute to diabetic dyslipidemia. Stimulation of N-deacetylase/N-sulfotransferase-1 activity by AngII inhibitors may provide cardiovascular protection 2.8.2.11 galactosylceramide sulfotransferase medicine inhibition of CST could be an option for the treatment of metachromatic leukodystrophy 2.8.2.11 galactosylceramide sulfotransferase medicine heterozygosity at SNP rs2267161 in the gene encoding cerebroside sulfotransferase confers increased risk of type 2 diabetes, females with the CC allele show lower insulin resistance 2.8.2.11 galactosylceramide sulfotransferase medicine the mechanism, indicating the crosstalk between kidney injury and specific liver functions, may prove useful to understand the situation where human hemodialysis patients have low levels of serum sulfatides 2.8.2.14 bile-salt sulfotransferase medicine assay for bile salt sulfotransferase renders it possible to estimate this enzyme in percutaneous liver biopsy specimens. By application of this technique it will be possible to study this enzyme in patients with various liver diseases 2.8.2.14 bile-salt sulfotransferase medicine aging does not influence the response to the hormonal and xenobiotic signaling for enzyme Sult2A1 induction 2.8.2.15 steroid sulfotransferase medicine isoenzyme STS plays important roles in regulating the in situ production of estrogens in breast carcinoma tissue, immunoreactivity of the enzymes is a potent prognostic factor for cancer 2.8.2.15 steroid sulfotransferase medicine characterization of the mechanism of regulation and action of DHEA-ST should lead to a better understanding of the control of adrenal androgen production as well as a better knowledge of the role of DHEAS in the androgen-and estrogen-sensitive disorders 2.8.2.17 chondroitin 6-sulfotransferase medicine missense mutation R304Q found in patients with a distinct form of spondyloepiphyseal dysplasia, SED Omani type, leads to complete loss of activity, resulting in significant reduction of both DELTAHexA-GalNAc(6S) and DELTAHexA(2S)-GalNAc(6S) and elevated levels of DELTAHexA-GalNAc(4S,6S). Defect in chondroitin sulfate chain sulfation results in chondrodysplasia with major involvement of the spine 2.8.2.20 protein-tyrosine sulfotransferase medicine isoform TPST1 expression is associated with the tumornodemetastasis stage and lymph node metastasis in patients with lung cancer 2.8.2.23 [heparan sulfate]-glucosamine 3-sulfotransferase 1 medicine the results provide evidence for specific epigenetic regulation of 3-OST genes resulting in altered heparan sulfate proteoglycans and point to a defect of heparan sulfate-3-O-sulfation as a factor in cancer progression 2.8.2.29 [heparan sulfate]-glucosamine 3-sulfotransferase 2 medicine possible role of 3-OST-2 in the spread of HSV-1 infection in the brain 2.8.2.29 [heparan sulfate]-glucosamine 3-sulfotransferase 2 medicine Silencing of the 3-OST-2 gene is present in a wide range of human cancers. Possible diagnostic and potentially therapeutic value. 2.8.2.29 [heparan sulfate]-glucosamine 3-sulfotransferase 2 medicine the results provide evidence for specific epigenetic regulation of 3-OST genes resulting in altered heparan sulfate proteoglycans and point to a defect of heparan sulfate-3-O-sulfation as a factor in cancer progression 2.8.2.29 [heparan sulfate]-glucosamine 3-sulfotransferase 2 medicine enzyme hypermethylation is an independent prognostic indicator for overall survival in node-negative stage I-II non-small cell lung cancer 2.8.2.30 [heparan sulfate]-glucosamine 3-sulfotransferase 3 medicine the results provide evidence for specific epigenetic regulation of 3-OST genes resulting in altered heparan sulfate proteoglycans and point to a defect of heparan sulfate-3-O-sulfation as a factor in cancer progression 2.8.2.30 [heparan sulfate]-glucosamine 3-sulfotransferase 3 medicine the enzyme is a prognostic marker in breast cancer 2.8.2.30 [heparan sulfate]-glucosamine 3-sulfotransferase 3 medicine specific HS sulfotransferases may serve as molecular markers and targets for cancer treatment 2.8.2.33 N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase medicine tumor-specific chondroitin sulfate modifications might be potential targets to influence tumor development 2.8.2.33 N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase medicine mRNA expressed by astrocytic tumor cells is associated with poor patient prognosis in case of astrocytic tumor, likely by enhancing chondroitin sulfate-E-unit-mediated tumor cell motility in the presence of pleiotrophin and/or midkine 2.8.3.5 3-oxoacid CoA-transferase medicine patients homozygous for T435N mutation of SCOT do not show permanent ketosis 2.8.3.5 3-oxoacid CoA-transferase medicine hereditary SCOT deficiency is one cause of ketoacidosis 2.8.3.5 3-oxoacid CoA-transferase medicine Succinyl-CoA:3-ketoacid CoA transferase deficiency causes episodic ketoacidosis 2.8.3.5 3-oxoacid CoA-transferase medicine dietary manipulation using ketone bodies in accordance with SCOT expression may be a novel therapeutic strategy for neuroblastoma 2.8.3.16 formyl-CoA transferase medicine bacterial oxalate-degrading function, in humans an accumulation of oxalic acid can result in a number of pathologic conditions, including hyperoxaluria, urolithiasis, renal failure, cardiomyopathy and cardiac conductance disorders 2.8.3.16 formyl-CoA transferase medicine gene therapy of hyperoxaluria 2.8.3.16 formyl-CoA transferase medicine potential therapeutic use in managing oxalate kidney stone disease in humans 2.8.3.18 succinyl-CoA:acetate CoA-transferase medicine the enzyme seems to be a logical target for broad-spectrum anti-parasitic drugs 3.1.1.1 carboxylesterase medicine enzyme can activate prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin to give 7-ethyl-10-hydroxycampothecin, i.e. SN-38, a topoisomerase inhibitor used in cancer therapy 3.1.1.1 carboxylesterase medicine human small intestine and liver show extensive hydrolase activity attributed to carboxylesterase, which is different from that in species normally used as experimental animals 3.1.1.1 carboxylesterase medicine intestinal carboxyesterase is the enzyme that activates doxazolidine carbamate prodrug Pentyl PABC-Doxaz. MCF-7 cells or U-373MG cells overexpressing the enzyme show dramatically reduced IC50 values for Pentyl PABC-Doxaz 3.1.1.1 carboxylesterase medicine isolation of mutant enzyme hCE1m6, which is 70fold more efficient in cleavage of the antitumor prodrug irinotecan-7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, i.e. CPT-11, than wild-type. Adenoviral-mediated delivery of mutant enzyme with human tumor cells results in up to 670fold reduction in the IC50 value for CPT-11 3.1.1.1 carboxylesterase medicine skin from the minipig back is an appropriate model for preclinical human skin studies, particularly breast skin 3.1.1.1 carboxylesterase medicine since the enzyme may be useful as a treatment for cocaine overdose, and may afford protection against chemical weapons like Sarin, Soman and VX gas, hCE1 could serve as both a drug and a drug target 3.1.1.1 carboxylesterase medicine the bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure 3.1.1.2 arylesterase medicine aryl esterase activitiy correlates positively with total antioxidant status, high density lipoprotein and apolipoprotein A-I 3.1.1.2 arylesterase medicine baseline and stimulated ARE activity is significantly lower in patients with chronic liver disease than in controls, serum ARE activity can be a suitable biomarker for the evaluation of the presence and severity of chronic liver damage 3.1.1.2 arylesterase medicine both PON1 bioavailability and catalytic activity are decreased in children with autism spectrum disorders 3.1.1.2 arylesterase medicine diminished paraoxonase and arylesterase activity is associated with particular stage, grade and CA-125 level of ovarian cancer 3.1.1.2 arylesterase medicine enzyme activity is reduced in subjects with type 1 and type 2 diabetes, the enzyme is associated with proteinuria in subjects with type 2 diabetes mellitus, there is an independent inverse association of enzyme mass with cystatin C Aboriginal subjects with type 2 diabetes 3.1.1.2 arylesterase medicine low paraoxonase-I activity in type 2 diabetes mellitus may contribute to increased cardiovascular risk via an effect on enhanced systemic low-grade inflammation 3.1.1.2 arylesterase medicine PON1 activity is lower in chronic hepatitis patients compared with the control subjects 3.1.1.2 arylesterase medicine PON1 moderately indicates cancer presence and regional metastasis, PON1 activity decreases in gastroesophageal cancers and corresponds to inflammation severity and cancer-related anemia, PON1's arylesterase activity reflects anemia severity, being correlated with hemoglobin, hematocrit, and iron 3.1.1.2 arylesterase medicine PON1 overexpression is associated with decreased diabetes-induced macrophage oxidative stress, decreased diabetes development, and decreased mortality 3.1.1.2 arylesterase medicine the arylesterase activity of PON1 is affected by critical ischemia of the lower limbs 3.1.1.2 arylesterase medicine biologic monitoring for AREase status among pesticide handlers may be warranted to identify individuals who are at particularly high risk of organophosphate-related health effect 3.1.1.2 arylesterase medicine serum ARE activity may be a suitable biomarker for identifying the presence and severity of chronic liver injury 3.1.1.2 arylesterase medicine paraoxonase 1 significantly protects against sarin and soman exposure in guinea pigs and supports the development of paraoxonase 1 as a catalytic bioscavenger for protection against lethal exposure of chemical warfare nerve agents exposure 3.1.1.2 arylesterase medicine the lower enzyme activity in metabolic syndrome are considered an independent risk factor for cardiovascular disease 3.1.1.2 arylesterase medicine ethanol consumption causes a significant decrease in liver paraoxonase activity. Gallic acid treatment partly restores this decreased paraoxonase activity. A gallic acid dose of 100 mg/kg shows highest restoring effect for paraoxonase activity. The activity of arylesterase is decreased in the ethanol group, but this decrease is not significant. Gallic acid treatment restores the loss of this activity due to ethanol exposure 3.1.1.2 arylesterase medicine in patients with ankylosing spondylitis with active disease, levels of serum triglycerides, total cholesterol, low denstiy lipoprotein and malondialdehyde are significantly elevated while high density liporpoteon, paraoxonase PON1 and arylesterase ARE levels are lower than those with no active ankylosing spondylitis. Decrease in the PON1/ARE activity leading to generation of oxidative stress may play an important role in the pathogenesis of ankylosing spondylitis. Activity of PON1/ARE in patients with ankylosing spondylitis seems to be strictly correlated with the activity of the inflammatory process 3.1.1.2 arylesterase medicine in patients with idiopathic Parkinson's disease, total antioxidant status levels are significantly lower than that of controls. Total oxidant status levels are higher than those of controls. Paraoxonase PON1 and arylesterase activities of patients are lower than those of controls. Serum levels of total and low density lipid cholesterol are significantly reduced in Parkinson's disease patients 3.1.1.2 arylesterase medicine in patients with relapsing-remitting multiple sclerosis, total antioxidant status levels are significantly lower than that of controls. Total oxidant status levels of the patients are higher than that of controls. Paraoxonase PON1 and arylesterase activities of the patients are lower, but not significantly, than those of controls. There is no correlation between serum PON1 activity and oxidaive stress index in patients with relapsing-remitting multiple sclerosis. Endogenousantioxidants may have been exhausted by increased oxidative stress and additional antioxidant treatment might be beneficial for these patients 3.1.1.2 arylesterase medicine in patients with selective serotonin reuptake inhibitor intoxication, the serum total antioxidant capacity levels and the paraoxonase and arylesterase activities are significantly lower, whereas the serum malondialdehyde levels are significantly higher than in the controls, indicating that decreased paraoxonase PON1 activity and increased oxidative stress represent alternative mechanisms in selective serotonin reuptake inhibitor toxicity 3.1.1.2 arylesterase medicine incubation of serum or high density lipoprotein from healthy subjects with very low density lipoprotein significantly decreases serum paraoxonase 1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated paraoxonase 1 lactonase or arylesterase activities by up to 32% or 46%, respectively. Very low density lipoprotein also inhibits recombinant paraoxonase 1 lactonase or arylesterase activities by up to 20% or 42%, respectively. Bezafibrate therapy to three hypertriglyceridemic patients (400 mg/day, for one month) significantly decreased serum triglyceride concentration by 67%, and increased serum high density lipoproteincholesterol levels by 48%. Paraoxonase 1 arylesterase or paraoxonase activities in the patients' high density lipoprotein fractions after drug therapy are significantly increased by 86-88%, as compared to paraoxonase 1 activities before treatment. High density lipoprotein-paraoxonase 1 protein levels significantly increased after bezafibrate therapy 3.1.1.2 arylesterase medicine quantification of arylesterase activity in routine clinical studies by monitoring the formation of acetic acid, upon the hydrolysis of phenyl acetate, using 10 microl of sample. The method accuracy is higher than 90% and intra-assay and inter-assay precisions are 96% and 95%, respectively. The procedure is suitable for use in human serum and heparinized plasma samples, while ethylenediaminetetra-acetic acid containing samples should be avoided 3.1.1.2 arylesterase medicine serum paraoxonase and arylesterase activities are significantly lower in patients with osteomyelitis compared to control individuals. Arylesterase activity is inversely correlated with triglyceride and cholesterol concentrations 3.1.1.2 arylesterase medicine use of 9-(4-chlorophenyloxycarbonyl)-10-methylacridinium triflate as a substrate for serum PON arylesterase activity assay. The apparent Km value of a serum sample for the substrate is 85 nmol/l, close to the Km value of recombinant human isoform PON1. Recombinant human PON1 in presence of CaCl2 shows at least 7.8 times selectivity over acetylcholinesterase and lipases. The method allows reliable, cost-saving, and specific determination in a buffer of physiological pH 3.1.1.2 arylesterase medicine paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications 3.1.1.3 triacylglycerol lipase medicine the enzyme can be used in enzyme replacement therapy treating pancreatic exocrine insufficiency 3.1.1.4 phospholipase A2 medicine C-terminal region of enzyme has bactericidal activity. Modulation of synthetic peptides based on the enzymic sequence, which have high bactericidal and endotoxin-neutralizing activity 3.1.1.4 phospholipase A2 medicine enzyme extracts from clinical strains isolated from children with gastroenteritis cause vacuolating and cytolytic effects on Chinese hamster ovary cells in tissue culture 3.1.1.4 phospholipase A2 medicine combination of sPLA2 activity and cardiovascular reactive protein values is more useful to detect incident risk of coronary artery disease than either biomarker alone. Prognostic value of plasma concentrations and activity of Lp-PLA2 in patients with coronary heart disease 3.1.1.4 phospholipase A2 medicine nPLA treatment protects the cell by anti-apoptotic as well as cell survival mechanisms 3.1.1.4 phospholipase A2 medicine PLA2 displays an inhibitory effect, independent from its catalytic activity, on tumor cell adhesion and migration, which is mediated via specific inhibition of integrins 3.1.1.4 phospholipase A2 medicine potential of PLA2 as a biomarker in screening neuroinflammatory disorders in both clinical and research settings 3.1.1.4 phospholipase A2 medicine the purified enzyme shows strong bactericidal activity against Burkholderia pseudomallei (minimum inhibitory concentration above 0.015 mg/ml) and Enterobacter aerogenes (minimum inhibitory concentration above 0.03 mg/ml) 3.1.1.4 phospholipase A2 medicine in mouse aorti rings, enzyme can induce a further contractile response on the 60 mM K+-induced contraction, with an EC50 of 369 nM 3.1.1.4 phospholipase A2 medicine bee venom-derived phospholipase A2 can be a promising treatment option for Parkinson's disease. It ameliorates motor dysfunction and modulates microglia activation in Parkinson's disease alpha-synuclein transgenic mice 3.1.1.5 lysophospholipase medicine LLPL activity is anti-atherogenic and the regulation of this enzyme might be a novel drug target for the treatment of atherosclerosis 3.1.1.5 lysophospholipase medicine cryptococcal phospholipase B1 is a virulence factor 3.1.1.5 lysophospholipase medicine Schistosome lysophospholipase may represent a new target for anti-schistosomal chemotherapy 3.1.1.5 lysophospholipase medicine the phospholipases and lysophospholipases expressed by eosinophils or other airway cells may represent therapeutic targets for blocking surfactant degradation, dysfunction and peripheral airway closure in asthma 3.1.1.5 lysophospholipase medicine schistosome lysophospholipase may represent a new target for anti-schistosomal-chemotherapy 3.1.1.5 lysophospholipase medicine the cytotoxic potential and signalling properties enable Legionella pneumophila PLA, LPLA enzymes to act as bacterial virulence factors, involved in severe lung disease 3.1.1.7 acetylcholinesterase medicine analysis of lung carcinoma cells and their adjacent tissues for enzyme activity. Both cholinesterase EC 3.1.1.7 and EC 3.1.1.8 activity drop in adenocarcinoma and in squamous cell carcinoma 3.1.1.7 acetylcholinesterase medicine chronic administration of tea polyphenol significantly reverses scopolamine-induced retention deficits in both step-through passive avoidance and spontaneous alternation behavioural tasks. Additionally, tea polyphenol inhibits enzyme activity and may be useful in treatment of Alzheimer’s disease 3.1.1.7 acetylcholinesterase medicine incubation of brain homogenates with galactose, galactose 1-phosphate and/or galactitol at concentrations typical for classical galactosaemia or galactokinase deficiency galactosaemia. Enzyme activity is significantly higher in hypothalamus compared with frontal cortex and hippocampus. Frontal cortex and hippocampus enzyme are significantly inhibited by galactose derivatives, whereas hypothalamus enyme activity remains unaltered 3.1.1.7 acetylcholinesterase medicine whole-body hypothermia increases the degree of substrate inhibition of enzyme, its maximum rate and its Km-value 3.1.1.7 acetylcholinesterase medicine inhibition of acetylcholinesterase and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer's disease 3.1.1.7 acetylcholinesterase medicine acetylcholinesterase (AChE) inhibition is the standard therapy for Alzheimer's disease (AD), a late-onset neurodegenerative pathology that impacts an individual's memory, motor coordination, and cognition in a progressive and eventually lethal manner. Alzheimer's disease has huge socioeconomic impact, and healthcare research in the twenty-first century has prioritized the development of therapeutic alternatives to treat this condition 3.1.1.8 cholinesterase medicine analysis of lung carcinoma cells and their adjacent tissues for enzyme activity. Both cholinesterase EC 3.1.1.7 and EC 3.1.1.8 activity drop in adenocarcinoma and in squamous cell carcinoma 3.1.1.8 cholinesterase medicine both pyridostigmine and pralidoxime significally decrease organophosphate induced mortality of a LD75 dose of paraoxon by inhibition of enzyme. Decrease in mortality when using both pyridostigmine and pralidoxime together is less than that achieved with their single use 3.1.1.8 cholinesterase medicine enzyme exogenously administered as a bioscavenger in Mus musculus. Enzyme activity reached peak levels in circulation at 10 and 24 h following i.p. and i.m. injections. Enzyme does not exhibit any toxicity. Analysis of oharmakokinetic parameters 3.1.1.8 cholinesterase medicine therapeutic effects of BChE on cocaine toxicity and organophosphorus agent poisoning, in order to be therapeutically useful, BChE must have a long circulatory residence time or associate as tetramers, full-length recombinant BChE produced for therapeutical use 3.1.1.8 cholinesterase medicine butyrylcholinesterase activity may serve as marker to predict the development of type 2 diabetes and or metabolic syndrome 3.1.1.8 cholinesterase medicine the efficient downstream processing scheme and functionality of regulated transgenic enzyme rrBChE confirm its promise as a cost-effective alternative to human BChE for prophylactic and therapeutic use 3.1.1.13 sterol esterase medicine pancreatic enzyme preparation is used in human pancreatic cystic fibrosis therapy 3.1.1.13 sterol esterase medicine selective inhibitors may be useful therapeutics for limiting cholesterol absorption 3.1.1.13 sterol esterase medicine enzyme overexpression results in elevation of free cholesterol and depletion of cholesteryl esters, which are resistant to compensatory responses by other enzymes of cholesterol homeostasis 3.1.1.13 sterol esterase medicine enzyme expression in human macrophages is a potential target for attenuation of foam cell formation and regression of atherosclerotic plaques 3.1.1.13 sterol esterase medicine lowering of cholesterol levels in plasma low-density lipoprotein by cardiovascular drugs such as lovastatin, simvastatin, amlodipine, besylate, nifedipine, and hydralazine hydrochloride may result from inhibition of cholesterol esterase 3.1.1.13 sterol esterase medicine macrophage-specific expression of enzyme in LDL receptor null mice leads to a significant reduction in the lesion ara and cholesterol content of high-fat, high-cholesterol diet-induced atherosclerotic lesions. Lesions do not show increase in free cholesterol, are less necrotic, and contain significantly higher numbers of viable macrophage foam cells. Higher enzyme-mediated free cholesterol efflux results in enhanced flux of free cholesterol from macrophages to gall bladder bile and feces in vivo 3.1.1.13 sterol esterase medicine LAL plays a essential role in development, homeostasis, and function of T cells, LAL deficiency impairs T cell development in the thymus 3.1.1.13 sterol esterase medicine inhibition of this enzyme is highly effective in the treatment of hypercholesterolemia 3.1.1.13 sterol esterase medicine hypocholesterolaemic mechanism of bitter melon aqueous extracts via inhibition of pancreatic cholesterol esterase and reduction of cholesterol micellar solubility 3.1.1.20 tannase medicine tanA detection via PCR is a useful method for the rapid and simple identification of Staphylococcus lugdunensis. Detection efficiency of tanA from feces is identical to that from pure culture. The tanA gene can be used as a standard identification marker. The high specificity allows for tanA to be used as an Staphylococcus lugdunensis identification marker in other assays, including DNA microarrays 3.1.1.23 acylglycerol lipase medicine MGL represents a target for the treatment of inflammatory pain 3.1.1.23 acylglycerol lipase medicine enzyme MAGL represents a potential target to treat diverse pathological conditions, including cancer 3.1.1.23 acylglycerol lipase medicine expression of macrophage MGLL is decreased in cancer tissues and positively correlated with the survival of cancer patients. Monoacylglycerol lipase is a switch for CB2/TLR4-dependent macrophage activation and a potential target for cancer therapy. Modulation of MGLL-CB2 axis in macrophages might be a promising strategy for cancer treatment 3.1.1.25 1,4-lactonase medicine PON1 overexpression is associated with decreased diabetes-induced macrophage oxidative stress, decreased diabetes development, and decreased mortality 3.1.1.25 1,4-lactonase medicine incubation of serum or high density lipoprotein from healthy subjects with very low density lipoprotein significantly decreases serum paraoxonase 1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated paraoxonase 1 lactonase or arylesterase activities by up to 32% or 46%, respectively. Very low density lipoprotein also inhibits recombinant paraoxonase 1 lactonase or arylesterase activities by up to 20% or 42%, respectively. Bezafibrate therapy to three hypertriglyceridemic patients (400 mg/day, for one month) significantly decreased serum triglyceride concentration by 67%, and increased serum high density lipoproteincholesterol levels by 48%. Paraoxonase 1 arylesterase or paraoxonase activities in the patients' high density lipoprotein fractions after drug therapy are significantly increased by 86-88%, as compared to paraoxonase 1 activities before treatment. High density lipoprotein-paraoxonase 1 protein levels significantly increased after bezafibrate therapy 3.1.1.28 acylcarnitine hydrolase medicine determination of acetylcarnitine for diagnosis of chronic fatigue syndrome 3.1.1.32 phospholipase A1 medicine acidotropic accumulation of cocaine in lysosomes inhibits acid phospholipase A1 and inactivates acid sphingomyelinase, inducing a mixed lysosomal lipidosis 3.1.1.32 phospholipase A1 medicine may provide a valuable tool for diagnostic and therapeutic approaches in hymenoptera venom allergy. Recombinant Ves v 1 is an essential component to assess the sensitisation of individuals to yellow jacket venom and its recombinant availability complemented with Ves v 5 and phospholipase A2 from honeybee venom (Api m 1) allows for clear assignment of sensitisation patterns 3.1.1.32 phospholipase A1 medicine homozygous mutation c.395dup/p.Gly133Argfs*26 in DDHD1 results in a complex form of hereditary spastic paraplegia associated with retinal dystrophy and a pattern of neurodegeneration with brain iron accumulation 3.1.1.32 phospholipase A1 medicine role of enzyme in oncogenesis and metastasis of colorectal cancer. Tumor depth and hematogenous metastasis independently positively correlate with phospholipase A1 expression. High expression is associated with shorter disease-free survival, although it is not an independent predictive factor 3.1.1.34 lipoprotein lipase medicine comparison of protein and mRNA levels of enzyme and several muscle lipid-binding proteins in healthy, nonobese, nontrained, moderately trained, and endurance-trained women and men. In the nontrained state, women have higher muscle RNA levels of several proteins related to lipid metabolism compared with men. In the endurance-trained state, only the gender difference in lipoprotein lipase mRNA persists 3.1.1.34 lipoprotein lipase medicine determination of enzyme and of hepatic triacylglycerol lipase activity and comparison with serum adiponectin levels in Japanese hyperlipidemic men. Co-linearity between insulin sensitivity and adiponectin as well as insulin sensitivity and enzyme/hepatic triacylglycerol lipase activity 3.1.1.34 lipoprotein lipase medicine enzyme significantly suppresses TNF-alpha-induced gene expression, and this suppression is reversed by tetrahydrolipstatin and heparinase. In contrast, enzyme synergistically enhances IFN-gamma-induced gene expression 3.1.1.34 lipoprotein lipase medicine expression of enzyme in transgenic rabbit, no significant difference in plasma glucose clearance rate between transgenic and control animals. Transgenic animals show reduced plasma levels for free fatty acids and glucose and increased postheparin plasma enzyme activity 3.1.1.34 lipoprotein lipase medicine heparin-resistant binding of monomeric enzyme to monocytes and macrophages. Enzyme-mediated binding of low density lipoproteins to cell surfaces is enhanced in presence of dexamethasone 3.1.1.34 lipoprotein lipase medicine measurement of enzyme activity using intravenous fat tolerance test before and after oral administration of glucose. Enzyme activity decreases to 78% and 73% of control levels 2 and 4 h after glucose administration, resp. Use of intravenous fat tolerance test for studying acute changes in enzyme activity 3.1.1.34 lipoprotein lipase medicine retinoid X receptor gamma-deficient mice, increase in activity of skeletal muscle enzyme isoform, but no increase in enzyme activity in adipose and cardiac tissue. Resistance of animals to gain in fat mass in response to high-fat feeding through up-regulation of enzyme activity in skeletal muscle 3.1.1.34 lipoprotein lipase medicine the intravenous fat tolerance test is a promising approach for studying acute changes in LPL activity in circulation 3.1.1.34 lipoprotein lipase medicine excess vascular wall LpL augments vascular dysfunction in the setting of inflammation 3.1.1.34 lipoprotein lipase medicine LPL mutations represent a risk factor which contributes to the development of cardiovascular disease 3.1.1.45 carboxymethylenebutenolidase medicine enzyme serves as a bioactivating hydrolase of olmesartan medoxomil, hydrolyzing the ester bond of the pro-drug type xenobiotics 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine the gene for the beta subunit of brain enzyme isoform I is identical to a causative gene for Miller-Dieker lissencephaly 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine plasma isozyme is a target of many clinical studies in inflammatory diseases, such as asthma, sepsis, and vascular diseases 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine recombinant plasma enzyme form can prevent or attenuate pathological inflammation in a number of animal models, it may have pharmacological potential in human inflammatory disease as well, overview 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine potential use of PAF-AH alpha2 as pharmacologically active protein to promote cell survival 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine in human neither in asthma nor in sepsis the recombinant enzyme shows sufficient efficiacy. In numerous animal models of inflammation or sepsis rPAF-AH is efficient, pointing out the extreme difficulty to extrapolate from small animal models to human beings 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine PAF-AH II exerts strong neuroprotective effects against ischemic injury. This results suggest a possibility for clinical use of this enzyme in cerebral ischemia 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine the use of PAF inactivator enhances the liver’s recovery from paracetamol intoxication and attenuates the severity of experimental liver injury, providing important means of improving liver function following paracetamol intoxication 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine an altered location of PAF-AH correlates with diseases such as coronary artery disease, hypercholesterolemia, paroxysmal atrial fibrillation and chronic kidney disease 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine elevated Lp-PLA2 levels are correlated to increased risk for cardiovascular events 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine lipoprotein associated phospholipase A2 is a cardiovascular risk marker, in addition, its inhibition reduces the generation of oxidized fatty acids 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine lipoprotein-associated phospholipase A2 is a biomarker that can be used to assess the risk for cardiovascular disease and events, in addition several studies suggest that the enzyme has a pathological role in the atherosclerotic disease process 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine lipoprotein-associated phospholipase A2 is among the multiple cardiovascular biomarkers that have been associated with increased cardiovascular disease risk 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine lipoprotein-associated phospholipase A2 is an emerging risk factor for cardiovascular disease 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine plasma platelet activating factor acetylhydrolase functions as a general anti-inflammatory scavenger by reducing the levels of the signaling molecule platelet activating factor 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase medicine serum platelet-activating factor acetylhydrolase is a potential inflammatory marker in type 1 diabetes 3.1.1.51 phorbol-diester hydrolase medicine the enzyme may prevent tumor promotion by phorbol diesters in skin 3.1.1.55 acetylsalicylate deacetylase medicine higher aspirin esterase activity contributes to the lowered response of diabetic platelets to aspirin-mediated antiplatelet therapy 3.1.1.56 methylumbelliferyl-acetate deacetylase medicine enzyme should serve as a genetic marker of retinoblstome 3.1.1.58 N-acetylgalactosaminoglycan deacetylase medicine the enzyme is a potential therapeutic target for antibiofilm therapies 3.1.1.67 fatty-acyl-ethyl-ester synthase medicine enzyme is responsible for the formation of fatty acid ethyl esters, which are mediators of ethanol-induced organ damage 3.1.1.67 fatty-acyl-ethyl-ester synthase medicine patients with liver or pancreatic disease release FAEE synthase into their plasma 3.1.1.70 cetraxate benzylesterase medicine cetraxate hydrochloride is a widely used antiulcer agent industrially produced 3.1.1.72 acetylxylan esterase medicine possible application of the enzyme in antibiotic production, e.g. in the deacetylation of cephalosporin C 3.1.1.73 feruloyl esterase medicine potential application of ferulic acid as antioxidant and anti-cancer agent 3.1.1.73 feruloyl esterase medicine potential use for providing ferulic acid as precursor for the synthesis of cinnamic acid and its derivatives as anti-cancer drugs and for antimicrobial, antiviral and anti-inflammatory agents 3.1.1.73 feruloyl esterase medicine caloric-restricted diet increases abundance of Bacteroidetes and Lactobacillus fermentum CRL1446 administration increases abundance of Bifidobacterium and Lactobacillus genus in mice. Lactobacillus fermentun CRL1446 exerts a bifidogenic effect under caloric-restricted conditions by increasing intestinal feruloyl esterase activity and modulating microbiota 3.1.1.75 poly(3-hydroxybutyrate) depolymerase medicine extracellular polyhydroxybutyrate depolymerase is an excellent thermostable candidate biocatalyst for environmental, industrial, and medical applications 3.1.1.77 acyloxyacyl hydrolase medicine constitutive overexpression of AOAH in vivo hasten recovery from lipopolysaccharide exposure without interfering with the normal acute inflammatory response 3.1.1.77 acyloxyacyl hydrolase medicine alveolar macrophages increase AOAH expression upon exposure to lipopolysaccharide and Aoah+/+ mice recover more rapidly than Aoah-/- mice from acute lung injury induced by nasally instilled lipopolysaccharide or Klebsiella pneumoniae. Aoah-/- mouse lungs have more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer lasting alveolar barrier damage. The persistently bioactive lipopolysaccharide in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Alveolar macrophages that lack AOAH maintain or increase their responses to bioactive lipopolysaccharides and sustained inflammation 3.1.1.77 acyloxyacyl hydrolase medicine in a murine neurogenic cystitis model, the gene encoding acyloxyacyl hydrolase is induced in the sacral spinal cord of pseudorabies virus-infected mice. Aoah-deficient mice exhibit increased vesicomotor reflex in response to bladder distension, consistent with spontaneous bladder hypersensitivity, and increased pelvic allodynia in neurogenic cystitis and postbacterial chronic pain models. Aoah deficiency results in greater bladder pathology and tumor necrosis factor production in pseudorabies virus neurogenic cystitis 3.1.1.79 hormone-sensitive lipase medicine inhibition of hormone-sensitive lipase may improve insulin sensitivity and blood glucose handling in type 2 diabetes. The utility of enzyme inhibition in diabetes treatment will depend on the presence or absence of adverse effects of inhibition in tissues beyond the adipocyte 3.1.1.79 hormone-sensitive lipase medicine cardiac HSL can be a therapeutic target for regulating diabetic cardiomyopathy 3.1.1.79 hormone-sensitive lipase medicine useful for the prevention of atherosclerosis 3.1.1.79 hormone-sensitive lipase medicine adipose triglyceride lipase Atgl and hormone-sensitive lipase Hsl mRNA expression is time-dependently increased by fasting, along with other fatty acid metabolism genes (Pparx02, Cd36, and Aox). ATGL and HSL protein levels are induced by 239 and 322%, respectively. There is an increase in ATGL phosphorylation at the AMPK-regulated serine 406 site in the 14-3-3 binding motif, and an increase in HSL phosphorylation at serines 565 and 660 that are regulated by AMPK and PKA, respectively 3.1.1.79 hormone-sensitive lipase medicine hyperleptinemia equally suppresses the food intake in wild-type and Hsl KO mice. Leptin-mediated fat loss and glucose-lowering are significantly blunted in the absence of HSL when leptin is overexpressed by recombinant adenovirus carrying leptin. Hsl KO mice have a tendency to retain more fat than wild-type mice in the face of hyperleptinemia 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase medicine lactonase SsoPox-W263I is significantly more effective than the tested quorum sensing inhibitors at their respective concentration optimum in inhibition of the virulence of 51 clinical Pseudomonas aeruginosa isolates from diabetic foot ulcers. SsoPox may be incorporated into medical devices such as functionalised catheters and antivirulence dressings 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase medicine the pathogen Pseudomonas aeruginosa uses quorum sensing to control virulence and biofilm formation. Enzymatic disruption of quorum sensing is a promising antiinfection therapeutic strategy that does not rely on antibiotics. Aii810, a cold-adapted N-acylhomoserine lactonase can attenuate Pseudomonas aeruginosa virulence factors and biofilm formation. It is an attractive enzyme for use as a therapeutic agent against Pseudomonas aeruginosa infection 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase medicine use of purified AiiATSAWB, as hypertonic suspension for inhalation to substitute the action of inactivated host's paraoxonase in treating Pseudomonas aeruginosa infection in cystic fibrosis patients 3.1.1.84 cocaine esterase medicine a series of experiments demonstrates the capacity of the longer acting mutant, CocE T172R/G173Q, to provide a long-lasting protection against cocaine-induced convulsion and lethality, and a dose-dependent and selective inhibition the ongoing self-administration of cocaine in rats. Potential usefulness of a suitable, stable, and long-acting form of CocE as a pharmacotherapy for cocaine abuse in humans 3.1.1.84 cocaine esterase medicine because of the high catalytic proficiency of cocE, it is an attractive candidate for novel protein-based therapies for cocaine overdose 3.1.1.84 cocaine esterase medicine CocE produces robust protection and reversal of cocaine toxicity and provides in vivo evidence for the therapeutic potential of CocE in the treatment of acute cocaine toxicity. Repeated use of CocE may gradually reduce the effectiveness of CocE as a protection or rescue treatment due to the production of anti-CocE antibodies 3.1.1.84 cocaine esterase medicine enhancing cocaine metabolism by administration of cocaine esterase (CocE) is a promising treatment strategy for cocaine overdose and addiction, because CocE is the most efficient native enzyme for metabolizing the naturally occurring cocaine. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only a few min at physiological temperature. Computational-experimental effort yields a CocE variant with a 30fold increase in plasma half-life both in vitro and in vivo 3.1.1.84 cocaine esterase medicine the high catalytic proficiency, lack of observable product inhibition, and ability to hydrolyze both cocaine and cocaethylene make cocE an attractive candidate for rapid cocaine detoxification in an emergency setting 3.1.1.84 cocaine esterase medicine cocaine esterase is used to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality 3.1.1.84 cocaine esterase medicine the wild type cocaine esterase cannot be used as a pharmacotherapy for cocaine abuse because of its 13.7-min half-life at 37°C 3.1.1.89 protein phosphatase methylesterase-1 medicine no difference in methylation of substrate PP2A catalytic subunit at residue Leu-309 in nonischemic heart failure samples compared with non-failing heart, and no statistical difference in expression of enzyme in ischemic and non-ischemic human heart failure samples compared with non-failing heart tissue 3.1.1.89 protein phosphatase methylesterase-1 medicine in a xenograft model of endometrial cancer, covalent PME-1 inhibitors decrease cell proliferation and invasive growth in vitro but have no effect in vivo at the concentrations tested. Depletion of PME-1 with shRNA in an endometrial cancer xenograft model significantly reduces tumor growth 3.1.1.111 phosphatidylserine sn-1 acylhydrolase medicine blood serum PS-PLA1 level is significantly higher in systemic lupus erythematosus (SLE) patients than in healthy controls, active rheumatoid arthritis and Sjoegren's syndrome patients. Although PS-PLA1 is significantly elevated in systemic sclerosis and Sjoegren's syndrome patients compared with healthy controls, PS-PLA1 is significantly higher in untreated SLE patients than in treated SLE patients and disease control patients. A cut-off value of 18.2 ng/ml distinguishes untreated SLE from disease control, with sensitivity and specificity of 71.4% and 57.5%, respectively. PS-PLA1 is significantly correlated with SLE Disease Activity Index (SLEDAI) and immunoglobulin G (IgG), and inversely correlated with white blood cell counts, lymphocyte counts, total complement hemolytic activity (CH50), complements C3, and C4 in SLE patients overall 3.1.1.111 phosphatidylserine sn-1 acylhydrolase medicine during infection with hepatitis C virus, PLA1A plays an important role in bridging the membrane-associated NS2-E2 complex and the NS5A-associated replication complex via its interaction with E2, NS2, and NS5A 3.1.1.116 sn-1-specific diacylglycerol lipase medicine diacylglycerol lipase alpha (DAGLA) may be a key determinant in tumoral progression and might be a therapeutic target in oral squamous cell carcinomas (OSCCs) 3.1.1.118 phospholipid sn-1 acylhydrolase medicine the enzyme is a target in colorectal cancer therapy 3.1.2.6 hydroxyacylglutathione hydrolase medicine cultivation of estrogen receptor positive MCF7 and estrogen receptor neagtive BT20 human breast cancer cells in presence of tamoxifen and 17beta-estradiol. Estradiol causes up to 60% decrease in enzyme mRNA in MCF7 cells, while there are no significant changes in presence of tamoxifen. In BT20 cells, tamoxifen causes a reduction of enzyme expression up to 85%. 3.1.2.6 hydroxyacylglutathione hydrolase medicine GLX2 serves as a pro-survival factor of the p53 family and plays a critical role in the normal development and in the pathogenesis of various human diseases, including cancer, diabetes, and neurodegenerative diseases 3.1.2.22 palmitoyl[protein] hydrolase medicine in vitro enzyme assay that can be readily used for the clinical diagnosis of both infantile neuronal ceroid lipofuscinosis patients and carrier 3.1.2.22 palmitoyl[protein] hydrolase medicine palmitoyl protein thioesterase 1, expressed in the human saliva is a reliable and non-invasive source for the diagnosis of infantile neuronal ceroid lipofuscinosis 3.1.2.22 palmitoyl[protein] hydrolase medicine enzyme may be useful as an adjunct to central nervous system-directed therapies and may be used as a starting point for modifications designed to improve brain delivery 3.1.2.22 palmitoyl[protein] hydrolase medicine if patients are diagnosed with any type of mental and/or physical retardation accompanied by strong and severe visual impairment, then the case physician may consider the possibility of infantile neuronal ceroid lipofuscinosis and conduct an examination of PPT activity level 3.1.2.22 palmitoyl[protein] hydrolase medicine homozygous palmitoyl-protein thioesterase PPT1 knockout mice reproduce the known features of infantile neuronal ceroid lipofuscinosis, developing signs of motor dysfunction at 5 months of age and death by around 8 months. PPT1 knockout mice treated with purified recombinant PPT1 corresponding to 12 mg/kg or 180 U/kg for a 25 g mouse administered intravenously weekly either from birth or beginning at 8 weeks of age surprisingly well tolerate the treatment and neither anaphylaxis nor antibody formation is observed. In mice treated from birth, survival increases from 236 to 271 days and the onset of motor deterioration is similarly delayed. In mice treated beginning at 8 weeks, no increases in survival or motor performance are seen. Outside the central nervous system, substantial clearance of autofluorescent storage material in many tissues is observed. Macrophages in spleen, liver and intestine are especially markedly improved, as are acinar cells of the pancreas and tubular cells of the kidney 3.1.3.1 alkaline phosphatase medicine hypophosphatasia is caused by deficiency of activity of the tissue-nonspecific alkaline phosphatase, resulting in a defect of bone mineralization. Anchorless enzymes tagged with an acidic oligopeptide are delivered efficiently to bone and function bioactively in bone mineralization, at least in vivo. Potential advantages for use of these tagged enzymes in enzyme replacement theraphy for hypophosphatasia 3.1.3.1 alkaline phosphatase medicine the control of endogenous inhibitors, such as cysteine, that interfere with the ability of tissue nonspecific alkaline phosphatase to regulate calcium pyrophosphate dihydrate crystal formation and dissolution in joints could be a potential therapeutic option for calcium pyrophosphate dihydrate crystal deposition disease 3.1.3.1 alkaline phosphatase medicine a circulating factor causes pyrophosphate deficiency by regulating TNAP activity and vascular calcification in renal failure may result from the action of this factor 3.1.3.1 alkaline phosphatase medicine the brush-border enzyme, IAP, has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding. It is likely that the IAP silencing that occurs during starvation is a key component of the gut mucosal barrier dysfunction seen in critically ill patients 3.1.3.1 alkaline phosphatase medicine this particular V406A mutation highlights the structural importance of the crown domain with respect to the catalytic function of TNSALP 3.1.3.1 alkaline phosphatase medicine TNAP is an essential component of serum calcification activity and that its role in the shotgun mechanism is to activate the serum nucleator of apatite crystal formation 3.1.3.1 alkaline phosphatase medicine in neonatal blood plasma, soluble 5'-nucleotidase and alkaline phosphatase mediate conversion of AMP to adenosine, whereas soluble adenosine deaminase catabolizes adenosine to inosine. Newborn blood plasma demonstrates substantially higher adenosine-generating 5'-nucleotidase and alkaline phosphatase activity and lower metabolizing adenosine deaminase activity than adult plasma. Abundant alkaline phosphatase expressed on the surface of circulating neonatal neutrophils is the dominant AMPase on these cells 3.1.3.1 alkaline phosphatase medicine alkaline phosphatase is commonly used for signal amplification in immunoassays. Elevated enzyme can interfere with contemporary, enzyme-dependent immunoassays, including DxIcTnI and DxI-hCG 3.1.3.2 acid phosphatase medicine the enzyme can be used as a marker for diagnosis and therapy control of cancer of the prostate gland 3.1.3.2 acid phosphatase medicine serum TRACP5b is a good marker for serum bone resorption in predialysis chronic kidney disease patients, as it is not affected by renal dysfunction 3.1.3.2 acid phosphatase medicine serum biomarker of prostate cancers 3.1.3.3 phosphoserine phosphatase medicine enzyme inhibition enhances the anticancer efficacy of 5-fluorouracil in colorectal cancer 3.1.3.3 phosphoserine phosphatase medicine the enzyme is a prognostic biomarker in colorectal cancer and positively correlated with depth of invasion and distant metastasis 3.1.3.4 phosphatidate phosphatase medicine loss of PAP activity contributes to fatty liver dystrophy phenotype. Insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity 3.1.3.4 phosphatidate phosphatase medicine LPP1 overexpressing fibroblasts show a severe inhibition of lyso-phosphatidic acid-induced migration in a wound healing assay. Intracellular actions of LPP1 play important functions in regulating lyso-phosphatidic acid-induced fibroblast migration through phospholipase D2, also controls platelet-derived growth factor-betabeta-induced phosphatidate formation 3.1.3.4 phosphatidate phosphatase medicine LPP3 acts as an ecto-phosphatase that contributes to the equilibration between FTY720 and FTY720-P in vivo 3.1.3.5 5'-nucleotidase medicine target for a number of therapeutic drugs since increased levels of the enzyme correlate with various disease states 3.1.3.5 5'-nucleotidase medicine the enzyme is a potential subunit vaccine candidate against NTHi disease 3.1.3.5 5'-nucleotidase medicine in liver of merosin-deficient dystrophic Lama2dy mice, enzyme level is 77% elevated compared to control. Liver of dystrophic animals contains active and inactive enzyme variants 3.1.3.5 5'-nucleotidase medicine in normal and AMP deaminase-deficient skeletal muscle, there are no significant differences between different enzyme sources in the activities of ecto- and cytosolic 5'-nucleotidase isoform, and no gender-specific difference. A weak inverse correlation is found between AMP deaminase activity and cytosolic enzyme activity 3.1.3.5 5'-nucleotidase medicine in patients with acute lymphoblastic leukemia, enzyme activity decreases during 6-mercaptopurine treatment to about 50% of initial activity. After 6 weeks of treatment, there is a significant negative correlation between thio-GMP levels and enzyme activity 3.1.3.5 5'-nucleotidase medicine CD73 may facilitate the adhesion, migration, and invasion of human breast cancer cells through its enzyme activity of generating adenosine 3.1.3.5 5'-nucleotidase medicine CD73 plays a role in attenuating intestinal ischemia-reperfusion-mediated injury 3.1.3.5 5'-nucleotidase medicine CD73 plays an important role in adenosine generation in the liver, the extracellular adenosine generated by CD73 is a critical mediator of hepatic fibrosis 3.1.3.5 5'-nucleotidase medicine determination of 5'-nucleotidase activity, especially in spermatozoa, can be useful to characterize different varicocele degrees and the sperm fertility potential 3.1.3.5 5'-nucleotidase medicine ecto-5'-nucleotidase is a marker of ER (-) breast carcinoma and elevated expression correlates with invasive mesenchymal cell phenotype 3.1.3.5 5'-nucleotidase medicine hepatic ischemia/reperfusion is associated with a significant induction of ecto-5'-nucleotidase transcript and protein, use of soluble ecto-5'-nucleotidase may be a potential therapeutic for hepatic ischemia 3.1.3.5 5'-nucleotidase medicine mouse and human platelet aggregation is completely inhibited after treatment with Crotalus atrox 5'-nucleotidase (5 units/ml) via generation of increased levels of extracellular adenosine and subsequent adenosine receptor signaling 3.1.3.5 5'-nucleotidase medicine phosphohydrolysis of AMP by CD73 on graft-resident or circulating cells diminishes transendothelial leukocyte trafficking and mitigates inflammatory and immune sequelae of cardiac transplantation via the A2B adenosine receptor, CD73 deficiency increases graft expression of cytokines, chemokines, and adhesion molecules, and aggravates cardiac allograft vasculopathy and graft tolerance 3.1.3.5 5'-nucleotidase medicine the activation of apoptosis caused by the knockdown of cN-II opens a new possibility for developing strategies aimed at overcoming tumour invasiveness and resistance to chemotherapy 3.1.3.5 5'-nucleotidase medicine in neonatal blood plasma, soluble 5'-nucleotidase and alkaline phosphatase mediate conversion of AMP to adenosine, whereas soluble adenosine deaminase catabolizes adenosine to inosine. Newborn blood plasma demonstrates substantially higher adenosine-generating 5'-nucleotidase and alkaline phosphatase activity and lower metabolizing adenosine deaminase activity than adult plasma. Supplementation with AMP inhibits whereas selective pharmacologic inhibition of 5'-nucleotidase enhances Toll-like receptor-mediated tumor necrosis factor TNF-alpha production in neonatal whole blood 3.1.3.5 5'-nucleotidase medicine knocking down the enzyme in melanoma cells does not influence cell invasion but abolishes their migration on tenascin C, indicating that an enzyme-tenascin C complex is involved in cell migration and invasion and thus in the regulation of melanoma progression 3.1.3.5 5'-nucleotidase medicine transgenic mice expressing a dominant active mutant of downstream regulatory element antagonist modulator, daDREAM, show a drastic reduction of the amount of transcript of Ca2+-activated nucleotidase. Ca2+-activated nucleotidase down-regulation is also found in neuroblastoma SH-SY5Y cells stably overexpressing wild type DREAM or daDREAM, thus providing a simple cell model to investigate the protein maturation pathway. The down-regulation of CANT1 is associated with reduced protein secretion and increased degradation rates 3.1.3.5 5'-nucleotidase medicine the enzyme is a target for papillary thyroid carcinoma therapy 3.1.3.6 3'-nucleotidase medicine leishmanial 3'-nucleotidase could become a target for chemotherapeutic attack because an enzyme with similar properties has not been detected in mammalian tissues 3.1.3.6 3'-nucleotidase medicine enzyme displays higher activity in parasites cultured in low phosphate medium. Both promastigotes grown in low or high phosphate medium are capable of inducing the release of neutrophil extracellular traps from human neutrophils in a dose- and time-dependent manner. Parasites grown in low phosphate have 2.4 times higher survival rate than high phosphate promastigotes. Neutrophil extracellular traps disruption is prevented by the treatment of the parasites with inhibitor ammonium tetrathiomolybdate. Inhibition of the enzyme by 3'-AMP, 5'-GMP, or ammonium tetrathiomolybdate decreases promastigote survival upon interaction with neutrophils 3.1.3.7 3'(2'),5'-bisphosphate nucleotidase medicine enzyme as a potential target of lithium therapy 3.1.3.7 3'(2'),5'-bisphosphate nucleotidase medicine the enzyme as a potential target of lithium therapy 3.1.3.7 3'(2'),5'-bisphosphate nucleotidase medicine mice deficient for bisphosphate 3'-nucleotidase Bpnt1 do not exhibit skeletal defects but instead develop severe liver pathologies, including hypoproteinemia, hepatocellular damage, and in severe cases, frank whole body edema and death. These phenotypes are accompanied by tissue-specific elevations of the substrate 3?-phosphoadenosine 5'-phosphate, up to 50fold in liver, repressed translation, and aberrant nucleolar architecture. The phenotypes of the Bpnt1 knockout are rescued by generating a double mutant mouse deficient for both 3'-phosphoadenosine 5'-phosphate synthesis and hydrolysis, consistent with a mechanism in which 3'-phosphoadenosine 5'-phosphate accumulation is toxic to tissue function independent of sulfation 3.1.3.9 glucose-6-phosphatase medicine arthritic rats present reduced activities of the hepatic enzyme 3.1.3.9 glucose-6-phosphatase medicine deficiency in enzyme causes glycogen storage disease type 1, and s large number of enzyme mutations is identified in glycogen storage disease type 1a patients 3.1.3.9 glucose-6-phosphatase medicine deficiency in enzyme causes glycogen storage disease type 1a 3.1.3.9 glucose-6-phosphatase medicine inhibitors of liver enzyme involved in either glycogenolysis or glyconeogenesis ara potential targets for development of new drugs as alternatives to the existing treatments of type 2 diabetes 3.1.3.9 glucose-6-phosphatase medicine the enzyme catalytic unit is a therapeutic target for the treatment of type 2 diabetes, and the putative D-glucose 6-phosphate transporter component of the system has become a therapeutic target as well 3.1.3.9 glucose-6-phosphatase medicine the enzyme deficiency is responsible for glycogen storage disease type I, starvation and diabetes cause a 2-3fold increase in enzyme activity in the liver 3.1.3.9 glucose-6-phosphatase medicine crucial enzyme involved in glucose homeostasis 3.1.3.9 glucose-6-phosphatase medicine IGRP is a member of the glucose-6-phosphatase family of proteins and the major autoantigen for autoimmune type 1 diabetes. DR0301-restricted IGRP-specific T cells present in 100% of healthy subjects and type 1 diabetes subjects. DR0401-restricted IGRP-specific T cells present in ca. 80% of the subjects. Cross-reactivity between IGRP and G6Pase-alpha epitopes for DR0401-restricted T cells 3.1.3.9 glucose-6-phosphatase medicine increased hexokinase activity and decreased glucose-6-phosphatase activity in the liver of the woodchuck model of hepatitis virus-induced hepatocellular carcinoma 3.1.3.9 glucose-6-phosphatase medicine inhibitory effect of silibinin on both hepatic glucose-6-phosphatase and gluconeogenesis may be of interest in treatment of type 2 diabetes 3.1.3.9 glucose-6-phosphatase medicine islet-specific glucose-6-phosphatase catalytic subunit-related protein is recognized as a major autoantigen for autoimmune type 1 diabetes. More than 80% of subjects with either DRB1*0401 or DRB1*0301 haplotype have islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD4+ T cell responses for at least one islet-specific glucose-6-phosphatase catalytic subunit-related protein epitope. Islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific T cells from both healthy and type 1 diabetes groups produce both gamma-interferon and interleukin-10 3.1.3.9 glucose-6-phosphatase medicine exposure of newborn rats to mercury increases the hepatic alanine aminotransferase activity by fold and glucose 6-phosphatase activity by 75%. Zinc pre-exposure prevents totally and partially these mercury alterations, respectively. In vitro, HgCl2 inhibits the serum and liver alanine aminotransferase by 22% and 54%, respectively, serum and liver lactate dehydrogenase by 53% and 64%, respectively, and liver and kidney glucose 6-phosphatase from 10- to 13-day-old rats by 53% and 41%, respectively 3.1.3.9 glucose-6-phosphatase medicine glucose-6-phosphatase-alpha expression is elevated in glioblastoma when compared to normal brain. Human-derived brain tumor initiating cells utilize the enzyme to counteract glycolytic inhibition induced by 2-deoxy-D-glucose and sustain malignant progression. Down-regulation of the enzyme renders the majority of these cells unable to survive glycolytic inhibition, and promotes glycogen accumulation through the activation of glycogen synthase and inhibition of glycogen phosphorylase. Brain tumor initiating cells that survive enzyme knockdown are less aggressive, displaying reduced migration, invasion, proliferation, and increased astrocytic differentiation 3.1.3.11 fructose-bisphosphatase medicine all calcitriol doses increase cancer patient peripheral blood monocyte enzyme activity to normal levels and decrease cytidine deaminase activity to undetectable levels within 48 h, with no significant change in 24-hydrolase activity. Enzyme activity changes are not associated with hypercalcemia 3.1.3.11 fructose-bisphosphatase medicine AMP site of FBPase may represent a potential drug target for reducing the excessive glucose produced by the gluconeogenesis pathway in patients with type 2 diabetes 3.1.3.11 fructose-bisphosphatase medicine calcitriol treatment-induced increase in FBPase activity in patient peripheral blood monocytes of cancer patients are potential early and sensitive non-hypercalcemia pharmacodynamic measures of calcitriol effects 3.1.3.11 fructose-bisphosphatase medicine excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes. FBPase inhibitors may provide a future treatment option 3.1.3.11 fructose-bisphosphatase medicine fructose-1,6-bisphosphatase inhibitors for the treatment of type 2 diabetes 3.1.3.11 fructose-bisphosphatase medicine oral administration of the prodrug, MB06322, to Zucker Diabetic Fatty rats leads to dose-dependent inhibition of gluconeogenesis and endogenous glucose production and consequently to significant blood glucose reduction 3.1.3.11 fructose-bisphosphatase medicine CS-917 as an FBPase inhibitor corrects postprandial hyperglycemia as well as fasting hyperglycemia 3.1.3.11 fructose-bisphosphatase medicine FBP-1 activity in urine as an indicator of damage to renal proximal tubules in children with idiopathic nephrotic syndrome (INS) is investigated. The overload of proximal renal tubules by proteins in children with idiopathic nephrotic syndrome releases FBP-1 into urine. FBP-1 activity in urine may therefore be considered as a marker of damage to the proximal renal tubules in children with idiopathic nephrotic syndrome 3.1.3.11 fructose-bisphosphatase medicine FBPase regulates endogenous glucose production and whole body glucose homeostasis in a liver-specific transgenic model. Transgenic mouse can serve as a model for testing human FBPase inhibitor compounds with the potential to treat patients with type 2 diabetes 3.1.3.11 fructose-bisphosphatase medicine upregulation of FBPase in pancreatic islet beta-cells, as occurs in states of lipid oversupply and type 2 diabetes, contributes to insulin secretory dysfunction 3.1.3.11 fructose-bisphosphatase medicine use of enzyme inhibitors in treatment of type 2 diabetes mellitus 3.1.3.11 fructose-bisphosphatase medicine compared with negative littermates, liver-specific FBPase transgenic mice have 50% less adiposity and eat 15% less food but do not have altered energy expenditure. The reduced food consumption is associated with increased circulating leptin and cholecystokinin, elevated fatty acid oxidation, and 3-beta-hydroxybutyrate ketone levels, and reduced appetite-stimulating neuropeptides, neuropeptide Y and Agouti-related peptide 3.1.3.11 fructose-bisphosphatase medicine fructose-1,6-bisphosphatase isoform FBP1 is uniformly depleted in over six hundred clear cell renal cell carcinoma tumors examined. FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive clear cell renal cell carcinoma cell of origin, thereby inhibiting a potential Warburg effect. In addition, in von Hippel-Lindau protein-deficient clear cell renal cell carcinoma cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic activity-independent manner, by inhibiting nuclear hypoxia-inducible factor function via direct interaction with the hypoxia-inducible factor inhibitory domain 3.1.3.11 fructose-bisphosphatase medicine recombinant enzyme can specifically bind to the membrane of human hepatic stellate cell line LX-2 and stimulates proliferation and activation of LX-2, provoking upregulation of key fibrosis-related factors, such as alpha-smooth muscle actin, collagen I and collagen III. In infected rat, the enzyme is ubiquitously detected on the bile duct epithelial cells and the surface of hyperplastic adenoma close to the resident worms and the liver parenchyma, respectively 3.1.3.12 trehalose-phosphatase medicine enzyme may serve as a potential target for antifungal drugs 3.1.3.12 trehalose-phosphatase medicine the enzyme can play a key role in the biosynthesis of trehalose compounds, such as trehalose mycolates, and may represent an excellent target site for chemotherapy against tuberculosis and other mycobacterial diseases 3.1.3.12 trehalose-phosphatase medicine may be a candidate for vaccine development for the control of tuberculosis 3.1.3.12 trehalose-phosphatase medicine immunization of Mastomys coucha with Brugia (B.) malayi trehalose-6-phosphate phosphatase confers considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis 3.1.3.16 protein-serine/threonine phosphatase medicine activating PP2A to dephosphorylate Bcl2 and/or increase Bcl2/p53 binding may represent an efficient and novel approach for treatment of hematologic malignancies 3.1.3.16 protein-serine/threonine phosphatase medicine MKP-1 inhibitors may have a use in cancer therapy 3.1.3.16 protein-serine/threonine phosphatase medicine PP2A acts as a tumor suppressor 3.1.3.16 protein-serine/threonine phosphatase medicine PP2A inhibition may offer a new therapeutic approach to the treatment of diseases caused by cerebral ischemia 3.1.3.16 protein-serine/threonine phosphatase medicine PP4 regulates both apoptosis and proliferation in human cells and the level of PP4 has a strong influence on gene mutation rate, which is crucial to oncogenesis 3.1.3.16 protein-serine/threonine phosphatase medicine calcineurin is a target in treatment of myasthenia gravis, clinical factors of patients associated with responsiveness to calcineurin inhibitors, overview 3.1.3.16 protein-serine/threonine phosphatase medicine protein phosphatase inhibitor-1-based therapeutic interventions may ameliorate cardiac dysfunction and remodeling in the failing heart, mechanism and mode of action, overview 3.1.3.22 mannitol-1-phosphatase medicine lack of mannitol metabolism in higher eukaryotes 3.1.3.25 inositol-phosphate phosphatase medicine a homozygous variant consisting of a 5-bp duplication leads to a frameshift and a premature stop codon (p.Ser165Trpfs*10) that cosegregates with the disease of intellectual disability in 26 genotyped family members 3.1.3.32 polynucleotide 3'-phosphatase medicine human Machado-Joseph disease patients' brain samples show a significant accumulation of DNA strand breaks. PNKP stably associates with ataxin-3, a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3, i.e. Machado-Joseph disease 3.1.3.36 phosphoinositide 5-phosphatase medicine examination of patients with Lowe oculocerebrorenal syndrome, MIM 309000, and their families for mutations in enzyme gene 3.1.3.36 phosphoinositide 5-phosphatase medicine a SHIP2-antisense oligonucleotide therapy can improve the decrease in insulin-induced glucose disposal observed after high-fat feeding. This effect can be retraced on a molecular level by an improvement in insulin-induced Akt phosphorylation 3.1.3.36 phosphoinositide 5-phosphatase medicine inhibition of hypothalamic 5ptase IV expression by this antisense approach results in reduced daily food intake and body weight loss. 5ptase IV is a powerful regulator of signaling through PI3-kinase in hypothalamus and may become an interesting target for therapeutics of obesity and related disorders 3.1.3.36 phosphoinositide 5-phosphatase medicine inhibition of SHIP2 for the prevention and/or treatment of type 2 diabetes 3.1.3.36 phosphoinositide 5-phosphatase medicine organization of the actin cytoskeleton via D-myo-phosphatidylinositol 4,5-bisphosphate is involved in the regulation of hepatocyte differentiation by the extracellular matrix 3.1.3.36 phosphoinositide 5-phosphatase medicine SHIP2 plays an important role in insulin-dependent signaling pathways controlling glucose and lipid, metabolsim in vivo. A fine tuning of SHIP2 expression/activation in target organs is likely to be beneficial to correct metabolic dysfunctions in pathological conditions such as insulin resistance diabetes melitus and obesity 3.1.3.43 [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase medicine overview, role of enzyme in diabetes and starvation 3.1.3.43 [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase medicine starvation and streptozotocin-induced diabetes cause decrease in isoform PDP2 activity and protein amount in heart and kidney, refeeding and insulin treatment resp. restore 3.1.3.43 [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase medicine pyruvate dehydrogenase phosphatase catalytic subunit PDP2 expression is decreased in memory Th17 T-cells from patients with systemic lupus erythematosus and forced expression of PDP2 in CD4+ T-cells from patients with systemic lupus erythematosus suppresses Th17 differentiation 3.1.3.43 [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase medicine pyruvate dehydrogenase phosphatase regulatory subunit expression at baseline and post-training are both correlated with whole body insulin sensitivity 3.1.3.43 [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase medicine pyruvate dehydrogenase subunit PDHA1 and pyruvate dehydrogenase phosphatase PDP1 are frequently amplified and overexpressed at both the gene and protein levels in prostate tumors 3.1.3.44 [acetyl-CoA carboxylase]-phosphatase medicine in pancreatic islets derived from diabetic rats, marked reduction of magnesium- and glutamate-sensitive enzyme activity 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase medicine the enzyme is a target for cancer chemotherapy 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase medicine enzyme regulation by hormones, overview 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase medicine overexpression of enzyme results in increase of glucokinase activity, interaction of enzyme with glucokinase at concentrations of glucose physiologically relevant for glucokinase activation, possible site for intervention in type 2 diabetes treatment 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase medicine PFKFB3 is constitutively expressed in human leukemias and solid tumor cells, inhibitors could act as antineoplastic agents 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase medicine pharmacological disruption of the PFKFB4 kinase domain may have clinical utility for the treatment of human cancers 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase medicine in colonic and bladder cancer cells, additive growth inhibitory effects are seen with phenformin and with an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3. The increased acidification of the culture medium and glucose uptake caused by phenformin is blocked by combined treatment with PFKFB3 inhibitors 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase medicine tumor suppressor p53 regulates the expression of PFKFB4 and p53-deficient cancer cells are highly dependent on the function of the enzyme. Depletion of PFKFB4 from p53-deficient cancer cells increases levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 is also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Depletion of PFKFB4-attenuated cellular biosynthetic activity and results in the accumulation of reactive oxygen species and cell death in the absence of p53. Silencing of PFKFB4-induces apoptosis in p53-deficient cancer cells in vivo and interferes with tumor growth 3.1.3.48 protein-tyrosine-phosphatase medicine overview on implications with human diseases and as therapeutic targets 3.1.3.48 protein-tyrosine-phosphatase medicine PTPalpha and PTP1B responsible for counteraction of insulin signaling, LAR and PTPalpha may act upon cell surface insulin receptors 3.1.3.48 protein-tyrosine-phosphatase medicine role of enzyme in angiogenesis and signaling, overexpression of enzyme decreases proliferation by 60% in human umbilical vein endothelial cells but not in smooth muscle cells or fibroblasts 3.1.3.48 protein-tyrosine-phosphatase medicine homozygous enzyme-deficient animal, hyperresponsive to insulin and leptin and resistant to diet-induced obesity. Liver-specific re-expression of PTP1B leads to marked attenuation of their enhanced insulin sensitivity in correlation with decreased insulin-stimulated tyrosyl phosphorylation of the insulin receptor and insulin receptor substrate 2-associated phosphatidylinositide 3-kinase activity. Preferential dephosphorylation of Y1162/1163 of insulin receptor 3.1.3.48 protein-tyrosine-phosphatase medicine transgenic mice overexpressing enzyme in muscle at levels similar to those observed in insulin-resistant humans. Insulin-stimulated insulin receptor tyrosyl phosphorylation and phosphatidylinositol 3'-kinase activity are impaired by 35% and 40-60% resp. Whole body glucose disposal and muscle glucose uptake are decreased by 40-50% 3.1.3.48 protein-tyrosine-phosphatase medicine PTP-1B antagonizes insulin signaling and is a potential therapeutic target for insulin resistance associated with obesity and type 2 diabetes 3.1.3.48 protein-tyrosine-phosphatase medicine the PTPB1 inhibitor JTT-551 improves glucose metabolism by enhancement of insulin signalling and can be useful in the treatment of type 2 diabetes mellitus 3.1.3.53 [myosin-light-chain] phosphatase medicine Ca2+-desensitizing hypoxic relaxation requires dephosphorylation of myosin phosphatase regulatory subunit 3.1.3.53 [myosin-light-chain] phosphatase medicine in response to portal hypertension, abundance of MYPT 1 subunit is significantly reduced and switches to the leucine-zipper positive isoform 3.1.3.53 [myosin-light-chain] phosphatase medicine upon induction of congestive heart failure, left ventricular function is reduced to about 30% with concomitant decrease in sensitivity to 8-Br-+cGMP and expression of leucine-zipper positive isoform of MYPT 1 subunit 3.1.3.53 [myosin-light-chain] phosphatase medicine DMBS maintains epithelial integrity, loss of DMBS causes cell shape changes, loss of localization of the apical markers cadherin and increased accumulations of phospho-myosin regulatory light chain and F-actin, DMBS regulates the reorganization of cytoskeleton through down-regulation of myosin II, DMBS fits many of the criteria for a potential neoplastic type tumor suppressor gene 3.1.3.53 [myosin-light-chain] phosphatase medicine myosin light chain phosphatase pathway is critical in regulating in vivo myofibroblast differentiation during wound healing and fibrocontractive diseases 3.1.3.53 [myosin-light-chain] phosphatase medicine MYPT1 is downregulated and switches to the splice variant isoform that codes for the COOH-terminal leucine zipper motif in the hypertension of pregnancy model. These changes in MP expression are prevented by treatment with the antihypertensive medicine hydralazine. Early and effective treatment of hypertension during pregnancy may be able to reverse some of the adverse effects on uterine perfusion and fetal development in this disease 3.1.3.53 [myosin-light-chain] phosphatase medicine congestive heart failure is associated with a decrease in the COOH-terminus leucine zipper and the myosin targeting subunit of MLPC expression 3.1.3.53 [myosin-light-chain] phosphatase medicine the expression of isovariants PPP1R12A, PPP1R12BLZ+, PPP1R16A and PPP1R16B mRNA is reduced in late pregnancy (not-in-labor) relative to non-pregnancy. PPP1R12ALZ+ and PPP1R12ALZ- mRNA levels are similar in the non-pregnant and pregnant not-in-labor groups. There is a further reduction in the uterine expression of PPP1R12ALZ+, PPP1R12CLZ+ and PPP1R12ALZ- mRNA with labor relative to the pregnant not-in-labor group. PPP1R12A, PPP1R12BLZ+, PPP1R16A and PPP1R16B mRNA levels are invariant between the not in labor and in-labor groups 3.1.3.55 caldesmon-phosphatase medicine as an immunomarker for smooth muscle neoplasms, caldesmon has a sensitivity of 100% (31 out of 31 smooth muscle neoplasms show positivity) and a specificity of 80% (89 out of 111 non-smooth muscle neoplasms do not show positivity) 3.1.3.56 inositol-polyphosphate 5-phosphatase medicine potential target for drugs 3.1.3.56 inositol-polyphosphate 5-phosphatase medicine depletion of the inositol polyphosphate 5-phosphatase PIPP (INPP5J) increases breast cancer cell transformation, but reduces cell migration and invasion. PIPP ablation accelerates oncogene-driven breast cancer tumor growth in vivo, but reduces metastasis by regulating AKT1-dependent tumor cell migration. PIPP mRNA expression is reduced in human ER-negative breast cancers associated with reduced long-term outcome 3.1.3.56 inositol-polyphosphate 5-phosphatase medicine genetic variation in INPP5A appears to have a role in susceptibility to arsenic toxicity. A single nucleotide polymorphism in the INPP5A gene (rs1133400) shows a significant gene-environment interaction with water arsenic on skin lesion risk 3.1.3.56 inositol-polyphosphate 5-phosphatase medicine in individuals exhibiting congenital muscular dystrophy, early-onset cataracts, and mild intellectual disability but normal cranial magnetic resonance imaging, bi-allelic mutations in isoform INPP5K are found. Mutations impair phosphatase activity toward phosphatidylinositol (4,5)-bisphosphate or alter the subcellular localization of INPP5K 3.1.3.57 inositol-1,4-bisphosphate 1-phosphatase medicine involvement of enzyme in hypertrophic signaling pathways in ventricular myocytes 3.1.3.64 phosphatidylinositol-3-phosphatase medicine Charcot-Marie-Tooth type 4B1 animal model created by Mtmr2 null mice 3.1.3.64 phosphatidylinositol-3-phosphatase medicine impairment of hJUMPY function is implicated in some cases of autosomal centronuclear myopathy (CNM) 3.1.3.64 phosphatidylinositol-3-phosphatase medicine loss of either MTMR2 or MTMR13 specifically causes Charcot-Marie-Tooth type 4B1 and B2 (CMT4B1 and CMT4B2) neuropathies, respectively 3.1.3.64 phosphatidylinositol-3-phosphatase medicine MTm1 deficient mice serve as an animal model for X-linked myotubular myopathy 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine calpain-mediated inhibition of enzyme is involved in the phosphatidylinositol 3,4-bisphosphate accumulation in thrombin-stimulated platelets 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine INPP4A is identified as a novel asthma candidate gene 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine physiological role of PI-4-phosphatase II in the proerythroblast by controlling erythropoetin-resonsiveness through a negative regualtion of the PI3K/Akt pathway is demonstrated 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine decreased expression of INPP4B correlates with poor outcome in both breast cancer and ovarian cancer patients, whereby the PI3K pathway is likely to play a major role in driving this subset of cancers. Loss of INPP4B expression may provide a marker for selecting patients who will respond to PI3K drugs 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine colorectal carcinoma cell lines HCT-116, SW-620, DLD-1, and WiDr express significantly lower levels of INPP4B protein than the normal colonic epithelial cell lines CCD-841 CoTr and FHC. INPP4B mRNA expression in the colorectal carcinoma cell lines is significantly lower than in the normal colonic epithelial cells. Normal colonic mucosa displays uniform and strong-to-moderate INPP4B immunoreactivity, whereas 60.7% and 76.5% of the primary and metastatic colorectal carcinoma tissue samples exhibit reduced INPP4B expression, respectively 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine in acute myeloid leukemia, isoform IPNPP4B is significantly overexpressed, in association with reduced responses to chemotherapy, early relapse, and poor overall survival, independent of other risk factors. Ectopic overexpression of INPP4B confers leukemic resistance to cytosine arabinoside, daunorubicin, and etoposide. Expression of phosphatase inert variant C842A fails to abrogate resistance of acute myeloid leukemiacells to chemotherapy in vitro or in vivo. Targeted suppression of endogenously overexpressed INPP4B by RNAi sensitizes acute myeloid leukemia cell lines and primary acute myeloid leukemia to chemotherapy 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine in prostate cancer cell lines INPP4B regulates androgen recetor transcriptional activity and the oncogenic signaling pathways Akt and PKC. In prostate cancer patient cohorts, a positive correlation between INPP4B expression and both androgen receptor mRNA levels and transcriptional output exists 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine in Triple-negative breast cancer cells, which lack expression of estrogen receptor, progesterone receptor, and amplification of HER2/Neu, silencing isoform INPP4B decreases basal phospho-Akt (pAkt) and cellular proliferation, and in most cases sensitizes cells to phosphatidylinositol-3-kinase PI3K-alpha and PI3K-beta isoform-specific inhibitors. Overexpression of INPP4B desensitizes cells to PI3K inhibitors in a phosphatase activity-dependent manner 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine inositol polyphosphate 4-phosphatase type II is a direct target of microRNA-590-3p. Enforced expression of microRNA-590-3p leads to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines. Overexpression of inositol polyphosphate 4-phosphatase type II can reduce microRNA-590-3p-induced cell proliferation and invasion as well as tumor growth, and decrease microRNA-590-3p-mediated upregulation of cyclin D1 and downregulation of p21 expression in prostate cancer cells 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine INPP4B is low expressed in osteosarcoma tissues and in osteosarcoma cell lines. INPP4B overexpression significantly decreases cell viability and induces apoptosis in SaOS2 and U2OS cells. Combination of INPP4B overexpression and poly-ADP ribose polymerase inhibitor rucaparib declines Myc, cyclin E1 and cyclin D1 expressions, enhances Bad, Bax, and cleaves caspase3 expressions, and blocks PI3K/AKT signal pathway in SaOS2 and U2OS cells. Combination of INPP4B overexpression and rucaparib inhibits tumor formation in vivo 3.1.3.66 phosphatidylinositol-3,4-bisphosphate 4-phosphatase medicine INPP4B manipulates cadherin switch in certain pancreatic ductal adenocarcinoma cell lines through a phosphorylated AKT-inactivation. The knockdown of INPP4B in AsPC-1 cells results in a more invasive phenotype, and overexpression of INPP4B in PANC-1 leads to partial reversion of mesenchymal status and impediment of in vitro invasion but not migration. E-cadherin is enriched in the early and sorting endosomes containing INPP4B which enables its recycling rather than degradation. INPP4B acts as an tumor suppressor in pancreatic ductal adenocarcinomas which attenuates AKT activation and participates in preservation of E-cadherin in endocytic pool and cellular membrane 3.1.3.67 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase medicine PTEN plays an important role in insulin-dependent signaling pathways controlling glucose and lipid metabolsim in vivo. A fine tuning of PTEN expression/activation in target organs is likely to be beneficial to correct metabolic dysfunctions in pathological conditions such as insulin resistance diabetes melitus and obesity 3.1.3.67 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase medicine results demonstrate an important role of PTEN in long term depression and suggest that alterations in PTEN can have an impact on learning and memory process 3.1.3.67 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase medicine paeonol effectively enhances the sensitivity of ovarian cancer cells to radiation by significantly altering regulation of the proteins of the PI3K/Akt pathway, in addition to downregulating VEGF and HIF-1alpha 3.1.3.75 phosphoethanolamine/phosphocholine phosphatase medicine may have implications for the diagnosis of hypophosphatasia and treatment of bone mineralization abnormalities such as osteomalacia and pathological soft-tissue ossification, a process clinically significant in atheroscleosis and heart failure 3.1.3.75 phosphoethanolamine/phosphocholine phosphatase medicine PHOSPHO1 plays a role in the initiation of matrix mineralization 3.1.3.75 phosphoethanolamine/phosphocholine phosphatase medicine role in the early stages of matrix mineralization 3.1.3.77 acireductone synthase medicine compared with normal brain tissues, the level of Enoph1 is markedly increased in glioma tissues. The glioma pathological grade is positively associated with the expression level of Enoph1. Knockdown of Enoph1 expression with siRNA markedly reduces cell proliferation, and significantly decreases cell migration. Knockdown of Enoph1 promotes its downstream protein, acireductone dioxygenase 1, to shift from the nucleus to the cytoplasm of U251 glioma cells, while membrane type 1-matrix metalloproteinase expression is significantly downregulated compared with the control group 3.1.3.78 phosphatidylinositol-4,5-bisphosphate 4-phosphatase medicine involvement of phosphatidylinositol 4,5-bisphosphate phosphatase in Salmonella-induced diarrhea is explored 3.1.3.78 phosphatidylinositol-4,5-bisphosphate 4-phosphatase medicine type I 4-phosphatase regulates nuclear phosphatidylinositol 5-phosphate levels, which in turn mediate p53-dependent apoptosis through interaction with inhibitor of growth protein-2 in response to genotoxic stress 3.1.3.82 D-glycero-beta-D-manno-heptose 1,7-bisphosphate 7-phosphatase medicine the enzyme is a target for combatting Gram-negative bacterial infection 3.1.3.86 phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase medicine SHIP-1 is a risk marker for acute ischemic stroke 3.1.3.95 phosphatidylinositol-3,5-bisphosphate 3-phosphatase medicine loss of myotubularin-related protein MTMR13 function in Charcot-Marie-Tooth disease type 4B patients may lead to alterations in isoform MTMR2 function and subsequent alterations in 3-phosphoinositide signaling 3.1.3.95 phosphatidylinositol-3,5-bisphosphate 3-phosphatase medicine mutations in the MTM1 gene are associated with theX-linked myotubular myopathy 3.1.3.106 2-lysophosphatidate phosphatase medicine highly expressed in normal fallopian tube epithelium, ACP6 expression is significantly reduced in ovarian cancer tumors and early in situ lesions. Downregulation of ACP6 in ovarian cancer cells is necessary and sufficient to support high-grade serous ovarian cancer proliferation, adhesion, migration, and invasion 3.1.4.1 phosphodiesterase I medicine ectonucleotide pyrophospatase/phosphodiesterase and adenosine deaminase in the platelets and ectonucleotide pyrophospatase/phosphodiesterasein the serum are decreased in patients with uterine cervix neoplasia treated by conization or radiotherapy in relation to the control and non-treated group 3.1.4.1 phosphodiesterase I medicine single nucleotide polymorphisms of the ENPP1 gene are associated with type 2 diabetic end-stage renal disease in African-Americans 3.1.4.1 phosphodiesterase I medicine variants on the nucleotide pyrophosphatase/phosphodiesterase-1 gene are associated with obesity and insulin resistance, the ENPP1 rs997509T allele can predispose obese children to metabolic syndrome and mpaired glucose tolerance and this variant may drive the association between the ENPP1 121Q allele and insulin resistance 3.1.4.1 phosphodiesterase I medicine the enzyme is a promising and attractive target for cancer treatment 3.1.4.1 phosphodiesterase I medicine the enzyme is a target for anticancer therapy 3.1.4.2 glycerophosphocholine phosphodiesterase medicine enzyme inhibition represents a targeting strategy in the treatment of breast cancer 3.1.4.3 phospholipase C medicine inactivation of thromboplastin, potential therapeutic value in cases of intravascular coagulation 3.1.4.3 phospholipase C medicine chemokine CCL2, i.e. MCP-1, enhances HIV-1 replication. Enzyme isoform PC-PLC is activated by HIV-1 R5 gp120 interaction with CCR5 and is required for NF-kB-mediated CCL2 production triggered by R5 gp120 in monocyte-derived macrophages 3.1.4.3 phospholipase C medicine isoform PC-PLC plays a critical role in the silica-associated inflammatory response of alveolar macrophage 3.1.4.3 phospholipase C medicine tumor suppressor PTEN is involved in both phospholipase C and phospholipase D activation pathways. Pathogenesis of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome has further aspects beyond activating the PI3K pathway 3.1.4.4 phospholipase D medicine the extracellular signal-regulated kinase/PLD2 coupling may provide potential pharmacological targets to control PLD-associated cellular dysfunctions 3.1.4.4 phospholipase D medicine enzyme activity in thymocytes is negatively correlated to their proliferative response fatty acids 3.1.4.4 phospholipase D medicine enzyme augments gonococcus invasion of cervical epithelia by interacting with Akt kinase in a hosphatidylinositol-(3,4,5)-trisphosphate-independent manner, resulting in subversion of normal cervical cell signaling 3.1.4.4 phospholipase D medicine enzyme is activated downstream of ERK1/2 kinases upon chemokine receptor CCR5 activation and plays a major role in promoting HIV-1 LTR transactivation and virus replication 3.1.4.4 phospholipase D medicine overexpression of enzyme isozymes in SNU 4784 cancer cell results in inhibition of taxotere-induced apoptotic cell death, accompanied by up-regulated expression of Bcl-2 and inhibited taxotere-induced activation of procaspase 3. Selective inhibition of phospholipase by specific siRNa leads to exacerbation of taxotere-induced apoptosis 3.1.4.4 phospholipase D medicine overexpression of tumor suppressor PTEN results in 30% increase in basal enzyme activity. Tumor suppressor PTEN is involved in both phospholipase C and phospholipase D activation pathways, therefore pathogenesis of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome has further aspects beyond activating the PI3K pathway 3.1.4.4 phospholipase D medicine suppression of TGFbeta signaling in MDA-MB-231 breast cancer cells is due to elevated acivity of phospholipase D2 and mediated by mTOR, i.e. Mammalian target of rapamycin, and by MAP kinase 3.1.4.4 phospholipase D medicine design of a safe and simple amphiphilic prodrug delivery system, based on the elevated expression of phospholipase D in cancer cells. The method utilizes the transphosphatidylation ability of bacterial PLD on alcohol groups and the hydrolysis activity of overexpressed PLD on phospholipids in cancer cells. Phosphatidyl-doxorubicin is synthesized by bacterial PLD. The prodrug can be selfassembled to nanoparticles with uniform size and doxorubicin can be selectively released in cancer cells triggered by the locally overexpressed PLD. The method can significantly prolong the half-life of doxorubicin in the tumors and decrease the distribution in heart and kidney 3.1.4.11 phosphoinositide phospholipase C medicine increased expression of R257H mutant PLC delta1 in patients with coronary spastic angina, enhanced PLC delta1 activity, but not beta or gamma, in patients suffering from essential hypertension, PLC delta2 plays a role in neoplastic evolution and could be a predictive marker of cancer transformation 3.1.4.11 phosphoinositide phospholipase C medicine PLC-gamma1 may permit the progression of some tumors 3.1.4.11 phosphoinositide phospholipase C medicine PLC-beta2 may constitute a molecular marker of breast tumor cells able to monitor the progression to invasive cancers and a target for novel therapeutic breast cancer strategies 3.1.4.11 phosphoinositide phospholipase C medicine the leptospiral enzyme is a biomarker candidate for the serodiagnosis and pathogenesis of leptospirosis 3.1.4.12 sphingomyelin phosphodiesterase medicine inhibiting or stopping N-SMase activity is an important strategy to prevent neuron death from ischemia 3.1.4.12 sphingomyelin phosphodiesterase medicine the sphingomyelin cycle is a potential therapeutic target for the prevention of wear debris induced osteolysis 3.1.4.12 sphingomyelin phosphodiesterase medicine activation of acid sphingomyelinase is necessary and sufficient for microparticle release from glial cells and define key molecular effectors of microparticle formation and IL-1beta release, thus, opening new strategies for the treatment of neuroinflammatory diseases 3.1.4.12 sphingomyelin phosphodiesterase medicine ASM plays a complex and varied role in brain development, as well as in the pathogenesis of several common neurological diseases, ASM is particularly intriguing as an antioncogenic drug, ASM is associated with the type A Niemann-Pick disease, atherosclerosis, Wilson disease, hepatic autoimmune disease, alcohol-induced liver disease, cerebral ischemia, emphysema, cystic fibrosis, and cancer 3.1.4.12 sphingomyelin phosphodiesterase medicine intrarectal instillation of recombinant human Alk-SMase once daily for 1 week significantly reduces the inflammation score and protects the colonic epithelium from inflammatory destruction in a rat colitis model 3.1.4.12 sphingomyelin phosphodiesterase medicine Niemann-Pick A disease is a lysosomal storage disorder caused by a deficiency in acid sphingomyelinase activity, repeated intracerebroventricular infusions of recombinant human acid sphingomyelinase reduce the aberrant lysosomal accumulation of cholesterol and are effective at improving the disease phenotype in the acid sphingomyelinase-knockout mouse as indicated by a partial alleviation of the motor abnormalities 3.1.4.12 sphingomyelin phosphodiesterase medicine recombinant human ASM has little or no effect on the growth of tumor cells at pH 7.4 even in combination with irradiation, however when the culture media is acidified to pH 6.5 to mimic the acidic microenvironment of solid tumors, ASM-mediated cell death is markedly enhanced when combined with irradiation 3.1.4.12 sphingomyelin phosphodiesterase medicine systemic administration of recombinant acid sphingomyelinase (rhASM) into ASM deficient mice by intranasal instillation results in hydrolysis of the abnormal storage of sphingomyelin in lysosomes of the liver, spleen and lung, pulmonary administration of rhASM may represent an alternative route of delivery to address the visceral pathology associated with ASM deficiency 3.1.4.12 sphingomyelin phosphodiesterase medicine acid sphingomyelinase activity and sphingomyelin presence are necessary for efficient infection of cells by ebolavirus, inhibition of the enzyme might be a threpeutic way 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine PDE11 inhibition has impacts on sperm quality. Reasonable caution is indicated for patients taking the prescribed dosages of tadalafil, a PDE5 inhibitor which could crossreact with human PDE11A splicing variants 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine PDE11 inhibition has impacts on sperm quality. Reasonable caution should by suggested in patients taking the prescribed dosages of tadalafil, a PDE5 inhibitor which could crossreact with human PDE11A splicing variants 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine enzyme inhibitors can reverse the time-dependent forgetting in the object recognition test. The efficacy of the different inhibitors is dependent on the time point of administration after acquisition. Support for a role for cGMP in early stages of memory formation and for cAMP in the late stages of memory formation 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine reactive oxygen-species mediated lung inflammation may be mediated at least in part by calcium and elevated enzyme activity associated with decreased caMP in both macorphages and epithelial cells 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, attributable to the relative amounts of enzyme isoforms PDE2A and PDE3A in endothelial cells 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine genetic disruption or pharmacological inhibition of PDE10A reverses behavioral abnormalities associated with subcortical hyperdopaminergia 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine inhibition of PDE10A represents an important new target for the treatment of schizophrenia and related disorders of basal ganglia function 3.1.4.17 3',5'-cyclic-nucleotide phosphodiesterase medicine PDE2 inhibition improved short-termobject recognition performance after an acute tryptophan depletion induced deficit 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine phosphodiesterase 5 inhibition is a therapeutic strategy for erectile dysfunction 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine potential role for the PDE5 inhibitor sildenafil as an adjunct for the treatment of preterm labor 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine the enzyme is suggested to be a potential target for the treatment of malaria 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine use of PDE5 inhibitors in the trteatment of erectile dysfunction and pulmonary hypertension 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine by blocking isoform PDE5, vardenafil may be used in bladder dysfunction by ameliorating irritative lower urinary tract symptoms 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine enzyme inhibitors can reverse the time-dependent forgetting in the object recognition test. The efficacy of the different inhibitors is dependent on the time point of administration after acquisition. Support for a role for cGMP in early stages of memory formation and for cAMP in the late stages of memory formation 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine enzyme isoform PDE5 mRNA and protein are markedly upregulated in hypertrophied human right ventricle 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine enzyme isoform PDE5 mRNA and protein are markedly upregulated in hypertrophied myocardium. Inhibition by sildenafil or MY-5445 significantly increases contractility in hypertrophied myocardium, but not in normal. Protein kinase G is suppressed in hypertrophied myocardium 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine increased intrarenal isoform PDE5 level mediates the blunted natriuretic response to atrial natriuretic peptide during pregnancy and may contribute to the physiological volume expansion. Atrial natriuretic peptide causes a fall in mean arterial pressure. Intrarenal sildenafil increases the natriuretic response and the rise in fractional excretion of sodium in pregnant rats to the virgin value. 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine 5 mg/kg/day sildenafil citrate administration to rats with acetic acid-induced colitis prevents lipid peroxidation, oxidant generation, cytokine production and neutrophil accumulation 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine application of 10 mg vardenafil inhibits sphincter of Oddi motility in patients with suspected sphincter of Oddi dysfunction and reduces basal sphincter of Oddi pressure, without significant adverse effects 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine chronic treatment with a high dose (80 mg/kg) of vardenafil protects the rat bladder from bladder outlet obstruction-induced contractile dysfunction to carbachol 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine estrogen withdrawal, but not testosterone withdrawal, is a risk factor for PDE5 inhibitor-induced flushing 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine impaired vascular cGMP signalling contributes to the development of diabetic vascular and cardiac dysfunction, which can be prevented by chronic phosphodiesterase-5 inhibition 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine in end-stage congestive cardiac failure, intravenous sildenafil causes reduction in systemic and pulmonary vascular resistance, sildenafil has a suitable hemodynamic profile for testing of reversibility of secondary pulmonary hypertension in congestive cardiac failure 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine inhibition of PDE5 decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine inhibition of PDE5 with T0156 prevents the reduced production of cyclic GMP and relaxation in tolerant aortas in response to nitroglycerin 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine men using PDE5 inhibitors are approximately 4times more likely to report condom breakage than men not using PDE5 inhibitors 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine oral PDE-5 inhibitors are the current first-line treatment for erectile dysfunction 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine oral PDE-5 inhibitors improve erectile functioning. PDE-5 inhibitors are more effective than placebo in improving sexual intercourse success. The proportion of men with improved erections is significantly greater among those treated with PDE-5 inhibitors than with placebo 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine pathological changes in ureteropelvic junction obstruction can be influenced by PDE5 inhibitors 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine PDE5 inhibition is an efficacious option for the treatment of erectile dysfunction 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine PDE5 inhibition suppresses RhoA/Rho-associated kinase-mediated MMP-2 production by pulmonary artery smooth muscle cells, which may contribute to the regulation of pulmonary vascular remodelling. Thus, PDE5 inhibition may benefit patients with pulmonary hypertension through multiple mechanisms of action 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine PDE5 inhibitor sildenafil prevents indomethacin-induced small-intestinal ulceration in rats, via a nitric oxide/cGMP-dependent mechanism 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine PDE5 inhibitors show a potential antifibrotic affect against Peyronie's disease plaque in animal models 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine PDE5-inhibitors can improve both lower urinary tract symptoms and erectile dysfunction by targeting various points in the different pathways by increasing cGMP or blocking the effects of norepinephrine and other secondary messengers 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine peripheral administration of the cGMP-PDE inhibitor zaprinast dramatically alters the inflammatory response of astrocytes and microglia/macrophages to focal brain injury, decreases oxidative stress and neurodegeneration, and increases angiogenesis and vascular endothelial growth factor expression 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine pharmacological inhibition of PDE5 by vardenafil significantly enhances the endothelium-dependent vasorelaxation in aortic rings rats exposed to peroxynitrite. Acute PDE5-inhibition is advantageous in the treatment of endothelial dysfunction induced by disturbed nitric oxide-cGMP pathway due to nitro-oxidative stress 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine phosphodiesterase type 5 inhibitors are considered first-line therapies for men with erectile dysfunction 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine phosphodiesterase-5 inhibitors promote nitric oxide activity and enhance vasodilation. Infusion of PDE5 inhibitor sildenafil alone reduceds systemic and pulmonary artery blood pressure, while maintaining cardiac output and oxygen delivery. Combined hemoglobin-based oxygen carriers and sildenafil infusion results in stable systemic blood pressure, cardiac output, and oxygen delivery 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine the combined pharmacotherapy with impaza and PDE5 inhibitors helps to prevent and/or considerably reduces the risk of posttraumatic erectile dysfunction in men with traumas and strictures of the urethra 3.1.4.35 3',5'-cyclic-GMP phosphodiesterase medicine treatment of mice with vardenafil (5 mg/kg daily for 4 weeks) decreases high density lipoprotein serum levels and the number of antral follicles as well as induces lesser lipid content in luteal cells 3.1.4.37 2',3'-cyclic-nucleotide 3'-phosphodiesterase medicine cells derived from transplanted marrow stromal cells can transform into cells resembling Schwann cells, whereas host-derived glial cells participate in formation of perineural compartments. The chemotactic migration of both host-derived and transplantation-derived cells bearing the enzyme in their plasma membrane may be attracted by stromal derived factor-1alpha produced locally 3.1.4.37 2',3'-cyclic-nucleotide 3'-phosphodiesterase medicine no association between genetic variation in the CNP enzyme gene and schizophrenia in the Han Chinese population 3.1.4.37 2',3'-cyclic-nucleotide 3'-phosphodiesterase medicine 2',3'-cyclic nucleotide 3'-phosphodiesterase single nucleotide polymorphism rs2070106 is potentially associated with schizophrenia 3.1.4.37 2',3'-cyclic-nucleotide 3'-phosphodiesterase medicine CNPase is associated with multiple sclerosis 3.1.4.37 2',3'-cyclic-nucleotide 3'-phosphodiesterase medicine the rs207016 genotype of CNP is not likely to contribute to the coordinated down-regulation of oligodendrococyte-related genes in schizophrenia 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine promotes tumor cell motility, experimental metastasis, and angiogenesis 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine stimulates cell proliferation, cell motility and angiogenesis 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine survival factor, preventing serum-deprivation induced apoptosis in fibroblasts through extracellular activation of LPA signaling pathway 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine tumor cell motility-stimulating factor 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine tumor cell motility-stimulating factor, implicated in the progression of tumor 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine tumor cell motility-stimulating factor, represents a potential target for cancer therapy 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine inhibitors of autotaxin can be used as a therapy for the treatment of cancer 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine the autotaxin-lysophosphatidic acid receptor axis is a rich therapeutic target in cancer 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine autotaxin is an attractive target for the anticancer therapeutics that inhibit angiogenesis, invasion, and migration 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine is an attractive target for cancer therapy 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase medicine autotaxin gene expression is significantly higher in neoplastic endometrium compared with normal tissue. The expression of autotaxin is significantly elevated in type I endometrial cancer compared to type II, in premenopausal women and in patients affected either by obesity or diabetes 3.1.4.41 sphingomyelin phosphodiesterase D medicine SMaseD induces apoptosis in human keratinocytes, which is associated with an increased expression of metalloproteinase-2 and -9. The use of metalloproteinase inhibitors, such as tetracycline, may prevent cell death and potentially may prevent tissue destruction after envenomation 3.1.4.41 sphingomyelin phosphodiesterase D medicine a molecular mechanism for Loxosceles venom nephrotoxicity is demonstrated that is dependent on the catalytic activity of phospholipase-D toxin 3.1.4.41 sphingomyelin phosphodiesterase D medicine recombinant SMase D can replace venom for anti-venom production and therapy 3.1.4.46 glycerophosphodiester phosphodiesterase medicine serological confirmation of louse-borne relapsing fever and determination of disease prevalence by assessment of anti-enzyme antibodies 3.1.4.46 glycerophosphodiester phosphodiesterase medicine relapsing fever spirochetes have enzymic activity while Lyme disease spirochetes have not 3.1.4.46 glycerophosphodiester phosphodiesterase medicine plays a role in glycerophosphocholine metabolism 3.1.4.46 glycerophosphodiester phosphodiesterase medicine to study if membrane protein D (PD)-induced protection against NTHI as a vaccine is due to antibodies that inhibit or neutralize its enzymatic activity, a GlpQ enzyme inhibition assay is developed, and serum samples collected from Finnish infants before and after Pnc-PD vaccination are analyzed for enzyme inhibition and anti-PD IgG antibody concentration. Before vaccination at age 2 months, the majority (84%) of infants has no detectable anti-PD IgG antibodies, and all are enzyme inhibition assay negative. At age 13 to 16 months, all infants receiving three or four doses of Pnc-PD have detectable anti-PD IgG antibodies and 36% of the infants receiving three doses and 26% of the infants receiving four doses of Pnc-PD are inhibition assay positive 3.1.4.46 glycerophosphodiester phosphodiesterase medicine the enzyme has immunogenic potential as a vaccine. Improvement of the GlpQ-based vaccine formulation, a DNA-based vaccine constructed by fusing Treponema pallidum GlpQ with interleukin-2, using chitosan nanoparticles as the vector, effectively attenuated the development of syphilitic lesions 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine insulin reduces serum enzyme levels in diabetics 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine glucose and insulin regulate enzyme mRNA levels 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine patients with liver disease have lower activites, those with renal disease have higher activities than healthy controls 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine enzyme activity is over 75% reduced in systemic inflammatory response syndrome, downregulation of enzyme could play an important role in the control of proinflammatory responses 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine enzyme may be involved in generation of circulating prognostic markers in cancer 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine serum enzyme activity is positively correlated with inflammatory markers and counts of monocytes and stab cells 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine baseline GPI-PLD levels correlate with the change in insulin sensitivity in response to the low-fat diet, whereas baseline insulin sensitivity correlates with the change in insulin sensitivity in response to the lowcarbohydrate diet, plasma GPI-PLD may serve as a clinical tool to determine the effect of a low-fat diet on insulin sensitivity 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine in a c-Myc transgenic disease model of liver cancer, serum GPI-PLD activity is increased 4fold in transgenic mice, while its tissue activity is reduced by 70% 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine in samples from steatohepatitis and hepatocellular carcinoma patients, serum GPI-PLD activity is increased 4fold, while its tissue activity is reduced by 60%. c-Myc influences GPI-AP signaling transcriptionally and posttranslationally and represses GPI-AP anti-proliferative signaling in tumors 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine the expression of GPI-PLD is dramatically down-regulated in both the brain and cerebrospinal fluids of Creutzfeldt-Jakob disease patients, while no differences in expression are observed in either the brains or cerebrospinal fluids specimens from Alzheimer's disease patients 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine the expression of GPI-PLD is dramatically down-regulated in the brains of scrapie-infected mice, especially in the caveolin-enriched membrane fractions. The decrease in GPI-PLD expression levels begins at the same time that prion proteins begin to accumulate in the infected brains 3.1.4.50 glycosylphosphatidylinositol phospholipase D medicine the hepatic mRNA level and circulating concentration of GPI-PLD are significantly augmented in diabetic mice 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine PDE4 may be of particular importance as an antidepressant target in that it is regulated by repeated treatment with both norepinephrine and serotonin reuptake inhibitors as well as by the PDE4 inhibitor rolipram 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine enzyme variants PDE4B and/or PDE4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine expression of phosphodiesterases PDE1A, PDE1C, PDE3B, and PDE5A is enhanced in pulmonary arterial smooth muscle cells from both patients with idiopathic pulmonary arterial hypertension or secondary pulmonary hypertension compared with control. Increase in phosphodiesterase isoforms, particularly in PDE1C, contributes to decreased cAMP levels and increased proliferation of pulmonary arterial smooth muscle cells in patients with pulmonary hypertension 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine interactions of PDE4D5 with both the N- and C-terminal domains of beta-arrestin are essential for beta2-adrenoceptor regulation 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine reactive oxygen-species mediated lung inflammation may be mediated at least in part by calcium and elevated enzyme activity associated with decreased caMP in both macorphages and epithelial cells 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine statistically significnat differences between cAMP-dependent phosphodiesterase activity in benign tumours and healthy control. Enzymatic activity in tumour groups analysed such as Warthin's tumour, pleomorphic adenoma. Or myoepithelioma, is about 50% lower than in control 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine PDE5 inhibition improved short-term object recognition performance after an acute tryptophan depletion induced deficit 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine isoform PDE7B is a drug target in chronic lymphocytic leukemia 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine PDE5 inhibition is a efficacious oral therapy for erectile dysfunction 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase medicine phosphodiesterase 4B mediates Streptococcus pneumoniae-induced mucin gene MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. PDE4B plays a critical role in MUC5AC induction. Topical and post-infection administration of rolipram into the middle ear potently inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation 3.1.4.54 N-acetylphosphatidylethanolamine-hydrolysing phospholipase D medicine the dorsomedial region of the ventromedial nucleus of the hypothalamusdisplays the necessary machinery for the endocannabinoid-mediated modulation of synaptic transmission of brain circuitries that regulate important hypothalamic functions such as feeding behaviors 3.1.4.54 N-acetylphosphatidylethanolamine-hydrolysing phospholipase D medicine effects of acute ethanol exposure to murine BV2 microglial cells. Ethanol downregulates microglial NAPE-PLD expression by activating cAMP/PKA and ERK1/2. Ethanol induces an increase in histone acetyltransferase activity which leads to higher levels of acetylation of histone H3 3.1.4.59 cyclic-di-AMP phosphodiesterase medicine a truncation in the cyclic diadenosine monophosphate phosphodiesterase enzyme, GdpP, is identified in 7 of the 10 Austrian isolates and 10 of the 11 UK clinical isolates of beta-lactam resistant Staphylococcus aureus. Complementation of four representative isolates with an intact copy of the GdpP gene restored susceptibility to penicillins and abolished the growth defects caused by the truncation 3.1.5.B1 dNTPase medicine in fibroblasts of patients with genetic mutations of deoxyguanosine kinase, SAMHD1 leads to manifestation of dNTP pool imbalance and DNA depletion. When SAMHD1 is silenced by siRNA transfection the composition of the mitochondrial dNTP pool approaches that of the controls, and DNA copy number increases 3.1.6.1 arylsulfatase (type I) medicine the enzyme can be accepted as the enzyme component of antitumor antibody-enzyme conjugates for target chemotherapy 3.1.6.1 arylsulfatase (type I) medicine use of immobilized and column-packed enzyme is an efficient alternative for the cleavage of urinary conjugates in clinical toxicology 3.1.6.1 arylsulfatase (type I) medicine leukocytes of patients with cerebral palsy show lower enzyme activity as compared to control. Km value for 4-nitrocatechol sulfate in patients' leukocytes is about 0.26 mM, in control 0.21 mM, whereas Vmax value in patients reaches only 58% of healthy control. All investigated patients reveal presence of the most common mutations associated with enzyme pseudodeficiency 3.1.6.1 arylsulfatase (type I) medicine very low enzymic activity in deciduum of women at 41 weeks of gestation, which reduce to a half at 42 weeks of gestation, while values of sulfatide concentrations increase 3.1.6.1 arylsulfatase (type I) medicine potential benefits of ARSA brain gene therapy in patients with metachromatic leukodystrophy, MLD 3.1.6.1 arylsulfatase (type I) medicine a one-time injection of human arylsufatase B into injured mouse spinal cord eliminates immunoreactivity for chondroitin sulfates within five days, and up to 9 weeks after injury. After a moderate spinal cord injury, locomotor recovery assessed by the Basso Mouse Scale in arylsulfatase B treated mice improves, compared to the buffer-treated control group, at 6 weeks after injection. After a severe spinal cord injury, mice injected with equivalent units of arylsulfatase B or bacterial chondroitinase ABC improve similarly and both groups achieve significantly more locomotor recovery than the buffer-treated control mice. Serotonin and tyrosine hydroxylase immunoreactive axons are more extensively present in mouse spinal cords treated with arylsulfatase B and chondroitinase ABC, and the immunoreactive axons penetrate further beyond the injury site than in control mice 3.1.6.1 arylsulfatase (type I) medicine assay for the diagnosis of metachromatic leukodystrophy. Determination of arylsulfatase A activity toward the natural substrate, galactosyl-3-sulfate ceramide or sulfatide, is performed using neat sulfatide without chemical modification. The hydrolyzed sulfatide is monitored upon inclusion of the colorimetric reagent Azure A. Within a clinical context, the method definitely discriminates between healthy subject samples and metachromatic leukodystrophy patient samples 3.1.6.2 steryl-sulfatase medicine - 3.1.6.2 steryl-sulfatase medicine increased activity in endocrine-dependent tumors 3.1.6.2 steryl-sulfatase medicine higher activity in primary mammary carcinoma 3.1.6.2 steryl-sulfatase medicine steryl-sulfatase deficient placenta has lower aromatase activity 3.1.6.2 steryl-sulfatase medicine also associated with multiple sulfatase deficiency 3.1.6.2 steryl-sulfatase medicine point mutations in 3 patients 3.1.6.2 steryl-sulfatase medicine deficiency in X-linked placental insufficiency and X-linked ichthyosis 3.1.6.2 steryl-sulfatase medicine 2-phenylindole sulfamates with antiproliferative activity in breast cancer cells are devoid of estrogenic activity and have the potential for in vivo application as steroid sulfatase inhibitors in the treatment of hormone-dependent breast cancer 3.1.6.2 steryl-sulfatase medicine blocking of dehydroepiandrosterone sulfate sulfatase activity could be prove to be clinically important in oestrogen-dependent tumors in pre-menopausal women 3.1.6.2 steryl-sulfatase medicine estrone sulfatase inhibitors can be used as drugs for the treatment of estrogen-dependent breast cancer 3.1.6.2 steryl-sulfatase medicine the expression of STS is an independent prognostic factor in breast cancer, STS is a new molecular target for the treatment of estrogen-dependent breast tumor post-selective estrogen receptor modulator and/or aromatase inhibitors 3.1.6.2 steryl-sulfatase medicine the STS inhibitors 3-sulfamoyloxy-N-propyl-16,17-seco-estra-1,3,5(10)-triene-16,17-imide and 3-sulfamoyloxy-N-(1’’-pyridin-3’’-ylmethyl)-16,17-seco-estra-1,3,5(10)-triene-16,17-imide are devoid of estrogenic activity and have therapeutic potential for the treatment of hormone-dependent breast cancer 3.1.6.2 steryl-sulfatase medicine X-linked ichthyosis is ascribed to the non-functional ES resulting from point and/or deletion mutations in the ES gene 3.1.6.2 steryl-sulfatase medicine administration of oestrone sulfamate to ovariectomised animal results in 3.5fold increase in the uterine weight. Coadministation of oestrone sulfamate and 667 COUMATE completely blocks enzyme activity and completely abrogates the ability of oestrone sulfamate to stimulate uterine growth 3.1.6.2 steryl-sulfatase medicine expression level of enzyme mRNA is significantly higher cumulus cells from patients with endometriosis than in control cumulus cells 3.1.6.2 steryl-sulfatase medicine No significant correlation among the expression of enzymes involved in intratumoral estrogen expression in endometrial carcinoma tissue. No significant differences between steroid sulfatase, estrogen sulfotransfarase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients 3.1.6.2 steryl-sulfatase medicine study on the effect of N-and C-terminal trucated enzyme mimicking enzyme deficiency in X-linked ichthyosis 3.1.6.2 steryl-sulfatase medicine analysis of enzyme activity and sulfuryl transferase activity in the 55 most frequent human brain tumors incuding glioblastomas, pituitatry adenomas, meningiomas, astrocytomas. Significant differences in enzyme activity among the investigated types of tumors, that do not depend on sex or age of subjects 3.1.6.2 steryl-sulfatase medicine benzothiophene sulfates of raloxifene and arzoxifene used as hormone replacement therapeutic agents are hydrolyzed by the enzyme, whereas the raloxifene 4'-phenolic sulfate is resistant. Tissue specific expression of sulfotransferase isoforms and of steroid sulfatase can be important in the inactivation and regeneration of the active form of hormone replacement therapeutic agents 3.1.6.2 steryl-sulfatase medicine method for the evaluation of aromatase and steryl-sulfatase activites in endometrial tumors using tritium-labeled steroids 3.1.6.2 steryl-sulfatase medicine remarkably different expression of enzyme isoforms in estrogen receptor alpha-positive and -negative breast carcinomas. Estrogen receptor alpha is an essential regulator of transcription 3.1.6.2 steryl-sulfatase medicine treatment of postmenopausal women with estrogen receptor-positie metastatic breast cancer using inhibitor 6-oxo-7,8,9,10,11,12-hexahydro-6H-cycloocta[c]chromen-3-yl sulfamate, i.e. STW64. Inhibitor almost completely blocks enzyme activity in peripheral blood lymphocytes and tumor tissues, inhibition is associated with significant reductions in serum concentrations of androstenediol and estrogens. Serum androstenedione concentration also decreases by up to 86%. Of eight patients that completed therapy, five show evidence of stable disease for up to 7 months 3.1.6.2 steryl-sulfatase medicine patients with no STS but estrogen sulfotransferase activity (-/+) have better clinical prognosis than all other activity pairs of these enzymes (+/-, +/+, -/-) 3.1.6.2 steryl-sulfatase medicine estrone sulfatase is a target enzyme in the treatment of hormone-dependent breast cancer 3.1.6.4 N-acetylgalactosamine-6-sulfatase medicine diagnosis of Morquio disease since extracts of Morquio fibroblasts are devoid of the enzyme 3.1.6.4 N-acetylgalactosamine-6-sulfatase medicine enzyme defect leads to mucopolysaccharidosis IVA 3.1.6.4 N-acetylgalactosamine-6-sulfatase medicine Morquio A is an autosomal recessive disease caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase, leading to the lysosomal accumulation of keratan-sulfate and chondroitin-6-sulfate 3.1.6.4 N-acetylgalactosamine-6-sulfatase medicine application of a combined assay for defects in iduronate-2-sulfatase (ID2S) leading to mucopolysaccharidosis II, and N-acetylgalactosamine-6-sulfatase (GALN) and N-acetylgalactosamine-4-sulfatase (ARSB) defects related to mucopolysaccharidosis IVA and MPS VI, respectively. The average enzyme activities of ID2S, GALN, and ARSB in random neonates are 19.6, 1.7, and 13.4 micromol/h/l, respectively. The average enzyme activities of ID2S, GALN, and ARSB in disease-affected individuals are 0.5, 0.3, and 0.3 micromol/h/l, respectively 3.1.6.4 N-acetylgalactosamine-6-sulfatase medicine GALNS activity (nmol/17 h/mg protein) is 0-7.4 in samples from mucopolysaccharidosis type IVA patients, as 19.85-93.7 in their parents and as 38.4-164 in the healthy controls. Statistically significant differences are observed between the three groups in terms of enzyme activity. There are no significant differences in enzyme activity by age. The female subjects in both the patient and parents groups show lower enzyme activity compared to the male subjects 3.1.6.4 N-acetylgalactosamine-6-sulfatase medicine in human prostate cancer tissues, the N-acetylgalactosamine-4-sulfatase ARSB activity is reduced and the galactosamine-N-acetyl-6-sulfatase GALNS activity is increased, compared to normal prostate tissue 3.1.6.8 cerebroside-sulfatase medicine - 3.1.6.8 cerebroside-sulfatase medicine arylsulfatase E defiecency in chondrodysplasia punctata 3.1.6.8 cerebroside-sulfatase medicine preferred polymorphism in alcohlism, A350G mutation 3.1.6.8 cerebroside-sulfatase medicine deficiency in metachromatic leukodystrophy, a sphingolipid storage disorder 3.1.6.8 cerebroside-sulfatase medicine enzyme effective in dispersing the cumulus cells of rabbit ova 3.1.6.8 cerebroside-sulfatase medicine assay of activity in leukocytes as a non-invasive diagnostic tool in patients with benign and malignant breast disease 3.1.6.8 cerebroside-sulfatase medicine metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of enzyme 3.1.6.8 cerebroside-sulfatase medicine the enzyme is implicated in most cases of metachromatic leukodystrophy 3.1.6.8 cerebroside-sulfatase medicine availability of AS-A on the sperm surface is important for the dispersion of cumulus layers of cumulus oocyte complexes 3.1.6.8 cerebroside-sulfatase medicine therapeutic levels of ARSA overexpression can be safetly achieved. ARSA-transduced cells efficiently repopulate the hematopoietic organs of RAG2-/- gamma-chain-/- mice. ARSA overexpression does not impair clonogenic capacity and multilineage differentiation of human HSPC cells, activation of other sulfatases and is thus unlikely to trigger metabolic imbalances. Moreover, ARSA overexpression does not impair immune functions, behavior and learning abilities 3.1.6.8 cerebroside-sulfatase medicine tyrosine sulfation facilitates secretion of ASA, which may have pathophysiological consequences 3.1.6.8 cerebroside-sulfatase medicine metachromatic leukodystrophy is caused by deficient activity of arylsulfatase A 3.1.6.8 cerebroside-sulfatase medicine enzyme replacement therapy is a therapeutic option for metachromatic leukodystrophy, caused by enzyme-deficiency, and other lysosomal disorders. This therapy depends on N-linked oligosaccharide-mediated delivery of intravenously injected recombinant enzyme to the lysosomes of patient cells 3.1.6.8 cerebroside-sulfatase medicine characterization of pathogenic variants C490R, P428L, N284K, P428L, H425R, Y225C and P428L, which were found when sequencing a cohort of 31 German metachromatic leukodystrophy families. Upon expression in immortalized, human multipotent mesenchymal stromal cells prepared from a patient deficient in ARSA activity, the seven mutants show ARSA activity of less than 10% when compared with wild type 3.1.6.8 cerebroside-sulfatase medicine mutation H231Q occurs in three patients belonging to a consanguineous family with late-infantile metachromatic leukodystrophy disorder MLD. The mutation leads to changes in the pre-mRNA secondary structure and in the ArsA protein structure 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine enzyme replacement in MPS IV feline fibroblast 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine deficiency in Maroteaux-Lamy syndrome, mucopolysaccharidosis type IV 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine application of recombinant enzyme may give improvement in mucopolysaccheridosis VI 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine deficiency of arylsulfatase B causes mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome) 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine mucopolysaccharidosis type VI is a lysosomal storage disease in which deficient activity of the enzyme arylsulfatase B impairs the stepwise degradation of the glycosaminoglycan dermatan sulfate 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis, overview 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine usage of ASB for enzyme replacement therapy in mucopolysaccharidosis type VI, overview 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine in prostatic malignancy, activity of arylsulfatase B declines. Arylsulfatase B may be useful as a biomarker of prostate cancer. In 82% of paired cases, the biochemical recurrences show lower arylsulfatase B immunostaining at the time of prostatectomy. Arylsulfatase B immunostaining is inversely associated with Gleason scores for epithelial and stromal compartments separately and in combination. Arylsulfatase B activity is significantly less in the malignant compared to normal tissue. In association with reduced arylsulfatase B activity, total sulfated glycosaminoglycans and chondroitin-4-sulfate content are increased in the malignant prostatic tissue, and the chondroitin-4-sulfate containing matrix proteoglycan versican is also increased 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine in the renal tissue of Dahl salt-sensitive rats exposed to high salt diet, arylsulfatase B activity is significantly less than in Dahl salt-sensitive rats exposed to low salt diet, and chondroitin-4-sulfate and total sulfated glycosaminoglycan content are significantly greater. A marked increase in chondroitin-4-sulfate disaccharidesis observed in the renal tissue of the rats exposed to high salt diet. Unsulfated, hyaluronan-derived disaccharides are increased in the rats on the low salt diet. In the rats on high salt diet, with lower arylsulfatase B activity and higher chondroitin-4-sulfate levels, cell-bound, high-molecular weight kininogen is greater and urinary bradykinin is lower. Arylsulfatase B activity in renal tissue and normal rat kidney cells declines when exogenous chloride concentration is increased in vitro 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine administration of recombinant enzyme as 2- and 4-h intravenous infusions using a feline model of mucopolysaccharidosis VI does not lead to significant differences in clinical outcomes such as urinary glycosaminoglycan excretion, tissue glycosaminoglycan storage, tissue galsulfase activity, and beta-glucuronidase but all are significantly different to control animals 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine application of a combined assay for defects in iduronate-2-sulfatase (ID2S) leading to mucopolysaccharidosis II, and N-acetylgalactosamine-6-sulfatase (GALN) and N-acetylgalactosamine-4-sulfatase (ARSB) defects related to mucopolysaccharidosis IVA and MPS VI, respectively. The average enzyme activities of ID2S, GALN, and ARSB in random neonates are 19.6, 1.7, and 13.4 micromol/h/l, respectively. The average enzyme activities of ID2S, GALN, and ARSB in disease-affected individuals are 0.5, 0.3, and 0.3 micromol/h/l, respectively 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine ARSB is reduced in cystic fibrosis cells and increases when defective cystic fibrosis transmembrane conductance regulator CFTR is repaired. The CFTR potentiator VRT-532 increases ARSB activity and expression to the level in normal bronchial epithelial cells. Concomitantly, total sulfated glycosaminoglycans and chondroitin 4-sulfate decline, secreted interleukin IL-8 increases, secreted IL-6 declines, and neutrophil chemotaxis to the spent media obtained from the potentiator-treated cystic fibrosis cells increases 3.1.6.12 N-acetylgalactosamine-4-sulfatase medicine in human prostate cancer tissues, the N-acetylgalactosamine-4-sulfatase ARSB activity is reduced and the galactosamine-N-acetyl-6-sulfatase GALNS activity is increased, compared to normal prostate tissue 3.1.6.13 iduronate-2-sulfatase medicine animal model for mucopolysaccharidosis 3.1.6.13 iduronate-2-sulfatase medicine deficiency in Hunters syndrome, mucopolysaccharidosis II 3.1.6.13 iduronate-2-sulfatase medicine endocytosis of the recombinant enzyme by human fibroblasts 3.1.6.13 iduronate-2-sulfatase medicine in humans, the inherited deficiency of the enzyme activity results in mucopolysaccharidosis type II, the Hunter syndrome 3.1.6.13 iduronate-2-sulfatase medicine the inherited deficiency results in mucopolysaccharidosis type II 3.1.6.13 iduronate-2-sulfatase medicine the inherited deficiency results in mucopolysaccharidosis type II, the Hunter syndrome 3.1.6.13 iduronate-2-sulfatase medicine the inherited deficiency results in mucopolysaccharidosis type II, the Hunter syndrome, studies of transfer of the recombinant enzyme into brain cells in vitro 3.1.6.13 iduronate-2-sulfatase medicine monoclonal antibodies demonstrate the capacity to differentiate progressive structural changes in iduronate-2-sulphatase and can be used to characterize the severity of mucopolysaccharidosis type II in patients based on variable denatured microstates 3.1.6.13 iduronate-2-sulfatase medicine analysis of 11 patients with mutations in the IDS gene leading to mucopolysaccharidosis type II. Structural alteration in the IDS protein results in its rapid degradation and/or insufficiency in processing 3.1.6.13 iduronate-2-sulfatase medicine analysis of mutations identified in patients with mucopolysaccharidosis type II. Mutations lead to aberrant precursor forms and loss of normal maturation of precursor. Mutant enzymes exhibit 2-4% of wild-type activity 3.1.6.13 iduronate-2-sulfatase medicine characterization of three mucopolysaccharidosis II patients with multiple aberrant transcripts due to three different point mutations. Mutations lead to production of only abnormally spliced transcripts (c.418+1G>C) or to abnormally spliced transcripts in addition to correctly spliced transcripts bearing the respective missence mutation (c.419G>T, and c.245C>T) 3.1.6.13 iduronate-2-sulfatase medicine identification of 10 different mutations in Taiwanese patients with mucopolysaccharidosis type I, mutations R468Q and R468W together accounting for 48% of mutations found. Due to overlapping significant wide range of enzyme activity in normal controls and in carriers of mutations, the level of enzyme activity cannot be used alone for carrier detection 3.1.6.13 iduronate-2-sulfatase medicine cognitive involvement is indicative of more severe disease and lower life expectancy in patients with mucopolysaccharidosis type II caused by a deficiency of iduronate-2-sulfatase: median age at death is significantly lower in patients who died in or before 1985 compared with those who died after 1985. Data from patients who died after 1985 may serve as a control in analyses of the effects of enzyme replacement therapy with idursulfase on mortality in patients with mucopolysaccharidosis type II. Idursulfase does not cross the blood-brain barrier in therapeutic quantities 3.1.6.13 iduronate-2-sulfatase medicine early treatment of mucopolysaccharidosis type II mice with one systemic injection of AAV2/5CMV-hIDS results in prolonged and high levels of circulating IDS that can efficiently and simultaneously rescue both visceral and central nervous system defects for up to 18 months after therapy 3.1.6.13 iduronate-2-sulfatase medicine efficacy of cord blood stem cell transplantation for Hunter disease (deficiency of IDS) is judged to be insufficient for the brain at 10 months post-therapy, but the pathological detection of donor-derived cells in the brain parenchyma suggests the potential of hematopoietic stem cell transplantation for treatment of neurological symptoms in Hunter disease 3.1.6.13 iduronate-2-sulfatase medicine idursulfase treatment appears to be safe and effective in adult Japanese patients with attenuated Mucopolysaccharidosis II 3.1.6.13 iduronate-2-sulfatase medicine measurement of plasma and/or leukocyte IDS activities does not discriminate adequately between mucopolysaccharidosis type II carriers and non-carriers 3.1.6.13 iduronate-2-sulfatase medicine use of enzyme-replacement therapy with recombinant human iduronate-2-sulfatase as a specific treatment for Hunter syndrome. Reductions in liver and spleen volume and in urinary glycoaminoglycan excretion in patients treated with idursulfase. In clinical trials, idursulfase is well tolerated, but in in some patients life-threatening anaphylactic reactions during infusion of idursulfase 3.1.6.13 iduronate-2-sulfatase medicine use of zebrafish as a novel tool to better understand lysosomal storage disorder pathogenesis 3.1.6.13 iduronate-2-sulfatase medicine effects of enzyme replacement therapy with iduronate 2-sulfatase on growth in young patients with mucopolysaccharidosis type II. Patients in group 1 received intravenous idursulfase at a standard dose of 0.58 mg/kg weekly for 52-288 weeks. The course of average growth curve for group 1 is very similar to growth pattern in group 2 naive to the enzyme. The average value of body height in subsequent years in group 1 is a little greater than in group 2, however, the difference is not statistically significant. In studied patients with mucopolysaccharidosis type II, idursulfase does not appear to alter the growth patterns 3.1.6.13 iduronate-2-sulfatase medicine application of a combined assay for defects in iduronate-2-sulfatase (ID2S) leading to mucopolysaccharidosis II, and N-acetylgalactosamine-6-sulfatase (GALN) and N-acetylgalactosamine-4-sulfatase (ARSB) defects related to mucopolysaccharidosis IVA and MPS VI, respectively. The average enzyme activities of ID2S, GALN, and ARSB in random neonates are 19.6, 1.7, and 13.4 micromol/h/l, respectively. The average enzyme activities of ID2S, GALN, and ARSB in disease-affected individuals are 0.5, 0.3, and 0.3 micromol/h/l, respectively 3.1.6.13 iduronate-2-sulfatase medicine structural models of the wild type and mutant IDS proteins resulting from 131 missense mutations identified in patients with mucopolysaccharidosis MPS II. The amino acid substitutions causing MPS II are widely spread over the enzyme molecule and the structural changes of the enzyme protein are generally larger in the severe group than in the attenuated one. The structural changes influence the disease progression 3.1.6.14 N-acetylglucosamine-6-sulfatase medicine endocytosis of the recombinant enzyme by human fibroblasts 3.1.6.14 N-acetylglucosamine-6-sulfatase medicine heparan sulfate storage disorder not keratan storage disorder 3.1.6.14 N-acetylglucosamine-6-sulfatase medicine normal activity in patient G.G.,cell line GM 2243 3.1.6.14 N-acetylglucosamine-6-sulfatase medicine Sanfilippo D Syndrome: N-acetylglucosamine 6-sulfate sulfatase deficiency, mucopolysaccharidosis type IIID 3.1.6.14 N-acetylglucosamine-6-sulfatase medicine defect in enzyme function leads to mucopolysaccharidosis type IIID, i.e. Sanfilippo syndrome Type D 3.1.6.14 N-acetylglucosamine-6-sulfatase medicine application of human N-acetylglucosamine 6-sulfatase, expressed in Chinese hamster ovary cells as a reversal agent for ultra-low molecular weight heparin. The enzyme removes a single 6-O-sulfo group at the non-reducing end of the ultra-low molecular weight heparin Arixtra (fondaparinux) effectively removing its ability to bind to antithrombin and preventing its inhibition of coagulation factor Xa 3.1.7.2 guanosine-3',5'-bis(diphosphate) 3'-diphosphatase medicine RelMtb is a key factor in Mycobacterium tuberculosis pathogenesis by regulating th intracellular concentration of (p)ppGpp. 3.1.8.1 aryldialkylphosphatase medicine enzymic activities in patiens with dementia or hyperlipidaemia 3.1.8.1 aryldialkylphosphatase medicine isozyme PON1 activity levels are 25-35% lower in people who were exposed to long-term ionizing radiation 3.1.8.1 aryldialkylphosphatase medicine relevance of enzyme polymorphism for modulating sensitivity to organometallic compounds 3.1.8.1 aryldialkylphosphatase medicine isozyme PON1 is effective at reducing the activity of phospholipid oxidation products 3.1.8.1 aryldialkylphosphatase medicine enzyme activity is closely connected with high density lipoprotein. Analysis of major factors modulating enzyme activity such as environmental chemicals, drugs, smoking, alcohol and implications for cardiovascular disease 3.1.8.1 aryldialkylphosphatase medicine enzyme hydrolyzes the potent inhibitor of human acetylcholinesterase, mono(diethylphosphoryl)obidoxime 3.1.8.1 aryldialkylphosphatase medicine in children with autism there are higher levels of total homocysteine, low enzyme activity and suboptimal levels of vitamin B12 3.1.8.1 aryldialkylphosphatase medicine no effect of caloric restriction upon triglyceride or total cholesterol concentration or on enzyme mRNA level. Enzyme activity tends to be higher in females and drops with caloric restriction in both genders. Variations in enzyme activity and apolipoprotein levels show gender-related differences that indicate a different adaptive strategy of male and female animals when faced with a period of food restriction 3.1.8.1 aryldialkylphosphatase medicine both PON1 bioavailability and catalytic activity are decreased in children with autism spectrum disorders 3.1.8.1 aryldialkylphosphatase medicine diminished paraoxonase and arylesterase activity is associated with particular stage, grade and CA-125 level of ovarian cancer 3.1.8.1 aryldialkylphosphatase medicine oxidative stress in coronary heart disease patients is maintained by systemic low-grade inflammation, which results in PON1 enzymatic activity exhaustion 3.1.8.1 aryldialkylphosphatase medicine PON1 activity is lower in chronic hepatitis patients compared with the control subjects 3.1.8.1 aryldialkylphosphatase medicine the enzyme carried by high-density lipoprotein, exerts a protective effect against oxidative damage of cells and lipoproteins, modulating the susceptibility of high-density lipoprotein to atherogenic modifications and has an anti-inflammatory role, low PON1 activity is a risk factor for cardiovascular disease 3.1.8.1 aryldialkylphosphatase medicine the RR-phenotype of Q192R with low PON1 activity towards paraoxon and diazoxon is significantly more frequent in newly diagnosed diabetes type 2 subjects compared with normal glucose tolerance subjects 3.1.8.1 aryldialkylphosphatase medicine human paraoxonase 1 is a catalytic bioscavenger for pre-treatment and therapy of organophosphorus compounds poisoning 3.1.8.1 aryldialkylphosphatase medicine paraoxonase 1 significantly protects against sarin and soman exposure in guinea pigs and supports the development of paraoxonase 1 as a catalytic bioscavenger for protection against lethal exposure of chemical warfare nerve agents exposure 3.1.8.1 aryldialkylphosphatase medicine PON1 shows potential as a prophylactic treatment against tabun exposure 3.1.8.1 aryldialkylphosphatase medicine the lower enzyme activity in metabolic syndrome are considered an independent risk factor for cardiovascular disease 3.1.8.1 aryldialkylphosphatase medicine the paraoxonase 1 polymorphism Q192R may play a minor role as a risk marker for developing lacunar infarctions in a group of Iranian population 3.1.8.1 aryldialkylphosphatase medicine ethanol consumption causes a significant decrease in liver paraoxonase activity. Gallic acid treatment partly restores this decreased paraoxonase activity. A gallic acid dose of 100 mg/kg shows highest restoring effect for paraoxonase activity. The activity of arylesterase is decreased in the ethanol group, but this decrease is not significant. Gallic acid treatment restores the loss of this activity due to ethanol exposure 3.1.8.1 aryldialkylphosphatase medicine in patients with ankylosing spondylitis with active disease, levels of serum triglycerides, total cholesterol, low denstiy lipoprotein and malondialdehyde are significantly elevated while high density liporpoteon, paraoxonase PON1 and arylesterase ARE levels are lower than those with no active ankylosing spondylitis. Decrease in the PON1/ARE activity leading to generation of oxidative stress may play an important role in the pathogenesis of ankylosing spondylitis. Activity of PON1/ARE in patients with ankylosing spondylitis seems to be strictly correlated with the activity of the inflammatory process 3.1.8.1 aryldialkylphosphatase medicine in patients with idiopathic Parkinson's disease, total antioxidant status levels are significantly lower than that of controls. Total oxidant status levels are higher than those of controls. Paraoxonase PON1 and arylesterase activities of patients are lower than those of controls. Serum levels of total and low density lipid cholesterol are significantly reduced in Parkinson's disease patients 3.1.8.1 aryldialkylphosphatase medicine in patients with relapsing-remitting multiple sclerosis, total antioxidant status levels are significantly lower than that of controls. Total oxidant status levels of the patients are higher than that of controls. Paraoxonase PON1 and arylesterase activities of the patients are lower, but not significantly, than those of controls. There is no correlation between serum PON1 activity and oxidaive stress index in patients with relapsing-remitting multiple sclerosis. Endogenousantioxidants may have been exhausted by increased oxidative stress and additional antioxidant treatment might be beneficial for these patients 3.1.8.1 aryldialkylphosphatase medicine in patients with selective serotonin reuptake inhibitor intoxication, the serum total antioxidant capacity levels and the paraoxonase and arylesterase activities are significantly lower, whereas the serum malondialdehyde levels are significantly higher than in the controls, indicating that decreased paraoxonase PON1 activity and increased oxidative stress represent alternative mechanisms in selective serotonin reuptake inhibitor toxicity 3.1.8.1 aryldialkylphosphatase medicine serum paraoxonase and arylesterase activities are significantly lower in patients with osteomyelitis compared to control individuals. Arylesterase activity is inversely correlated with triglyceride and cholesterol concentrations 3.1.8.1 aryldialkylphosphatase medicine use of organophosphorus hydrolase OpdA prevents lethality in an African green monkey model of acute organophosphrus poisoning. Treated monkeys received 1.2 mg/kg OpdA iv immediately after poisoning with dichlorvos. In Opda-treated animals, heart andrespiratory rates are unchanged from baseline over a 240-minute observation period. AChE activityslowly declines, but remains above 25% of baseline for the entire duration. Dichlorvos concentrationsreach a mean peak of 0.19 microg/ml at 40 min after poisoning and decrease to a mean of 0.05 microg/ml at 240 min 3.1.8.1 aryldialkylphosphatase medicine h-PON1 is a strong candidate for the development of therapeutic intervention against many diseases due to its anti-inflammatory, anti-oxidative, anti-atherogenic, anti-diabetic, anti-microbial, and organophosphate (OP)-detoxifying properties in humans 3.1.8.1 aryldialkylphosphatase medicine human paraoxonase 1 (h-PON1) is a potential candidate for the development of antidote against organophosphate (OP) compounds poisoning in humans. Insufficient organophosphate-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced organophosphate-hydrolyzing activity 3.1.8.1 aryldialkylphosphatase medicine paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications 3.1.8.1 aryldialkylphosphatase medicine PON1 activity and expression levels are important for determining susceptibility to organophosphorus compounds intoxication and risk of developing diseases related to inflammation and oxidative stress 3.1.8.1 aryldialkylphosphatase medicine PON1 shows great promise as a biotherapeutic due to its role in atherosclerosis and because of its ability to hydrolyze a broad range of organophosphates, including pesticides and nerve agents such as sarin, soman, and VX 3.1.8.2 diisopropyl-fluorophosphatase medicine OPH is also being used in medical applications as an antidote or a therapeutic in preventing organophosphorous poisoning 3.1.8.2 diisopropyl-fluorophosphatase medicine enzyme DFPase can be used as in vivo detoxifying agent for elimination of organophosphorus chemicals, used as pesticides and warfare nerve agent, e.g. sarin, soman, or tabun 3.1.8.2 diisopropyl-fluorophosphatase medicine human paraoxonase 1 (h-PON1) is a potential candidate for the development of antidote against organophosphate (OP) compounds poisoning in humans. Insufficient organophosphate-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced organophosphate-hydrolyzing activity 3.1.11.2 exodeoxyribonuclease III medicine study of a novel strategy using enzyme for direct sequencing of double-stranded DNA by MALDI-TOF mass spectroscopy 3.1.11.2 exodeoxyribonuclease III medicine study of a simple and efficient technique for the generation of a series of multiple competitor DNA fragments for competitive PCR, based on a wild-type gene, by making use of enzyme 3.1.11.2 exodeoxyribonuclease III medicine the enzyme is helpful for PCR amplification of long DNA templates 3.1.11.2 exodeoxyribonuclease III medicine the sequential degradation of completely rhodamine-labeled DNA by enzyme could be the key to a future single-molecule sequencing 3.1.13.1 exoribonuclease II medicine new factor in the IFN-mediated antiviral barrier against HIV-1 3.1.13.2 exoribonuclease H medicine the enzyme is a major target for the chemotherapy of human immunodeficiency syndrome, AIDS 3.1.13.2 exoribonuclease H medicine HSV-1 DNA polymerase is a crucial target for antivirals against HSV-1 infection 3.1.13.4 poly(A)-specific ribonuclease medicine leukemic cells from patients with acute lymphoblastic leukemia and acute myeloid leukemia display altered expression for CNOT6, CNOT6L, CNOT7 deadenylase and poly(A)-specific ribonuclease with most significant alterations for poly(A)-specific ribonuclease and CNOT7 mRNA levels. In acute lymphoblastic leukemia, a significant amount of poly(A)-specific ribonuclease is phosphorylated 3.1.15.1 venom exonuclease medicine some phenolic glycoside derivatives show inhibitory activity against snake venom phosphodiesterase I. Compounds are potential candidates for the therapy of snake bites 3.1.21.1 deoxyribonuclease I medicine inhibition of viral synthesis by DNase I in cell cultures 3.1.21.1 deoxyribonuclease I medicine inhaled DNase I into the airways reduces viscoelasticity of sputum, improves lung function of cystic fibrosis patients 3.1.21.1 deoxyribonuclease I medicine improvement of respiratory tract functioning in patients with cystic fibrosis 3.1.21.1 deoxyribonuclease I medicine analysis of genetic polymorphisms and correlation between genotype and its activity. Study on allele frequencies in DNase1 polymorphisms and polymorphisms in intron 4, designated HumDN1 3.1.21.1 deoxyribonuclease I medicine enzymatic activity assay for determination of enzyme stability. Method bases on a colorimetric endpoint activity assay using degradation of a DNA/methyl green complex and is feasible on an automated analyzer system within a rather short time. Application of method proves the reliability of enzyme during aerosolization with inhalation devices 3.1.21.1 deoxyribonuclease I medicine use of DNase I pre-treatment significantly increases the reliability and sensitivity of immunodetection of CIP/KIP cyclin-dependent kinase inhibitors. Applications in developmental neurobiology and cancer diagnosis 3.1.21.1 deoxyribonuclease I medicine DNase 1 activity is important to prevent immune stimulation and therefore its reduction or loss may result in a high risk to produce ANAs thus contributing to a potential prerequisite to develop a systemic lupus erythematosus-like disease. Survival of DNase 1-treated mice is longer that non-treated mice 3.1.21.1 deoxyribonuclease I medicine DNAse I/cdtB gene chimera has therapeutic applications for inhibiting the proliferation of cancer cells 3.1.21.1 deoxyribonuclease I medicine early use of dornase alpha provides nutritional benefits, thus is significantly associated with a higher body mass index percentile over time. Children who received dornase alpha before age two have an average body mass index percentile that is 10.2 percentiles greater than children who have not 3.1.21.1 deoxyribonuclease I medicine extracellular DNase 1 is implicated in the chromatin breakdown of necrotic cells in vitro. Connection between DNase 1 activity and the development of human systemic lupus erythematosus. Systemic lupus erythematosus patients have lower DNase 1 activity than patients with rheumatoid arthritis and scleroderma. Usage of DNase 1 as a therapeutic agent in systemic lupus erythematosus 3.1.21.1 deoxyribonuclease I medicine single nucleotide polymorphism in exon 8, is associated with several diseases 3.1.21.1 deoxyribonuclease I medicine usage of DNase 1 as a therapeutic agent in systemic lupus erythematosus 3.1.21.1 deoxyribonuclease I medicine DNase I activity activity in systemic Lupus erythematosus patients is lower than in healthy controls. DNase I activity is in positive correlation with systemic Lupus erythematosus activity index-2K, levels of antinuclear, anti-dsDNA, anti-nucleosome and anti-histone antibodies and in negative correlation with complement component C3 concentration. An increase of DNase I activity characterizes relapse in most SLE patients, although it does not reach the levels of healthy individuals 3.1.21.1 deoxyribonuclease I medicine patients with type 2 diabetes show a significant elevation of DNase I activity in serum, and increase in DNase I expression is observed in the pancreas of diabetic persons 3.1.21.1 deoxyribonuclease I medicine rats with diabetes induced by streptozotocin injection and high fat diet show a significant elevation of DNase I activity in serum, and increase in DNase I expression is observed in the pancreas of diabetic rats. High glucose induces both DNase I and caspase-3 expression and at the same time increases apoptosis rate of INS-1 cells 3.1.21.1 deoxyribonuclease I medicine treatment of established 72 h biofilms with 100 microg per ml of DNase for 24 h induces incomplete Listeria monocytogenes biofilm dispersal, with about 25% biofilm remaining compared to control. Addition of proteinase K completely inhibits biofilm formation, and 72 h biofilms including those grown under stimulatory conditions are completely dispersed with 100 microg per ml proteinase K 3.1.21.3 type I site-specific deoxyribonuclease medicine identification of a putative restriction-modification system EcoA0ORF42P in the commensal Escherichia coli strain A0 34/86 (O83: K24: H31), which is efficiently used at Czech paediatric clinics for prophylaxis and treatment of nosocomial infections and diarrhoea of preterm and newborn infants. This type I R-M system is a member of the type IB family, but is not an isoschizomer of either any prototype of the type IB members or any sequenced putative IB R-M systems. It is designated as EcoAO83I, the DNA recognition sequence of the EcoAO83I is GGA(8N)ATGC. Combination of the classical biochemical and bacterial genetics approaches with comparative genomics may contribute effectively to further classification of many other putative type-I enzymes, especially in clinical samples 3.1.21.7 deoxyribonuclease V medicine in xeroderma pigmentosum patients, topical application of liposome-encapsulated T4 endonuclease V reduces the incidence of basal cell carcinomas by 30% and of actinic keratoses by more than 68% 3.1.21.10 crossover junction endodeoxyribonuclease medicine development of antiviral agents against poxviruses 3.1.21.10 crossover junction endodeoxyribonuclease medicine its deficiency may lead to genome instability and cancer 3.1.21.10 crossover junction endodeoxyribonuclease medicine the absence of RuvA and RuvB orthologues in humans suggests that RuvA and RuvB may serve as potential targets for clinically useful small molecule enhancers of moxifloxacin 3.1.22.1 deoxyribonuclease II medicine polymorphisms in the DNase II gene might play important roles in controlling renal disorder among patients with systemic lupus erythematosus 3.1.22.1 deoxyribonuclease II medicine epidermal growth factor triggers a cleavage of Leukocyte Elastase Inhibitor precursor into L-DNase II, its subsequent enzymatic activation and nuclear translocation. Epidermal growth factor-induced cell death can be blocked by paraptosis inhibitor AIP-1/alix 3.1.22.1 deoxyribonuclease II medicine incubation of retinal cells in the presence of corticoids induces a specific and dose-dependent reduction of cell viability. L-Dnase II is not involved 3.1.22.1 deoxyribonuclease II medicine DNase II in macrophage lysosomes is responsible for definitive erythropoiesis in mouse fetal liver 3.1.22.1 deoxyribonuclease II medicine DNase II in Trichinella spiralis are secreted into circulation to cleave undigested DNA from apoptotic host cells, which reduces the innate immune response. The role played by DNase II in Trichinella spiralis may be a self-protective mechanism. DNase IIbeta or DNase II of Trichinella spiralis can be considered a candidate protein for therapy of autoimmune diseases, DNase II–deficient diseases, or cancer 3.1.22.1 deoxyribonuclease II medicine high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent. LEI inhibits cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis 3.1.22.1 deoxyribonuclease II medicine immunization of healthy rabbits with DNase II produces IgGs with intrinsic DNase and RNase activities. 10% of the total IgG DNase and RNase activities belong to anti-idiotypic antibodies to DNase II (ca. 0.1% of total pIgGs), while 90% of the activities do not interact with Sepharose bearing antibodies against DNase II and might be antibodies to nucleic acids bound to DNase II. Fraction of abzymes hydrolyzing both DNA and RNA can contain subfraction of antibodies against DNase II 3.1.22.1 deoxyribonuclease II medicine is involved in apoptosis, LEI/LDNase II is activated mostly after metabolic stress 3.1.22.1 deoxyribonuclease II medicine non-synonymous single nucleotide polymorphisms in the DNase II gene may have clinical implications in relation to the prevalence of autoimmune diseases 3.1.22.1 deoxyribonuclease II medicine the enzymes DNase II-1 and DNase II-7 are the potential target molecules for anti-Trichinella vaccine for blocking both larval invasion and development 3.1.25.1 deoxyribonuclease (pyrimidine dimer) medicine application of the enzyme packaged in an engineered liposome delivery vehicle to humans suffering the disease xeroderma pigmentosum due to DNA damage by UV radiation reverses the defective repair in these cells, it traverses the stratum corneum, reaches the nuclei of living skin cells, and enhances the repair of UV-induced cyclobutane pyrimidine dimers 3.1.26.5 ribonuclease P medicine catalytic RNase P RNA from Synechocystis sp. may be an active agent for Hepatitis C virus interventions 3.1.26.5 ribonuclease P medicine RNase P ribozyme variant (with a point mutation at nucleotide 95 of RNaseP catalytic RNA G95U that increases the rate of cleavage, and another mutation at A200C that enhances substrate binding of the ribozyme) is highly effective in inhibiting herpes simplex virus 1 gene expression 3.1.26.5 ribonuclease P medicine RNase P RNA is a drug target for aminoglycoside-arginine conjugates 3.1.26.5 ribonuclease P medicine ability to purify large amounts of M1 RNA, 20fold greater level from transformed cells than that from untransformed cells. M1GSs (tethered to the 3' end of M1 RNA by a spacer of 20-50 nt is a guide sequence (13-16 nt) that base pairs with the target RNA and has an unpaired 3'-RCCA needed for interacting with M1 RNA) degrades the oncogenic chimera BCR-ABL mRNA specifically and halted cancer development in mammalian cells when the guide sequence is designed to target the fusion region 3.1.26.5 ribonuclease P medicine feasibility to develop Salmonella-mediated gene transfer of RNase P ribozymes as an effective approach for gene-targeting applications 3.1.26.5 ribonuclease P medicine RNase P technology is a potential antiviral agent. Advantage of the external guide sequences technology over the M1GSs technology in therapy is the use of the endogenous RNase P enzyme and external guide sequences are much shorter than M1GSs. Advantage of random external guide sequences technique is that it will identify target sites that are accessible for binding of an antisense oligo and at the same time identify if these target sites are suitable substrates for cleavage by RNase P holoenzyme. M1GS technology works efficiently in inhibition of viral pathogenesis in immunodeficient mice 3.1.26.5 ribonuclease P medicine Acinetobacter baumannii is a problematic pathogen that is commonly resistant to multiple antibiotics. The RNase P endonucleolytic activity is characterized by having structural but not sequence substrate requirements. This property leads to development of EGS technology, which consists of utilizing a short antisense oligonucleotide that when forming a duplex with a target RNA induces its cleavage by RNase P. External guide sequence (EGS) technology can be a viable option for designing therapeutic alternatives to treat multiresistant Acinetobacter baumannii infections 3.1.26.5 ribonuclease P medicine construction of external guide sequences (EGSs) from a variant to target the mRNA encoding herpes simplex virus 1 (HSV-1) major transcription regulator ICP4, which is essential for the expression of viral early and late genes and viral growth. The EGS variant induces human RNase P cleavage of ICP4 mRNA sequence 60times better than the EGS generated from a natural pre-tRNA. A decrease of about 97% and 75% in the level of ICP4 gene expression and an inhibition of about 7,000- and 500-fold in viral growth are observed in HSV infected cells expressing the variant and the pre-tRNA-derived EGS, respectively. The study shows that engineered external guide sequences (EGSs) can inhibit HSV-1 gene expression and viral growth. The results demonstrate the potential for engineered EGS RNAs to be developed and used as anti-HSV therapeutics 3.1.26.5 ribonuclease P medicine two different technologies are developed to use RNase P as a tool for RNA knockdown. In one of these, an external guide sequence (EGS), which mimics a tRNA precursor, a well-known natural RNase P substrate, is used to target an RNA molecule for cleavage by endogenous RNase P. Alternatively, a guide sequence can be attached to M1 RNA, the (catalytic) RNase P RNA subunit of Escherichia coli. The guide sequence is specific for an RNA target, which is subsequently cleaved by the bacterial M1 RNA moiety. These approaches are applicable in both bacteria and eukaryotes. The RNase P EGS and M1GS technologies to knockdown specific RNAs are useful strategy in combating infectious diseases. External guide sequence (EGS) and M1 guide sequence (M1GS) successfully reduced bacterial viability, malaria replication and viral infections in cell cultures, and, to a lesser extent, in multicellular organisms. Salmonella-based oral delivery of EGS and M1GS appears to be an attractive way to combat some viral infections in mice and possibly other organisms 3.1.26.12 ribonuclease E medicine extraordinarily long antisense RNAs of 3.5 and 7 kb protect a set of mRNAs from RNase E degradation that accumulate during phage infection. These antisense RNA-mRNA duplex formations mask single-stranded recognition sites of RNase E, leading to increased stability of the mRNAs. The interactions directly modulate RNA stability and provide an explanation for enhanced transcript abundance of certain mRNAs during phage infection 3.1.26.13 retroviral ribonuclease H medicine genotypical and statistical analyzes in HIV-1 reverse transcriptase from antiretroviral treatment-naive and antiretroviral treatment-experienced patients. Within the RNase H domain, change K451 is present in 11% of treatment-experienced patients, but not in treatment-naive patients 3.1.26.13 retroviral ribonuclease H medicine the E312Q, G333E, G335D, V365I, A371V and A376S substitutions in RNase H subdomain of HIV-1 reverse transcriptase are present in 26% of subtype B, whereas the G335D and A371V substitutions are commonly observed in 69% and 75% of non-B HIV-1 isolates, respectively. A significant decline is observed in the viral loads of patients that are infected with HIV-1 carrying these substitutions and are subsequently treated with triple drug regimens, even in the case where zidovudine is included in such regimens. Generally, such single substitutions at the connection subdomain or RNase H domain have no influence on drug susceptibility in vitro by themselves. Instead, they generally enhance zidovudine resistance in the presence of excision-enhancing mutations. However, N348I, A376S and Q509L do confer varying amounts of nevirapine resistance by themselves, even in the absence of excision-enhancing mutations 3.1.26.13 retroviral ribonuclease H medicine within the RNase domain, mutation K451R is present in viral isolates of 11% of antiviral treatment-experienced patients but remaining 100% conserved among treatment-naive patients 3.1.26.13 retroviral ribonuclease H medicine activating the RNase H prematurely inside the virus particles destroys the viral genome and abrogates viral infectivity 3.1.31.1 micrococcal nuclease medicine possible target for the anti-malarial therapy tested by RNAi 3.1.31.1 micrococcal nuclease medicine as staphylococcal nuclease domain-containing protein 1 mRNA is overexpressed in cancer cells, the growth of these cells is suppressed following staphylococcal nuclease domain-containing protein 1 knock-down in vitro, thus representing a promising prostate cancer biomarker and therapeutic target, evidence for the diagnostic potential of staphylococcal nuclease domain-containing protein 1 in prostate surgical specimens equivalent or better than that of alpha-methylacyl-CoA racemase 3.1.31.1 micrococcal nuclease medicine capsid-targeted viral inactivation as an antiviral strategy against classical swine fever infection, the fusion protein Cap-SNase can inhibit effectively the production of classical swine fever virus, resulting in a reduction in infectious titers 3.2.1.1 alpha-amylase medicine the enzyme is a possible target for treatment of diabetes type 2 3.2.1.1 alpha-amylase medicine the inhibition of alpha-amylase can significantly reduce the post-prandial increase of blood glucose and therefore can be an important strategy in the management of blood glucose level in type 2 diabetic and borderline patients 3.2.1.3 glucan 1,4-alpha-glucosidase medicine enzyme inhibitors are very effective in controlling blood glucose levels, and thus are lead candidates for the treatment of type 2 diabetes 3.2.1.10 oligo-1,6-glucosidase medicine possibility for use as molecular marker in diagnosis of colon adenocarcinoma 3.2.1.10 oligo-1,6-glucosidase medicine in type 2 diabetic patients enhanced SI enzyme activity may cause hyperglycemia, and aggravates diabetic conditions, the results of the study could be important for development of inhibitors 3.2.1.10 oligo-1,6-glucosidase medicine the enzyme can serve as therapeutic target for the treatment of digestive disorders or their sequelae 3.2.1.10 oligo-1,6-glucosidase medicine metabolic enzyme sucrase-isomaltase is one of the most frequently mutated genes in a cohort of 105 chronic lymphocytic leukemia patients. Mutations result in loss of enzyme function by preventing the biosynthesis of catalytically competent sucrase-isomaltase at the cell surface. Mutations impair enzyme function by altering its trafficking along the secretory pathway. Loss-of-function mutations in sucrase-isomaltase result in gene expression patterns that depict ample metabolic reprogramming, pinpointing sucrase-isomaltase as a putative player in the cancer-associated metabolic switch 3.2.1.11 dextranase medicine - 3.2.1.11 dextranase medicine plays a role in dental caries 3.2.1.11 dextranase medicine partial hydrolysis of native dextran in the preparation of blood substitutes 3.2.1.11 dextranase medicine enzyme plays a role in controlling both the adhesive properties of extracellular glucan and the ability to utilize extracellular glucan as a nutrient source 3.2.1.11 dextranase medicine present in the biofilm known as dental plaque 3.2.1.11 dextranase medicine treatment of dental plaque 3.2.1.11 dextranase medicine less oxidised dextrans conjugating proportionally less 5-aminosalicylic acid successfully hydrolysed by dextranase, suggest their potential applications for the treatment of Crohn’s disease in the distal ileum and proximal colon 3.2.1.11 dextranase medicine isoform Dex410 effectively inhibits the Streptococcus mutans bio­film growth in coverage, biomass, and water-soluble glucan by more than 80, 90, and 95%, respectively. For short-term use of 1.5 months in animal experiment, both Dex410 and the commercial mouth­wash Biotene have a significant inhibitory effect on caries, while for 3 months use, only Dex410 shows significant inhibitory effect on dental caries 3.2.1.11 dextranase medicine dextranase can inhibit the adhesive ability of Streptomyces mutans. It inhibits biofilm formation and removes previously formed biofilms. The minimum biofilm inhibition and reduction concentrations (MBIC50 and MBRC50) of dextranase are 2 U/ml and 5 U/ml, respectively 3.2.1.11 dextranase medicine enzyme impedes the formation of Streptococcus mutans biofilm to some extent. Teeth rinsing product reagents, including carboxybenzene, ethanol, sodium fluoride, and xylitol have no effects on enzyme activity 3.2.1.14 chitinase medicine resequencing of all 12 AMCase exons in three diverse populations: African Americans, Puerto Ricans, and Mexicans leads to identification of 21 variants including four 5-untranslated region variants, nine non-synonymous single nucleotide polymorphisms, four synonymous single nucleotide polymorphisms, a 3-untranslated region single nucleotide polymorphism, and three intronic single nucleotide polymorphisms. Among the non-synonymous single nucleotide polymorphisms eight variants are common to all three racial groups single nucleotide polymorphisms: A290G, N45D, G296A, D47N, G339T, R61M, G461A, G102R, A531G, K125R, G1172A, V339I, T1218C, F354S, and G1452T, G432V. Minimal linkage disequilibrium is exhibited between these variants with the exception of single nucleotide polymorphisms A290G, G296A, and G339T. The G339T single nucelotide polymorphism is associated with asthma protection in some populations 3.2.1.15 endo-polygalacturonase medicine despite the significant sequence homology and the conserved surface-exposed epitopes LLP-PG represents a low-allergenic member of pollen PGs 3.2.1.17 lysozyme medicine by inhibiting Clostridium perfringens type A and its alpha-toxin production, hen egg white lysozyme shows potential for use in the treatment and prevention of necrotic enteritis and other Clostridium perfringens type A related animal diseases 3.2.1.17 lysozyme medicine influence of carboxylic acid and ester groups at the end of poly lactic acid/poly (DL-lactide-co-glycolide) based polymer on the rate of release and biological activity of lysozyme as a model protein from in situ gel forming controlled release formulations 3.2.1.17 lysozyme medicine the marine lysozyme is a potent antitumor molecule, which may inhibit tumor growth and inhibit angiogenesis. This lysozyme may have a therapeutic value in antitumor drug development 3.2.1.17 lysozyme medicine the structure of gp144 might be useful for the development of new antibacterial reagents for preventing and treating Pseudomonas aeruginosa infections 3.2.1.17 lysozyme medicine establishment of a precise fluorimetric assay for determination and characterisation of lysozyme activity immobilised in the initial in situ formed pellicle. For in situ pellicle formation, bovine enamel slabs were fixed on maxillary splints and carried by six subjects for different times on buccal and palatal sites. The mean immobilised activity over all samples amounted to 68.67 U/cm2. The enzyme activity exposed at the pellicles' surfaces increases in a time-dependant manner and shows a Michaelis-Menten kinetic. Chlorhexidine and black tea reduce lysozyme activity of the in situ pellicle significantly 3.2.1.17 lysozyme medicine Hen egg white lysozyme amyloid fibrils cause extensive aggregation of human erythrocytes and lipid vesicles without any significant lysis. The membrane activity of lysozyme fibrils suggests that the interaction of lysozyme fibrils with cellular membranes could be a contributing factor under conditions of human lysozyme amyloidosis 3.2.1.18 exo-alpha-sialidase medicine construction of highly infectious laryngotracheitis virus expressing H5 hemagglutinin and/or N1 neuraminidase and use in ocular immunization of chickens. Animals immunized with laryngotracheitis virus expressing neuraminidase N1 died after subsequent H5N1 avian influenzy virus challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either laryngotracheitis virus expressing hemagglutinin H5 alone, or hemagglutinin H5 and neuramindase N1 simultaneously, survived without showing any clinical signs 3.2.1.18 exo-alpha-sialidase medicine in fibroblasts from patients with sialidosis, oversialylated lysosomal membrane protein Lamp-1 enhances lysosomal exocytosis. Silencing of Lamp-1 reverts this phenotype by interfering with the docking of lysosomes at the plasma membrane 3.2.1.18 exo-alpha-sialidase medicine in macrophages from isoform Neu1 deficient mice, a model for sialidosis, oversialylated lysosomal membrane protein Lamp-1 enhances lysosomal exocytosis. Silencing of Lamp-1 reverts this phenotype by interfering with the docking of lysosomes at the plasma membrane. In Neu1-/- mice the excessive exocytosis of serine proteases in the bone niche leads to inactivation of extracellular serpins, premature degradation of VCAM-1, and loss of bone marrow retention 3.2.1.18 exo-alpha-sialidase medicine isoform Neu2 mRNA and enzymatic activity are significantly increased in hypertrophic myofibers. Constitutive activation of AKT or Igf-1 treatment as well as treatment with vasopressin or trichostatin results in rise in Neu2 activity. Myofiber atrophy obtained by dexamethasone treatment or starvation triggers a significant loss of Neu2 activity and is paralleled by downregulation of Neu2 transcript levels 3.2.1.18 exo-alpha-sialidase medicine isoform Neu3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3, even when partial, totally inhibits cell's capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition and ultimately its down-regulation and an higher responsiveness of myoblasts to the apoptotic stimuli 3.2.1.18 exo-alpha-sialidase medicine isolation of mutants from H5N1-infected patients to explain the molecular basis of resistance to oseltamivir. Mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding 3.2.1.18 exo-alpha-sialidase medicine low activity of lysosomal sialidase in cells of rhabdomyosarcoma PA-23 tumor clones correlates with high metastatic potential 3.2.1.18 exo-alpha-sialidase medicine mice vaccinated with an engineered enzymatically deficient mutant trans-sialidase containing the catalytic domain without the immunodominant shed acute phase antigen repeats SAPA, are highly protected against Trypanosoma cruzi infection. Adult male BALB/c mice immunized with mutant protein are protected against challenge with a lethal dose of Trypanosoma cruzi trypomastigotes. The protected immunized mice developed no clinical or tissue evidence of infection throughout the study 3.2.1.18 exo-alpha-sialidase medicine neuraminidase activity is significantly higher in septic patients compared with nonseptic patients and healthy volunteers. Desialylation by increased neuramindase activity may contribute to the alternations in red blood cell rheology 3.2.1.18 exo-alpha-sialidase medicine study on functional compatibility of hemagglutinin and neuraminidase on the oligosaccharide level, through measuring the receptor-binding and substrate specificities of reassortant/passage human-avian variant virus pairs. Selection of the high-yield variants of the human-avian reassortants leads either to twofold decrease in the affinity of HA for most alpha2-3-sialosides and the appearance of affinity for alpha2-6-sialosides like in the H3N2 reassortant, or to decreasing the hemagglutinin affinity for Neu5Acalpha2-3Galbeta1-3GlcNAc and Neu5Acalpha2-3Galbeta1-3(Fucalpha1-4)GlcNAc in the H3N1 reassortant, or to enhancing the ability of neuraminidase to discriminate between alpha2-3/2-6 substrates in the H4N1 reassortant 3.2.1.18 exo-alpha-sialidase medicine study on susceptibility of Neu3 transgenic mice to induction of colonic aberrant crypt foci by azoxymethane. Injection of with azoxymethane results in decreased GM3 and increased lactosylceramide content in transgenic colon mucosa. Up-regulation of Neu3 is important to the promotion stage of colorectal carcinogenesis 3.2.1.18 exo-alpha-sialidase medicine the induction of hST3Gal V, which synthesizes ganglioside GM3 and reduction of Neu3 by PMA, are linked for the expression of differentiation marker protein, CD41b surface antigen. Neu3 overexpression inhibits the PMA-induced ERK1/2 and p38 MAPK phosphorylation in the K-562 cells. Down-regulation of expression of CD41b surface antigen is dependent on expression of Neu3 gene. Neu3 inhibitor 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid induces morphological changes, showing megakaryocytic differentiation of K562 cells, with expression of CD41b surface antigen, while specific glucosylceramide synthase inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol inhibits megakaryocytic differentiation of K-562 cells. Molecular mechanisms involved in Neu3-involved inhibition of CD41b surface antigen expression in K-562 cells include that Neu3 degrades membrane sialic acids and the resulting signaling pathway of the PKC/ERKs/p38 MAPK is down-regulated, causing a decrease in CD41b surface antigen expression and inhibition of megakaryocytic differentiation of K562 cells 3.2.1.18 exo-alpha-sialidase medicine treatment of red blood cells with enzyme modifies their shape in a dose-dependent fashion. Cells become more spherical, and alterations remain for at least ten hours. Changes are similar to changes during sepsis 3.2.1.18 exo-alpha-sialidase medicine treatment with Clostridium perfringens neuraminidase which is highly homologous to human Neu1 decreases human smooth muscle cell proliferation, even in cultures that do not deposit elastin. Pretreatment of aortic smooth muscle cells with exogenous neuraminidase abolishes their mitogenic responses to recombinant platelet-derived growth factor PDGF-BB and insulin-like growth factor IGF-2 3.2.1.18 exo-alpha-sialidase medicine bacterial neuraminidases functions as the predominant neuraminidase when influenza virus neuraminidase is inhibited to promote the spread of infection and to inactivate the neutralization activity of saliva. Neuraminidase from bacterial flora in patients may reduce the efficacy of neuraminidase inhibitor drugs during influenza virus infection 3.2.1.20 alpha-glucosidase medicine recombinant enzyme is taken up by cultured fibroblasts and skeletal muscle cells from glycogenosis type II patients, and is shown to correct the storage phenotype. Endocytosed enzyme is localised to the lysosome and shows evidence of intracellular processing to a more mature form 3.2.1.20 alpha-glucosidase medicine glycogen storage disease is caused by lysosomal acid alpha-glucosidase deficiency. When injected intravenously, the recombinant enzyme from mouse milk corrects the acid alpha-glucosidase deficiency in heart and skeletal muscle of glycogen storage disease type II knockout mice 3.2.1.20 alpha-glucosidase medicine combination of biochemical and structural investigations will give a lot of information for developing enzyme enhancement therapy (EET) for Pompe disease 3.2.1.20 alpha-glucosidase medicine inhibitors from Spiraea cantoniensis could be physiologically useful for treatment of diabetes 3.2.1.20 alpha-glucosidase medicine inhibitors may serve as lead to develop drugs for treatment of type 2 diabetes 3.2.1.20 alpha-glucosidase medicine inhibitors of alpha-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs 3.2.1.20 alpha-glucosidase medicine one therapeutic approach for decreasing postprandial hyperglycemia is to retard absorption of glucose by inhibition of alpha-glucosidase. Bromophenols of Grateloupia elliptica have potential as natural nutraceuticals to prevent diabetes mellitus because of their high alpha-glucosidase inhibitory activity 3.2.1.20 alpha-glucosidase medicine enzyme inhibition as therapeutic target for diabetes, in cancer, viral infections and in lysosomal storage diseases 3.2.1.20 alpha-glucosidase medicine potential target for antidiabetic therapy 3.2.1.20 alpha-glucosidase medicine potential treatment for Pompe disease 3.2.1.20 alpha-glucosidase medicine target for therapy of type 2 diabetes, antitumor activites, antiviral activites 3.2.1.20 alpha-glucosidase medicine therapeutic target for type II diabetes 3.2.1.20 alpha-glucosidase medicine the enzyme can serve as therapeutic target for the treatment of digestive disorders or their sequelae 3.2.1.20 alpha-glucosidase medicine enzyme activity measured at the first month after microsurgical vasoepididymostomy is an early and independent predictor of patency and natural pregnancy 3.2.1.21 beta-glucosidase medicine potential target for antidiabetic therapy 3.2.1.22 alpha-galactosidase medicine seroconversion from blood group B to 0 of human erythrocytes 3.2.1.22 alpha-galactosidase medicine Fabry disease is a X-linked inborn error of glycolipid metabolism caused by deficiency of the lysosomal enzyme alpha-galactosidase A. An improved method of production of recombinant alpha-galactosidase A for use in humans is needed in order to develop new approaches for enzyme therapy. Purified recombinant enzyme is taken up by fibroblasts derived from fabry disease patients and normal enzyme levels can be restored under theses conditions 3.2.1.22 alpha-galactosidase medicine Fabry disease is an X-linked genetic disorder resulting from a deficiency of alpha-galactosidase activity. Correlation of structural changes and clinical and biochemical phenotypes is demonstrated. Structural investigation is useful for elucidating the bases of Fabry disease and clinical treatment 3.2.1.22 alpha-galactosidase medicine transgenic mouse expressing human mutant alpha-galactosidase R301Q in an endogenous enzyme deficient background is a biochemical animal model for studying active site specific chaperone therapy for Fabry disease 3.2.1.22 alpha-galactosidase medicine determinantion of alpha-galactosidase A activity in samples from patients with Fabry disease and healthy controls. Average enzyme activity in dried blood spot samples prepared using EDTA tubes is higher compared to those spotted directly irrespective of disease status 3.2.1.22 alpha-galactosidase medicine enzyme activity is detected in unstimulated whole saliva and mainly due to isoform A activity. Activity is higher in unclarified samples than in clarified ones and shows wide daily variations. Activity in whole salivea is significantly higher than in glandular saliva. There is no difference in activity according to gender, blood type, and secretor status 3.2.1.22 alpha-galactosidase medicine Fabry disease is a lysosomal storage disorder caused by deficient lysosomal alpha-galactosidase A activity. Rapid degradation of mutant R301Q is observed in TgM/KO mouse fibroblasts treated with brefeldin A, and the amount of R301Q enzyme markedly increases by pretreatment with 1-deoxygalactonojirimycin starting 12 h prior to addition of brefeldin A. The enhancement of alpha-galactosidase A activity and its protein level by 1-deoxygalactonojirimycin-treatment is selectively observed in brefeldin A-treated COS-7 cells expressing R301Q 3.2.1.22 alpha-galactosidase medicine in male patients with Fabry disease, an X-linked disorder of glycosphingolipid metabolism caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, treatment with agalsidase alfa, i.e. alpha-galactosidase A produced by gene activation in a human cell line, does not affect proteinuria. Agalsidase alfa may stabilize kidney function 3.2.1.22 alpha-galactosidase medicine in patients with sporadic Parkinson's disease, the activities of alpha-D-galactosidase A are significantly decreased, compared to age- and sex-matched healthy controls. No significant differences in activities of other ten lysosomal acid hydrolases are observed 3.2.1.22 alpha-galactosidase medicine T-cells from normal controls resond with 28% increase in alpha-galactosidase activity to treatment with 1-deoxygalactonojirimycin. In cells from patients with Fabry disease, response depends on he mutantion and ranges from no increase to fully normal activity. In normal cells and in cells from patients responding more than 25%, an increase in the mature lysosomal form of enzyme is observed after treatment. In the group of intermediate respoders with increases of 7-25% in activity upon treatment, an increase in protein stain but incomplete processing of the enzyme to the mature form is detected 3.2.1.22 alpha-galactosidase medicine the enzyme is used for Fabry disease diagnosis, since in leukocytes, pre-incubation at 50°C for 60 min is effective to differentiate Fabry disease patients from healthy controls 3.2.1.23 beta-galactosidase medicine design of CHO-K1 cells to produce feline beta-galactosidase for potential use in preclinical trials in a cat model of GM1 gangliosidosis 3.2.1.23 beta-galactosidase medicine enzyme may be suitable for the use as a digestive supplement for the alleviation of lactose intolerance 3.2.1.23 beta-galactosidase medicine investigation of the pattern and mechanism of distribution of beta-galactosidase in the adult GM1-galgliosidosis mouse brain upon hippocampla injection of an adeno-associated viral vector encoding beta-galactosidase. Distribution in brain is by diffusion, by axonal transport within the neurons from the site of production, and by cerebrospinal fluid flow in the perivascular space of Virchow-Robin. Evidence of axonal transport of vector-encoded mRNA 3.2.1.23 beta-galactosidase medicine transfection of beta-galactosidase gene to fibroblast cells in culture using liposomes. 24 h after transfection, treated cells show a higher specific enzyme activity than untreated cells. Cells maintained in culture for 7 days show values similar to those of untreated patients with GM1 gangliosidosis 3.2.1.23 beta-galactosidase medicine use of enzyme as a digestive supplement 3.2.1.24 alpha-mannosidase medicine the key enzyme in N-glycan processing is a target in the development of anticanver therapies 3.2.1.24 alpha-mannosidase medicine determination of the activity of alpha-mannosidase, beta-mannosidase, beta-glucocerebrosidase, beta-galactosidase and beta-hexosaminidase in cerebrospinal fluid of patients suffering from dementia with Lewis bodies, Alzheimer's disease, fronto-temporal dementia and controls. alpha-Mannosidase activity shows a marked decrease across all the pathological groups as compared to controls 3.2.1.24 alpha-mannosidase medicine inhibition of N-glycan processing in the endoplasmic reticulum attenuates endoplasmic reticulum stress-induced cell death by increasing high-mannose type oligosaccharides that reduce protein aggregation, such as amyloidogenesis 3.2.1.24 alpha-mannosidase medicine inhibition of N-glycan processing in the endoplasmic reticulum attenuates endoplasmic reticulum stressinduced cell death by increasing high-mannose type oligosaccharides that reduce protein aggregation, such as amyloidogenesis 3.2.1.25 beta-mannosidase medicine mutation c.1922G>A, i.e. R641H, natural mutant identified in a patient with beta-mannosidisis. Patient is homozygous for the mutation, which leads to a residual activity of about 7% in the patient's leukocytes, 11% in lymphoblasts and 14% in plasma. Expression in transfected cells also results in 7% residual activity 3.2.1.28 alpha,alpha-trehalase medicine urinary trehalase is a specific marker of renal tubular damage 3.2.1.28 alpha,alpha-trehalase medicine analysis of enzyme activities in intestinal mucosal samples. Of 200 patients, most of whom complained of abdominal symptoms and diarrhoea, 18 had total alpha,alpha-trehalase deficiency and 39 had partial deficiency 3.2.1.28 alpha,alpha-trehalase medicine treatment of weaning rats with lyophilized Saccharomyces boulardii results in significant increase in alpha,alpha-trehalase activity in the endoluminal fluid and the intestinal mucosa. Discussion of oral administration of Saccharomyces boulardii to patients with digestive symptoms caused by trehalose intolerance 3.2.1.31 beta-glucuronidase medicine a high varability in the expression of beta-Glc in human liver and kidney. Therefore cleavage of drug glucuronides that accumulate during chronic therapy or are used as prodrugs can show a wide interindividual variability in humans, which might result in variable response to drugs 3.2.1.31 beta-glucuronidase medicine the potent beta-glucuronidase activity caused by the glucuronic acid conjugates from xenobiotics and endogenous compounds is a prime factor in the etiology of colon cancer 3.2.1.31 beta-glucuronidase medicine when beta-glucuronidase producing bacteria infect the bile, the pH of the bile becomes raised, the high pH and bile induce the enzyme, and then bilirubin gallstones can be easily formed 3.2.1.31 beta-glucuronidase medicine after liver injury induced by ontraperitoneal injections of N-nitrosodimethylamine, a significant increase is observed in beta-glucuronidase levels in the serum, liver homogenate, and subcellular fractions, but not in the nuclear fraction, concomitant with a maximum lysosomal fragility on day 21 during the induced fibrosis 3.2.1.31 beta-glucuronidase medicine measurement of beta-glucuronidase activity has no additive clinical value following a parathion overdose in humans 3.2.1.31 beta-glucuronidase medicine bronchoalveolar lavage fluid of children with culture-positive bacterial inflammation displays a significant increase of beta-glucuronidase activity. beta-Glucuronidase activity shows superior predictive ability for bacterial lung infection than other markers of inflammation 3.2.1.33 amylo-alpha-1,6-glucosidase medicine diagnosis, even prenatal, of type III glycogen storage disease: marked decrease or absence of amylo-1,6-glucosidase, glycogen debranching enzyme 3.2.1.33 amylo-alpha-1,6-glucosidase medicine study on patients with Glycogen Storage Disease Type III. Inactivation of either enzymatic activity is sufficient to cause Glycogen Storage Disease Type III disease. The carbohydrate binding domain of amylo-1,6-glucosidase,4-alpha-glucanotransferase plays a major role to coordinate its functions and regulation by the ubiquitin-proteasome system 3.2.1.35 hyaluronoglucosaminidase medicine increasing absorption of fluids in dermal clysis, increasing diffusion of injected substances 3.2.1.35 hyaluronoglucosaminidase medicine enzyme is the target for immunotherapy of allergen reaction 3.2.1.35 hyaluronoglucosaminidase medicine as major hyaluronidases in human cells, HYAL1 and HYAL2 may control intercellular interactions and microenvironment of tumour cells providing excellent targets for cancer treatment 3.2.1.35 hyaluronoglucosaminidase medicine this recombinant hyaluronidase can be applied for biochemical or medical purposes 3.2.1.35 hyaluronoglucosaminidase medicine human cancers grown in SCID mice regress dramatically following administration of purified testicular hyaluronidase. Hyaluronidase treatment also prevents lymph node invasion in a murine model for T-cell lymphoma 3.2.1.35 hyaluronoglucosaminidase medicine hyaluronidase correlates with tumor progression which is documented in tumors of the male genito-urinary tract, in prostate and urinary bladder cancers. Aggressiveness of other human cancers also correlates with hyaluronidase, including breast and laryngeal cancer 3.2.1.35 hyaluronoglucosaminidase medicine hyaluronidase promotes Leishmania establishment in murine skin 3.2.1.35 hyaluronoglucosaminidase medicine hyaluronidases are added to anticancer regimens, particularly in Europe. Tumors previously resistant to chemotherapy become sensitive when hyaluronidase is added. The enzyme may decrease intratumoral pressure, permitting drugs to penetrate the malignancy. Studies are available suggesting that hyaluronidase has intrinsic anti-tumor activity 3.2.1.35 hyaluronoglucosaminidase medicine it is assessed whether hyaluronic acid and HYAL-1 can predict progression to muscle invasion and recurrence among patients with non-muscle-invasive bladder carcinoma. In a cohort of 178 bladder carcinoma specimens HA and HYAL-1 expression is evaluated by immunohistochemistry and graded for intensity and area of staining. Association of HA and HYAL-1 staining with bladder carcinoma recurrence and muscle invasion is evaluated by univariate and multivariate models. HYAL-1 is a potential prognostic marker for predicting progression to muscle invasion and recurrence 3.2.1.35 hyaluronoglucosaminidase medicine the codelivery of hyaluronidase enzyme with oncolytic adenoviruses is analysed to determine whether it improves the spread of the virus throughout tumors, thereby leading to a greater overall antitumor efficacy in tumor models: In mice injected with the adenovirus Ad5/35GFP and hyaluronidase (50 U), a significant increase in the number of GFP-expressing cells is observed when compared with animals injected with virus only. When the oncolytic adenoviruses Ad5OV or Ad5/35 OV are codelivered with 50 U of hyaluronidase, a significant delay in tumor progression is observed, which translates into a significant increase in the mean survival time of tumor-bearing mice compared with either of the monotherapy-treated groups. Furthermore, the mice that receive the combination of Ad5/35 OV and hyaluronidase show the best antitumor efficacy 3.2.1.35 hyaluronoglucosaminidase medicine the effect of anticoagulants on plasma HAase activity is evaluated and compared with the serum HAase activity that is devoid of anticoagulants. The plasma HAase activity in the presence of the recommended concentration of EDTA is highly comparable to that of the serum HAase activity. In contrast, citrated or heparinized plasma record a significantly reduced level of activity than that of the serum HAase activity. EDTA-treated plasma samples are a better choice compared with heparin and citrated samples to assess the HAase activity 3.2.1.35 hyaluronoglucosaminidase medicine hyaluronidase 1 is a prognostic indicator for both local recurrence and progression of non-muscle-invasive bladder cancer after transurethral resection 3.2.1.35 hyaluronoglucosaminidase medicine intravitreous injection of ovine hyaluronidase to patients with persistent vitreous hemorrhage is efficacious and has a favorable safety profile 3.2.1.35 hyaluronoglucosaminidase medicine isoforms of hyaluronidase are predictors of a prostate cancer of good prognosis 3.2.1.35 hyaluronoglucosaminidase medicine hyaluronidase improves pharmacokinetic profiles of HI-6 dichloride and HI-6 dimethansulfonate. Hyaluronidase is supposed to increase tissue permeability and diminishes discomfort caused by the intramuscular injection 3.2.1.35 hyaluronoglucosaminidase medicine bovine hyaluronidase is an adjuvant for infiltration anesthesia. By degrading hyaluronan in the extracellular matrix, hyaluronidase increases membrane permeability, thereby rendering tissues more permeable to injected fluids. As a consequence, hyaluronidase reduces viscosity of hyaluronan which improves tissue diffusion and the resorption rate of excess fluids. Co-administration of hyaluronidase is a potential option to enhance the effectiveness of local anesthesia, increasing the analgesic efficacy with respect to the anesthetized area per time (e.g., subcutaneous and intramuscular injections). Hyaluronidase is used in ophthalmic surgery in combination with local anesthetics for peritubular, retrotubular or sub-Tenon's anesthesia and is established in other surgical disciplines, including dermatosurgery. Injection of hyaluronidase-based fillers in aesthetic dermatology 3.2.1.36 hyaluronoglucuronidase medicine increasing absorption of fluids in dermal clysis, increasing diffusion of injected substances 3.2.1.39 glucan endo-1,3-beta-D-glucosidase medicine allergenic properties of enzyme are due to IgE-binding epitopes on its surface 3.2.1.39 glucan endo-1,3-beta-D-glucosidase medicine Fra e 9 is a allergenic beta-1,3-glucanase from ash pollen. Both the N- and C-terminal domains retain comparable IgE-binding capacity when assayed with allergic sera 3.2.1.39 glucan endo-1,3-beta-D-glucosidase medicine the enzyme is an immunostimulatory antigen. Glu-176, a conserved catalytic residue in GH16 endo-beta-1,3-glucanases, is essential for Rv0315 to induce immunological responses 3.2.1.B43 keratanase II medicine an LC-MS/MS assay utilising keratan sulphate disaccharides derived from keratanase-II digestion provides a sensitive and specific means for quantitation of urinary keratan sulfate, a screening biomarker for Morquio A. The C-terminally truncated, recombinant keratanase-II meets all performance requirements and can be produced in a rapid and reproducible manner 3.2.1.B43 keratanase II medicine sulfated type 2 carbohydrate chains are known tumor-associated carbohydrate antigens (TACAs). The enzyme efficiently catalyzes the transglycosylation reaction of the sulfated Lewis X (Galbeta(1->4)[Fucalpha(1->3)]GlcNAc(6-OSO3-)) oxazoline derivative, thereby giving the su-Lex dimer as the main product in good yields 3.2.1.45 glucosylceramidase medicine - 3.2.1.45 glucosylceramidase medicine Gaucher disease, sphingolipoidose 3.2.1.45 glucosylceramidase medicine enzyme replacement therapy 3.2.1.45 glucosylceramidase medicine an inherited deficiency in this enzyme leads to the onset of Gaucher disease 3.2.1.45 glucosylceramidase medicine in fibroblasts of patients with Niemann-Pick disease type C, the cholesterol storage affects the stability of enzyme, decreasing its mass and activity 3.2.1.45 glucosylceramidase medicine more than 150 enzyme gene mutations are described in Gaucher patients 3.2.1.45 glucosylceramidase medicine mutations in the gene that incodes enzyme cause the Gaucher disease 3.2.1.45 glucosylceramidase medicine the enzyme gene mutations are encounterd in individuals with parkinsonism 3.2.1.45 glucosylceramidase medicine enzyme activity is decreased in psoriatic skin compared to normal control, increased in lesional compared to non-lesional psoriatic skin. Alterations in water permeability barrier in lesional psoriatic skin can serve as a trigger for the upregulation of the expression of enzymes like glycosylceramide-beta-glucosidase with consequent stimulation of ceramide generation 3.2.1.45 glucosylceramidase medicine Gaucher disease mouse models 3.2.1.45 glucosylceramidase medicine lentivirus-mediated gene transfer results in high-level glucocerebrosidase expression in multiple tissues without any evidence of local or systemic toxicity. Lentivirus-mediated gene transfer may respresent an effective method of achieving widespread and persistent therapeutic benefit for the treatment of patients with Gaucher disease 3.2.1.45 glucosylceramidase medicine manipulating the endoplasmic reticulum environment with chemical chaperones can correct the instability of mutant enzyme (causing Gaucher disease) 3.2.1.45 glucosylceramidase medicine measurement of lysosomal glucocerebrosidase activity in mouse liver using a fluorescence-activated cell sorter assay. This assay should be applicable to investigation of other Gaucher disease treatments in both human and animal models 3.2.1.45 glucosylceramidase medicine recombinant human acid beta-glucosidase stored in tobacco seed is stable, active and taken up by human fibroblasts. The recombinant enzyme can be used for enzyme replacement therapy 3.2.1.45 glucosylceramidase medicine determination of the activity of alpha-mannosidase, beta-mannosidase, beta-glucocerebrosidase, beta-galactosidase and beta-hexosaminidase in cerebrospinal fluid of patients suffering from dementia with Lewis bodies, Alzheimer's disease, fronto-temporal dementia and controls. beta-Glucocerebrosidase activity is selectively reduced in dementia with Lewis bodies, further suggesting that this enzyme might specifically be impaired in synucleinopathies 3.2.1.45 glucosylceramidase medicine glucocerebrosidase mutations exert a large effect on susceptibility for Lewis body disorders at the individual level but are associated with a modest population-attributable risk in individuals of European ancestry 3.2.1.45 glucosylceramidase medicine inhibitors 5-((4-methylphenyl)thio)-quinazoline 2,4-diamine and 5-(3,5-dichlorophenoxy)-N-(4-pyridinyl)-2-furamide raise the levels of functional GCase 1.5–2.5-fold in N370S or F213I Gaucher disease fibroblasts. Treated fibroblasts from patients with Gaucher disease show decreased levels of enzyme in their endoplasmic reticulum and increased levels in lysosomes. Compound stabilizes a domain III active-site loop 3.2.1.45 glucosylceramidase medicine isofagomine enhances mutant enzyme activity in pre-treated N370S/N370S and F213L/L444P patient fibroblasts with Gaucher disease 3.2.1.45 glucosylceramidase medicine mutations N370S and L444P are the most prevalent among patients with Gaucher disease. Two missense changes S356F, L296V are associated with the severe phenotype of type 1 Gaucher disease. Mutation 303e305delCAC was identified in a homozygous state in one patient type 1 or type 3 3.2.1.45 glucosylceramidase medicine study on children with type 3 Gaucher disease who had received enzyme replacement therapy or a bone marrow transplant. 60% of subjects have intelectual skills below average with significant discrepancies between verbal and performance IQ. No correlation between intelligence measures and genotype or the extent of systemic involvement. The dosage, age at initiation, and the length of enzyme replacement therapy had no significant effect on IQ scores 3.2.1.45 glucosylceramidase medicine GBA mutations are associated with pathologically purer Lewy body disorders, characterized by more extensive (cortical) Lewy body, and less severe Alzheimer disease pathological findings and are a useful marker for Lewy body disorders 3.2.1.45 glucosylceramidase medicine GBA mutations represent a significant risk factor for the development of Parkinson’s disease 3.2.1.45 glucosylceramidase medicine imiglucerase is used in enzyme replacement therapy for Gaucher disease 3.2.1.45 glucosylceramidase medicine enzyme activity is a marker of heterozygous GBA1 mutation Parkonson's disease 3.2.1.46 galactosylceramidase medicine twitcher mouse, a model for globoid cell leucodystrophy 3.2.1.46 galactosylceramidase medicine enzymatic diagnosis 3.2.1.46 galactosylceramidase medicine enzyme deficiency in globoid cell leucodystrophy or Krabbe disease 3.2.1.46 galactosylceramidase medicine economical and fast histochemical way to distinguish neural cells expressing galactocerebrosidase from thoses that are deficient. This method enables the assessment of enzyme activity in virally-transduced cells as well as the biodistribution of galactocerebrosidase activity in Twitcher mice under gene or cell therapy 3.2.1.46 galactosylceramidase medicine electrospray mass spectrometry combined with the use of biotinylated substrate conjugates and bioaffinity purification represents a new approach for the diagnosis of lysosomal storage disease, Krabbe disease 3.2.1.46 galactosylceramidase medicine findings could lead to an improved therapy for globoid cell leukodystrophy, GLD, or Krabbe disease 3.2.1.46 galactosylceramidase medicine globoid cell leukodystrophy, GLD or Krabbe disease, is caused by loss-of-fuction mutations in the GALC gene, injection of GALC improves the survival of the mouse model of GLD 3.2.1.46 galactosylceramidase medicine diagnosis of Krabbe disease 3.2.1.46 galactosylceramidase medicine lysosomal galactocerebrosidase GALC, which is defective in globoid cell leukodystrophy, is involved in the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids. Both insufficient and supraphysiologic GALC activity by inherited genetic deficiency or forced gene expression in patients' cells and in the disease model induce alterations of the intracellular content of the bioactive GALC downstream products ceramide and sphingosine, and thus affect hematopoietic stem/progenitor cell survival and function and the functionality of the stem cell niche 3.2.1.46 galactosylceramidase medicine mutations involved in Krabbe's disease are widely distributed throughout the protein. Mutations that are likely to result in severe misfolding include E114K and S257F in the TIM barrel, L364R and W410G in the beta-sandwich domain, and G537R and L629R in the lectin domain. Mutation E215K is exposed on the surface of the TIM barrel. The mutation confers an opposite charge on the same face as the substrate-binding pocket suggesting that the mechanism of disease for this mutation will involve the perturbation of a binding face for an activating factor. Residue P302 that is found on the surface of GALC very close to the substrate-binding pocket is mutated to arginine in Krabbe's disease. The beta-sandwich domain of a long loop forms an integral part of the substrate-binding site. R380 at the tip of this loop directly binds the galactose molecule in the active site, its mutation to tryptophan or leucine leads to severe infantile Krabbe's disease 3.2.1.46 galactosylceramidase medicine enhancers of beta-galactocerebrosidase are identified as potential small molecules therapies for Krabbe Disease 3.2.1.46 galactosylceramidase medicine incubation of human fibroblasts from patients bearing nonsense mutations with PTC124 (premature termination codon, a well-characterized compound known to induce ribosomal read-through) and NMDI1 (nonsense-mediated mRNA decay inhibitor 1) increases the levels of mRNA and rescues galactocerebrosidase enzymatic activity in a dose-dependent manner. The low but sustained expression of beta-galactocerebrosidase in oligodendrocytes is sufficient to improve the morphology of the differentiated cells. The in vitro approach provides the basis for further investigation of ribosomal read-through as an alternative therapeutic strategy to ameliorate the quality of life in selected Krabbe's disease patients 3.2.1.48 sucrose alpha-glucosidase medicine sucrase-isomaltase SI is a marker enzyme of the absorptive villose cells in adult small intestine, human intestinal sucrase-isomaltase help develop a specific inhibitor of sucrase, to retard the absorption of sucrose in the intestinal tract of diabetic patients 3.2.1.48 sucrose alpha-glucosidase medicine one therapeutic approach for decreasing postprandial hyperglycemia is to retard absorption of glucose by inhibition of alpha-glucosidase. Bromophenols of Grateloupia elliptica have potential as natural nutraceuticals to prevent diabetes mellitus because of their high a-glucosidase inhibitory activity 3.2.1.49 alpha-N-acetylgalactosaminidase medicine potential application in the field of erythrocyte conversion technology 3.2.1.49 alpha-N-acetylgalactosaminidase medicine the enzyme can be employed as a diagnostic/prognostic tool for patients with salivary gland adenocarcima 3.2.1.49 alpha-N-acetylgalactosaminidase medicine The enzyme is able to remove at neutral pH alpha-1,3-bound residues of N-acetylgalactosamine from glycoproteins of blood group A-substances and A-erythrocytes, converting them into 0 group substances 3.2.1.49 alpha-N-acetylgalactosaminidase medicine the enzyme may be useful for enzymic conversion of type A2 to universally transfusable type O red blood cells, potential application in the field of solid organ transplantation 3.2.1.49 alpha-N-acetylgalactosaminidase medicine use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease 3.2.1.49 alpha-N-acetylgalactosaminidase medicine alpha-N-acetylgalactosaminidase is an efficient enzyme for production of universal O blood cells 3.2.1.50 alpha-N-acetylglucosaminidase medicine antenatal diagnosis of heritable lysosomal storage diseases 3.2.1.50 alpha-N-acetylglucosaminidase medicine the use of secreted enzyme in future enzyme and gene replacement therapy protocols will by severely limited due to its small degree of mannose-6-phosphorylation 3.2.1.50 alpha-N-acetylglucosaminidase medicine the enzyme is a possible candidate for enzyme replacement therapy, a method for cell entry or transduction has to be found 3.2.1.50 alpha-N-acetylglucosaminidase medicine expression of human NaGlu in the central nervous system of mucopolysaccharidosis IIIB mice by an i.c. injection approach. The treatment slows the disease progression by mediating widespread recombinant NaGlu expression in the central nervous system, resulting in the reduction of brain lysosomal storage pathology, significantly improved cognitive function and prolonged survival. The therapeutic benefit of i.c. recombinant adeno-associated viral vector delivery is dose-dependent and can be attribute solely to the central nervous system transduction because the procedure does not lead to detectable transduction in somatic tissues 3.2.1.50 alpha-N-acetylglucosaminidase medicine a minimum threshold of about 20% of wild type residual enzyme activity levels is required to completely prevent accumulation of heparan sulfate in Sanfilippo syndrome type B patient fibroblasts. BMN 250 cellular uptake under very limiting and transient exposure conditions occurs in sufficient amounts to reach this threshold 3.2.1.51 alpha-L-fucosidase medicine recombinant enzyme will extend the proven efficiacy of enzyme replacement therapy in lysosomal storage disorders e.g. fucosidosis 3.2.1.51 alpha-L-fucosidase medicine deficiency in enzyme activity is associated with fucosidosis 3.2.1.51 alpha-L-fucosidase medicine the differentiation of HT-29 colon cancer cells can be used as a model to study the alteration of the enzyme alpha-L-fucosidase during the progression of the tumoural processs 3.2.1.51 alpha-L-fucosidase medicine has a role in the intimate species signature interactions between sperm and oocyte. Relevance for reproductive function in nature or in assisted reproductive technologies 3.2.1.51 alpha-L-fucosidase medicine quality of semen is affected in part by the loss in the activity of alpha-fucosidase, which may be useful in early diagnosis of the loss in reproductive capacity during the course of trypanosomiasis and fertility tests 3.2.1.51 alpha-L-fucosidase medicine progression-free survival significantly longer in high FUCA activity group than in low FUCA activity group, not correlated to clinical response to trastuzumab but maybe useful as biomarker for predicting progression-free survival for trastuzumab treatment, serum FUCA activity correlates with early detection in hepatocellular carcinoma 3.2.1.51 alpha-L-fucosidase medicine may be useful as a biomarker for predicting the progression-free survival of for trastuzumab treatment 3.2.1.51 alpha-L-fucosidase medicine gastric cancer cells infected with Helicobacter pylori secrete isoform Fuc2A. Fuc2A is essential for Helicobacter pylori adhesion, in particular to the gastric cancer- and duodenal ulcer-specific strains. FUCA2 significantly enhances the expression of Lewis x antigen in Helicobacter pylori, which is critical for bacterial cell adhesion in the pathogenesis and defense strategy to escape host surveillance 3.2.1.51 alpha-L-fucosidase medicine the enzyme is an indicator of poor prognosis for patients with advanced-stage triple-negative breast cancer 3.2.1.52 beta-N-acetylhexosaminidase medicine diagosis of Tay-Sachs disease 3.2.1.52 beta-N-acetylhexosaminidase medicine veterinary medicine: increased level of enzyme in secreted milk can be detected by diagnosis test for mastitis of the mammary gland of cows 3.2.1.52 beta-N-acetylhexosaminidase medicine therapeutic approach for Sandhoff disease 3.2.1.52 beta-N-acetylhexosaminidase medicine drugs inhibiting N-acetyl-beta-D-hexosaminidase activity, such as iminocyclitols, may be useful in cholesteatoma treatment 3.2.1.52 beta-N-acetylhexosaminidase medicine enzyme enhancement therapy utilizing small molecules as pharmacological chaperones is a promising therapeutic approach to treat late-onset forms of Tay-Sachs disease and Sandhoff disease, as well as other lysosomal storage diseases 3.2.1.52 beta-N-acetylhexosaminidase medicine N-acetyl-beta-hexosaminidase may be considered as a new tumour marker in pleomorphic adenoma 3.2.1.52 beta-N-acetylhexosaminidase medicine 2-acetamido-1,2,4-trideoxy-1,4-imino-L-arabinitol, N-benzyl-2-acetamido-1,2,4-trideoxy-1,4-imino-L-arabinitol, and N-butyl-2-acetamido-1,2,4-trideoxy-1,4-imino-L-arabinitol are potent and selective inhibitors of beta-N-acetylhexosaminidase and may be useful as therapeutic agents for treating adult Tay-Sachs and Sandhoff diseases 3.2.1.52 beta-N-acetylhexosaminidase medicine activity of HEX and its isoenzyme A determined in the serum and urine can be used as a potential marker of pancreatic adenocarcinoma 3.2.1.52 beta-N-acetylhexosaminidase medicine GlcNAcase may be an important factor in the formation of paucimannosidic core N-glycans in Drosophila S2 cells. It may be possible to express complex glycoproteins in engineered Drosophila S2 cells by suppressing GlcNAcase in the N-glycosylation pathway 3.2.1.52 beta-N-acetylhexosaminidase medicine HEX and its isoenzymes' activity significantly correlate with the progression of lactation 3.2.1.52 beta-N-acetylhexosaminidase medicine HEX is present in larynx cancer tissue 3.2.1.55 non-reducing end alpha-L-arabinofuranosidase medicine enzyme has been shown to be of interest in connection with a new concept of cancer chemotherapy 3.2.1.58 glucan 1,3-beta-glucosidase medicine panomycocin is a natural antifungal agent against Candida infections. It is most active against Candida tropicalis, Candida pseudotropicalis and Candida glabrata with MIC90 values of 0.001 mg/ml. It displays significant activity against Candida albicans and Candida parapsilosis with MIC90 values of 0.004 and 0.002 mg/ml, respectively. For candida krisei the MIC90 value is 0.008 mg/ml 3.2.1.58 glucan 1,3-beta-glucosidase medicine panomycocin is active in vitro against fungal strains that cause superficial infections. Probable use as a topical antifungal agent 3.2.1.58 glucan 1,3-beta-glucosidase medicine enzyme is the major immunodominant antigen of Pythium insidiosum, causative agent of pythiosis, a life-threatening infectious disease of humans and animals in tropical and subtropical areas 3.2.1.58 glucan 1,3-beta-glucosidase medicine enzyme Exo1 is a major intracellular immunoreactive protein that can trigger host immune responses during infection 3.2.1.59 glucan endo-1,3-alpha-glucosidase medicine the enzyme has a potential as a caries preventive agent, due to the ability to remove the biofilms created by oral bacteria in vitro and to reduce plaque formation in vivo 3.2.1.59 glucan endo-1,3-alpha-glucosidase medicine potent enzyme for removal of dental plaque and hydrolysis of alpha-1,3-glucan in fungal cell walls 3.2.1.62 glycosylceramidase medicine absorption of quercetin-3-glucoside requires hydrolysis by the enzyme, absorption of quercetin-4’-glucoside requires both an interaction with sodium-dependent glucose transporter and hydrolysis by the enzyme 3.2.1.62 glycosylceramidase medicine enzyme plays a major role in metabolism of glycosylated phytochemicals 3.2.1.62 glycosylceramidase medicine perfusion of jejunum and ileum of rats with quercetin-3-glucoseide, enzyme is involved in in vivo intestinal uptake of quercetin-sugars 3.2.1.62 glycosylceramidase medicine LPH is a marker for the terminal differentiation phases of the intestinal development in mice, inactivation of gata 4 has no effect on the mRNA expression of LPH, inactivation of hnf1 results in 50% reduced mRNA levels, specific intestinal genes have differential requirements for gata 4 and hnf1 3.2.1.62 glycosylceramidase medicine rotavirus infection impairs LPH activity in intestinal cells, the decrease in enzyme activity is not Ca2+- and cAMP-dependent, the LPH biosynthesis, stability, and expression is not modified, the impairment of lactase enzymatic activity during rotavirus infection results from an inhibitory action of the secreted non-structural rotavirus protein NSP4 3.2.1.62 glycosylceramidase medicine mutant form G1363S of LPH is involved in the pathogenesis of congenital lactase deficiency 3.2.1.63 1,2-alpha-L-fucosidase medicine 1,2-alpha-L-fucosynthase, derived from an inverting alpha-glycosidase (AfcA) and from a glycosidase with an unusual reaction mechanism, may serve as a promising tool to create biologically active compounds that can be used not only for prebiotics but also for clinical treatments aimed to regulate various cellular processes and infectious diseases 3.2.1.65 levanase medicine pathogenicity of periodontal disease 3.2.1.65 levanase medicine enhancing effect on the immune system and other physiological functions 3.2.1.65 levanase medicine mitogenic for human B lymphocytes and activates the alternative complement pathway 3.2.1.68 isoamylase medicine diagnosis of acute pancreatitis in humans 3.2.1.70 glucan 1,6-alpha-glucosidase medicine the use of iminosugars is applied in preventing dental caries by inhibiting the activity of the dextran glucosidases 3.2.1.76 L-iduronidase medicine the enzyme is a target for enzyme replacement therapy of lysosomal storage disorders of mucopolysaccharidosis type I patients, the therapy depends on efficient uptake of recombinant enzyme into tissues of patients 3.2.1.76 L-iduronidase medicine the enzyme is a target for enzyme replacement therapy of mucopolysaccharidosis type I patients 3.2.1.76 L-iduronidase medicine the recombinant enzyme is used in enzyme relacement therapy of the Hurler form of mucopolysaccharidosis type I, MPSI, the enzyme is administered intraventricularly in to 31 Sprague-Dawley rat brains showing penetration of the brain and uptak into neurons and glial cells, rat tissue distribution of human recombinant enzyme activity, overview 3.2.1.76 L-iduronidase medicine administration of a high dose of the enzyme or development of a recombinant alpha-L-iduronidase containing many mannose 6-phosphate residues is required for further improvement of enzyme replacement therapy for skeletal disorders caused by mucopolysaccharidosis I 3.2.1.76 L-iduronidase medicine as there is a difference in IDUA structural change between the severe mucopolysaccharidosis type I group and the attenuated one, except for a couple of mutations, structural analysis can help predict the clinical outcome of the disease 3.2.1.76 L-iduronidase medicine commercially available recombinant human laronidase (Aldurazyme) infusion is safe and effective in stabilizing or improving pulmonary function and physical endurance. Preclinical trials of the enzyme in the canine, dog and feline model and clinicial trials with affected patients with mucopolysaccharidosis type I 3.2.1.76 L-iduronidase medicine currently approved laronidase dose regimen, to treat the lysosomal storage disorder mucopolysaccharidosis type I, has similar efficacy and potentially improved safety compared to regimens using higher doses, regardless of dose frequency. The approved 0.58 mg/kg/week laronidase dose regimen provides near-maximal reductions in glycosaminoglycan storage and the best benefit-to-risk ratio. The 1.2 mg/kg every 2 weeks regimen may be an acceptable alternative for patients with difficulty receiving weekly infusions, but the long-term effects of this regimen are unknown. In general, laronidase therapy is safe and well tolerated in all treatment groups 3.2.1.76 L-iduronidase medicine long-term clinical benefit and safety of laronidase in attenuated patients with mucopolysaccharidosis I. Laronidase effectively treats respiratory dysfunction, poor endurance, restricted mobility, hepatomegaly, and decreased quality of life. Prompt disease recognition and early and sustained treatment with laronidase will maximize these important benefits of treatment 3.2.1.76 L-iduronidase medicine the benefit of enzyme replacement therapy with recombinant laronidase before hematopoietic stem cell transplantation for mucopolysaccharidosis I is linked to improvement in patient's pretransplantation condition and thus tolerance of such intensive therapy. Short-term use of laronidase is not associated with increased risk of either graft-versus-host-disease or graft failure 3.2.1.76 L-iduronidase medicine effectiveness of enzyme replacement therapy with laronidase on the range of motion of upper extremities and influence on activities of daily living of patients with mucopolysaccharidosis type I, MPS I, overview. MPS I has a spectrum of clinical severity, and is subdivided into three phenotypes: Hurler syndrome, that is severe, Hurler-Scheie syndrome, that is intermediate, and Scheie syndrome, that is attenuated 3.2.1.76 L-iduronidase medicine hIDUA is used for enzyme replacement therapy in MPS I patients 3.2.1.76 L-iduronidase medicine the enzyme is useful in treatment of mucopolysaccharidosis type I, MPS I. In three patients with attenuated MPSA I, treated by laronidase, patients 2 and 3 display significant cognitive improvement within 2 years, and patients 1 and 3 display improvement, on MRI scans of the brain, overview 3.2.1.76 L-iduronidase medicine the enzyme is useful in treatment of mucopolysaccharidosis type I, MPS I, by enzyme replacement therapy 3.2.1.76 L-iduronidase medicine intrathecal administration of recombinant human IDU, with potential dosing every 2-3 months, may provide benefit for the treatment of central nervous system disease in mucopolysaccharidosis type I patients 3.2.1.76 L-iduronidase medicine a clone overexpressing the enzyme and, after encapsulation in alginate microcapsules, correcting MPS I human skin fibroblasts.These capsules can be surgically implanted in sites which are difficult to reach such as the brain of animal models and can be an approach for the treatment of MPS I and other lysosomal storage disorders 3.2.1.76 L-iduronidase medicine alpha-L-iduronidase is used in enzyme replacement therapy approved for mucopolysaccharidosis type I treatment 3.2.1.78 mannan endo-1,4-beta-mannosidase medicine mixed maltooligosacchrides produced by the enzyme exhibit in vitro anti-tumorigenic activity on human colon cancer HT29 cells 3.2.1.84 glucan 1,3-alpha-glucosidase medicine degradation of Streptococcus mutans biofilms, treatment of dental caries 3.2.1.84 glucan 1,3-alpha-glucosidase medicine removal of oral biofilms; possible active ingredients in chewing gum, mouthwash, dental gel, toothpaste 3.2.1.96 mannosyl-glycoprotein endo-beta-N-acetylglucosaminidase medicine use of enzyme for synthesis of a human immunodeficiency virus type 1 glycopeptide with potent anti-HIV activity 3.2.1.102 blood-group-substance endo-1,4-beta-galactosidase medicine the absence of the alphaGal epitope or the exposed N-acetylglucosamine terminal in transgenic mice expressing the enzyme can play a critical role in the proliferation of basal keratinocytes and differentiation of them into the spinous cells 3.2.1.102 blood-group-substance endo-1,4-beta-galactosidase medicine for ABO-incomatible transplantation 3.2.1.103 keratan-sulfate endo-1,4-beta-galactosidase medicine the enzyme reduces viscosity of alpaca semen by 48% 3.2.1.105 3alpha(S)-strictosidine beta-glucosidase medicine plays central role in indole alkaloid biosynthesis 3.2.1.106 mannosyl-oligosaccharide glucosidase medicine treatment of Pompe Disease 3.2.1.108 lactase medicine absorption of quercetin-3-glucoside requires hydrolysis by the enzyme, absorption of quercetin-4’-glucoside requires both an interaction with sodium-dependent glucose transporter and hydrolysis by the enzyme 3.2.1.108 lactase medicine enzyme plays a major role in metabolism of glycosilated phytochemicals 3.2.1.108 lactase medicine findings facilitate genetic testing and enable genetic counseling for congential lactase deficiency, CLD 3.2.1.108 lactase medicine in irritable bowel syndrome, IBS, patients, genotyping of C/T_13910 and G/A_22018 polymorphisms predicts gastrointestinal symptoms after lactose ingestion and are a diagnostic tool for lactose intolerance 3.2.1.108 lactase medicine the T/G-13915 variant is the founder mutation of lactase persistence, the result has implications for genetic testing of adult-type hypolactasia 3.2.1.108 lactase medicine the use of new substrates for the measurement of lactase activity provides a new method for the noninvasive diagnosis of hypolactasia 3.2.1.108 lactase medicine among 107 milk-drinking Somali camel-herders from Ethiopia, eight polymorphic sites are identified in the enhancer sequence in an intron of a neighboring gene MCM6 which modulates lactase transcription in vitro. -13915*G and -13907*G are each significantly associated with lactase persistence. Allele -14009*G has borderline association with lactase persistence, but loses significance after correction for multiple testing. Sequence diversity of the enhancer is significantly higher in the lactase persistent members of this and a second cohort compared with non-persistent members of the two groups 3.2.1.108 lactase medicine analysis of sequence variants of lactase persistence/lactase non-persistence LP/LNP in subjects originating from Northern Russia. The prevalence of the -13910C/C genotype among 148 patients was 28.4%. A G to A variant residing 13914 bp upstream from the LCT gene, -13914G/A, was identified in one participant carrying the -13910C/C genotype. The -13914G/A variant in heterozygous state is associated with increased lactase activity, suggesting that the increased lactase activity is most likely to be associated with the -13914G/A variant 3.2.1.108 lactase medicine the C allele of the T-13910C polymorphism causing lactose intolerance is associated with lower dietary calcium intake and serum calcium levels but not with bone mineral density or fractures. The associations observed with height and vertebral area were the result of population stratification 3.2.1.108 lactase medicine C/T-13910 cis-acting regulatory variant located around 14 kb upstream of lactase gene completely correlates with lactase phenotype in Indian children. The genetic testing for the C/T -13910 variant may be helpful in the diagnosis of adult-type hypolactasia in Indian children 3.2.1.112 2-deoxyglucosidase medicine potential target to increase effectiveness of 2-deoxy-D-glucose in chemotherapy and viral infections 3.2.1.113 mannosyl-oligosaccharide 1,2-alpha-mannosidase medicine the class I alpha-mannosidases can be used as drug targets to inhibit the demannosylation of HBV, thereby improving the binding of the virus to DC-SIGN and disrupting the immune tolerance to prevent and treat viral infection 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase medicine enzyme deficiency causes congenital dyserythropoietic anemia with splenomegaly and various additional abnormalities and complications 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase medicine reduced expression of Man II in the autosomal genetic HEMPAS disease, i.e. hereditary erythroblastic multinuclearity associated with positive acidified serum 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase medicine alpha-mannosidase IIx is an isozyme of MII. Either MII or alpha-mannosidase IIx can biochemically compensate for the deficiency of the other in vivo, and either of two is required for late embryonic and early postnatal development 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase medicine promising target for drug development in anti-tumor therapies, ability of seven available docking programs to predict the binding mode and binding affinity of alpha-mannosidase II inhibitors 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase medicine single nucleotide polymorphisms in MAN2A1 may be a genetic factor for inflammatory bowel disease 3.2.1.117 amygdalin beta-glucosidase medicine chemotherapy, conjugate with antibody 3.2.1.123 endoglycosylceramidase medicine release of glycans from the ceramide moieties of glycosphingolipids by endoglycoceramidase II treatment in order to analyze structures of glycosphingolipids in normal human colorectal epithelial cells, and characteristic alterations of oligosaccharide structures in malignant transformation 3.2.1.127 1,6-alpha-L-fucosidase medicine progression-free survival significantly longer in high FUCA activity group than in low FUCA activity group, not correlated to clinical response to trastuzumab but maybe useful as biomarker for predicting progression-free survival for trastuzumab treatment 3.2.1.127 1,6-alpha-L-fucosidase medicine using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector function 3.2.1.129 endo-alpha-sialidase medicine degradation of non-toxic modified polysialic acid hydrogel scaffold in neuro-regenerative tissue engineering (4.26 microgram enzyme + 39 mg hydrogel), in phosphate buffered saline (400 microl, pH 7.4), at 37°C, degradation speed 2-11 days depending on cross-linker amount (0.6, 0.8, 2 equivalents diepoxyoctane, no activity with 3 equivalents diepoxyoctane), hydrogel was coated with collagen I, poly-L-lysine/collagen I, or diluted matrigel for neurite formation in PC12 cells 3.2.1.129 endo-alpha-sialidase medicine degradation of non-toxic modified polysialic acid hydrogel scaffold in neuro-regenerative tissue engineering: no degradation in 12 days with 1 microg/ml active enzyme + 105 cubic mm hydrogel in phosphate buffered saline (pH 7.4), at room temperature, increase to 4 microg/ml at end of week 2 initiates degradation, total degradation after 4 weeks, hydrogel was coated with poly-L-lysine, poly-L-ornithine-laminin or collagen for neurite formation in neonatal and adult rat Schwann cells, neural rat stem cells, and dorsal root ganglionic cells from rats 3.2.1.129 endo-alpha-sialidase medicine investigation of possible role of polysialic neural cell adhesion molecules in the pathophysiology of epilepsy 3.2.1.129 endo-alpha-sialidase medicine a noncatalytic enzyme is used for detecting small-cell lung cancer circulating tumor cells 3.2.1.129 endo-alpha-sialidase medicine the enzyme recognizes polysialic acid, an oncofetal antigen characteristic for high malignant tumors of neuroendocrine origin 3.2.1.130 glycoprotein endo-alpha-1,2-mannosidase medicine cocaine-induced paranoia is associated with 6 single-nucleotide polymorphisms in European American families and 9 single-nucleotide polymorphisms in African American families. Association of MANEA single-nucleotide polymorphisms with cocaine dependence in both family samples is much weaker. The A allele of the 3' untranslated region single-nucleotide polymorphism rs9387522 is associated with increased risk of cocaine-induced paranoia 3.2.1.132 chitosanase medicine the chitosanase has promising benefit as antibiofilm agent against biofilm forming pathogenic bacteria and has promising application as alternative antibiofilm agents to combat the growing number of multidrug resistant pathogen-associated infections, especially in situation where biofilms are involved 3.2.1.133 glucan 1,4-alpha-maltohydrolase medicine synthesis of acarvisione-simmondsin, a novel compound with both antiobesity and hypoglycemic activity 3.2.1.133 glucan 1,4-alpha-maltohydrolase medicine pierarin (daidzein 8-C-glucoside), can be used to treat coronary heart disease, cardiac infarction, problems in ocular blood flow, sudden deafness, and alcoholism. However puerarin cannot be given by injection due to its low solubility in water. To increase its solubility, puerarin is transglycosylated using Bacillus stearothermophilus maltogenic amylase. Two major transfer products are alpha-D-glucosyl-(1,6)-puerarin and alpha-D-maltosyl-(1,6)-puerarin. The solubility of the transfer products is 14 and 168 times higher than that of puerarin, respectively 3.2.1.143 poly(ADP-ribose) glycohydrolase medicine DNA repair factor XRCC1 is involved in regulating a poly(ADP-ribose)-mediated apoptotic cell death 3.2.1.143 poly(ADP-ribose) glycohydrolase medicine enzyme activity modulates the inflammatory response and tissue events associated with spinal cord trauma and participates in target organ damage under these conditions 3.2.1.143 poly(ADP-ribose) glycohydrolase medicine treatment of wild-type mice with pharmacological inhibitors GPI 16552 or GPI 18214 shows a protective effect in dinitrobenzene sulfonic acid-induced colitis. Mice lacking the functional 110 kDa isoform of enzyme are resistant to colon injury by dinitrobenzene sulfonic acid. Mucosa of mutant mice colon tissue shows reduction of myeloperoxidase activity and attenuated staining for intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Overproduction of proinflammatory factors tumor necrosis factor alpha and interleukin 1beta and activation of cell death signaling pathway are inhibited in these mice 3.2.1.143 poly(ADP-ribose) glycohydrolase medicine since combination of poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase inhibition in chemotherapy does not produce increased HeLa cell death, strate­gies that target poly(ADP-ribose) metabolism for the improved treatment of cancer may be required to target poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase individually in order to optimize cancer cell death 3.2.1.143 poly(ADP-ribose) glycohydrolase medicine the enzyme is a potential target for neuroprotective treatments for retinal degeneration 3.2.1.143 poly(ADP-ribose) glycohydrolase medicine the enzyme is a promising therapeutic target for the treatment of Chagas' disease 3.2.1.166 heparanase medicine heparanase-1 is an approach towards developing new therapeutics suitable for the treatment of cancer or inflammatory diseases. The identification of only a single predominant functional heparanase suggests that if its activity can be inhibited, other heparanases may not be available to cover for it. Heparanase-inhibiting compounds might interfere with physiological processes such as wound healing and tissue-repair 3.2.1.166 heparanase medicine upregulation of heparanase may be a novel therapeutic approach in the prevention and treatment of osteoporosis 3.2.1.166 heparanase medicine increased heparanase levels are most often associated with reduced patient survival post operation, increased tumor metastasis and higher microvessel density 3.2.1.166 heparanase medicine specific inhibitors for heparanase are important for suppression of tumor progression and metastasis 3.2.1.169 protein O-GlcNAcase medicine the enzyme is a drug target for the treatment of Alzheimer's and cardiovascular disease 3.2.1.207 mannosyl-oligosaccharide alpha-1,3-glucosidase medicine inhibitors of the enzyme are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes 3.2.2.5 NAD+ glycohydrolase medicine CD157-deficient neutrophils from patients with paroxysmal nocturnal hemoglobinuria are characterized by a severely impaired diapedesis 3.2.2.5 NAD+ glycohydrolase medicine CD38 rather than poly-ADP-ribose polymerase PARP-1, is an important source of ADP-ribose in mouse neutrophils and dendritic cells that use ADP-ribose as a secong messenger. ADP-ribose controls calcium influx and chemotaxis when cells are activated through chemokine receptors that rely on CD38 and cyclic ADP-ribose for activity 3.2.2.5 NAD+ glycohydrolase medicine treatment of lymphokine-activated killer cells with interleukin IL-8 results in internalization of CD38, which co-localizes with nonmuscle myosin heavy chain IIA and tyrosine kinase Lck. Blebbistatin blocks the internalization 3.2.2.5 NAD+ glycohydrolase medicine tumor necrosis factor alpha upregulates CD38. Induced CD38 expression enhances inflammatory gene expression by decreasing ERK1/2 phosphorylation and increasing NF kappaB activation. It negatively affects the expression of osteoclast markers. CD38 may reduce osteoclastogenesis and increase inflammatory gene induction by decreasing cellular histone deacetylase activity 3.2.2.5 NAD+ glycohydrolase medicine CovR and CovS two-component regulatory system regulates the Nga activity, which is considered important in the pathogenesis of STSS streptococcal toxic shock syndrome 3.2.2.5 NAD+ glycohydrolase medicine vaccination with CagL has protective efficacy in mice 3.2.2.9 adenosylhomocysteine nucleosidase medicine potential target for chemotherapeutic intervention, nucleoside analogues which inhibit the nucleosidase could kill invading microorganisms by perturbing methylation processes and polyamine levels 3.2.2.9 adenosylhomocysteine nucleosidase medicine 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase is thought to be an ideal target for therapeutic drug design as the enzyme is present in many microbes but not in mammals. The inhibition of MTAN leads to a build-up of toxic byproducts that affect various microbial pathways such as quorum sensing, biological methylation, polyamine biosynthesis, and methionine recycling. The design of nucleosidase-specific inhibitors is complicated by its structural similarity to the human MTA phosphorylase. Structural comparison of 5'-methylthioadenosine phosphorylase and MTA/AdoHcy nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design 3.2.2.9 adenosylhomocysteine nucleosidase medicine inhibitors of methylthioadenosine/S-adenosylhomocysteine nucleosidase are anti-infective drugs against various bacterial pathogens 3.2.2.9 adenosylhomocysteine nucleosidase medicine inhibitors of MTA/SAH nucleosidase are anti-infective drugs against various bacterial pathogens 3.2.2.16 methylthioadenosine nucleosidase medicine potential chemotherapeutic agent 3.2.2.17 deoxyribodipyrimidine endonucleosidase medicine topical DNA repair enzyme application may be a clinically useful approach of photo-protection in humans. The most useful role for T4 endonuclease V would be its inclusion in sun-block 3.2.2.21 DNA-3-methyladenine glycosylase II medicine overexpression of MPG can result in increased kill of tumor cells using lower doses of harmful alkylating agents such as temozolomide and cross-linking agents such as cisplatin, use of lower doses of chemotherapeutic agents, which will decrease the emergence of drug-resistant tumor cells and decrease the need fro stem-cell support, leading to an increased patient response and a better quality of life for the patient 3.2.2.21 DNA-3-methyladenine glycosylase II medicine MPG overexpression is paradoxically associated with increased suspectibility to DNA damage, up-regulation of this gene may suggest a functional role in breast carcinogenesis, animal models using transgenic mice overexpressing the enzyme are being developed to determine the in vivo role of MPG in breast carcinogenesis 3.2.2.21 DNA-3-methyladenine glycosylase II medicine sulfur mustard, or mustard gas, bis-(2-chloroethyl)sulfide is carcinogenic to humans, acutely toxic to the skin, repiratory tract and eyes and causes a delayed bone marrow depression, knowledge of the DNA damage caused by this agent and the cellular defenses against this damage are of fundamental importance 3.2.2.21 DNA-3-methyladenine glycosylase II medicine recombinant expression of enzyme and targeting to mitochondria or nucleus of primary astrocytes. Increasing enzyme activity significantly increases base excision repair kinetics in both the mitochondria and nuclei. Increased nuclear enzyme activity results in cell death in astrocyte cultures treated with methylnitrososurea 3.2.2.22 rRNA N-glycosylase medicine - 3.2.2.22 rRNA N-glycosylase medicine RIP proteins display a variety of activities in addition to rRNA N-glycosidase activity, antiviral, antifungal, apoptosis-inducing, antitumor, immunosuppressive, and HIV-1 integrase inhibitory activity, because of their translational inhibitory activity and other pharmacological properties, they have been regarded as having great potential for use as selective cell-killing agents 3.2.2.22 rRNA N-glycosylase medicine trichosanthin is a potent HIV-1 inhibitor 3.2.2.22 rRNA N-glycosylase medicine antifungal activity toward Physalospora piricola, Mycosphaerella arachidicola, Fusarium oxysporum, and Coprinus comatus 3.2.2.22 rRNA N-glycosylase medicine trichoanguin examined for preparation of immunotoxins, with a great potential for application as an effective chemotherapeutic agent for the treatment of various cancers or AIDS 3.2.2.22 rRNA N-glycosylase medicine chinese medicinal herb capable of removing phlegm and treating cough 3.2.2.22 rRNA N-glycosylase medicine TCS used as abortifacient in China 3.2.2.22 rRNA N-glycosylase medicine DNA damaging activity of gelonin may be responsible for the elimination of the parasite 6 Kb extrachromosomal mitochondrial DNA of Plasmodium falciparum infected erythrocytes 3.2.2.22 rRNA N-glycosylase medicine gelonin acts as immunotoxin 3.2.2.22 rRNA N-glycosylase medicine MAP shows antifungal activity 3.2.2.22 rRNA N-glycosylase medicine PAP acts as immunotoxin 3.2.2.22 rRNA N-glycosylase medicine saporin acts as immunotoxin 3.2.2.22 rRNA N-glycosylase medicine the enzyme shows antifungal activity 3.2.2.22 rRNA N-glycosylase medicine trichosanthin is immunogenic and leads to IgE production in humans, Trichosanthes kirilowii is a traditional chinese medicine plant, root tubers containing trichosanthin cause abortion, overview 3.2.2.22 rRNA N-glycosylase medicine construct of recombinant gelonin fused to cytokine B lymphocyte stimulator to specifically target quiescent B-CLL lymphocytes. The construct specifically binds and internalizes through cell-surface receptor BAFF-R into CD19 B-CLL lymphocytes and induces apoptosis at nanomolar concentrations. In contrast, rGel alone is not able to internalize into these leukemic lymphocytes. Mechanistically, the construct inhibits protein synthesis with an IC50 of less than 3 nM compared with more than 5000 nM for rGel toxin alone 3.2.2.22 rRNA N-glycosylase medicine construction of a chimeric antibody using variable region genes of anti-ricin monoclonal antibody 4C13 which can neutralize the toxicitiy of ricin, and human constant region genes. The chimeric antibody blocks ricin-induced cytotoxicity to SP2/0 cells 3.2.2.22 rRNA N-glycosylase medicine construction of a immunotoxin consisting of the non-toxic type 2 ribosome-inactivating protein nigrin b linked to the monoclonal anti-human CD105 antibody 44G4. The immunotoxin kills specifically mouse fibroblasts expressing the biomarker CD105 with an IC50 value of 0.6 nM while nigrin does it at 0.24 microM. The immunotoxin accumulates in a perinuclear region 3.2.2.22 rRNA N-glycosylase medicine construction of chimeric toxin composed of saporin, a cleavable adapter, and human epidermic growth factor. Presence of the saponins saponinum album or quillajasaponin enhances cytotoxicity of the construct more than 1000fold and decreases IC50 values from 2.4 nM in absence of saponin to 0.18 pM in presence of saponinum album. Quillajasaponin enhances the cytotoxicity both on control cells lacking epidermal growth factor receptor and on target cells, while saponinum album is target cell receptor specific 3.2.2.22 rRNA N-glycosylase medicine coupling of an anti-CD38 monoclonal antibody to saporin-S6 and treatment of selected human CD38+ cell ines and CD38+ neoplastic cells from a NonHodgkin Lymphoma patient. In HBL6, Raji and L540 cells protein synthesis is completely inhibited by the conjugate at 100 pM. CD38+ cells from the patient wee completely eliminated after treatment at 10 nM while CFU-c rescue by bone marrow precursors was maintained 3.2.2.22 rRNA N-glycosylase medicine cubic morphology lyotropic mesophases containing galactose amphiphiles exhibit high specificity ricin uptake with high dissociation constants and high capactities, and may be used as ricin antitoxins 3.2.2.22 rRNA N-glycosylase medicine development of an oropharyngeal aspiration model for ricin lethal challenge and antibody administration. When polyclonal anti-deglycosylated ricin A chain antibody is administered between 1-18 h after ricin challenge, all mice survive, while delayed treatment to 24 h results in 30% survival. Protective effects of antibody correlate with inhibition of apoptosis in lungs in vivo and in RAW264.7 macrophage and Jurkat cells in vitro 3.2.2.22 rRNA N-glycosylase medicine disruption of vascular leak syndrome-inducing site and of ribotoxic site. Injection i.m. into mice protects them against a ricin challenge of 10 LD50s. Injection into humans shows that the mutant is safe and elicits ricin-neutralizing antibodies in five of five individuals in the high-dose group 3.2.2.22 rRNA N-glycosylase medicine evaluation of cytotoxicity of ricin A chain and ricin A chain fusion protein with enhanced green fluorescent protein in HeLa and HEP-G2 cells following fluid-phase endocytosis. Fusion protein ahs a similar toxicity like ricin A chain. After endocytosis, ricin A chain reaches the endoplasmic reticulum 3.2.2.22 rRNA N-glycosylase medicine expression of A chain in Escherichia coli with His-tag and purification. Construction of replication-deficient ricin B chain adenovirus-green fluorescent protein fusion protein. When used individually, neither A chain nor B chain protein is toxic to human cell lines HEK 293, HeLa, SMMC 7721, and HL 7702, and entry of A chain into cells infected with the fusion contruct is confirmed. When applied together, significant cell death is observed in all cell lines tested 3.2.2.22 rRNA N-glycosylase medicine following encapsulation in negatively charged liposomes, the cytotoxicity of ricin in chinese hamster ovary cells is markedly reduced. Lactose has no effect on the binding, internalization, and cytotoxicity of liposomal ricin. Both monensin and NH4Cl markedly enhance the cytotoxicity of liposomal ricin. The extent of exocytosis of free ricin is much higher as compared to liposomal ricin 3.2.2.22 rRNA N-glycosylase medicine fusion of the CTL epitope from the pneumonia virus of mice phosphoprotein to the mature 5'-terminus of the ricin A chain of the non-toxic mutant RTA6K-R180H. Fusion protein elicits a CD8+ T-cell response in mice directed against pneumonia virus of mice, and the T-cell response resulting from inoculation with the ricin-peptide fusion molecule delays the onset of virus-induced disease 3.2.2.22 rRNA N-glycosylase medicine in HeLa cells, ricin transport to the trans-Golgi network is inhibited when the small GTPase Rab6A messenger RNA levels are reduced by more than 40% and less than 75%. However, when Rab6A mRNA is reduced by more than 75% and Rab6A’mRNA is simultaneously up-regulated, the inhibition of ricin sulfation is abolished. The depletion of both Rab6A and Rab6A’ gives a stronger inhibition of ricin sulfation than what is observed knocking down the two isoforms separately 3.2.2.22 rRNA N-glycosylase medicine injection of ricin A chain or of Ricinus communis agglutinin into rat eyes at 0.01 nM bring about acute retinal inflammation and necrosis 3.2.2.22 rRNA N-glycosylase medicine injection of trichosanthin into rat eyes causes distinct retinal changes at 1 nM. Toxic effects are most pronounced in the cells of the outer nuclear layer, less pronounced on those of the inner nuclear layer, and little on the ganglion cells. Apoptosis is the predominant type of cell death induced by trichosanthin 3.2.2.22 rRNA N-glycosylase medicine isolation of monoclonal IgA antibodies active against ricin A chain or ricin B chain, respectively, that neutralize ricin in a Vero cell cytotoxicity assay, block toxin-induced interleukin-8 release by the human macrophage cell line 28SC, and protect polarized epithelial cell monolayers from ricin-mediated protein synthesis inhibition 3.2.2.22 rRNA N-glycosylase medicine major histocompatibility complex class I tetramers H2-Db assembled using streptavidin conjugated to the ribosome-inactivating protein saporin. These tetramers inhibit ribosome activity in vitro, retain the T-cell receptor-binding specificity of their nontoxic counterparts, and are internalized by 100% of target cells, leading to cell death in 72 hours. Cytotoxicity is dependent on the tetramer dose and avidity for the T cell 3.2.2.22 rRNA N-glycosylase medicine mice co-inoculated with purified recombinant ricin b chain plus 90-amino acid peptide from the simian rotavirus SA-11 nonstructural protein, NSP4 or heat denatured NSP490/ricin B chain fusion protein generate higher titers of serum anti-NSP490 IgG antibodies than mice immunized with NSP490 peptide alone, immunostimulatory function of ricin B chain 3.2.2.22 rRNA N-glycosylase medicine ricin interacts with the ER degradation enhancing alpha-mannosidase I-like protein EDEM responsible for redirecting aberrant proteins for ER-associated protein degradation and with Sec61alpha, and both kifunensin and puromycin enhance these interactions. Overexpression of EDEM strongly protects against ricin. In presence of kifunensin, EDEM promotes retranslocation of ricin from the ER to the cytosol 3.2.2.22 rRNA N-glycosylase medicine ricin stimulates human monocyte/macrophage cell line 28SC to secrete interleukin IL-8. IL-8 induction can be blocked by brefeldin A. After ricin exposure, p38 mitogen activated protein kinase levels are elevated. Treatment of cells with p38 mitogen activated protein kinase inhibitor SB203580 suppresses ricin-mediated IL-8 release 3.2.2.22 rRNA N-glycosylase medicine ricin toxicosis in a 12-week-old Mastiff puppy results in acute vomitting, diarrhea, and lethargy and subsequent death after several hours. Histopathologic findings include superficial necrotizing enteritis of the jejunum and occasional, random foci of coagulative necrosis in the liver 3.2.2.22 rRNA N-glycosylase medicine study on ricin A chain vaccine RTA 1-33/44-198 developed by protein engineering. Adsorption of the vaccine to aluminium hydroxide produces a small change in secondary structure that significantly stabilizes the protein to thermal denaturation 3.2.2.22 rRNA N-glycosylase medicine study on the cytotoxicity of ricin encapsulated in various liposomes. Cytotoxicity against CHO pro- cells is significnatly dependent on the charge on the surface of liposomes. Maximum cytotoxicity is observed by delivering ricin through negatively charged liposomes. Monensin enhances the cytotoxicity with maximum potentiation on delivery through positively charged liposomes and depending on the density of distearylphosphatidylethanolamine-mPEG-2000 on their surface 3.2.2.22 rRNA N-glycosylase medicine study on the endosome to Golgi transport of ricin in cell line LY-B deficient in serine palmitoyltransferase and in wildtype CHO-K1 cells in presence/absence of the inhibitor of sphingolipid biosynthesis, myriocin. Depletion of sphingolipids results in increased sensitivity to ricin. Endosome to Golgi transport of ricin is increased in sphingolipid-deficient cells. Additionally, cholesterol depletion inhibits endosome to Golgi transport even in cells with reduced levels of sphingolipids 3.2.2.22 rRNA N-glycosylase medicine treatment with dimethylsulfoxide and lipopolyamine administration both generate substantial cellular sensitization to ricin and a chemical conjugate of urokinase plasminogen activator and saporin used as anticancer toxin. Major site for the dimethylsulfoxide-facilitated entry of saporin into the cytosol is an endosomal trafficking step preceeding cargo delivery to the late endosome. Senitization effects are specific for saporin and suggest a translocation of saporin via endosomal disruption 3.2.2.22 rRNA N-glycosylase medicine the conserved alpha-helix is considered as a potential target for the prevention and treatment of ribosome-inactivating protein poisoning 3.2.2.22 rRNA N-glycosylase medicine C-terminal enzymatically active ricin A chain variants are specifically cleaved by HIV-1 protease both in vitro and in HIV-infected cells and the products mediate specific inhibitory effect towards HIV replication. Upon proteolysis, the processed variants show enhanced antiviral effect with low cytotoxicity towards uninfected cells 3.2.2.22 rRNA N-glycosylase medicine the enzyme is used in the official Chinese medicine to induce abortion and to treat hydatidiform mol 3.2.2.22 rRNA N-glycosylase medicine the minimum inhibitory concentrations of recombinant balsamin for various pathogens ranges between 1.56 and 12.5 microg/ml 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine cells from children with Down's syndrome do not display an effective DNA repair after treatment with 10 mM hydrogen peroxide. No difference in the sensitivity to DNA-damaging agents and the efficacy of DNA repair due to age and gender in children with Down's syndrome is observed 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine expression of enzyme in human cells from patients belonging to Cockayne syndrome complementation groups A and B completely corrects the repair deficiency in both CS-A and CS-B cells. The sensitivity of CS-B cells to elevated concentrations of potassium bromate is not compensated by expression of enzyme 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine expression of enzyme-green fluorescent protein fusion protein in human bladder cells. Cells expressing the fusion protein repair 8-oxoguanine and abasic sites at accelerated rates and are resistant to the oxidizing carcinogen potassium bromate 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine lymphocytes of rats exposed to thinner fumes exhibits a significant increase in enzyme-sensitive DNA sites compared with control. The most abundant base oxidation product is 8-oxoguanine, which is the main substrate of enzyme 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine melatonin can have a protective effect against oxidative DNA damage by chemical inactivation of a DNA-damaging agent as well as by stimulating DNA repair, but key factors such as DNA-formaidopyrimidine glycosylase, endonuclease III are not affected by melatonin 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine no correlation between the S1245C polymorphism of the OGG! Gene and gastric cancer. In contrast, there is a strong correlation between gastric cancer occurrence, impaired DNA repair in human lymphocytes, and the G135C polymorphism of the RAD51 gene 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine significant amounts of 85% of enzyme-sensitive DNA sites are found in smokers, and considerably high but not significant amounts in passive non- and ex-smokers, 51 and 37%, respectively 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine study on the polymorphism 23A to G in the DNA repair gene XPA. Presence of the A allele is associated with higher levels of DNA damage as well as with higher activity of the OGG1 8-oxoguanidine DNA glycosylase. In individuals with the A allele, OGG1 repair activity also increases with age 3.2.2.23 DNA-formamidopyrimidine glycosylase medicine treatment of cells with 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone generates formamidopyrimidine glycosylase sensitive DNA sites with cell-type dependent differences in adduct frequency and time 3.2.2.26 futalosine hydrolase medicine MqnB in Helicobacter pylori is an attractive target for the development of specific anti-Helicobacter pylori drugs 3.2.2.27 uracil-DNA glycosylase medicine inhibition of UNG is a rational therapeutic strategy for infections with poxviruses 3.2.2.29 thymine-DNA glycosylase medicine 5-fluorouracil is used in clinical cancer therapy. The status of TDG expression in a cancer is likely to determine its response to 5-fluorouracil-based chemotherapy 3.2.2.29 thymine-DNA glycosylase medicine the enzyme is a highly suitable anti-melanoma drug target 3.3.2.6 leukotriene-A4 hydrolase medicine the lipid metabolic activity of enzyme plays a central role in the control of polymorphonuclear leukocyte function and in the development of inflammation, the regulation of enzyme presents a novel potential target for anti-inflammatory therapy 3.3.2.6 leukotriene-A4 hydrolase medicine enzyme overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of esophageal adenocarcinogenesis 3.3.2.6 leukotriene-A4 hydrolase medicine the product is a classical chemoattractant, triggers adherence and aggregation of leukocytes to the endothelium, modulates immune responses, participates in the host-defence against infections and is a mediator of PAF-induced lethal shock 3.3.2.6 leukotriene-A4 hydrolase medicine the enzyme catalyses the hydrolysis of leukotriene A4 into the proinflammatory substance leukotriene B4 3.3.2.6 leukotriene-A4 hydrolase medicine findings suggest that agents affecting LTB4 biosynthetic pathway may prove useful for primary or secondary prevention of heart attacks 3.3.2.6 leukotriene-A4 hydrolase medicine LTA4H appears to be a promising target for development of drugs for prevention and treatment of atherosclerosis and its associated thrombotic complications 3.3.2.6 leukotriene-A4 hydrolase medicine the 5-Lox/LTA4H pathway is involved in 7,12-dimethylbenz[alpha]anthracene induced oral carcinogenesis and may be targeted for chemoprevention of oral cancer 3.3.2.6 leukotriene-A4 hydrolase medicine understanding the molecular alterations that influence primary effusion lymphoma development will aid in the identification of novel therapeutic targets, as well as potential risk factors for this desease 3.3.2.6 leukotriene-A4 hydrolase medicine LTA4H is significantly associated with coronary artery disease 3.3.2.6 leukotriene-A4 hydrolase medicine inhibition of LTB4 synthesis may be beneficial in the treatment of severe asthma and viral exacerbations of asthma, in which neutrophilic inflammation is more prominent 3.3.2.6 leukotriene-A4 hydrolase medicine inhibition of this enzyme can be a valid method in the treatment of inflammatory response exhibited through leukotriene B4 3.3.2.6 leukotriene-A4 hydrolase medicine LTB4 can serve as a biomarker for evaluating bestatin efficacy in colorectal cancer and the antitumor effects of bestatin through its targeting of LTA4H 3.3.2.9 microsomal epoxide hydrolase medicine high EPHX1 activity is associated with an increased risk for lifetime asthma, which varies by glutathione S-transferase P1 Ile105Val genotype and by residential proximity to major roads. Among children with glutathione S-transferase P1 105Val/Val genotype, those who have high EPHX1 phenotype have a fourfold increased risk of lifetime asthma. Among children living within 75 metres of a major road, those with high EPHX1 activity had a 3.2-fold higher lifetime asthma risk. The results are similar for current, early persistent and late onset asthma 3.3.2.9 microsomal epoxide hydrolase medicine incubation of ovaries in a neonatal mouse ovarian culture system in presence of 7,12-dimethylbenz[a]anthracene. At 1 mM 7,12-dimethylbenz[a]anthracene, follicle loss and increased microsomal epoxide hydrolase protein are measured by 6 h. mRNA encoding epoxide hydrolase markedly increases after 2 days of incubation, and this increase precedes accelerated follicle loss at 4 days 3.3.2.9 microsomal epoxide hydrolase medicine investigation on the expression and genetic polymorphism of microsomal epoxide hydrolase in non-small cell lung cancer patients. Enzyme is expressed in 83% of biopsies analyzed, and the major allelic expression pattern is fast type (Tyr113) in exon 3 (90.3%) and slow type (His139) in exon 4 (100%). A significant difference in patient survival is found when enzyme expression and adriamycin-containing chemotherapy are used to group patients. With respect to cancer risk and disease progression, the expression level of enzyme seems as important as genetic polymorphism 3.3.2.9 microsomal epoxide hydrolase medicine investigation on the influence of single nucleotide polymorphisms in EPHX1 on well characterized chronic obstructive pulmonary disease and intermediate phenotypes. The EPHX1 exon 3 polymorphism is not associated with an increased risk of chronic obstructive pulmonary disease, nor is the EPHX1 exon 4 polymorphism. In addition, none of the EPHX1 haplotypes are associated with an increased risk of any chronic obstructive pulmonary disease phenotype 3.3.2.9 microsomal epoxide hydrolase medicine significant association of prostate cancer risk with exon 3 variant genotypes of microsomal epoxide hydrolase alone or in combination with tobacco users, whereas in exon 4 genotypes, no association is observed. T/C polymorphism of CYPA1 gene is an additional predisposing factor 3.3.2.9 microsomal epoxide hydrolase medicine study on polymorphisms of microsomal epoxide hydrolase. Genotype frequencies of exon 3 are Tyr113Tyr 50.4%, Tyr113His 42.1%, His113His 7.5%, and on exon 4 His139His 69.2%, His139Arg 28.6%, Arg133Arg 2.2% 3.3.2.9 microsomal epoxide hydrolase medicine study on the effect of enzyme genotype on risk of myocardial infarction of smokers and non-smokers among patients with a first acute non-fatal myocardial infarction. EPHX1 genotype is not associated with risk of myocardial infarction, regardless of smoking status, and does not play a significant role in the development of coronary heart disease 3.3.2.9 microsomal epoxide hydrolase medicine EPHX1 does not play a role in the initiation of pancreatic inflammation or cancer 3.3.2.9 microsomal epoxide hydrolase medicine genetic mEPHX variants are positively associated with viral-related hepatocellular carcinoma risk 3.3.2.9 microsomal epoxide hydrolase medicine patients with exon 3 genotypes (Tyr113His, His113His) and 113His allele are at risk of squamous cell esophageal cancer, none of haplotype combinations of exon 3 (Y113H) and exon 4 (H139R) polymorphisms show modulation of risk for squamous cell esophageal cancer 3.3.2.9 microsomal epoxide hydrolase medicine polymorphisms in the microsomal epoxide hydrolase gene (EPHX1 His113-His113 genotype) are associated with chronic obstructive pulmonary disease 3.3.2.9 microsomal epoxide hydrolase medicine the exon 3 His genotype of the mEH gene polymorphism alone or in combination with tobacco-users are significantly associated with the risk of sporadic bladder cancer 3.3.2.9 microsomal epoxide hydrolase medicine there is no association of EPHX1 gene variation with susceptibility to chronic obstructive pulmonary disease or disease severity 3.3.2.9 microsomal epoxide hydrolase medicine there is no risk-modifying effect of genetic polymorphisms in microsomal epoxide hydrolase on head and neck carcinogenesis, except for the predicted high activity variant H139R in patients with hypopharyngeal carcinoma 3.3.2.10 soluble epoxide hydrolase medicine enzyme inhibition is used in treatment of hypertension 3.3.2.10 soluble epoxide hydrolase medicine the enzyme is a target for regulation of blood pressure, and inhibition of inflammation, atherosclerosis, kidney failure, and cancer progression 3.3.2.10 soluble epoxide hydrolase medicine the enzyme is a therapeutic target for control of blood pressure 3.3.2.10 soluble epoxide hydrolase medicine the enzyme is a therapeutic target in therapeutic intervention in renal hydrodynamic regulation and blood pressure control 3.3.2.10 soluble epoxide hydrolase medicine expression of soluble epoxide hydrolase is significantly lower in stroke-prone than in stroke-resitant rats. Identification of 3 polymorphisms that significantly influence promoter transcriptional activity in vitro 3.3.2.10 soluble epoxide hydrolase medicine kinetic analysis of the effects of human enzyme polymorphisms on the N-terminal phosphatase activity of soluble epoxide hydrolase activity 3.3.2.10 soluble epoxide hydrolase medicine mice with targeted disruption of the Ephx2 gene coding for soluble epoxide hydrolase have normal heart anatomy and basal contractile function, but have higher fatty acid epoxide:diol ratios in plasma and cardiomyocytes cell culture media. The heart have improved recovery of left ventricular developed pressure and less infarction after 20 min ischemia, compared with wild-type. Perfusion with 14,15-epoxyeicosa-5(Z)-enoic acid before ischemia abolishes this cardioprotective phenotype. Enzyme null mice exhibit increased cardiac expression of glycogen synthase kinase-3beta phosphoprotein after ischemia 3.3.2.10 soluble epoxide hydrolase medicine ovariectomized female rats with and without estradiol replacement undergoing 2-h middle cerebral artery occlusion. Estradiol reduces basal and post-ischemic soluble epoxide hydrolase expression. Middle cerebral artery occlusion strongly induces mRNA levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 1beta, which is attenuated in enzyme knock-outs, but not by enzyme inhibitors 3.3.2.10 soluble epoxide hydrolase medicine semi-quantitative evaluation of staining intensity of soluble epoxide hydrolase and several cytochromes in different malignant tissues. Soluble epoxide hydrolase expression in renal and hepatic malignant neoplasms and surrounding non-malignant tissues is significantly decreased, whereas expression is increased in seminoma 3.3.2.10 soluble epoxide hydrolase medicine allelic variation of EPHX2 is associated with heart failure 3.3.2.10 soluble epoxide hydrolase medicine EPHX2 contributes to the risk of subclinical cardiovascular disease 3.3.2.10 soluble epoxide hydrolase medicine genetic variation in or near the EPHX2 gene contributes to the risk of ischemic stroke 3.3.2.10 soluble epoxide hydrolase medicine inhibition of sEH leads to antihyperalgesia 3.3.2.10 soluble epoxide hydrolase medicine sEH inhibitors may be useful in the treatment of patients with atherosclerotic cardiovascular disease 3.3.2.10 soluble epoxide hydrolase medicine sEH is a target for the treatment of hypertension and vascular inflammation 3.3.2.10 soluble epoxide hydrolase medicine sEH is a target for the treatment of hypertension, inflammatory diseases, pain, diabetes, and stroke 3.3.2.10 soluble epoxide hydrolase medicine sEH is a therapeutic target against acute nephrotoxicity 3.3.2.10 soluble epoxide hydrolase medicine soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo and reduce the infarct size 3.3.2.10 soluble epoxide hydrolase medicine soluble epoxide hydrolase is a susceptibility factor for heart failure 3.3.2.10 soluble epoxide hydrolase medicine soluble epoxide hydrolase is a susceptibility factor for heart failure, EPHX2 mRNA expression is down-regulated in individuals with heart failure 3.3.2.10 soluble epoxide hydrolase medicine soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy 3.3.2.10 soluble epoxide hydrolase medicine the activity of sEH plays a significant role in determining the magnitude of acute hypoxic vasoconstriction 3.3.2.10 soluble epoxide hydrolase medicine the presence of the rs1042032 variant allele (polymorphism of 3'-untranslated region A/G) in EPHX2 is associated with a protective role for allograft function 3.3.2.10 soluble epoxide hydrolase medicine sEH enzyme gains considerable attention as a therapeutic target for cardiovascular diseases 3.3.2.10 soluble epoxide hydrolase medicine sEH is a potential therapeutic target in the treatment of ischemic stroke 3.3.2.10 soluble epoxide hydrolase medicine sEH is a potential therapeutic target in the treatment of ischemic stroke. Treatment of acute ischemic stroke with sEH inhibition, overview 3.3.2.10 soluble epoxide hydrolase medicine since the metabolism of EETs by sEH reduces or eliminates their bioactivity, inhibition of sEH has become a therapeutic strategy for hypertension and inflammation 3.3.2.10 soluble epoxide hydrolase medicine inhibition of soluble epoxide hydrolase by orally active inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid is effective in persistently reducing blood pressure in female spontaneously hypertensive rats when 12-(3-adamantan-1-yl-ureido)-dodecanoic acid is applied during the perinatal phase. This is accompanied by marked increases in major renal arachidonic acid epoxides and decreases in renal lipoxygenase products of arachidonic acid. Early inhibition of SEH induces a delayed increase in renal 5-HETE at 24 weeks, in contrast to a decrease at 2 weeks. Inhibition of SEH in female spontaneously hypertensive rats from 8 to 12 weeks does not reduce blood but causes profound decreases in renal 15(S)-HETrE, LTB4, TBX2, 5-HETE, and 20-HETE and increases in TriHOMEs. In male spontaneously hypertensive rats, blood pressure reduction after perinatal AUDA is transient 3.3.2.10 soluble epoxide hydrolase medicine intratracheal instillation of benzo(a)pyrene significantly suppresses NF-kappaB translocation, sEH, thioredoxin reductase and catalase activities in lung tissue. Glycyrrhizic acid oral administration at 50 and 100 mg/kg body weight significantly shows protection of lung epithelium by suppression of caspases activities in lung tissue and reduction of total protein, total cells, elastase activity. Results indicate a strong correlation between amelioration of sEH and thioredoxin reductase activities, and NF-kappaB activation 3.3.2.10 soluble epoxide hydrolase medicine modulation of the vascular response mediated through adenosine A2A receptor using aortas from mice fed a 4% NaCl high salt or 0.45% NaCl low salt diet for 4-5 weeks. Compared with NS, HS vessels show increased CYP2J2 and A2A adenosine receptor expression but decreased sEH, CYP4A, and A1 adenosine receptor expression. Data suggest that in mice fed low salt containing diet, upregulation of arterial A1 receptor causes vasoconstriction via increased sEH and CYP4A proteins. In mice fed high salt-containing diet, upregulation of A2A receptor protein triggers vascular relaxation through ATP-sensitive channels via upregulation of CYP2J2 enzyme 3.3.2.10 soluble epoxide hydrolase medicine relative expression of sEH is lower at both the mRNAand protein levels in HepG2 cells than in other cells with the same amount of total RNA or protein loaded. Transcription factor SP-1 is involved in the decrease in the transcription of sEH as a result of DNA methylation in HepG2 cells, which might contribute to epigenetic mechanism-induced carcinogenesis in hepatocytes 3.3.2.10 soluble epoxide hydrolase medicine sEH is synthesized in adipocytes and expression levels increase upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels do not differ in the fat pads from mice receiving a regular or a high-fat diet, total adipose sEH activity is higher in the obese mice. Peroxisome proliferator-activated receptor gamma agonists increase the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo 3.3.2.10 soluble epoxide hydrolase medicine study on the mechanism behind adenosine-induced vascular response in high salt-fed eNOS+/+ and eNOS-/- mice. Compared to low salt diet, high salt diet increases CYP2J2 in eNOS+/+ and eNOS-/- mice, but decreases sEH in eNOS+/+ and eNOS-/- animals. Similarly, CYP4A decreases in high salt-fed-eNOS+/+ and -eNOS-/- animals. Data suggest that low salt diet causes reduced-vasodilation in both eNOS+/+ and eNOS-/- background via sEH and CYP4A 3.3.2.10 soluble epoxide hydrolase medicine because of its central physiological role in disease states such as cardiac hypertrophy, diabetes, hypertension, and pain, the enzym is used as a therapeutic target 3.3.2.10 soluble epoxide hydrolase medicine brain microvascular endothelial cells from female brain are more resistant to ischemic injury compared to male cells due to lower expression of soluble epoxide hydrolase 3.3.2.10 soluble epoxide hydrolase medicine treatment with soluble epoxide hydrolase inhibitors can reduce acute kidney injury 3.3.2.10 soluble epoxide hydrolase medicine upregulation of the enzyme in proximal tubular cells in chronic proteinuric kidney diseases may mediate proteinuria-induced renal damage, while enzyme inhibition by increasing renal eicosanoid levels can prevent the progression of chronic proteinuric kidney diseases 3.3.2.11 cholesterol-5,6-oxide hydrolase medicine in breast cancer tissue, cholesterol epoxide hydrolase ChEH metabolizes cholesterol-5,6-epoxide into cholestane-3beta,5alpha,6beta-triol, which is transformed into the oncometabolite 6-oxo-cholestan-3beta,5alpha-diol by 11beta-hydroxysteroid-dehydrogenase 11betaHSD2. ChEH inhibition and 11betaHSD2 silencing inhibit 6-oxo-cholestan-3beta,5alpha-diol production and tumor growth. Patient breast cancer samples show significantly increased 6-oxocholestan-3beta,5alpha-diol levels and greater ChEH and 11betaHSD2 protein expression compared with normal tissues, and 11betaHSD2 and ChEH overexpression correlate with a higher risk of patient death 3.4.11.1 leucyl aminopeptidase medicine enzyme is a target for inhibitor design 3.4.11.1 leucyl aminopeptidase medicine production of polyketide antibiotics 3.4.11.1 leucyl aminopeptidase medicine the enzyme is a candidate for vaccine production 3.4.11.1 leucyl aminopeptidase medicine antimalarial activity of aminopeptidase inhibitors 3.4.11.1 leucyl aminopeptidase medicine serodiagnostic marker against active filarial infection 3.4.11.1 leucyl aminopeptidase medicine recombinant FgLAP has a potential as a vaccine candidate against Fasciola gigantica 3.4.11.1 leucyl aminopeptidase medicine enzyme PaAP is a therapeutic target for preventing Pseudomonas aeruginosa infection and combating biofilm-related complications 3.4.11.2 membrane alanyl aminopeptidase medicine enzyme is a target for inhibitor design 3.4.11.2 membrane alanyl aminopeptidase medicine the enzyme might be a therapeutic target in pathological processes, such as tumor proliferation and/or angiogenesis associated with cancer development 3.4.11.2 membrane alanyl aminopeptidase medicine aminopeptidase N and dipeptidyl peptidase IV have a functional role in sebaceous gland and their inhibition may affect Acne vulgaris pathogenesis 3.4.11.2 membrane alanyl aminopeptidase medicine aminopeptidase N-null mice develop normally without physiological alterations and can undergo physiological angiogenesis but show a severely impaired angiogenic response under pathological conditions 3.4.11.2 membrane alanyl aminopeptidase medicine anti-CD13 monoclonal antibodies induce homotypic aggregation of monocytic U-937 cells, independently of their effect on enzymatic activity. The induction is related to binding to a specific site on the Cd13 molecule and independent of integrins. During homotypic aggregation, CD13 actively redistributes to the zones of cell-cell contact 3.4.11.2 membrane alanyl aminopeptidase medicine asparagine-glycine-asparagine-targeted liposomal doxorubicin binds specifically to cells expressing the enzyme. Upon binding, the drug is internalized through the endosomal pathway. In mice bearing human prostate cancer xeongrafts, significant growth inhibition of tumors is observed upon treatment with asparagine-glycine-asparagine-targeted liposomal doxorubicin 3.4.11.2 membrane alanyl aminopeptidase medicine Bacillus thuringiensis Cry1Ab toxin binds to cadherin through loops 2 and 3 of domain II promoting the formation of the pre-pore inducing some structural changes, then the pre-pore interacts with aminopeptidese N through beta-16 of domain III promoting membrane insertion of the toxin and cell death 3.4.11.2 membrane alanyl aminopeptidase medicine CD13 is a crucial mediator of galectin-3-induced angiogenesis in endothelial cells 3.4.11.2 membrane alanyl aminopeptidase medicine daily intraperitoneal administration of bestatin after inoculation of ovarian cancer cells results in a decrease of peritoneal dissemination and in prologed survival of animals 3.4.11.2 membrane alanyl aminopeptidase medicine enzyme is immunogenic in humans. Use as a diagnostic antigen in an ELISA using sera from patiens with acute and chronic brucellosis. The assay shows 100% specificity and 100% sensitivity and no cross-reaction to crude extracts from Rhizobium tropici, Ochrobactrum anthropi, Yersinia enterocolitica, or Escherichia coli 3.4.11.2 membrane alanyl aminopeptidase medicine exposure of blood basophils from patients allergic to grass pollen, birch pollen, or house dust mites to their respective allergen results in up-regulation of CD13 in all sensitized individual, whereas in healthy controls no increase is seen. Increase in CD13 requires extracellular calcium and is counteracted by preincubation of cells with staurosporin or LY294002 3.4.11.2 membrane alanyl aminopeptidase medicine in peritoneal metastasis model using nude mice, combination treatment with paclitaxel and bestatin causes a synergistic increase of survival time 3.4.11.2 membrane alanyl aminopeptidase medicine inhibition of CD13 by ubenimex enhances the effectiveness of radiotherapy, with ubenimex acting as a radiosensitizer both in vitro and in vivo 3.4.11.2 membrane alanyl aminopeptidase medicine inhibition of enzyme in angiotensin type 1 receptor-blocked rats augments the natriuretic response to angiotensin III 3.4.11.2 membrane alanyl aminopeptidase medicine intraembryonic aorta-gonads-mesonephros derived stromal cells strongly express aminopeptidase N/CD13. Enzymatic activity decreases temporarily after irradiation injury, then increases to higher level 4 h after irradiation and returns to the pre-irradiation level 24-48 h after the irradiation 3.4.11.2 membrane alanyl aminopeptidase medicine key role for galectin-3 in CD13-mediated homotypic aggregation of monocytic cells. Anti-CD13 monomclonal antibodies induce homotypic aggregation on monocytes. Lactose and anti-galectin-3 antibodies completely abrogate this aggregation. Galectin-3 co-immunoprecipitates with CD13 from resting U-937 cells, and this association decreases during the aggregation process 3.4.11.2 membrane alanyl aminopeptidase medicine negative correlation between the expression of CD13 and chemosensitivity to paclitaxel in various ovarian carcinoma cells. Suppression of CD13 by inhibitor bestatin or by siRNA results in significant increase in paclitaxel-sensitivity 3.4.11.2 membrane alanyl aminopeptidase medicine no relationship between the expression of CD13 and clinical variables and pathologic variables of the patients with ovarian cancer. Expression of CD13 is significantly more pronounced in samples obtained in primary laparatomies as compared to samples from secondary cytoreductions 3.4.11.2 membrane alanyl aminopeptidase medicine noninvasive imaging and quantifying of tumor-associated CD13 expression by planar fluorescence refectance imaging and three-dimensional fluorescence mediated tomography using cyclo-[Cys-Asn-Gly-Arg-Cys]-Gly-Lys coupled to the near infrared fluorophore Cy5.5 3.4.11.2 membrane alanyl aminopeptidase medicine overall survival rate of patients with gastric carcinoma with negative aminopeptidase N/CD13 expression is significantly lower than that of patients with positive aminopeptidase N/CD13 expression. Aminopeptidase N/CD13 expression is negatively associated with lymph node metastasis 3.4.11.2 membrane alanyl aminopeptidase medicine positive correlation between CD13 expression and migratory potential in various ovarian cancer cell lines, and significant decrease in the proliferative and migratory abilities of cell lines after the addition of enzyme inhibitor bestatin or its inhibiton by siRNA 3.4.11.2 membrane alanyl aminopeptidase medicine pre-treatment of CD24+Cd25+ T-cells with aminopeptidase N inhibitor phebestin substantially enhances the suppressive activity of these cells and increases expression levels of transforming growth factor TGF-beta1 and FoxP3 and ameliorates acute colitis 3.4.11.2 membrane alanyl aminopeptidase medicine simultaneous application of inhibitors to dipeptidyl peptidase IV and aminopeptidase N leads to a more profound reduction of the clinical severity of the experimental autoimmune encephalomyelitis compared to the use of dipeptidyl peptidase IV or aminopeptidase N inhibitors alone 3.4.11.2 membrane alanyl aminopeptidase medicine simultaneous application of inhibitors to dipeptidyl peptidase IV and aminopeptidase N significantly suppresses DNA synthesis and markedly increases TGF-beta1 production in mitogen- or anti-CD3-stimulated T cells 3.4.11.2 membrane alanyl aminopeptidase medicine study on expression of CD13 in patients with non-small cell lung cancer. The 5-year survival rate in patients with CD13+ tumors is significantly lower than those whose tumors are negative for CD13 3.4.11.2 membrane alanyl aminopeptidase medicine treatment of cell with aminopeptidase N siRNA increases total cellular Na+K+-ATPase activity and basolateral Na+K+-ATPase abundance about twofold. Overexpression of the enzyme reduces Na+K+-ATPase activity and basolateral abundance by 50%. The effect is mediated via angiotensin IV and angiotensin IV receptor signaling 3.4.11.2 membrane alanyl aminopeptidase medicine treatment of mice with a combination of radiation and ubenimex results in significant prolongation of the tumor-doubling time 3.4.11.2 membrane alanyl aminopeptidase medicine CD13 may be an important target for molecular therapy of early stage acute B-cell leukemia 3.4.11.3 cystinyl aminopeptidase medicine development of stable second generation inhibitors of IRAP based on the AT4 ligands angiotensin IV or LVV-H7 may provide the opportunity for the development of therapeutics for memory loss in patients Altheimer's disease 3.4.11.3 cystinyl aminopeptidase medicine P-LAP is an independent prognosticator of clinical outcome in patients with endometrial carcinoma. Assessment of the P-LAP status provides clinically useful prognostic information in patients with endometrial carcinoma 3.4.11.3 cystinyl aminopeptidase medicine P-LAP is available for evaluation of avarian epithelial malignancy and also as target for molecular therapy 3.4.11.3 cystinyl aminopeptidase medicine the enzyme is suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma 3.4.11.3 cystinyl aminopeptidase medicine activities of soluble cystyl aminopeptidase do not differ between diabetic and control rats in both hippocampus and hypothalamus. Membrane-bound cystyl aminopeptidase is about 2.5foldincreased in the hypothalamus and 5fold increased in the hippocampus 3.4.11.3 cystinyl aminopeptidase medicine blocking of alpha-1adrenoceptor by doxazosin increases enzyme activity in male, but not in female thalamus. Increased capacity of males to degrade vasopressin and to regulate cardiovascular homeostasis 3.4.11.3 cystinyl aminopeptidase medicine enzyme isoform IRAP is involved in increasing malignant potential of endometrial cancer mediated by insulin. Endometrial adenocarcinoma A-MEC cells expressing the enzyme exhibit a significant growth-stimulatory effect compared with control. They have a remarkably high level of p85PI3K protein and show a higher degree of AKT phosphorylation by insulin stimulation 3.4.11.3 cystinyl aminopeptidase medicine marked decrease of membrane-bound cystinyl aminopeptidase activity in clear cell renal carcinoma cell, papillary renal carcinoma cell, and chromophobe renal carcinoma cell compared to surrounding non-tumor tissue. Minor and non-significant changes of enzyme activity in soluble fractions of carcinoma cells 3.4.11.3 cystinyl aminopeptidase medicine Otsuka Long Evans Tokushima Fatty rats, model of type II Diabetes mellitus, show significantly lower cell surface IRAP equilibrium activity than control. Time to reach equilibrium is significantly longer and adipocytes isolated from the model rats demonstrate both a delay and a reduction in 3-O-methyl-D-glucose uptake 3.4.11.3 cystinyl aminopeptidase medicine plasma activities of cystinyl-, aspartyl-, and glutamyl-aminopeptidase are decreased by 39.4%, 24.9%, and 33.3%, respectively, in patients with Parkinson's disease 3.4.11.3 cystinyl aminopeptidase medicine excessive activity of vasopressinase is probably responsible for gestational diabetes insipidus 3.4.11.5 prolyl aminopeptidase medicine biochemical tests for Neisseria gonorrhoeae of rely on the activity of prolyliminopeptidase. The overall prevalence of enzyme-negative isolates is about 4.3% with significant geographical variation and higher frequency of these isolates among men who have sex with men 3.4.11.5 prolyl aminopeptidase medicine chromogenic substrate tests for Neisseria gonorrhoeae based on the activity of prolyliminopeptidase should be combined with other tests. A study of a prolyliminopeptidase-negative subtype among Neisseria gonorrhoeae isolates in Australia reveals that up to 22% of isolates may be negative for enzyme activity 3.4.11.5 prolyl aminopeptidase medicine widespread dissemination, mainly among men who have sex with men, of indistinguishable and highly related genotypes that have evolved from a single N gonorrhoeae PIP-negative serovar IB-4 strain among several countries worldwide. An increased awareness of PIP-negative N gonorrhoeae strains is crucial 3.4.11.7 glutamyl aminopeptidase medicine the enzyme might be a target in treatment of salt-dependent hypertension with RB150 as an antihypertensive agent 3.4.11.7 glutamyl aminopeptidase medicine aminopeptidases play an important role in the regulation of blood pressure, and in the regulation of other pathophysiological processes such as angiogenesis, antigen-presentation, and fertility most probably by mediating the metabolism of some peptide substrates 3.4.11.7 glutamyl aminopeptidase medicine APA is a new potential therapeutic target for the treatment of certain forms of hypertension 3.4.11.7 glutamyl aminopeptidase medicine central APA is a potential therapeutic target for the treatment of hypertension 3.4.11.7 glutamyl aminopeptidase medicine enzyme is a promising target for new anti-malarial drug development 3.4.11.7 glutamyl aminopeptidase medicine RB150 is the first oral active prodrug inhibiting brain but not systemic renin-angiotensin system activity, strongly reducing blood pressure several hours after a single administration 3.4.11.7 glutamyl aminopeptidase medicine results suggest that APA, APN, AngIII and AT2R are potentially important targets for disorders characterized by Na+ and fluid retention, such as hypertension and congestive heart failure 3.4.11.7 glutamyl aminopeptidase medicine the development of GluAP inhibitors as potential antihypertensive agents offers new perspectives of therapy 3.4.11.7 glutamyl aminopeptidase medicine glutamyl-aminopeptidase spectrofluorometric activity and immunohistochemical expression in clear-cell, papillary and chromophobe renal cell carcinomas, and in renal oncocytoma. Glutamyl-aminopeptidase activity in both the membrane-bound and soluble fractions is sharply decreased and its immunohistochemical expression shows mild staining in the four histological types of renal tumours. Soluble and membrane-bound glutamyl-aminopeptidase activities correlate with tumour grade and size in clear cell renal cell carcinoma 3.4.11.7 glutamyl aminopeptidase medicine urinary excretion of glutamyl aminopeptidase is increased in cisplatin-treated rats. Enzyme can be detected in urine samples with immunological methods, its excretion correlates with the extent of renal dysfunction in cisplatin-treated rats 3.4.11.9 Xaa-Pro aminopeptidase medicine significant inhibition of enzyme after repeated oral dosage of angiotensin-converting enzyme inhibitor enalapril, but not of imidapril. Induction of dry cough by ACE inhibitors may be related to accumulation of bradykinin 3.4.11.10 bacterial leucyl aminopeptidase medicine recombinant FgLAP has a potential as a vaccine candidate against Fasciola gigantica 3.4.11.14 cytosol alanyl aminopeptidase medicine coexpression of Drosophila puromycin-sensitive aminopeptidase and beta-amyloid in the flies' brains improves their lifespan, protects against locomotor deficits, and reduces brain beta-amyloid levels by clearing the beta-amyloid plaque-like deposits. Puromycin-sensitive aminopeptidase localizes to the cytoplasm. Therefore, puromycin-sensitive aminopeptidase and beta-amyloid are unlikely to be in the same cellular compartment. Beta-amyloid is not a proteolytic substrate for puromycin-sensitive aminopeptidase in vitro. The enzymatic activity of puromycin-sensitive aminopeptidase is not required for rescuing beta-amyloid toxicity in neuronal SH-SY5Y cells 3.4.11.16 Xaa-Trp aminopeptidase medicine chemotherapeutic target, involved in heart disease, metastasis, inflammation 3.4.11.16 Xaa-Trp aminopeptidase medicine model system for enterocytic differentiation, but caution necessary because of inhomogenities concerning enzyme expression within cell lines 3.4.11.18 methionyl aminopeptidase medicine MetAP2 is a molecular target for antiangiogenesis and anticancer therapy 3.4.11.18 methionyl aminopeptidase medicine the modification of the active site residue His79 by the inhibitors fumagillin and ovalicin may prevent the action of the enzyme on proteins or peptides involved in angiogenesis. These compounds may be effective pharmacological agents against pathogenic and resistant forms of Escherichia coli and other microorganisms 3.4.11.18 methionyl aminopeptidase medicine enzyme expression is increased in 8 out of 12 tumor samples. Reduction of enzyme level by MAP1D shRNa does not result in any difference of proliferation, cell survival, or cell numbers, but cells exhibit a dramatically reduced potential to form colonies in soft agar 3.4.11.18 methionyl aminopeptidase medicine enzyme inhibitor PPI-2458 inhibits proliferation of human fibroblast-like synviocytes derived from patients with rheumatoid arthritis with a growth inhibitory concentration of 0.04 nM. Growth inhibition is linked to enzyme inhibition 3.4.11.18 methionyl aminopeptidase medicine enzyme MetAP2 activity is elevated in all human colorectal adenocarcinomas examined compared with normal tissue. Immunohistochemistry shows moderate to strong cytoplasmic positivity for enzyme with increased intensity in the invasive tumor component 3.4.11.18 methionyl aminopeptidase medicine in colon cancer cell line HT-29, expression of enzyme is inversely correlated to cell density 3.4.11.18 methionyl aminopeptidase medicine inhibitor A357300 in combination with cyclophosphamide sustains tumor regression and inhibits establishment and growth rate of hematogenous metastatic deposits following tail vein inocculation in CHP-134 neuroblastoma cells 3.4.11.18 methionyl aminopeptidase medicine inhibitor PPI-2458 potently inhibits growth of several non-Hodgkin's lymphoma cell lines in a manner correlating with enzyme inhibition 3.4.11.18 methionyl aminopeptidase medicine recombinant MetAP1 is able to provide considerable protection to mice against a Babesia microti challenge infection based on a reduction in peak parasitemia levels and earlier clearance of the parasite as compared with control mice 3.4.11.21 aspartyl aminopeptidase medicine enzyme is not present in the urine of healthy rats, however, it is readily detected in the urine in rat models of mild and heavy proteinuria. Urinary levels correlate with the severity of proteinuria 3.4.11.22 aminopeptidase I medicine a haplotype in the ERAP1 and ERAP2 locus (rs27044[G] rs30187[T] rs2549782[T]) is significantly associated with ankylosing spondylitis. ERAP1 single nucleotide polymorphism rs30187[T] is associated with ankylosing spondylitis 3.4.11.22 aminopeptidase I medicine the ERAP1 gene shows borderline association with preeclampsia in Australian and Norwegian populations 3.4.11.22 aminopeptidase I medicine the specific ERAP1 haplotype, rs27044/10050860/30187-CCT is strongly associated with increased risk of ankylosing spondylitis, while a second specific ERAP1 haplotype, rs30187/26618/26653-CTG, reduces the disease risk 3.4.11.22 aminopeptidase I medicine exposure of human peripheral blood mononuclear cells to isoform ERAP1 polymorphic variant proteins as well as ERAP1 overexpression increases inflammatory cytokine and chemokine production, and enhances immune cell activation. ERAP1 is able to activate innate immunity via multiple pathways, including the NOD-like receptor NLRP3 inflammasome. These responses vary if autoimmune disease-associated variants of ERAP1 are examined in the assay systems. Blocking ERAP1 cellular internalization augments IL-1beta production 3.4.11.22 aminopeptidase I medicine in both HeLa-B27 and C1R-B27 cells, the proportion of 9-mer HLA-B27-bound peptides is decreased by isoform ERAP1 silencing, whereas the percentages of longer peptides, 11-13 mer, are increased. Following ERAP1 silencing, C-terminally extended peptides are readily identified. These are better able to bind to HLA–B27 than N-terminally extended peptides lacking an arginine at position 2. In both HeLa-B27 cells and mouse fibroblasts expressing HLA-B27, the absence of ERAP1 reduces peptide recognition by HLA-B27-restricted immunodominant viral HLA–B27 epitope KK10-specific cytotoxic T-lymphocytes. Presence of an ankylosing spondylitis-protective variant of ERAP1, K528R, as compared to wild-type ERAP1, reduces the peptide recognition by KK10 cytotoxic T lymphocytes following transfection with extended KK10 minigenes 3.4.11.22 aminopeptidase I medicine two-photon fluorescent probe SNCL exhibits high sensitivity toward ERAP1, with about a 95-fold fluorescence enhancement at 550 nm. SNCL can be applied for monitoring ERAP1 in tumor tissue with an imaging depth of 50-120 microm 3.4.13.9 Xaa-Pro dipeptidase medicine enzyme is a possible target for doxycyclin-induced inhibition of collagen synthesis in the treatment of osteoarthritis 3.4.13.9 Xaa-Pro dipeptidase medicine elevated pH-value in vaginal fluid accompanied by high sialidase and high enzyme activity are associated with low and verly low birth weight and early preterm at less than 35 or 32 weeks gestation 3.4.13.9 Xaa-Pro dipeptidase medicine enzyme activity in normal human erythrocyte is strongly enhanced by Gly, L-Ala, L-Ser with MnCl2 and enhanced by D-Leu and D-Val. L-Val and L-Leu are strong inhibitors. Enzyme activity in a patient with enzyme deficiency is also enhanced by Gly, L-Ala, and L-Ser and by D-Leu and L-Val, L-Leu is inhibitory 3.4.13.9 Xaa-Pro dipeptidase medicine no statistical difference in serum enzyme activity between postmenopausal osteoporotic, postmenopausal nonosteoporotic and premenopausal healthy women. No significant correlations between serum enzyme level and any biomarkers of bone turnover as well as bone mineral density 3.4.13.9 Xaa-Pro dipeptidase medicine patients with severe phenotype of enzyme deficiency showing infection, hepatosplenomegaly, thrombocytopenia, classic skin ulcers, and multisystem involvement. Enzyme activity in patients is nearly undetectable due to a single nucleotide mutation c.793 T>C in exon 11, resulting in a premature stop codon at amino acid residue 265 3.4.13.9 Xaa-Pro dipeptidase medicine teloid tissue shows up to 4fold increase in enzyme activity compared to normal skin. Elevated enzyme activity is accompanied by increase in concentrations of aminoterminal propeptide of type I procollagen and carboxyterminal telopeptide of type I collagen and increased collagen turnover index 3.4.13.9 Xaa-Pro dipeptidase medicine prolidase activity in bronchial asthma and pathogenesis is significant as a collagen turnover indicator and can be used in both to evaluate pathogenesis and prognosis 3.4.13.9 Xaa-Pro dipeptidase medicine prolidase-loaded chitosan nanoparticles permit to restore prolidase activity in prolidase deficiency fibroblasts for 8 days 3.4.13.9 Xaa-Pro dipeptidase medicine serum prolidase activity is significantly associated with the presence and severity of coronary artery disease, elevated serum prolidase activity may be an independent predictor of coronary atherosclerosis 3.4.13.9 Xaa-Pro dipeptidase medicine the presence of atrial fibrillation in patients with severe mitral stenosis may be associated with the plasma prolidase activity 3.4.13.9 Xaa-Pro dipeptidase medicine the serum prolidase enzyme activity of patients with steatohepatitis is significantly increased compared with the patients with simple steatosis and controls, serum prolidase enzyme activity is positively correlated with the grade of liver fatty infiltration, lobular inflammation, non-alcoholic fatty liver disease activity score, and stage of fibrosis, serum prolidase enzyme activity is the best predictor for distinguishing steatohepatitis from simple steatosis 3.4.13.9 Xaa-Pro dipeptidase medicine Recombinant human prolidase is used for enzyme replacement therapy in prolidase deficiency 3.4.13.19 membrane dipeptidase medicine dicarboxypeptidase activity of testis angiotensin-converting enzyme is required for fertility. Animals carrying mutant enzyme without catalytic activity generate 1 embryo from 22 plugged females compared to 153 embryos from 19 females in wild-type 3.4.13.20 beta-Ala-His dipeptidase medicine diabetic patients with the CDDP1 Mannheim variant(shortest allelic form) are less susceptible for nephropathy 3.4.13.20 beta-Ala-His dipeptidase medicine CNDP1 secretion is significantly higher in cells expressing variants with more than five leucines in the signal peptide of the protein. This explains why individuals homozygous for the 5L allele have low serum carnosinase activity and why diabetic patients homozygous for CNDP1 5L are protected against diabetic nephropathy 3.4.13.20 beta-Ala-His dipeptidase medicine liver-specific expression of enzyme in db/db mice, a model of type 2 diabetes. Transgenic mice shows reduced body weight as a result of glucosuria. Fasting plasma glucose as well as hemoglobin A1C levels rise earlier and remain higher throughout their life than in control animals. Serum fasting insulin levels are low and elevated by L-carnosine feeding. Insulin resistance and insulin secretion are not significantly affected by L-carnosine serum levels. Instead, a significant correlation of L-carnosine levels with beta-cell mass is observed 3.4.13.20 beta-Ala-His dipeptidase medicine no difference in allele or genotype frequency between centenarians and their control group, or between vascular patiens and their control group. Detection of a rare 8-leucine allele, of a rare duplication, p.L13_V15dup, and a frameshift deletion, L17fsX20 3.4.13.20 beta-Ala-His dipeptidase medicine study on carnosinase activity in patients with Alzheimer's disease and with mixed dementia. Enzyme activity levels in the mixed disease group are significantly lower than the Alzheimer's disease group and the mixed disease group demonstrates a significant trend with carnosidase activity decreasing with duration of disease. Both Alzheimer and mixed disease patients on any demetia medication have higher carnosinase activity compared to those not taking a dementia medication, and enzyme activity is higher in patients who regurlarly exercise compared to those who do not exercise regurlarly 3.4.13.20 beta-Ala-His dipeptidase medicine the renoprotective effect of L-carnosine on ischemic acute renal failure is induced by its conversion to L-histidine and L-histamine and is mediated through the activation of histamine H3 receptors in the central nervous system 3.4.13.20 beta-Ala-His dipeptidase medicine monoclonal antibody RYSK173 recognizes a sequence within the transition metal binding site of CNDP1. The CN-1 RYSK173 proportion appears overall increased in end-stage renal disease patients, yet it decreases during hemodialysis possibly as a consequence of a relative increase in transition metal bound enzyme 3.4.13.20 beta-Ala-His dipeptidase medicine serum CNDP1 concentrations associate with CNDP1 genotype and renal function in patients with type 2 diabetes mellitus. CNDP1 (CTG)5 homozygous patients with type 2 diabetes mellitus with diabetic nephropathy have significantly lower CNDP1 concentrations and activity than those without nephropathy. Lower serum CNDP1 concentrations correlate with impaired renal function and to a lesser extend with the CNDP1 genotype 3.4.13.22 D-Ala-D-Ala dipeptidase medicine enzyme may be a target for drug design to reverse clinical vancomycin resistance 3.4.13.22 D-Ala-D-Ala dipeptidase medicine key drug target in circumventing clinical vancomycin resistance 3.4.13.22 D-Ala-D-Ala dipeptidase medicine VanX is an excellent target for the generation of inhibitors 3.4.13.22 D-Ala-D-Ala dipeptidase medicine Enterecoccus faecium carrying plasmid pHVH-V1511 is capable of nosocomial transmission and may develop clinical resistance to vancomycin. Strains may not be detected using standard culture methods for vancomycin-resistant enterococci 3.4.13.22 D-Ala-D-Ala dipeptidase medicine Mycobacterium abscessus is an pulmonary pathogen in humans. The enzyme induces dendritic maturation via toll-like receptor 4 and its downstream signaling pathways, such as the mitogen-activated protein kinase and nuclear factor kappa B pathways. Enzyme-treated dendritic cells stimulate the proliferation of T cells and promote Th1 polarization 3.4.14.1 dipeptidyl-peptidase I medicine mast cell DPPI harms the septic host. DPPI is a novel potential therapeutic target for treatment of sepsis 3.4.14.1 dipeptidyl-peptidase I medicine assay for enzymic activity in urinary samples to diagnose for Papillon-Lefevre syndrome PLS, which is caused by mutations in both alleles of the cathepsin C. The absence of active CatC and its proform in the urine is a strong and reliable indicator for PLS and useful in the early diagnosis of PLS. In contrast, 100% of urine samples from control subjects of any age and gender contained measurable amounts of active CatC. Nonsense, frameshift and missense mutations all result in a total absence of CatC or CatC fragments in the urine of PLS patients 3.4.14.1 dipeptidyl-peptidase I medicine mouse experimental autoimmune encephalomyelitis (EAE) model. In myelin oligodendrocyte glycoprotein EAE, CatC positive cells infiltrate the central nervous system at an early stage prior to any clinical signs, in comparison to wild-typemice. Cystatin F expression is not observed at this stage, but appears later within shadow plaques. CatC expression is found in chronic demyelinated lesions but is not associated with cystatin F expression, and CatCKD EAE mouse shows delayed demyelination 3.4.14.1 dipeptidyl-peptidase I medicine study of expression and activity levels of DPPI and its association with rheumatoid arthritis progress in a collagen-induced arthritis rat-model. Increased DPPI activities in synovial fluids, serum, and bone-marrow homogenates of collagen-induced arthritis rats are associated with rheumatoid arthritis severities progress. MMP2/9 expressions in synovial fluids and bone-marrow show different patterns. High DPPI activities are associated with granulocytes differentiations in-vivo in blood of collagen-induced arthritis rats. In-vitro cell models, DPPI up-regulates the proliferation of primary bone-marrow granulocytes of normal rats, but inhibits that of collagen-induced arthritis rats. DPPI up-regulates and presence of inhibitor Gly-Phe-CHN2 down-regulates mast cell intracellular DPPI and chymase activities. Inhibitor Gly-Phe-CHN2 also inhibits the LTB4-activated neutrophils and neutrophil-elastase activities 3.4.14.2 dipeptidyl-peptidase II medicine mRNA expression in ipsilateral and contralateral cortices. Dipeptidyl peptidase II and aminopeptidase N are up-regulated ipsilaterally from 6 h to 7 days post ischemia. IPC1755, a non-selective protease inhibitor, reveals a significant reduction of cortical lesions after transient cerebral ischemia 3.4.14.4 dipeptidyl-peptidase III medicine DPP III could be a marker for endometrial carcinoma cells 3.4.14.4 dipeptidyl-peptidase III medicine knowing whether lysosomal enzymes are involved in vivo in the Fas apoptotic pathway may be of some help to explore specific therapeutic targets for cell death inhibition in several severe liver pathologies 3.4.14.4 dipeptidyl-peptidase III medicine multiple tumor derived cell lines show concurrent expression and a comparable in vitro translational efficiency for mRNA variants DPP III V-I and II 3.4.14.5 dipeptidyl-peptidase IV medicine enzyme is a potential target for treatment of metabolic diseases 3.4.14.5 dipeptidyl-peptidase IV medicine enzyme is an important target in therapy of cancer 3.4.14.5 dipeptidyl-peptidase IV medicine specific inhibition of the enzyme shows efficacy in the treatment of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide is a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine dipeptidyl peptidase IV inhibitors are a promising new therapeutic approach for the management of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine inhibition of DPP-IV can be an effective approach to treat type 2 diabetes mellitus by potentiating insulin secretion. 6-{2-[2-(5-cyano-4,5-dihydropyrazol-1-yl)-2-oxoethylamino]ethylamino}nicotinonitrile, i.e. KR-62436, could be good lead compound for further development as a new anti-diabetic agent 3.4.14.5 dipeptidyl-peptidase IV medicine (2-(4-((2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl)-2-oxoethyl)amino)-4-methyl-1-piperidinyl)-4-pyridinecarboxylic acid (i. e. ABT-279) is a very potent, selective, effective, and well-tolerated inhibitor useful for the treatment of diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione is a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. Potential for once-daily treatment of type 2 diabetics 3.4.14.5 dipeptidyl-peptidase IV medicine a DPP-IV inhibitor (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) in combination with glybenclamide or nateglinide may be a promising option for the treatment of type 2 diabetes, and particularly, for controlling postprandial hyperglycemia in the clinic 3.4.14.5 dipeptidyl-peptidase IV medicine addition of sitagliptin 50 mg b.i.d. to ongoing metformin therapy improves 24-h glycaemic control and beta-cell function, and is generally well tolerated in patients with type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine application of dipeptidyl peptidase IV inhibitors in managing type 2 diabetes mellitus 3.4.14.5 dipeptidyl-peptidase IV medicine both sitagliptin and vildagliptin improve metabolic control in type-2 diabetes, both in monotherapy and in combination with metformin and thiazolidinediones. DPP-4 inhibition is safe and well tolerated, the risk of hypoglycaemia is minimal, an DPP-4 inhibition is body-weight neutral. DPP-4 inhibition is suggested to be a first-line treatment of type-2 diabetes, particularly in its early stages in combination with metformin 3.4.14.5 dipeptidyl-peptidase IV medicine CD26 inhibition may represent a novel approach to increasing the efficacy and success of hematopoietic stem cell/hematopoietic progenitor cell transplantation, especially under conditions of limiting donor cell yield 3.4.14.5 dipeptidyl-peptidase IV medicine CD26 is an appropriate molecular target for renal cell carcinoma therapy. Anti-CD26 mAb treatment leads to loss of tumorigenicity. The potent antitumor effect of anti-CD26 mAb may be used in the future as novel therapeutic approaches against various CD26-positive malignancies, including renal cell carcinoma 3.4.14.5 dipeptidyl-peptidase IV medicine CD26 on donor human cord blood cells is a negative regulator of the engraftment of long-term repopulating cells. CD26 inhibitor treatment of donor cells prior to transplant has the ability to improve long-term engraftment 3.4.14.5 dipeptidyl-peptidase IV medicine CD26/DP IV is a nonredundant inhibitory receptor controlling T cell activation and Th1-mediated autoimmunity, and may have important therapeutic implications for the treatment of autoimmune CNS disease 3.4.14.5 dipeptidyl-peptidase IV medicine co-administration of the dipeptidyl peptidase-4 inhibitor sitagliptin and metformin is well tolerated in patients with type 2 diabetes and does not alter the steady-state pharmacokinetics of either agent 3.4.14.5 dipeptidyl-peptidase IV medicine coadministration of a single oral CSA dose with a single dose of sitagliptin modestly increases maximal plasma concentration of sitagliptin 3.4.14.5 dipeptidyl-peptidase IV medicine combination of DPP IV inhibitor with low dose of thiazolidinedione can interact synergistically to represent a therapeutic advantage for the clinical treatment of type 2 diabetes without the adverse effects of haemodilution and weight gain associated with thiazolidinediones 3.4.14.5 dipeptidyl-peptidase IV medicine combined action of DP IV and aminopeptidase N inhibitors markedly increases TGF-beta1 production associated with the observed immunosuppressive effects. In vivo, targeting both DP IV and aminopeptidase N leads to a potent treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis 3.4.14.5 dipeptidyl-peptidase IV medicine dipeptidyl peptidase-4 inhibitor is approved in the United States for the treatment of type 2 diabetes. The absolute bioavailability of sitagliptin final market image tablets is approximately 87%. Food does not affect the pharmacokinetics of sitagliptin and therefore can be administered without regard to food generally well tolerated when administered orally or intravenously 3.4.14.5 dipeptidyl-peptidase IV medicine dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibition increases active glucagon-like peptide 1 levels and improves glucose tolerance and islet function with improved islet topography in mice with a beta-cellspecific overexpression of human islet amyloid peptide. These findings support the potential value of DPP-4 inhibition in the treatment of diabetes with the potential of normalizing islet function 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibition sufficient to double postprandial glucogon-like peptide 1 and lower glucose concentrations in people with type 2 diabetes does not alter gastric emptying or the rate of systemic appearance of ingested glucose 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibitor therapy in the treatment of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibitors and their potential role in the management of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibitors are antidiabetogenic drugs, that are effective as monotherapy in patients inadequately controlled with diet and exercise and as add-on therapy in combination with metformin, thiazolidinediones, and insulin. The DPP-4 inhibitors are well tolerated, carry a low risk of producing hypoglycemia, and are weight-neutral 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibitors are effective agents for achieving blood glucose control 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibitors as therapy for type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibitors effectively stimulate insulin secretion, suppress glucagon release, and improve glucose control in patients with type 2 diabetes. These agents are well tolerated and have a low incidence of adverse effects 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-IV inhibitors appear to have excellent therapeutic potential in the management of type 2 diabetes as monotherapy or in combination with existing agents, such as metformin. Their pharmacokinetic and pharmacodynamic profiles support once-daily dosing, with sustainable reductions in glycosylated hemoglobin levels and relatively few adverse effects 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-IV inhibitors are potentially important therapies in diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-IV inhibitors in treatment of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal. The combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-IV is a target for the treatment of type 2 diabetes. The inhibitors vildagliptin and saxagliptin are well tolerated and reduce blood glucose and HbA1c levels in diabetic patients 3.4.14.5 dipeptidyl-peptidase IV medicine environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema 3.4.14.5 dipeptidyl-peptidase IV medicine functional role of dipeptidyl peptidase IV and aminopeptidase N in the sebaceous gland apparatus and for their inhibitors, used alone or in combination, as substances possibly affecting acne pathogenesis in a therapeutic manner 3.4.14.5 dipeptidyl-peptidase IV medicine genetic or environmental factors that decrease DPPIV activity might increase the risk of angiotensin-converting enzyme inhibitor-associated angioedema 3.4.14.5 dipeptidyl-peptidase IV medicine glucagon-like peptide-1-based therapy is a treatment for type 2 diabetes. It is executed either by GLP-1 mimetics or by dipeptidyl peptidase-IV inhibitors. In type 2 diabetes, the two strategies reduce hemoglobin A1c by 0.6% to 1.1% from baseline levels of 7.7% to 8.5%. They are efficient both in monotherapy and in combination with metformin or thiazolidinediones. Both treatments are well tolerated with low risk of hypoglycemia 3.4.14.5 dipeptidyl-peptidase IV medicine imidazopiperidine amides as dipeptidyl peptidase IV inhibitors for the treatment of diabete, pharmacokinetic properties 3.4.14.5 dipeptidyl-peptidase IV medicine in a 24-week study, sitagliptin 100 mg once daily added to ongoing pioglitazone therapy is effective and well tolerated in these patients with type 2 diabetes who had not achieved adequate glycemic control with pioglitazone alone 3.4.14.5 dipeptidyl-peptidase IV medicine in genetically susceptible animals, inhibition of DPP IV increases arterial blood pressure via Y1 receptors when elevated blood pressure is reduced with antihypertensive drugs provided that the sympathetic nervous system is functional 3.4.14.5 dipeptidyl-peptidase IV medicine in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses is associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nM or greater, and an augmentation of active glucagon-like peptide-1 and glucose-dependent insulinotropic peptide levels of 2fold or higher after an oral glucose tolerance test 3.4.14.5 dipeptidyl-peptidase IV medicine in pre-diabetic subjects, a 12-week treatment with vildagliptin markedly increases postmeal levels of active glucagon-like peptide 1 and gastric inhibitory polypeptide, improves both alpha- and beta-cell function, decreases postprandial hyperglycemia and decreases A1C levels. Vildagliptin is well tolerated and weight neutral and does not cause hypoglycemia 3.4.14.5 dipeptidyl-peptidase IV medicine inhibition of CD26 may be one way to enhance engraftment of limiting numbers of stem cells during cord blood transplantation 3.4.14.5 dipeptidyl-peptidase IV medicine inhibition of dipeptidylpeptidase IV activity as a therapy of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine major clinical trials with DPP-IV inhibitors as monotherapy and as add-on therapy in patients with type 2 diabetes. The magnitude of HbA1c reduction with DPP-IV inhibitors depends upon the pretreatment HbA1c values, but there seems to be no change in body weight, and very low rates of hypoglycaemia and gastrointestinal disturbance with these agents. DPP-IV inhibitors represent a major class of oral antidiabetic drug and their metabolic profile offers a number of unique clinical advantages for the management of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine metformin decreases the plasma DPP IV activity, limiting the inactivation of exogenously administered GLP-1 and improving glycaemic control 3.4.14.5 dipeptidyl-peptidase IV medicine monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine oral dipeptidyl peptidase-4 inhibitors may prove valuable in the treatment of diabetes, given their effectiveness in reducing glycated hemoglobin with neutral weight effects and without the adverse events associated with other agents. Dipeptidyl peptidase-4 inhibitors appear to improve islet function and may modify the course of diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine pharmacokinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149, double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects 3.4.14.5 dipeptidyl-peptidase IV medicine pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with promising therapeutic applications for the treatment of several pathophysiological states related to neurodegenerative diseases. However, its use for therapeutic applications is actually limited by its restricted bioavailability and rapid degradation. N-terminal modifications confer resistance to dipeptidyl peptidase IV, a major proteolytic process involved in PACAP degradation 3.4.14.5 dipeptidyl-peptidase IV medicine possible use of nateglindide in combination with incretin hormones for type 2 diabetes therapy. The use of nateglinide as a prandial insulin-releasing agent may partly rely on inhibition of degradation of glucagon-lioke peptide-1 as well as beta-cell K(ATP) channel inhibition 3.4.14.5 dipeptidyl-peptidase IV medicine potential treatment of type 2 diabetes with the short-acting dipeptidyl peptidase IV inhibitor PSN-9301, drug evaluation 3.4.14.5 dipeptidyl-peptidase IV medicine pre-clinical and clinical studies on DPP-IV inhibitors demonstrate significant potential for their application as therapeutic agents in the managment of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine sitagliptin is a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Use of sitagliptin as adjunct therapy to sulfonylureas and metformin. An advantage of sitagliptin use is that it appears to be free from the adverse effects of weight gain and hypoglycemia that are associated with currently available treatments 3.4.14.5 dipeptidyl-peptidase IV medicine sitagliptin is a highly selective DPP-4 inhibitor for the treatment of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine sitagliptin is a selective DPP-4 inhibitor that enhances intact incretin levels and improves 24-h glycemic control in patients with type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine sitagliptin is one-daily, orally active, potent and selective DPP-4 inhibitor, which reduces both fasting and postprandial glucose levels and improves summary measures of beta-cell function to produce clinically meaningful reductions in HbA1c concentrations. Efficiacy as both a monotherapy and in combination with merformin or pioglitazone, without causing weight gain 3.4.14.5 dipeptidyl-peptidase IV medicine sitagliptin significantly improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus who have inadequate glycaemic control on exercise and diet 3.4.14.5 dipeptidyl-peptidase IV medicine the addition of sitagliptin compared with glipizide provides similar HbA1c-lowering efficacy over 52 weeks in patients with type 2 diabetes on ongoing metformin therapy. Sitagliptin is generally well tolerated, with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide 3.4.14.5 dipeptidyl-peptidase IV medicine the dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients 3.4.14.5 dipeptidyl-peptidase IV medicine the dipeptidyl peptidase-IV inhibitor vildagliptin improves glycemic control in patients with type 2 diabetes by increasing alpha and beta-cell responsiveness to glucose. Co-administration of warfarin (a vitamin K antagonist widely used for long-term prevention of thrombosis) does not alter the pharmacokinetics of vildagliptin 3.4.14.5 dipeptidyl-peptidase IV medicine the DPP-4 inhibitor sitagliptin in diabetes therapy. Sitagliptin is effective, well tolerated and safe in clinical studies. Sitagliptin es effective in monotherapy and combination therapieswith metformin or glitazones. Sitagliptin does not show an increased incidence of hypoglycemic events 3.4.14.5 dipeptidyl-peptidase IV medicine the DPP-4 inhibitor sitagliptin is effective in treatment of type 2 diabetes. Overview of the mechanisms of action, pharmacology and clinical trial results of sitagliptin. DPP-4 inhibitors could be used in prediabetic stages and the very early stages of diabetes to slow or prevent the progression of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine the oral dipeptidyl peptidase 4 inhibitors vildagliptin, sitagliptin, and saxagliptin are efficious both alone and in association with other oral anti-diabetic agents and may be administered in a single daily dose. They have substantial advantages with respect to other anti-diabetic drugs, since they involve a low risk of hypoglycemia and do not affect body weight 3.4.14.5 dipeptidyl-peptidase IV medicine the pharmacokinetics of rosiglitazone will not be altered when coadministered with sitagliptin in patients with type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine the review focuses mainly on the preclinical studies underlying the development DPP IV inhibitors appropriate for diabetes therapy and their proposed mode of action, and summarized the clinical experience to date 3.4.14.5 dipeptidyl-peptidase IV medicine therapy for type 2 diabetes mellitus with dipeptidyl peptridase-IV inhibitors 3.4.14.5 dipeptidyl-peptidase IV medicine there is no significant difference in exposure to vildagliptin in patients with mild, moderate or severe hepatic impairment. Therefore, no dose adjustment of vildagliptin is necessary in patients with hepatic impairment 3.4.14.5 dipeptidyl-peptidase IV medicine use of DPPIV inhibitors could increase the risk of promoting an already existing intestinal tumour and may support the potential of colon cancer cells to metastasize 3.4.14.5 dipeptidyl-peptidase IV medicine vildagliptin is a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. No adjustment in dosage based on pharmacokinetic considerations is required should vildagliptin be coadministered with amlodipine, valsartan, or ramipril in patients with type 2 diabetes and hypertension 3.4.14.5 dipeptidyl-peptidase IV medicine vildagliptin is a DPP-4 inhibitor with pancreatic islet enhancement activity for treatment of patients with type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine vildagliptin is a novel antidiabetic agent that is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV, the enzyme responsible for degradation of the incretin hormones. No dose adjustment is necessary when vildagliptin and digoxin are coadministered 3.4.14.5 dipeptidyl-peptidase IV medicine vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing alpha- and beta-cell responsiveness to glucose. Vildagliptin displays approximately dose-proportional pharmacokinetics over the 25-mg to 200-mg dose range, and administration with food has no clinically relevant effect on vildagliptin pharmacokinetics 3.4.14.5 dipeptidyl-peptidase IV medicine coadministration of DPP-4 inhibitor vildagliptin with either glyburide or pioglitazone in patients with diabetes type 2 improves postprandial glycemic control 3.4.14.5 dipeptidyl-peptidase IV medicine dipeptidyl peptidase IV inhibitors can reduce fat infiltration in the liver and thus be a potential treatment for non-alcoholic fatty liver disease 3.4.14.5 dipeptidyl-peptidase IV medicine dipeptidyl peptidase IV is a target for the treatment of type 2 diabetes mellitus 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibition augments postprandial lipid mobilization and oxidation and increases endogenous glucagon-like peptide 1 activity, resulting in improved glycemic control in patients with type 2 diabetes mellitus 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-4 inhibition is an oral therapy for type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine DPP-IV is a target for the treatment of type 2 diabetes 3.4.14.5 dipeptidyl-peptidase IV medicine concurrent measurement of adenosine deaminase and dipeptidyl peptidase IV can aid in diagnosing tuberculous pleural effusion 3.4.14.5 dipeptidyl-peptidase IV medicine DPIV is a type 2 diabetes therapeutic target 3.4.14.5 dipeptidyl-peptidase IV medicine DPPIV expression may be an in vivo marker of tumor sensitivity to paclitaxel treatment 3.4.14.5 dipeptidyl-peptidase IV medicine DPPIV/CD26 demonstrate potential as biomarkers for chronic fatigue syndrome 3.4.14.5 dipeptidyl-peptidase IV medicine the DPP-IV activity decreases in mucopolysacharidoses I patients undergoing enzyme replacement therapy, indicating that it can be a useful biomarker for monitoring the efficacy of treatment in mucopolysacharidoses disease 3.4.14.5 dipeptidyl-peptidase IV medicine dipeptidyl peptidase IV functions as a chemorepellent of human neutrophils 3.4.14.5 dipeptidyl-peptidase IV medicine dipeptidyl peptidase IV might be responsible for the shallow implantation of the placenta due to its inhibition of the invading ability of extravillous trophoblasts, causing preeclampsia at later stage of pregnancy 3.4.14.5 dipeptidyl-peptidase IV medicine enzyme is able to truncate the commercial amyloid beta40 and amyloid beta42 peptides, to hinder the fibril formation by them and to participate in the disaggregation of preformed fibrils of these peptides. Dipeptidyl peptidase IV hinders the peptide aggregation/fibrillation during 3-4 days incubation in 20 mM phosphate buffer, pH 7.4, 37°C by 50-80%. In the presence of dipeptidyl peptidase IV, the preformed fibrils are disaggregated by 30-40% 3.4.14.5 dipeptidyl-peptidase IV medicine in a murine model of acute respiratory distress syndrome, aspirated bleomycin induces a significant increase in the number of neutrophils in the lungs after 3 d. Oropharyngeal aspiration of dipeptidyl peptidase IV inhibits the bleomycin-induced accumulation of mouse neutrophils 3.4.14.5 dipeptidyl-peptidase IV medicine mRNA expression in ipsilateral and contralateral cortices. At day 3 post-ischemia, dipeptidyl peptidase IV, 8 and aminopeptidase N are identified in activated microglia and macrophages in the ipsilateral cortex. Seven days post artery occlusion, dipeptidyl peptidase IV immunoreactivity is found in the perikarya of surviving cortical neurons of the ipsilateral hemisphere. At the same time point, dipeptidyl peptidase IV, 8 and aminopeptidase N are targeted in astroglial cells. Total dipeptidyl peptidase IV, 8 and 9 activities remain constant in both hemispheres until day 3 post experimental ischemia, but are increased to 165% in the ipsilateral cortex at day 7. Dipeptidyl peptidase II and aminopeptidase N are up-regulated ipsilaterally from 6 h to 7 days post ischemia. IPC1755, a non-selective protease inhibitor, reveals a significant reduction of cortical lesions after transient cerebral ischemia 3.4.14.5 dipeptidyl-peptidase IV medicine significant levels of enzyme activity are present in commercial human serum albumin. This activity is abolished using a specific DPP-IV inhibitor. Fully 70 to 80% DPP-IV activity remains at 60°C compared with the 37°C incubate. No DPP-IV activity is present in recombinant human serum albumin, suggesting that DPP-IV activity is present only in serum albumin produced using the Cohn fractionation process. DPP-IV activity contributes to the formation of aspartate-alanine diketopiperazine, a known immunomodulatory molecule from the N terminus of human albumin, could account for some of the clinical effects of commercial human serum albumin 3.4.14.5 dipeptidyl-peptidase IV medicine association between peptidases and aggressive and externalizing behaviors. DPP-IV is significantly and positively associated with the Child Behavior Checklist attention problems, aggressive and externalizing behavior subscales. There is a negative correlation between the peptidase and age and Tanner stage. DPP-IV is associated with alpha2-globulin (positively) and IgG3 (inversely) levels 3.4.14.5 dipeptidyl-peptidase IV veterinary medicine inhibition of intragraft DPP IV enzymatic activity significantly reduces ischemia/reperfusion-associated pulmonary injury, allowing for successful transplantation after 18 h of ischemia 3.4.14.5 dipeptidyl-peptidase IV veterinary medicine inhibiting intragraft DPP IV enzymatic activity in a rat single-lung transplantation model abolishes ischemia/reperfusion injury after extended ischemia 3.4.14.9 tripeptidyl-peptidase I medicine adeno-associated virus 2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for late infantile neuronal ceroid lipofuscinosis 3.4.14.9 tripeptidyl-peptidase I medicine [Ala-Ala-Phe]2-rhodamine 110 and [Arg-Nle-Nle]2-rhodamine 110 are specific substrate for determining TPP-I activity and intracellular localization in living cells. These substrates can be a valuable tool for studying the neuronal pathology underlying classical late-infantile neuronal ceroid lipofuscinosis 3.4.14.9 tripeptidyl-peptidase I medicine mutations in tripeptidyl-peptidase I underlie the classic late-infantile form of neuronal ceroid lipofuscinoses (CLN2), the most common neurodegenerative disorders of childhood 3.4.14.10 tripeptidyl-peptidase II medicine TPPIIcan be targeted for inhibition of tumor therapy resistance 3.4.14.10 tripeptidyl-peptidase II medicine isoform TPPII can regulate sperm maturation by modulating intracellular Ca2+ stores via the type 3 ryanodine receptor. Tripeptidyl peptidase II antagonists strongly activate the cAMP/PKA signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation. In the absence of Ca2+, TPPII antagonists elevate the intracellular Ca2+ levels in sperm, resulting in a marked improvement in sperm movement, capacitation, acrosome reaction, and the in vitro fertilizing ability. This antagonist-induced release of intracellular Ca2+ can be blocked by the inhibitors of ryanodine receptors which are the main intracellular Ca2+ channels responsible for releasing stored Ca2+ 3.4.14.10 tripeptidyl-peptidase II medicine TPP2 mRNA and protein are significantly up-regulated in oral squamous cell carcinoma-derived cells compared with human normal oral keratinocytes. Suppression of TPP2 expression with shRNA significantly inhibit cellular proliferation compared with the control cells. In addition, appropriate localization of cellular proliferation and spindle assembly checkpoint molecules MAD2 and upregulation of CCNB1 are observed in TPP2 knockdown oral squamous cell carcinoma cells. TPP2 expression in primary oral squamous cell carcinomas is significantly greater than that in the normal oral counterparts, and the TPP2-positive cases are significantly correlated with tumor size 3.4.15.1 peptidyl-dipeptidase A medicine acein-2 as well as acein-1 can be used as a starting material for anti-hypertensive drugs against ACE 3.4.15.1 peptidyl-dipeptidase A medicine genistein has a potentially preventive role against cardiovascular diseases. Genistein inhibits the expression of angiotensin-converting enzyme via estrogen receptor and subsequently ERK1/2 signaling pathway in rat aortic endothelial cells. Down-regulation of the angiotensin-convering enzyme with a consequent change in circulating levels of angiotensin II, vasorelaxant angiotensin(1-7) and bradykinin plays an important role in cardiovascular effects of genistein through the ERK1/2 pathway 3.4.15.1 peptidyl-dipeptidase A medicine inhibition of the angiotensin-converting enzyme protects against the progression of several cardiovascular diseases. Because of its dual role in regulating angiotensin II and bradikinin levels, the positive clinical effects of ACE inhibitors are thought to be the consequence of concomitant reductions in the production of angiotensin II and the degradation of bradykinin 3.4.15.1 peptidyl-dipeptidase A medicine monoclonal antibodies recognizing the C-terminal domain of human ACE are useful tools for quantification of testicular isoform of angiotensin I-converting enzyme expression on human live and fixed spermatozoa and further adequate analysis of the tACE role in reproduction. The development of adequate quantitative assays of expression of the testicular isoform of angiotensin I-converting enzyme on the surface of ejaculated spermatozoa might be important for further studies about the role of the enzyme in male fertility 3.4.15.1 peptidyl-dipeptidase A medicine the peptide Val-Leu-Ile-Val-Pro is resistant to digestion by proteases of the gastrointestinal tract. The antihypertensive property of this peptide derived from glycinin might find importance in the development of therapeutic functional foods 3.4.15.1 peptidyl-dipeptidase A medicine a combination of angiotensin-converting enzyme inhibitors and diuretic or angiotensin-converting enzyme and calcium channel blockers is effective in lowering blood pressure and decreasing cardiovascular events 3.4.15.1 peptidyl-dipeptidase A medicine ACE2 overexpression may provide a therapeutic strategy for atherosclerosis by inhibiting production of monocyte chemoattractant protein-1 (MCP-1) induced by angiotensin II. ACE2 produces beneficial effects on prevention of atherosclerosis 3.4.15.1 peptidyl-dipeptidase A medicine although angioedema induced by angiotensin-converting enzyme inhibitor is a non-frequent side effect, primary care physicians should be aware of it, informing their patients about these complications and diagnosing it as early as possible 3.4.15.1 peptidyl-dipeptidase A medicine angioedema is a rare but potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Angioedema due to angiotensin-converting enzyme inhibitors usually appears during the first weeks of treatment. Late-onset anioedema is often unrecognized 3.4.15.1 peptidyl-dipeptidase A medicine angioedema provoked by angiotensin-converting enzyme inhibitors. Complement 1 inhibitor is effective in reversing angioedema provoked by angiotensin-converting enzyme inhibitors 3.4.15.1 peptidyl-dipeptidase A medicine angiotensin-converting enzyme inhibition (lisinopril) and AT1 receptor blockade reduce the tubular damage and apoptosis in the contralateral testes after unilateral testicular torsion. The beneficial effect of these drugs may arise from inhibition of ischemic process resulting from increased sympathetic activity and elimination of insults subsequent to dysregulation of the renin-angiotensin system 3.4.15.1 peptidyl-dipeptidase A medicine angiotensin-converting enzyme inhibition confers renoprotection in adriamycin nephropathy by reducing intrarenal angiotensin II and augmenting expression of N-acetylseryl-aspartyl-lysyl-proline that together attenuate signaling of mitogen-activated protein kinase and its downstream proinflammatory and fibrinogenic properties 3.4.15.1 peptidyl-dipeptidase A medicine angiotensin-converting enzyme inhibitors are an important treatment option for hypertension, especially when elevated blood pressure exists in the presence of diabetes mellitus, chronic kidney disease, or congestive heart failure. Inhibition of the renin-angiotensin system when utilized along with other antihypertensive medications is particularly effective in hypertensive patients with type 2 diabetes, chronic kidney disease, and vascular disorders. The effectiveness of blockers of the renin-angiotensin system is enhanced by maximizing the daily dose and combining the medications with thiazide diuretics 3.4.15.1 peptidyl-dipeptidase A medicine angiotensin-converting enzyme inhibitors show beneficial effects on cardiovascular end points. Although angiotensin II receptor blockers have a better side effect profile than angiotensin-converting enzyme inhibitors, angiotensin-converting enzyme inhibitors may remain the treatment of choice in the majority of patients as they are cheaper and have extensive data from randomized trials on their clinical efficiacy 3.4.15.1 peptidyl-dipeptidase A medicine antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides from a sesame protein hydrolysate in spontaneously hypertensive rats. Sesam peptide powder would be a beneficial ingredient for preventing and providing therapy against hypertension and its related diseases 3.4.15.1 peptidyl-dipeptidase A medicine benazepril induces isolated visceral angioedema: a rare and under diagnosed adverse effect of angiotensin converting enzyme inhibitors 3.4.15.1 peptidyl-dipeptidase A medicine casein hydrolysate containing VPP and IPP improves the vascular endothelial dysfunction in subjects with mild hypertension. The continuous intake of VPP and IPP could help to prevent cardiovascular diseases in hypertensive subjects 3.4.15.1 peptidyl-dipeptidase A medicine chronic angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy combined with diuretic therapy is associated with increased episodes of hypotension in noncardiac surgery 3.4.15.1 peptidyl-dipeptidase A medicine chronic inhibition of angiotensin II synthesis from birth specifically reduces the development of adiposity in the rat 3.4.15.1 peptidyl-dipeptidase A medicine combination therapy with an angiotensin-converting enzyme inhibitor and beta-adrenoceptor blocker without intrinsic sympathomimetic activity should be used in the therapy of chronic heart failure 3.4.15.1 peptidyl-dipeptidase A medicine combined use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improves outcomes in patients with heart failure more than an evidence-based dose of angiotensin-converting enzyme inhibitor alone 3.4.15.1 peptidyl-dipeptidase A medicine despite evidence of fetal complications associated with angiotensin-converting enzyme inhibitor use during pregnancy, the number of pregnant women with pregnancy-related ACE inhibitor exposures increases steadily between 1986-2003. Better methods are needed to reduce fetal exposure to potentially teratogenic prescribed medications 3.4.15.1 peptidyl-dipeptidase A medicine diabetic nephropathy can be delayed by the use of angiotensin-converting enzyme inhibitors 3.4.15.1 peptidyl-dipeptidase A medicine functional variants of the angiotensinogen gene contribute to the variability of antihypertensive responses to angiotensin-converting enzyme inhibitor monotherapy in individuals of African ancestry, with genotype determining wether or not responses occur 3.4.15.1 peptidyl-dipeptidase A medicine in the early phase of diabetes, the angiotensin-converting enzyme inhibitorramipril reverses glomerular overexpression and activation of some critical growth factor pathways and increases protection against oxidative stress. These effects involve B2-kinin receptor activation 3.4.15.1 peptidyl-dipeptidase A medicine increased endothelial NO synthase expression and activity might contribute to the beneficial effects of angiotensin-converting enzyme inhibitor therapy in the treatment of coronary artery disease and heart failure 3.4.15.1 peptidyl-dipeptidase A medicine irbesartan add-on therapy on top of angiotensin-converting enzyme inhibitor and beta-blockers in the treatment of systolic herat failure could further improve symptoms, exercise capacity and quality of life 3.4.15.1 peptidyl-dipeptidase A medicine long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction 3.4.15.1 peptidyl-dipeptidase A medicine modulation of the renin-angiotensin system by enalapril is important for body weight regulation and can be of beneficial effect in the treatment of obesity and related diseases 3.4.15.1 peptidyl-dipeptidase A medicine patients who present to hospital after an overdose of angiotensin converting enzyme inhibitor should be considered for discharge if hypotension has not occurred within 6 h of ingestion 3.4.15.1 peptidyl-dipeptidase A medicine patients with hypertension due to primary aldosteronism are sometimes placed on angiotensin-converting enzyme inhibitors in accordance with guidelines applying to the general hypertensive population. The authors believe this practice is inappropriate because of the inability of angiotensin-converting enzyme inhibitors to lower blood pressure in patients with low renin levels. Pleiotropic effects of angiotensin-converting enzyme inhibitors are unlikely to provide significant benefits in the absence of blood pressure reduction. Angiotensin-converting enzyme inhibitors should be discouraged for the majority of patients with primary aldosteronism, even in face of renal or cardiac disease 3.4.15.1 peptidyl-dipeptidase A medicine patients with left ventricular dysfunction have an increased risk of adverse events leading to discontinuation on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker combination therapy compared with angiotensin-converting enzyme inhibitor alone. This excess risk, coupled with a lack of consistent mortality benefit, suggests that angiotensin receptor blocker should not routinely be added to angiotensin-converting enzyme inhibitor therapy for left ventricular dysfunction 3.4.15.1 peptidyl-dipeptidase A medicine peptide derived from tuna dark muscle would be a beneficial ingredient for functional food or pharmaceuticals against hypertension and its related diseases 3.4.15.1 peptidyl-dipeptidase A medicine pooled meta-analysis of randomized placebo-controlled trials suggests that tissue angiotensin-converting enzyme inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure 3.4.15.1 peptidyl-dipeptidase A medicine possible cardioprotective effect of during treatment of American tegumentary leishmaniasis with meglumine antimoniate 3.4.15.1 peptidyl-dipeptidase A medicine purified human ACE converts amyloid beta-protein1-42 to amyloid beta-protein1-40. ACE regulates Abeta1-42/Abeta1-40 ratio in vivo by converting secreted Abeta1-42 to Abeta1-40 and degrading Abetas. The upregulation of ACE activity can be a novel therapeutic strategy for Alzheimer’s disease 3.4.15.1 peptidyl-dipeptidase A medicine purified human ACE converts amyloid beta-protein1-42 to amyloid beta-protein1-40. ACE regulates Abeta1–42/Abeta1-40 ratio in vivo by converting secreted Abeta1-42 to Abeta1–40 and degrading Abetas. The upregulation of ACE activity can be a novel therapeutic strategy for Alzheimer’s disease 3.4.15.1 peptidyl-dipeptidase A medicine renin-angiotensin system-inhibiting drugs seem to protect against cancer in individuals with the DD genotype, which is associated with high levels of angiotensin I-converting enzyme 3.4.15.1 peptidyl-dipeptidase A medicine short-term ramipril treatment adequately reduces angiotensin-converting enzyme activity and blood pressure, but has no significant effects on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and intramuscular triacylglycerol content in obese insulinresistant subjects 3.4.15.1 peptidyl-dipeptidase A medicine standing and supine blood pressure decreases significantly in both autosomal-dominant polycystic kidney disease patients and controls after the administration of enalapril on low and high-sodium intakes, with no differences between the two groups 3.4.15.1 peptidyl-dipeptidase A medicine the expression level of G-protein coupled receptor kinase mRNA shows the severity of CHF. Angiotensin converting enzyme inhibitor abolishes the enhanced expression of G-protein coupled receptor kinase. Angiotensin converting enzyme inhibitor mediated transcriptional regulation of G-protein coupled receptor kinase gene documents a mechanism of beta-adrenergic receptor regulation, and may provide, at least in part, a potential mechanism responsible for the beneficial effect of angiotensin converting enzyme inhibitor in the treatment of congestive heart failure 3.4.15.1 peptidyl-dipeptidase A medicine the use of angiotensin-converting enzyme inhibitors is associated with a significant reduction in pneumonia risk and, apart from blood pressure-lowering properties, may be useful in the prevention of pneumonia in patients with diabetes 3.4.15.1 peptidyl-dipeptidase A medicine the use of spironolactone and angiotensin-converting enzyme inhibitor combination, in general practice, is largely inappropriate. This could explain an increased incidence of severe hyperkalemia. A risk management plan is needed to obtain a careful selection of patients who derive benefit from therapy and to minimise the risk of hyperkalemia 3.4.15.1 peptidyl-dipeptidase A medicine treating heart failure patients with angiotensin-converting enzyme inhibitors may result in zinc deficiency 3.4.15.1 peptidyl-dipeptidase A medicine treatment with angiotensin-converting enzyme inhibitors is of benefit in reducing the progression of renal damage in young patients with moderately proteinuric IgA nephropathy 3.4.15.1 peptidyl-dipeptidase A medicine triple blockade (addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker) of the renin-angiotensin-aldosterone system is effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade 3.4.15.1 peptidyl-dipeptidase A medicine ACE inhibition is a therapeutic target in treating peripheral occlusive arterial disease 3.4.15.1 peptidyl-dipeptidase A medicine ACE inhibitors may contribute to the reduction of the risk of community-acquired pneumonia 3.4.15.1 peptidyl-dipeptidase A medicine ACE is associated with stable coronary artery disease 3.4.15.1 peptidyl-dipeptidase A medicine angiotensin-converting enzyme is a potential target for treatment of Alzheimer's disease 3.4.15.1 peptidyl-dipeptidase A medicine ACE is an ideal target, clinically and nutritionally, in the treatment of hypertension 3.4.15.1 peptidyl-dipeptidase A medicine angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers decrease cardiovascular mortality and slow the progression of renal disease in non-transplant patients. Their impact on kidney transplant is associated with a better graft survival, overview 3.4.15.1 peptidyl-dipeptidase A medicine enzyme inhibition, leading to bradykinin potentiation, is a therapeutic strategy in heart failure for bradykinin-induced systemic arterial vasodilatation 3.4.15.1 peptidyl-dipeptidase A medicine enzyme inhibitors are useful in treatment of hypertension and heart failure, as well as for peritoneal dialysis patients, because inhibit the local tissue renin-angiotensin system, which results in less development of peritoneal fibrosis and a longer life for the peritoneal membrane, overview 3.4.15.1 peptidyl-dipeptidase A medicine evaluation of effects of angiotensin-converting enzyme inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure, overview 3.4.15.1 peptidyl-dipeptidase A medicine hypertension is a global health problem, and angiotensin I (ANG I)-converting enzyme (ACE) inhibitors are largely used to control this pathology 3.4.15.1 peptidyl-dipeptidase A veterinary medicine angiotensin-converting enzyme inhibitors are recommended in dogs and cats with chronic renal failure. They decrease the glomerular capillary pressure, have antiproteinuric effects, tend to delay the progression of chronic renal failure and to limit the extent of renal lesions 3.4.15.1 peptidyl-dipeptidase A veterinary medicine candesartan (angiotensin II type 1 receptor blocker) and enalapril (angiotensin-converting-enzyme inhibitor) during healing after reperfused ST-elevation myocardial infarction prevent rather than worsen adverse remodeling of infarct zone collagens and left ventricular diastolic dysfunction, supporting the clinical use of ARBs and ACEIs during subacute reperfused ST-elevation myocardial infarction 3.4.15.1 peptidyl-dipeptidase A veterinary medicine the combination of an angiotensin converting enzyme inhibitor and spironolactone is safe in elderly small dogs with mitral valve disease with normal serum urea nitrogen and creatinine concentrations 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase medicine an inhibitor of activated TAFI might be used as a therapeutic agent in venous thrombotic diseases 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase medicine E112D could be a highly sensitive and specific early predictor of preeclampsia among woman with chronic hypertension 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase medicine the results could provide new therapeutic opportunity for the treatment of infection 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase medicine the validity of prolylcarboxypeptidase as a site specific therapeutic that could mitigate inflammatory injury is discussed 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase medicine E112D polymorphism in the PRCP gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril treatment in hypertensive patients of Anhui Province, China 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase medicine analysis of prolyl carboxypeptidase activity in serum of 50 stroke patients at admission, and at 24 h, 72 h and 7 days after stroke onset. The decrease in prolyl carboxypeptidase levels in the first 24 h after stroke onset is associated with stroke severity and an unfavourable short-term stroke outcome. High National Institutes of Health Stroke scale scores and infarct volumes at admission are related with a more pronounced decrease of prolyl carboxypeptidase in the first 24 h after stroke 3.4.16.2 lysosomal Pro-Xaa carboxypeptidase medicine prolyl carboxypeptidase and prolyl endopeptidase regulate insulin receptor substrate IRS-1 stability and PI3K/AKT activation in pancreatic cancer 3.4.16.4 serine-type D-Ala-D-Ala carboxypeptidase medicine Brucella spp. cause abortion in domestic animals and undulant fever in humans, DAP contributes to resistance against NO, which is required for the intracellular growth of the bacterium 3.4.16.4 serine-type D-Ala-D-Ala carboxypeptidase medicine clinical defense against bacterial infections, DD-peptidases are the killing targets of beta-lactams 3.4.16.4 serine-type D-Ala-D-Ala carboxypeptidase medicine bacterial DD-peptidases are still an enticing target for antibacterial agents 3.4.16.4 serine-type D-Ala-D-Ala carboxypeptidase medicine DD-peptidases are targets for antibiotic designs 3.4.16.4 serine-type D-Ala-D-Ala carboxypeptidase medicine PBP1b could be a target for antibacterial agents 3.4.16.4 serine-type D-Ala-D-Ala carboxypeptidase medicine VanX, being a required enzyme for bacterial antibiotic resistance, should be a key target in circumventing clinical vancomycin resistance 3.4.17.1 carboxypeptidase A medicine design of mechanism-based, specific inhibitors to cure disease caused by enzyme overfunction 3.4.17.1 carboxypeptidase A medicine evaluation of an antibody-directed enzyme-prodrug therapy for anticancer treatment using the A33 antigen, the enzyme, and methotrexate-phenylalanine as prodrug, overview 3.4.17.1 carboxypeptidase A medicine assay of total-carboxypeptidase A, the active form of CPA and pro CPA, in serum might be useful for the surveillance of early-stage pancreatic carcinoma 3.4.17.1 carboxypeptidase A medicine carboxypeptidase A is an interesting biomedical target enzyme as it is involved in prostate cancer 3.4.17.1 carboxypeptidase A medicine fusion protein design is successful in providing targeted inhibition of tumor growth in prostate cancer, the design can be used to construct other fusion genes 3.4.17.1 carboxypeptidase A medicine increased activity of carboxypeptidase A has been demonstrated in plasma samples from patients with pancreatitis 3.4.17.1 carboxypeptidase A medicine mast cell-proteases are considered as promising drug targets 3.4.17.1 carboxypeptidase A medicine mc-CPA is an essential effector molecule providing a very rapid and life-saving response of toxin neutralization in vivo 3.4.17.1 carboxypeptidase A medicine mutations that results in near undetectable activity of aspartocyclase correlate with Canavan Disease, a neurodegenerative disorder usually fatal during childhood 3.4.17.1 carboxypeptidase A medicine results offer new opportunities for intervention and therapy of initiation and progression of autoimmune diseases 3.4.17.1 carboxypeptidase A medicine the avidin-biotin-PEGylated-carboxypeptidase complex has a great potential as a therapeutic protein delivery system for solid tumor prodrug targeting 3.4.17.1 carboxypeptidase A medicine engaged in prostate cancer 3.4.17.1 carboxypeptidase A medicine addition of CPA-directed antibodies to Plasmodium berghei-containing blood meal significantly reduces the mosquito infection rate in the test group compared to control and blocks the parasite development in the midgut 3.4.17.1 carboxypeptidase A medicine knock-down of CPA4 decreases cancer cell proliferation of Bel-7402 cells. In serum-free culture, downregulated CPA4 suppresses the sphere formation capacities of tumour cells. Upregulated CPA4 in Hep-G2 cells increases the proliferation and sphere formation capacity. The protein expression of CD133, ALDH1 and CD44 also increases in cells with upregulated CPA4. In vivo, the overexpression of CPA4 in tumour cells that are subcutaneously injected into nude mice markedly increases the growth of the tumours 3.4.17.2 carboxypeptidase B medicine cpbAs1 can be introduced as a transmission-blocking vaccine candidate in regions where Anopheles stephensi is the main malaria vector 3.4.17.3 lysine carboxypeptidase medicine data support the thesis that thrombin-activable CPB has broad anti-inflammatory properties 3.4.17.6 alanine carboxypeptidase medicine possible penicillin target 3.4.17.8 muramoylpentapeptide carboxypeptidase medicine comparison of 82 ampicillin-resistant Enterococcus faecium isolates from clinical infections. Sequence data reveal the existence of 19 different PLP5 alleles with a difference in 16 amino acid positions spanning from residue 414 to 632. Each allele presents at least five amino acid substitutions (His470/Gln, Asn496/Lys, Ala499/Thr, Glu525/Asp, and Glu629/Val). No correlation between amino acid sequence polymorphism of PBP5 and levels of ampicillin resistance is detected. The levels of PLP5 mRNA expression varies between strains and does not always correlate with levels of ampicillin resistance in clinical isolates 3.4.17.8 muramoylpentapeptide carboxypeptidase medicine PBP5 mRNA and protein levels are increased in subclade A1 and A2 ampicillin-resistant strains compared to those in clade B and subclade A2 ampicillin-susceptible strains. There is evidence of major clade-associated rearrangements in the region upstream of PBP5, including large DNA fragment insertions, deletions, and single nucleotide polymorphisms, that may be associated with the differential regulation of PBP5 levels between the Enterococcus faecium clades 3.4.17.10 carboxypeptidase E medicine allyl isothiocyanate induces colon inflammation 3.4.17.10 carboxypeptidase E medicine enzyme is a potentially important drug target 3.4.17.10 carboxypeptidase E medicine the polymorphism 801 C to T in the carboxypeptidase E exon5 gene may contribiute to the angiographical characteristics of coronary atherosclerosis 3.4.17.10 carboxypeptidase E medicine carboxypeptidase E is a prediction marker for tumor recurrence in early-stage hepatocellular carcinoma 3.4.17.10 carboxypeptidase E medicine N-terminal truncated carboxypeptidase E (CPEDELTAN) expression is associated with poor prognosis of lung adenocarcinoma. CPEDELTAN may present a molecular biomarker for predicting recurrence and metastasis of lung adenocarcinoma 3.4.17.11 glutamate carboxypeptidase medicine enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs 3.4.17.11 glutamate carboxypeptidase medicine the enzyme is used in antibody-directed enzyme prodrug therapy, ADEPT, e.g. against colorectal carcinoma expressing carcinoembryonic antigen, overview 3.4.17.11 glutamate carboxypeptidase medicine potential use in antibody directed enzyme prodrug therapy (ADEPT) 3.4.17.11 glutamate carboxypeptidase medicine CPG2 possesses several properties that make it suitable for suicide gene therapy 3.4.17.11 glutamate carboxypeptidase medicine carboxypeptidase G2 is a bacterial enzyme that is currently employed in a range of targeted cancer chemotherapy strategies such as gene-directed enzyme prodrug therapy (GDEPT). These therapeutic strategies would benefit from robust imaging strategies that afford high spatial and temporal resolution images of the biodistribution of carboxypeptidase G2 activity. Employing dynamic nuclear polarization (DNP) and natural abundance 13C magnetic resonance spectroscopy (MRS), the carboxypeptidase G2-mediated conversion of a novel hyperpolarized reporter probe 3,5-difluorobenzoyl-L-glutamic acid to 3,5-difluorobenzoic acid and L-glutamic acid is observed in vitro. The potential for translation in vivo will primarily depend on the 13C relaxation times and this appears to be an important limiting factor in the case of 3,5-difluorobenzoyl-L-glutamic acid 3.4.17.11 glutamate carboxypeptidase medicine glutamate carboxypeptidase inhibition is evident for a neuroprotective role in several chronic models of chemotherapy-induced peripheral neuropathy and claims an approach for the clinical treatment of this pathology 3.4.17.11 glutamate carboxypeptidase medicine glutamate chemical exchange saturation transfer magnetic resonance imaging GluCEST-MRI is an attractive method for metabolic imaging of glutamate. The change in glutamate concentration measured with GluCEST MRI could provide a noninvasive biomarker of carboxypeptidase G2 activity, in addition to acting as a surrogate for prodrug activation and the concentration of activated drug in the tumor 3.4.17.11 glutamate carboxypeptidase medicine design of a series of circular permutations of the medically important enzyme, carboxypeptidase G2, that show similar structure and stability to the wild-type, while retaining equivalent enzymatic activity in most cases. One of the circular permutants confers methotrexate resistance when expressed in Escherichia coli similarly to wild-type carboxypeptidase G2. The circular permutants provide a promising starting point for generating a protease regulatable form of carboxypeptidase G2, which will be valuable in advancing directed enzyme-prodrug chemotherapy technology 3.4.17.11 glutamate carboxypeptidase medicine side effects of methotrexate especially hepatotoxicity limits clinical applications of this anticancer agent. Carboxypeptidase G2 fused to the transactivator transduction domain (TAT) is administrated for the treatment of elevated plasma concentrations of methotrexate. TAT-CPG2 significantly prevents methotrexate-induced oxidative stress by decreasing the formation of reactive oxygen species (ROS) and increasing the content of glutathione (GSH) and catalase activity. Both native and denatured TAT-carboxypeptidase G2 strongly protect HepG2 cells against methotrexate-induced oxidative stress and apoptosis. Intracellular delivery of carboxypeptidase G2 might provide a new therapeutic strategy for protecting against methotrexate mediated cytotoxicity 3.4.17.11 glutamate carboxypeptidase medicine the enzyme is used in drug detoxification when cancer patients have excessive levels of the anti-cancer agent methotrexate 3.4.17.12 carboxypeptidase M medicine CPM might be an important target for the development of new drugs to treat inflammatory diseases and cancer 3.4.17.12 carboxypeptidase M medicine the present data could lead to improved IHC tests in lung adenocarcinomas when the prognostic value of EGFR expression needs to be evaluated for a target therapy especially when EGFR gene exhibited to mutations 3.4.17.12 carboxypeptidase M medicine patients with chronic persistent atrial fibrillation have reduced amounts of CPM mRNA and protein in the atrial tissue 3.4.17.12 carboxypeptidase M medicine tumor cells of renal cell carcinoma subtypes lose carboxypeptidase M expression upon dedifferentiation. There is a correlation between low carboxypeptidase M expression and tumor cell type. Carboxypeptidase M staining is intense on phagocytotic tumor-associated macrophages, and enzyme is also detected in the tumor-associated vasculature. Coexistence of carboxypeptidase M and the epidermal growth factor receptor is detected in papillary renal cell carcinoma 3.4.17.12 carboxypeptidase M medicine expression is positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage in colorectal cancer 3.4.17.12 carboxypeptidase M medicine the rs12812500 variant of the carboxypeptidase M gene may increase silicosis susceptibility by affecting the expression of carboxypeptidase M, which may contribute to silicosis susceptibility with biological plausibility 3.4.17.16 membrane Pro-Xaa carboxypeptidase medicine results from the study could provide new therapeutic opportunity for the treatment of infection 3.4.17.17 tubulinyl-Tyr carboxypeptidase medicine TCP may be a target for developing novel therapeutic strategies against advanced stages of cancers. Inhibitors of TCP, by reversing abnormal detyrosinated tubulin accumulation in tumor cells, may impair tumor progression 3.4.17.20 Carboxypeptidase U medicine agents that improve the efficiency of TAFI to downregulate fibrinolysis might become available for the treatment of bleeding disorders such as hemophilias A and B 3.4.17.20 Carboxypeptidase U medicine a range of fibrinolytic kinetic values and the contribution of thrombin activatable fibrinolysis inhibitor in normal subjects are established. Study of disease states involving potential hypofibrinolysis can be conducted using this system to link fibrinolytic vulnerability and thrombophilia 3.4.17.20 Carboxypeptidase U medicine argatroban enhances fibrinolysis via a differential inhibition of thrombin-mediated activation of TAFI and factor XIII 3.4.17.20 Carboxypeptidase U medicine coagulation pathway in patients with non-small-cell lung cancer (NSCLC) is investigated: The TAFI activity, prothrombin fragment 1 + 2 levels, and tissue factor pathway inhibitor activity are significantly higher in patients with lung cancer than in subjects in the control group. There is no statistically significant associations between TAFI activity levels and patient age, sex, body mass index, histopathology, or stage of disease 3.4.17.20 Carboxypeptidase U medicine important differences in the hemostatic parameters between the patients with hypothyroidism and healthy controls are found. Increased FVII, TM, and TAFI and decreased FV, FVIII, vWF, protein C, protein S, and TFPI in these patients represent a potential hypercoagulable and hypofibrinolytic state, possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications in patients with hypothyroidism 3.4.17.20 Carboxypeptidase U medicine in Hashimoto thyroiditis, patients have high levels of TAFI activity compared to controls. A high level of TAFI activity suggests fibrinolytic deficit or thrombotic tendency in hypothyroid patients and this deficit is persistent after L-thyroxine replacement 3.4.17.20 Carboxypeptidase U medicine it is investigated whether it is possible to detect the activation of the proCPU/CPU system during therapeutic thrombolysis of patients with acute ischemic stroke: activation of the proCPU system during intravenous recombinant tissue plasminogen activator and intra-arterial administration of urokinase in patients with acute ischemic stroke is shown 3.4.17.20 Carboxypeptidase U medicine no significant difference in lipid parameters is determined between patients with polycystic ovary syndrome and healthy controls. In addition, no difference in CIMT measurements and TAFI levels between patients with polycystic ovary syndrome and healthy controls is shown 3.4.17.20 Carboxypeptidase U medicine pregnancy is associated with elevated plasma TAFI antigen levels but no additional effect of gestational diabetes is found on plasma TAFI antigen levels beyond pregnancy 3.4.17.20 Carboxypeptidase U medicine proCPU activation and its relatedness to efficacy and safety of thrombolytic therapy in ischemic stroke patients is investigated. In 12 patients with ischemic stroke who are treated with intravenous or intraarterial thrombolysis, venous blood samples are taken at different time points before, during and after thrombolytic therapy. No correlations between maximal CPU activity or proCPU consumption and patient or stroke characteristics are found. Maximal CPU activity is associated with evolution of the clinical deficit and achieved recanalisation. ProCPU consumption is related to the risk of intracranial hemorrhage, mortality and final infarct volume 3.4.17.20 Carboxypeptidase U medicine results provide evidence for a role of TAFI in arterial thrombosis in rats and suggest that TAFI inhibition could be explored as an attractive target for the development of new antithrombotic drugs 3.4.17.20 Carboxypeptidase U medicine results suggest that women with polycystic ovary syndrome have impaired fibrinolysis, as reflected by increased TAFI. This impairment can contribute to the risk of cardiovascular disease in polycystic ovary syndrome 3.4.17.20 Carboxypeptidase U medicine TAFI as well as plasminogen activator inhibitor-1 plasma levels in inflammatory bowel disease patients are compared with healthy controls. Mean plasma plasminogen activator inhibitor-1 levels are significantly higher in both ulcerative colitis patients and Crohn’s disease patients compared with healthy controls. Mean plasma TAFI levels are significantly lower in both ulcerative colitis patients and Crohn’s disease patients compared with healthy controls. These results suggest an imbalance of fibrinolysis in inflammatory bowel disease patients 3.4.17.20 Carboxypeptidase U medicine TAFI is present in the gastric mucosa and it may play a role in the pathogenesis of Helicobacter pylori infection-associated gastroduodenal disorders 3.4.17.20 Carboxypeptidase U medicine TAFI plays an important role in the deterioration of organ dysfunction in sepsis and the inhibitor of TAFIa protects against sepsis-induced tissue damage through regulation of fibrinolysis and inflammation 3.4.17.20 Carboxypeptidase U medicine TAFI-mediated inhibition of plasmin generation plays a role in the pathogenesis of glomerulonephritis, and it might constitute a novel molecular target for therapy 3.4.17.20 Carboxypeptidase U medicine the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects is assessed. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia are pooled. Only high factor VIII levels are associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects shows interaction with high TAFI levels. High TAFI levels are not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families 3.4.17.20 Carboxypeptidase U medicine the extent of TAFI activation over time in normal plasma and factor VIII deficient plasma (FVIII-DP) is analysed and it is determined whether soluble thrombomodulin can correct the lysis defect in factor VIII deficient plasma. TAFI activation increases as the concentration of factor VIII increases. Factor VIII at a level of 10% fully corrects the lysis defect in spite of the extent of TAFI activation being only one half that obtained with 100% factor VIII. In addition, thrombomodulin increases TAFI activation sufficiently to correct the premature lysis defect in factor VIII-deficient plasma 3.4.17.20 Carboxypeptidase U medicine the increased risk of thrombosis in thrombophilia patients is not only ascribable to an increased thrombin generation, but also high levels of proCPU and the presence of the 325Ile genotype tip the balance towards thrombotic tendency even further 3.4.17.20 Carboxypeptidase U medicine the proCPU system is not of major importance in the bleeding pathogenesis of these patients. The higher proCPU levels in the patients may even modestly counteract the bleeding tendency 3.4.17.20 Carboxypeptidase U medicine this study aims to assess concomitantly the effects of fenofibrate therapy on thrombin-activatable fibrinolysis inhibitor concentrations and endothelial functions in patients with metabolic syndrome. Twenty-five patients are enrolled in the study. Fenofibrate decreases thrombin-activatable fibrinolysis inhibitor levels and improves endothelial function in metabolic syndrome and, thus, suggests a potential for protection against cardiovascular effects 3.4.17.20 Carboxypeptidase U medicine the decrease in proCPU concentration in the first 72 h after stroke onset correlates with more severe stroke, unfavourable stroke evolution, and poor longterm stroke outcome 3.4.17.21 Glutamate carboxypeptidase II medicine detection of cancerous cells in prostrate or blood, target for diagnostic and therapeutic strategies in prostrate cancer, immunotherapy, antibody therapy 3.4.17.21 Glutamate carboxypeptidase II medicine design of inhibitors may lead to effective neuroprotective agents, possibility to employ GCPII inhibitors in stroke therapy 3.4.17.21 Glutamate carboxypeptidase II medicine GCPII inhibitors are attractive candidates for clinical treatment trials in amylotrophic lateral sclerosis 3.4.17.21 Glutamate carboxypeptidase II medicine inhibitors of NAADLADase protect against chronic glutamate-mediated motor neuron degeneration and may prove therapeutic towards amyotrophic lateral sclerosis 3.4.17.21 Glutamate carboxypeptidase II medicine NAALADase inhibition may provide a new aproach for the treatment of both neurodegenerative disorders and peripheral neuropathies 3.4.17.21 Glutamate carboxypeptidase II medicine the enzyme is an important marker in the diagnosis of prostate cancer 3.4.17.21 Glutamate carboxypeptidase II medicine for establishing new strategies to treat peripheral neuropathies 3.4.17.21 Glutamate carboxypeptidase II medicine glutamate carboxypeptidase II is a therapeutic target for neurodegeneration and prostate cancer 3.4.17.21 Glutamate carboxypeptidase II medicine glutamate carboxypeptidase II may represent a viable therapeutic target for intervention on psychiatric disease 3.4.17.21 Glutamate carboxypeptidase II medicine maternal total homocysteine concentration is affected by C1561T polymorphism, maternal GCPII C1561T variant is associated with neonatal methylmalonic acid concentration 3.4.17.21 Glutamate carboxypeptidase II medicine urea-based, low molecular weight ligands of glutamate carboxypeptidase II have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer 3.4.17.21 Glutamate carboxypeptidase II medicine enzyme is recognized as a major antigen during histoplasmosis. The titer against N-acetylated alpha-linked acidic dipeptidase is significantly increased in the patient sera 3.4.17.21 Glutamate carboxypeptidase II medicine glutamate carboxypeptidase II is present in human blood, and its concentration within a healthy population varies between 1.3 and 17.2 ng/ml in volunteers not diagnosed with prostate cancer 3.4.17.21 Glutamate carboxypeptidase II medicine glutamate carboxypeptidase II is effective in preclinical models of neurological disorders associated with excessive activation of glutamatergic systems. The study validates the use of hydroxamate-based inhibitors in the treatment of a chronic neurological disorder such as neuropathic pain 3.4.17.21 Glutamate carboxypeptidase II medicine inhibitors of glutamate carboxypeptidase II with distinct chemical scaffolds are efficacious in several neurological models wherein excess glutamatergic transmission is presumed pathogenic. These include animal models of neuropathic pain, peripheral neuropathy, stroke, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia, epilepsy, traumatic brain injury, addiction, and cognition 3.4.17.21 Glutamate carboxypeptidase II medicine the enzyme is a putative target for the treatment of both prostate cancer and neuronal disorders associated with glutamate excitotoxicity 3.4.17.21 Glutamate carboxypeptidase II medicine the enzyme is a reliable in vivo marker of re-endothelialisation after percutaneous vascular intervention and that glutamate carboxypeptidase II-positron emission tomography is the first non-invasive in vivo molecular imaging technique that can demonstrate and quantify re-endothelialisation. As a further perspective, well-powered studies in patients undergoing percutaneous vascular intervention need to confirm the potential of GCPII-PET for imaging the crucial process of arterial re-endothelialisation after injuring the vessel wall 3.4.17.21 Glutamate carboxypeptidase II medicine the enzyme is an important diagnostic marker of prostate cancer progression and a putative target for the treatment of both prostate cancer and neuronal disorders associated with glutamate excitotoxicity. For the development of novel therapeutics, mouse models are used. Differences in enzymatic activity and inhibition profile are small. Therefore, mouse glutamate carboxypeptidase II can approximate human glutamate carboxypeptidase II in drug development and testing. On the other hand, significant differences in glutamate carboxypeptidase II tissue expression must be taken into account when developing novel glutamate carboxypeptidase II-based anticancer and therapeutic methods, including targeted anticancer drug delivery systems, and when using mice as a model organism 3.4.17.22 metallocarboxypeptidase D medicine CpD is significantly downregulated in CD14 positive cells isolated from patients with lupus erythematosus. Moreover, it is shown that downregulation of CpD leads to downmodulation of TGF-beta itself, suggesting a role for CpD in a positive feedback loop, providing further evidence for a role of this enzyme in lupus erythematosus 3.4.17.22 metallocarboxypeptidase D medicine for duck hepatitis B virus and probably all other avian hepadnaviruses, carboxypeptidase D (CPD) is shown to be indispensable for infection. The striking correlation of the infection competition activity of duck hepatitis B virus-preS polypeptides with their ability to bind duck carboxypeptidase D suggests that it is this molecule which is addressed and inactivated at the surface of hepatocytes 3.4.17.22 metallocarboxypeptidase D medicine CpD is part of an autoregulatory feedback loop in which it is both upstream and downstream of transforming growth factor-beta signaling 3.4.17.22 metallocarboxypeptidase D medicine CpD is part of the transforming growth factor-beta pathway and is dysregulated in patients with Lupus erythematosus and other autoimmune diseases 3.4.17.22 metallocarboxypeptidase D medicine CPE, probably in combination with CPD, has a functional role in normal placental development, specifically in control of giant cell and glycogen cell growth. In addition, Cpe together with Cpd is an upstream determinant of interspecies hybrid placental dysplasia, whose lack produces placental phenotypes reminiscent of interspecies hybrid placental dysplasia. Pathways regulated by these enzymes are not only important in placentation, but potentially also for speciation in the genus Mus 3.4.17.22 metallocarboxypeptidase D medicine essential for duck hepatitis B virus infection. PreS-induced CPD conformational changes may play an important role in the fusion of the viral and cellular membrane 3.4.17.22 metallocarboxypeptidase D medicine for infection of primary duck hepatocytes with duck hepatitis B virus, binding of the pre-S domain of the large surface protein to the cellular glycoprotein gp180 as a ubiquitous carboxypeptidase is required 3.4.17.22 metallocarboxypeptidase D medicine is not involved in hepatitis B virus infection 3.4.17.22 metallocarboxypeptidase D medicine CPD, nitrotyrosine, and proliferation marker Ki67 levels are higher in prostate cancer than in benign tissue and tend to colocalize, along with phospho-Stat5. The CPD-Arg-NO pathway may be involved in the regulation of prostate cancer cell proliferation 3.4.17.22 metallocarboxypeptidase D medicine knocking out CpD gene expression provides one solution to eliminating C-terminal lysine heterogeneity for therapeutic antibody production 3.4.17.22 metallocarboxypeptidase D medicine The CPD-Arg-nitric oxide pathway contributes to breast cancer progression in vitro and in vivo. There are progressive increases in CPD, nitrotyrosine, Ki67, and Cullin-3 from low levels in benign tissues to high levels in ductal carcinoma in situ, low-grade, high-grade, and triple-negative breast cancer. CPD and nitrotyrosine staining are closely associated, implicating CPD in nitric oxide production 3.4.17.23 angiotensin-converting enzyme 2 medicine potential important target in cardio-renal disease 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2 protects against acute lung injury in several animal models of acute respiratory distress syndrome. Increasing ACE2 activity might be a novel approach for the treatment of acute lung failure in several diseases 3.4.17.23 angiotensin-converting enzyme 2 medicine angiotensin-converting enzyme 2 is a target for gene therapy for hypertension disorders 3.4.17.23 angiotensin-converting enzyme 2 medicine chronic treatment with the AT1R antagonist almesartan induces a fivefold increase in ACE2 mRNA in the aorta which leads to a significant increase in aortic angiotensin(1-7) protein expression. These effects are associated with significant decreases in aortic medial thickness and may represent an important protective mechanism in the prevention of cardiovascular events in hypertensive subjects 3.4.17.23 angiotensin-converting enzyme 2 medicine identification of ACE2 as a receptor for SARS-CoV will contribute to the development of antivirals and vaccines 3.4.17.23 angiotensin-converting enzyme 2 medicine recombinant ACE2 can protect mice from severe acute lung injury 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE-2 protects against lung fibrogenesis by limiting the local accumulation of the profibrotic peptide angiotensin II 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2 is a functional receptor for the causative agent of severe acute repiratory syndrome, the SARS coronavirus, ACE2 also plays a role in the development of liver fibrosis and subsequent cirrhosis 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2 is a key factor for protection from ARDS/acute lung injury and it functions as a critical SARS receptor in vivo, recombinant ACE2 protein might not only be a treatment to block spreading of SARS but also to protect SARS patients from developing lung failure 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2 may be a target for therapeutic interventions that aim to reduce albuminuria and glomerular injury 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2 protects murine lungs from acute respiratory distress syndrome 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2 activators are a reliable approach which could lead to the development of a novel class of antihypertensive and cardioprotective drugs 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2 offers a new target for the treatment of hypertension and other cardiovascular diseases 3.4.17.23 angiotensin-converting enzyme 2 medicine administration of ACE2 activators may be a valid strategy for antihypertensive therapy 3.4.17.23 angiotensin-converting enzyme 2 medicine differential regulation of ACE2 activity during the progression of atherosclerosis suggest that this novel molecule of the renin–angiotensin system may play a role in the pathogenesis of atherosclerosis 3.4.17.23 angiotensin-converting enzyme 2 medicine enhancing ACE2 action may serve to provide additional therapeutic benefits patients with cardiovascular and diabetic kidney disease. Increased ACE2 activity by the use of human recombinant ACE2 and/or a small molecule activator(xanthenone) of ACE2 may represent potential new therapies for lung, cardiovascular and kidney diseases by providing dual beneficial effects by antagonizing angiotensin II action while generating angiotensin-(1-7) 3.4.17.23 angiotensin-converting enzyme 2 medicine reduction of ACE2 expression by RNA interference promotes the proliferation of cultured pancreatic cancer cells. ACE2 may have clinical potential as a novel molecular target for the treatment of pancreatic ductal adenocarcinoma 3.4.17.23 angiotensin-converting enzyme 2 medicine soluble ACE2 activity is a biomarker in heart failure, and in hypertension 3.4.17.23 angiotensin-converting enzyme 2 medicine angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2 of certain species can be utilized by SARS-CoV-2. SARS-CoV-2 tends to utilize ACE2 of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2. SARS-CoV-2 has a high genetic relationship with a bat coronavirus (BatCoV RaTG13) with a 96% genomic nucleotide sequence identity. The close phylogenetic relationship to Bat RaTG13 provides evidence for a bat origin of SARS-CoV-2. Direct transmission of the virus from bats to humans is unlikely due to the lack of direct contact between bats and humans (in Wuhan, China). There are probably intermediate hosts transmitting SARS-CoV-2 to humans. Combined phylogenetic analysis and critical site marking is used to predict the utilizing capability of ACE2 from different animal species by SARS-CoV-2. It is confirmed that pangolin (Manis javanica), cat (Felis catus), cow (Bos taurus), buffalo (Bubalus bubalis), goat (Capra hircus), sheep (Ovis aries) and pigeon (Columba livia) ACE2 might be utilized by SARS-CoV-2, indicating potential interspecies transmission of the virus from bats to these animals and among these animals 3.4.17.23 angiotensin-converting enzyme 2 medicine angiotensin-converting enzyme 2 (ACE2) fused to the Fc portion of immunoglobulin neutralizes SARS-CoV-2 in vitro. Provision of soluble recombinant human ACE2 protein can be beneficial as a novel biologic therapeutic to combat or limit infection progression caused by coronaviruses that utilize ACE2 as a receptor. If given in its soluble form as an appropriate recombinant ACE2 protein, a new tool may be at hand to combat the spread of coronavirus in susceptible individuals by limiting coronavirus attachment to the cell membranes, cell entry, and replication 3.4.17.23 angiotensin-converting enzyme 2 medicine antibodies and small molecular inhibitors that can block the interaction of the enzyme (ACE2) with the receptor binding domain can to combat the virus SARS-CoV-2 3.4.17.23 angiotensin-converting enzyme 2 medicine plasma ACE2 activity independently increases the hazard of adverse long-term cardiovascular outcomes in patients with obstructive coronary artery disease. Above-median plasma ACE2 activity is associated with major adverse cardiovascular events and heart failure hospitalisation 3.4.17.23 angiotensin-converting enzyme 2 medicine plasma kininase II or ACE levels are significantly increased by 18% in untreated diabetics when compared with healthy volunteers. After treatment for 6 weeks with metformin hydrochloride 500 mg twice daily there is a significant decrease of 20% in their ACE levels. Plasma prekallikrein levels are raised significantly by 28% in diabetic patients in contrast with the control subjects and the levels are reduced by 44% after treatment with metformin hydrochloride. NO levels are significantly decreased in plasma by 56% and in urine by 62% in untreated diabetic patients as compared with the healthy subjects. In treated diabetic patients' samples, there is an increase of 50% in plasma and 37% in urine samples compared to untreated patients 3.4.17.23 angiotensin-converting enzyme 2 medicine potential therapeutic approach to ACE2-mediated COVID-19. Treatment with a soluble form of ACE2 may exert dual functions, slow viral entry into cells and hence viral spread and protect the lung from injury 3.4.17.23 angiotensin-converting enzyme 2 medicine regulation of NF-kappaB and ACE2 by specific Ang II type 1 receptor AT1 and Ang II type 2 receptor AT2 antagonists in a nongenetic model of type 2 diabetic nephropathy. The AT1 receptor and AT2 receptor antagonists lead to the repression and activation of the NF-kappaB signalling pathway, respectively. The blockade of AT2 receptor leads to an increase in ACE2 expression 3.4.17.23 angiotensin-converting enzyme 2 medicine investigation of reverse genetic-rescued SARS-CoV-2 viruses in K18-hACE2 mice. The genetic-rescued SARS-CoV-2 viruses will facilitate basic understanding of SARS-CoV-2 and the preclinical development of COVID-19 therapeutics 3.4.17.23 angiotensin-converting enzyme 2 medicine 17-beta-estradiol may reduce SARS-CoV-2 infection of lung epithelial cells 3.4.17.23 angiotensin-converting enzyme 2 medicine ACE2-overexpressing A549 cell-derived microparticles are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered microparticles dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages. Then, ACE2-overexpressing A549 cell-derived microparticles increase the endosomal pH but decrease the lysosomal pH in alveolar macrophages, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. In addition, ACE2-overexpressing A549 cell-derived microparticles also inhibit the proinflammatory phenotype of alveolar macrophages, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects 3.4.17.23 angiotensin-converting enzyme 2 medicine among 226000 SARSCoV-2 sequences, 1573 missense mutations are found in the spike gene, and 226 of them were within the receptor-binding domain region that directly interacts with human ACE2. Modeling shows that most of the 74 missense mutations in the receptor-binding domain region of the interaction interface have little impact on spike binding to ACE2, whereas several within the spike receptor-binding domain increase the binding affinity toward human ACE2 thus making the virus likely more contagious 3.4.17.23 angiotensin-converting enzyme 2 medicine analysis of variations in SARS-CoV-2 spike protein and hACE2 receptor protein and their interaction in the infection scale. Interactions of hACE2 variants with SARS-CoV-2 variants are very strong for G726R-G476S, R768W-V367F, Y252N-V483A, Y252N-V367F, G726R-V367F, N720D-V367F and N720DF486L, and weak for P263S-S383C, RBD-H378R, G726R-A348T 3.4.17.23 angiotensin-converting enzyme 2 medicine binding of SARS-CoV-2 spike protein, variant omicron B.1.1.529, to ACE2 is inhibited by caffeic acid hexoside (-6.4 kcal/mol, RMSD 2.382 A) and phloretin (-6.3 kcal/mol, RMSD 0.061 A) from Sargassum wightii, which interact with crucial residues Asn417, Ser496, Tyr501, and His505 of the spike protein. 5alpha-Cholestan-3beta-ol, 2-methylene- (-6.0 kcal/mol, RMSD 3.074 A) from Corallina officinalis shows inhibitory effect against the omicron receptor-binding domain mutated residues Leu452 and Ala484 3.4.17.23 angiotensin-converting enzyme 2 medicine circulating extracellular vesicles that express ACE2 isolated from human plasma or cells neutralize SARS-CoV-2 infection by competing with cellular ACE2. Compared to vesicle-free recombinant human ACE2, ACE2 from extracellular vesicles shows a 135fold higher potency in blocking the binding of the viral spike protein receptor-binding domain, and a 60- to 80fold higher efficacy in preventing infections by both pseudotyped and authentic SARS-CoV-2. ACE2 from extracellular vesicles protects human ACE2 transgenic mice from SARS-CoV-2-induced lung injury and mortality. ACE2 from extracellular vesicles inhibits the infection of SARS-CoV-2 variants alpha, beta, and delta with equal or higher potency than for the wild-type strain 3.4.17.23 angiotensin-converting enzyme 2 medicine coexpression of intermediate filament protein vimentin with ACE2 increases SARS-CoV-2 entry in HEK-293 cells, and shRNA-mediated knockdown of vimentin significantly reduces SARS-CoV-2 infection of human endothelial cells. Incubation of A-549 cells expressing ACE2 with purified vimentin increases pseudotyped SARS-CoV-2 spike protein entry. The S-protein receptor-binding domain is sufficient for spike protein interaction with vimentin. Extracellular vimentin binds to SARS-CoV-2 spike protein and facilitates SARS-CoV-2 infection 3.4.17.23 angiotensin-converting enzyme 2 medicine compounds benzyl (6aS,9aS)-10-benzyl-4-[benzyl(methyl)amino]-8-(cyclopropanecarbonyl)-6a,7,8,9,9a,10-hexahydrocyclopenta[b]pyrimido[4,5-e][1,4]diazepine-6(5H)-carboxylate, benzyl (6aS,9aS)-4-[benzyl(methyl)amino]-8-(cyclopropanecarbonyl)-10-[(4-methylphenyl)methyl]-6a,7,8,9,9a,10-hexahydrocyclopenta[b]pyrimido[4,5-e][1,4]diazepine-6(5H)-carboxylate and benzyl (6aS,9aS)-4-[benzyl(methyl)amino]-10-[(4-chlorophenyl)methyl]-8-(cyclopropanecarbonyl)-6a,7,8,9,9a,10-hexahydrocyclopenta[b]pyrimido[4,5-e][1,4]diazepine-6(5H)-carboxylate inhibit the interactions between SARS-CoV-2 spike receptor-binding domain and ACE2 by modulating ACE2 without impairing its enzymatic activity necessary for normal physiological functions. The compounds suppress viral infection in cultured cells by inhibiting the entry of ancestral and variant SARS-CoV-2 3.4.17.23 angiotensin-converting enzyme 2 medicine expression of ACE2 increases during aging in human lungs. ACE2 expression increases upon telomere shortening or dysfunction in cultured mammalian cells. This increase is controlled at the transcriptional level, and ACE2 promoter activity is DNA damage response-dependent. Both pharmacological global DNA damage response inhibition of ATM kinase activity and selective telomeric DNA damage response inhibition by the use of antisense oligonucleotides prevent ACE2 upregulation following telomere damage 3.4.17.23 angiotensin-converting enzyme 2 medicine expression of ACE2 increases during aging in lungs. ACE2 expression increases upon telomere shortening or dysfunction in mice. This increase is controlled at the transcriptional level, and ACE2 promoter activity is DNA damage response-dependent. Both pharmacological global DNA damage response inhibition of ATM kinase activity and selective telomeric DNA damage response inhibition by the use of antisense oligonucleotides prevent ACE2 upregulation following telomere damage 3.4.17.23 angiotensin-converting enzyme 2 medicine expression of both ACE2 and TMPRSS2 genes is necessary to support SARS-CoV-2 infection and replication in DF1 cells and a nonpermissive sub-lineage of MDCK cells. Titers of SARS-CoV-2 in these cell lines are comparable to those observed in control Vero cells. Permissive replication of SARS-CoV-2 is not found in pig or horse. Cells expressing genes from either bat species tested demonstrate temporal replication of SARS-CoV-2 that peaks early and is not sustained 3.4.17.23 angiotensin-converting enzyme 2 medicine in lung tissues collected from mice that were sub-chronically exposed to air or 0.8 ppm ozone for three weeks, the ACE2 transcripts are significantly elevated in the parenchyma, but not in the extrapulmonary airways and alveolar macrophages. A significant proportion of additional known SARS-CoV-2 host susceptibility genes are upregulated in alveolar macrophages and parenchyma from ozone-exposed mice 3.4.17.23 angiotensin-converting enzyme 2 medicine inhibition of SARS-CoV-2 spike protein binding to ACE2 by a higher-affinity variant of the B38 monoclonal antibody, containing mutantion F27Q in the heavy chain (F27Q), which can bind to the rececptor-binding domain more tightly, and by Ty1 alpaca nanobody, i.e.a 38 amino acid peptide inhibitor taking components from Ty1. The peptide exhibits improved affinity for the rececptor-binding by up to 100fold, and like B38 mutant, it can outclass the binding affinity of ACE2 with the rececptor-binding domain 3.4.17.23 angiotensin-converting enzyme 2 medicine interaction of ACE2 and SARS-CoV-2 Omicron spike protein. The mutations in the Omicron variant at residues 493, 496, 498, and 501 restore ACE2 binding efficiency that would be lost as a result of other mutations such as K417N 3.4.17.23 angiotensin-converting enzyme 2 medicine interaction with Sars-CoV2 spike protein mutants. The N501Y receptor-binding domainmutant binds to ACE2 with higher affinity due to improved pi-pi stacking and pi-cation interactions. The higher binding affinity of the E484K mutant is caused by the formation of additional hydrogen bond and salt-bridge interactions with ACE2. Both the mutants bind to the B38 neutralizing antibody with reduced affinity due to the loss of several hydrogen-bonding interactions 3.4.17.23 angiotensin-converting enzyme 2 medicine patients younger than 70 years old, patients with eosinophilic asthma, and inhaled corticosteroids non-users are associated with higher levels of blood serum ACE2. Blood eosinophils and fractionated exhaled nitric oxide levels are positively correlated with serum ACE2 3.4.17.23 angiotensin-converting enzyme 2 medicine SARS-CoV and SARS-CoV-2 spike proteins have similar charge distributions and electrostatic features when binding with ACE2. The complex structures of ACE2 and the spike proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. SARS-CoV-2 forms 19 pairs of hydrogen bonds with high occupancy to ACE2, compared to 16 pairs between SARS-CoV and ACE2. SARS-CoV viruses prefer sticking to the same hydrogen bond pairs, while SARS-CoV-2 tends to have a larger range of selections on hydrogen bonds acceptors 3.4.17.23 angiotensin-converting enzyme 2 medicine SARS-CoV-2 spike protein binds ACE2. A dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization has a binding affinity of 16 nM for the SARS-CoV-2 spike receptor-binding domain, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 microM 3.4.17.23 angiotensin-converting enzyme 2 medicine SARS-CoV-2 spike protein binds to ACE2. Bromelain-derived peptide DYGAVNEVK interacts with several critical receptor-binding domain binding residues responsible for the adhesion of the receptor-binding domain to hACE2. Molecular dynamics simulations reveal stable interactions between DYGAVNEVK and receptor-binding domain variants, as well as free binding energy calculations. The bromelain-derived peptide inhibition at the binding site of the receptor-binding domain and ACE2 is competitive 3.4.17.23 angiotensin-converting enzyme 2 medicine SARS-CoV-2 spike protein-ACE2 binding is strongly blocked by ritonavir and naloxegol. The two ligands stabilize both the entire receptor-binding domain and the binding site key residues, ensuring efficient blocking of the key receptor-binding domain residues which are involved in receptor-binding domain-ACE2 interaction. Naloxegol and ritonavir are the most potently blocking ligands, followed by far by sofosbuvir and remdesivir 3.4.17.23 angiotensin-converting enzyme 2 medicine values of 438.1 and 219 microM ibuprofen as well as 204.7 microM flurbiprofen significantly reduce viral load in Caco-2 cells, while etoricoxib and paracetamol have no consistent, significant effect on viral load 3.4.18.1 cathepsin X medicine cathepsin X inhibitor causes neuroprotection via its inhibition of the activation of microglia. Cathepsin X can be a potential therapeutic target for neuroinflammatory disorders 3.4.19.1 acylaminoacyl-peptidase medicine blood acylpeptide hydrolase activity is a sensitive marker for exposure to some organophosphate toxicants 3.4.19.1 acylaminoacyl-peptidase medicine inhibition of acylpeptide hydrolase activity is related to cognitive improvement. Potential biomarker for organophosphate exposure in the screening for neurotoxicity. Possible participation of acylpeptide hydrolase in processes of synaptic plasticity. May play a predominant role in the control of presynaptic biopeptide concentrations that are contained in synaptic vesicles and released to the synaptic space exerting a neuromodular effect at a postsynaptic level 3.4.19.1 acylaminoacyl-peptidase medicine pharmaceutical target for the treatment of Alzheimer’s disease 3.4.19.1 acylaminoacyl-peptidase medicine reliable biomarker for some organophosphate pesticides that show higher specificity for acylpeptide hydrolase than for cholinesterases 3.4.19.1 acylaminoacyl-peptidase medicine the enzyme may constitute a new therapeutic target for the treatment of a number of pathologies 3.4.19.3 pyroglutamyl-peptidase I medicine the natural oligosaccharide gum from Hakea gibbosa is an effective non-competitive inhibitor. The natural gum may be a promising additive not only for its sustained-release and mucoadhesive properties, but also for its ability to slow the enzymatic degradation of therapeutic polypeptides incorporated in dosage forms 3.4.19.3 pyroglutamyl-peptidase I medicine diabetes mellitus affects the levels of hippocampal and hypothalamic PAP-I activities, which may change the metabolic control of its susceptible physiological peptide substrates in the brain 3.4.19.3 pyroglutamyl-peptidase I medicine overexpression of active PPI in Leishmania major impairs differentiation from the procyclic promastigote to the infective metacyclic promastigote. PPI does not protect against the natural antimicrobial peptide gomesin 3.4.19.3 pyroglutamyl-peptidase I medicine profiles of macrophage and renal PAP activities may be considered into the elaboration of new potential strategies for preventing nephrotoxicity during cyclosporin treatment 3.4.19.3 pyroglutamyl-peptidase I medicine examination of Peptoclostridium difficile isolates from children with hematological malignancies, diarrhoea and from healthy neonates. All strains from children with hematological malignancies react with the substrate for L-pyrrolidone arylamidase 3.4.19.3 pyroglutamyl-peptidase I medicine analysis of enzymic activity in serum of controls and patients diagnosed with pancreatitis, hepatitis, and liver cirrhosis. Pyroglutamyl-aminopeptidase activity decreases selectively in liver cirrhosis compared with all the rest of groups 3.4.19.3 pyroglutamyl-peptidase I medicine healthy post-menopausal women show higher values of pyroglutamyl-peptidase I activity than pre-menopausal women. No differences are found in serum pyroglutamyl-peptidase activity between pre- and post-menopausal women with breast cancer. Only post-menopausal women with breast cancer show lower values of pyroglutamyl-peptidase activity than control women 3.4.19.5 beta-aspartyl-peptidase medicine isoform ASRGL1 is not the asparaginase responsible for the antitumor effects elicited by treatment with guinea pig serum 3.4.19.6 pyroglutamyl-peptidase II medicine inhibitors of the enzyme may be used to enhance the therapeutic actions of TRH and to investigate the functions of thyrotropin-releasing hormone and pyroglutamyl-peptidase II 3.4.19.6 pyroglutamyl-peptidase II medicine involvement of thyrotropin-releasing hormone during emotionally charged situations, which is inactivated by PPII 3.4.19.6 pyroglutamyl-peptidase II medicine pyroglutamyl peptidase II inhibitors may be used to enhance the therapeutic actions of thyrotropin releasing hormone 3.4.19.6 pyroglutamyl-peptidase II medicine animals drinking a 2.5% NaCl solution for 7 d present body weight reduction. Despite their negative energy balance, they avoid food and have increased hypothalamic paraventricular nucleus thyrotropin releasing hormone expression and thyroid-stimulating hormone serum levels. Increased medial basal hypothalamic pyroglutamyl-aminopeptidase II activity in dehydration-induced anorexia rats might counteract their high thyrotropin releasing hormone release 3.4.19.9 folate gamma-glutamyl hydrolase medicine gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Expression of gamma-glutamyl hydrolase correlates with poor prognosis 3.4.19.9 folate gamma-glutamyl hydrolase medicine genoproteomic mining of urothelial cancer suggests gamma-glutamyl hydrolase and diazepam-binding inhibitor as putative urinary markers of outcome after chemotherapy 3.4.19.9 folate gamma-glutamyl hydrolase medicine the relationships between the reduced folate levels in the colorectal cancer tissue after leucovorin administration and the gene-expression levels of folate-metabolizing enzymes and folate transporters is investigated. A multivariate logistic regression analysis reveals that low gamma-glutamyl hydrolase gene expression is a predictive factor for a high reduced folate level after leucovorin administration 3.4.19.9 folate gamma-glutamyl hydrolase medicine overexpression of gamma-glutamyl hydrolase significantly decreases chemosensitivity of MDA-MB-435 cells to 5-fluorouracil and methotrexate at all folate concentrations as expected. In contrast, in HCT116 cells this predicted effect is observed only at very high folate concentration, and as the folate concentration decreases this effect becomes null or paradoxically increases. Inhibition of gamma-glutamyl hydrolase significantly increases chemosensitivity of both cancer cells to 5-fluorouracil at all folate concentrations. gamma-Glutamyl hydrolase inhibition significantly decreases chemosensitivity of both cancer cells to methotrexate at all folate concentrations. In both modulation systems and cell lines, the magnitude of chemosensitivity effect incrementally increases as folate concentration increases 3.4.19.12 ubiquitinyl hydrolase 1 medicine ubiquitin hydrolase Uch-L1 could be an attractive target for the development of new therapeutic approaches to Alzheimer's disease 3.4.19.12 ubiquitinyl hydrolase 1 medicine activation of UCH-L1 may be a useful therapeutic approach for treating Alzheimer’s disease. Administration of a UCH-L1 fused to the transduction domain of the HIV-transactivator protein to supplement endogenous UCH-L1 has a protective effect on memory loss in a mouse model of Alzheimer’s disease. It restores long term potentiation and contextual memory to normal levels, whereas levels of the regulatory subunit of protein kinase A decrease, which, in turn, leads to increased levels of phosopho-cAMP response element binding protein 3.4.19.12 ubiquitinyl hydrolase 1 medicine class of 3-amino-2-keto-7H-thieno[2,3-b]pyridin-6-one derivatives as UCH-L1 inhibitors provide useful tools for investigating the role of UCH-L1 in normal cellular physiology, as well as in pathological conditions, such as Parkinson’s disease and some forms of cancer 3.4.19.12 ubiquitinyl hydrolase 1 medicine expression of UCH-L1 is increased during long-term facilitation, which is related to synaptic plasticity and learning 3.4.19.12 ubiquitinyl hydrolase 1 medicine interactions of mutant or carbonyl-modified UCH-L1 with other proteins constitute one of the causes of not only familial Parkinson’s disease, but also sporadic Parkinson’s disease. Carbonyl-modified and mutant UCH-L1 share common properties, e.g. adopt a similar aberrant structure, promote tubulin polymerization, show decreased ubiquitin binding, and both increased insolubility and interactions with proteins over 30 kDa compared with the wild-type 3.4.19.12 ubiquitinyl hydrolase 1 medicine overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy 3.4.19.12 ubiquitinyl hydrolase 1 medicine overexpression of UCHL1 significantly attenuates tumor necrosis factor-alpha–induced nuclear factor-kappa B activity in vascular cells and increases inhibitor of kappa B-alpha, possibly through the attenuation of kappa B-alpha ubiquitination, leading to decreased neointima in the balloon-injured artery 3.4.19.12 ubiquitinyl hydrolase 1 medicine Parkinson disease-associated UCH-L1 is regulated by reversible monoubiquitination involving auto-deubiquitination 3.4.19.12 ubiquitinyl hydrolase 1 medicine possible involvement of UCH-L1 and UCH-L3 in the pathogenesis and progression of breast cancer. High UCH-L1 mRNA level is significantly associated with negative estrogen receptor status and negative progesterone receptor status. Patients with both UCH-L1 and UCH-L3 mRNA high tumors show a significantly poorer prognosis than those in the UCH-L1 or UCH-L3 mRNA low group 3.4.19.12 ubiquitinyl hydrolase 1 medicine sperm acrosomal UCHs are involved in sperm-zona pellucida interactions and antipolyspermy defense. Modulation of spermal UCH activity may facilitate the management of polyspermy during in vitro fertilization and provide insights into male fertility. Recombinant UCHs reduce polyspermy and proportionally increase the rate of monospermic fertilization during in vitro fertilization. Oocyte-secreted UCHs are not necessary for antipolyspermy defense during in vitro fertilization 3.4.19.12 ubiquitinyl hydrolase 1 medicine targeting the UCH37-Smad7 complex may provide a new approach for treating human diseases in which there is overt up-regulation in TGF-beta signalling activity. Competing effects of ubiquitin ligases and DUBs in complex with Smad7 can serve to fine-tune responses to TGF-betas under various physiological and pathological conditions 3.4.19.12 ubiquitinyl hydrolase 1 medicine transient ischemia induces selective delayed motor neuronal death and affects the profile of expression of ubiquitin, parkin, and UCH-L1. Vulnerability of motor neuron of the spinal cord may be partially attributed to the different response in ubiquitin-mediated stress response after transient ischemia 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCH-L1 deficiency and impairment of the ubiquitin-dependent protein degradation pathway contributes to increased cell death observed in many lysosomal storage disorders 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCH-L1 has a putative but still undefined role in the ubiquitin-dependent protein degradation pathway. Postmortem analysis of human brains shows this pathway to be compromised in Alzheimer’s disease. A polymorphism in the UCH-L1 gene increases the risk of Alzheimer’s disease in females and also effects the risk of Parkinson’s disease in Asian populations 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCH-L1 is a potent molecular biomarker for monitoring early stage of neurodegeneration occurring under oxidative stress in elderly people of advanced age 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCH-L1 is an important component of the ubiquitin-proteasome system and is linked to Parkinson´s, Huntington´s, Alzheimer´s disease and other neurodegenerative disorders. UCH-L1 is an attractive target for the development of new therapeutic approaches to Alzheimer´s disease 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCH-L1 is required for maintenance of memory in a passive avoidance test, exploratory behaviour in a novel environment, and a transcription-dependent component of theta-burst stimulation-induced long-term potentiation in area CA1 of the hippocampus 3.4.19.12 ubiquitinyl hydrolase 1 medicine Uch-L1 is required for normal synaptic and cognitive function. Uch-L1 activity plays a role in normal contextual fear learning. Transduction of Uch-L1 protein fused to the transduction domain of HIV-transactivator protein restores normal enzymatic activity and synaptic function both in hippocampal slices treated with oligomeric Ab and in the APP/PS1 mouse model of Alzheimer’s disease. Intraperitoneal injections with the fusion protein improve the retention of contextual learning in APP/PS1 mice over time. Beneficial effect of the Uch-L1 fusion protein is associated with restoration of normal levels of the protein kinase A-regulatory subunit IIa, PKA activity, and cAMP response element binding protein phosphorylation 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCH-L1 is selectively expressed on the plasma membrane of mouse ova, where it may regulate membrane penetration by spermatozoa. The unique expression patterns of UCH-L1 and UCH-L3 suggest that these proteins have distinct functions during oogenesis and embryogenesis. UCH-L1 functions in the polyspermy block during mammalian fertilization 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCHL-1 expression is a contributory factor in the abnormal protein aggregation in dementia with Lewy bodies. Putative therapeutic target in the treatment of dementia with Lewy bodies 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCHL1 is aberrantly regulated in frontotemporal dementia and parkinsonism linked to chromosome 17 3.4.19.12 ubiquitinyl hydrolase 1 medicine Uchl3-deficient mice represent a model for adultonset retinal degeneration associated with mitochondrial impairment 3.4.19.12 ubiquitinyl hydrolase 1 medicine mono-ubiquitin and ubiquitin dimers may regulate the enzymatic functions of UCH-L1 in vivo 3.4.19.12 ubiquitinyl hydrolase 1 medicine UCH-L1 expression seems to be associated with the metastatic potential of human renal cell carcinoma cell SN12C clones 3.4.19.12 ubiquitinyl hydrolase 1 medicine uchl1 genes as novel targets of alpha-tocopherol deficiency may offer molecular correlates of well documented descriptions of neuromuscular dysfunctions in alpha-tocopherol-deficient rodents 3.4.19.12 ubiquitinyl hydrolase 1 medicine membrane-associated farnesylated UCH-L1 is a therapeutic target for Parkinson's disease 3.4.19.12 ubiquitinyl hydrolase 1 medicine expression of isoform UCHL1 is elevated in osteosarcoma compared with normal bone tissue. UCHL1 expression level is correlated with tumor maximum diameter, high rate of lung metastases and short survival time. Knockdown of UCHL1 in osteosarcoma cell MG-63 inhibits cell proliferation and significantly increases cell population in the G1 phase. Cyclins promoting G1/S phase transition are reduced after UCHL1 knockdown, including cell cycle regulator cyclin D1, cyclin E1 and CDK6. Inhibition of UCHL1 in MG-63 cells dramatically induces cell apoptosis. Downregulation of UCHL1 in MG-63 significantly inhibits cell invasion. There is a positive correlation between UCHL1 expression level and the Akt and ERK phosphorylation status 3.4.19.12 ubiquitinyl hydrolase 1 medicine melanoma cells show a a widespread loss or reduced expression of ubiquitin C-terminal hydrolase UCHL1, which is directly correlated with promoter DNA hypermethylation. The subset of melanoma cells, which still express UCHL1, shows altered growth properties and tolerances against reactive oxygen species as compared to UCHL1-negative cells. UCHL1 may function as a new diagnostic biomarker or therapeutic target for the treatment of UCHL1-positive melanomas 3.4.19.12 ubiquitinyl hydrolase 1 medicine ubiquitin C-terminal hydrolase UCH-L3 is upregulated in normal or non-metastatic prostate cancer cells and is downregulated in metastatic prostate cancer cell lines. Knockdown of UCH-L3 in normal prostate cell line RWPE1 promotes epithelial-to-mesenchymal transition, an important process for cancer cell invasion and metastasis. The induction of epithelial-to-mesenchymal transition by UCH-L3 knockdown results in an increase of cell migration and invasion. Overexpression of UCH-L3 in highly metastatic prostate cancer cell line PC3 reverses epithelial-to-mesenchymal transition but an active site mutant of UCH-L3 does not 3.4.19.13 glutathione gamma-glutamate hydrolase medicine pharmacokinetics of S-(2-(4-chlorophenoxy)-2-methylpropanoyl)glutathione, i.e. clofibryl-S-acyl-glutathione, in urine of rats. gamma-Glutamyltransferase-mediated degradation of S-(2-(4-chlorophenoxy)-2-methylpropanoyl)glutathione leads primarily to the formation and excretion of clofibryl-N-acyl-cysteine products rather than the S-acyl-N-acetylcysteine conjugate. Clofibryl-S-acyl-glutathione is degraded to clofibryl-N-acyl-cysteinylglycine, clofibril-N-acyl-cysteine and their respective S-methylated products. The mercapturic acid conjugate is found as a minor product 3.4.19.13 glutathione gamma-glutamate hydrolase medicine the metabolism of S-(5-hydroxy-2-pentyltetrahydrofuran-3-yl)glutathione in the V79 GGT cell line is associated with a considerable increase of cytotoxicity. The cytotoxic effect is dose- and time-dependent, with 100% cellular death at 200 mM S-(5-hydroxy-2-pentyltetrahydrofuran-3-yl)glutathione after 24 h incubation in V79 GGT cells 3.4.19.13 glutathione gamma-glutamate hydrolase medicine the relatively small increase of glutathione amount in the presence of oxidative and electrophilic agents such as hydrogen peroxide or N-ethylmaleimide compared to other thiol reactive agents is not due to increased gamma-glutamyltranspeptidase-mediated degradation of glutathione 3.4.19.13 glutathione gamma-glutamate hydrolase medicine treatment of rats with diclofenac results in accumulation of diclofenac-N-acyl-cysteinylglycine and diclofenac-N-acyl-cysteine in bile, albeit only about 1% of the administered dose of diclofenac within 6 h 3.4.19.13 glutathione gamma-glutamate hydrolase medicine lysate from a gamma-glutamyl transpeptidase Ggt mutant strain shows a decrease of the capacity to inhibit Jurkat T cell proliferation. Incubation of Jurkat T cells with recombinantly expressed Ggt results in an impaired proliferation, and cell death is involved. A similar but more pronounced inhibitory effect is also seen on primary murine CD4+ T cells, CD8+ T cells, and CD19+ B cells. Supplementation with glutamine restores normal proliferation of the cells, whereas supplementation with reduced glutathione strengthens the enzyme-mediated inhibition of proliferation. Ggt treatment abolishes secretion of IL-4 and IL-17 by CD4+ T cells, without affecting secretion of IFN-gamma. Helicobacter suis outer membrane vesicles are a possible delivery route of Ggt to lymphocytes residing in the deeper mucosal layers 3.4.21.1 chymotrypsin medicine pancreatitis treatment 3.4.21.1 chymotrypsin medicine treatment of gastroenterological diseases 3.4.21.1 chymotrypsin medicine study of the clinical utility of trypsin/chymotrypsin combination in tissue repair. Trypsin/chymotrypsin oral combination is a promising treatment to facilitate healing of traumatic injuries. It promotes speedier recovery and better resolution of inflammatory signs and symptoms due to tissue injury than several of the other existing enzyme preparations. It demonstrates analgesic effects and reduces pain associated with healing. The trypsin/chymotrypsin combination shows efficacy and safety in accidental injuries, surgical and orthopedic injuries, burns, and sciatica 3.4.21.1 chymotrypsin medicine the enzyme is successfully immobilized on a non-leaching material surface to provide a new material able to inhibit biofilm colonization. The multiple-target nature of the protease activity allows the new material to be used with a broad-spectrum activity against polymicrobial infections, including drug-resistant strains 3.4.21.B1 hyaluronan-binding serine protease medicine FSAP accumulation in coronary atherosclerotic lesions, is due to either local synthesis by monocytes/macrophages, or uptake from the plasma due to plaque hemorrhage. Higher expression of FSAP in unstable plaques may destabilize plaque through reducing vascular smooth muscle cell proliferation/migration and altering the hemostatic balance 3.4.21.B1 hyaluronan-binding serine protease medicine plays a role in physiologic function of the pericellular environment of the vasculature. Proteolytically inactivates growth factors. May regulate angiogenic processes, like neovascularisation during tissue remodelling, wound repair or tumor progression. May contribute to extravascular fibrin deposition and inflammatory processes in the injured lung 3.4.21.B1 hyaluronan-binding serine protease medicine proangiogenic potential of HABP, which, in combination with a profibrinolytic activity, directs the physiological function of this plasma protease to processes in which clot lysis, cell motility and neovascularisation are pivotal processes, e.g., in wound healing, tissue repair and tumour progession 3.4.21.B1 hyaluronan-binding serine protease medicine role in atherosclerosis, contributes to vascular fibroproliferative inflammatory diseases in the context of pericellular proteolysis of the extracellular matrix, growth factor activity and haemostasis 3.4.21.B1 hyaluronan-binding serine protease medicine the G534E variant of FSAP is a risk locus for chronic hepatitis C virus(HCV)-induced liver fibrosis and cirrhosis by determining platelet-derived growth factor BB (PDGF-BB)–mediated hepatic stellate cell proliferation through a single amino acid substitution in FSAP. FSAP G534E might be useful for risk stratification in patients with HCV infection 3.4.21.B1 hyaluronan-binding serine protease medicine FSAP measures are higher in women compared with age-matched men. The extent of coronary artery calcification in women is positively associated with total FSAP, but negatively associated with the specific activity of FSAP. No difference in FSAP measures is observed in men 3.4.21.B1 hyaluronan-binding serine protease medicine FSAP-alpha2-antiplasmin complex levels are markedly elevated in patients with Gram-negative sepsis as compared with controls. The FSAP level increases by 16.82 AU/ml in patients with melioidosis after adjustment for the effect of diabetes melitus in the regression model. FSAP activation is correlated with nucleosome release. No difference in FSAP activation on admission is seen between survivors and non-survivors, but the extent of FSAP activation correlates with stage of the disease 3.4.21.B1 hyaluronan-binding serine protease medicine HABP2 is an important regulator of lung cancer progression. HABP2 expression is increased in several subtypes of patient non-small cell lung cancer samples. HABP2 overexpression increases LMW-HA-induced urokinase plasminogen activator activation, migration, and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increases primary tumor growth rates in nude mice by about 2fold and lung metastasis by about 10fold compared to vector control cells 3.4.21.2 chymotrypsin C medicine carriers of CTRC mutations may be at a higher risk of developing endoplasmic reticulum stress in the exocrine pancreas. Endoplasmic reticulum stress may contribute to parenchymal damage in chronic pancreatitis through acinar cell apoptosis 3.4.21.B2 granzyme M medicine granzymes are differentially expressed in distinct sub-populations of peripheral blood lymphocytes 3.4.21.B2 granzyme M medicine GrzM plays a role in the host response to murine CMV infection, but is not critical for NK cell-mediated cytotoxicity, NK and T cell development and homeostasis and NK cell-mediated tumor rejection 3.4.21.B2 granzyme M medicine GzmM initiates caspase-dependent apoptosis, induces DNA fragmentation, but not DNA nicking, Pro-Ject protein transfection reagent can efficiently transport GZmM into target cells 3.4.21.B2 granzyme M medicine in the presence of perforin, the protease activity of GrM rapidly and effectively induces target cell death, but does not feature obvious DNA fragmentation, occurs independently of caspases, caspase activation, and perturbation of mitochondria 3.4.21.B2 granzyme M medicine granzyme M is expressed by human cytomegalovirus-specific CD8+ T cells both in latently infected healthy individuals and in transplant patients during primary human cytomegalovirus infection. Host cell heterogeneous nuclear ribonucleoprotein K is a physiological granzyme M substrate. Granzyme M most efficiently cleaves heterogeneous nuclear ribonucleoprotein K in the presence of RNA at multiple sites, thereby likely destroying heterogeneous nuclear ribonucleoprotein K function. Host cell heterogeneous nuclear ribonucleoprotein K is essential for hman cytomegalovirus replication not only by promoting viability of human cytomegalovirus-infected cells but predominantly by regulating viral immediate-early 2 protein levels. Granzyme M decreases viral immediate-early 2 protein expression in human cytomegalovirus-infected cells 3.4.21.B2 granzyme M medicine use of granzyme M as an alternative component of human cytolytic fusion proteins. Upon fusion to the humanized single-chain antibody fragment (scFv) H22 which specifically binds to CD64, an FccRI receptor overexpressed on activated myeloid cells and leukemic cells, the humanized cytolytic fusion protein specifically targets the acute myeloid leukemia cell line HL60 in vitro and is cytotoxic with an IC50 between 1.2 and 6.4 nM. These findings are confirmed ex vivo using leukemic primary cells from patients, which are killed by granzyme M despite the presence of the granzyme B inhibitor serpin B9 3.4.21.4 trypsin medicine commercial-level production of trypsin in transgenic maize, the availability of this reagent should allow for the replacement of animal-derived trypsin in the processing of pharmaceutical proteins 3.4.21.4 trypsin medicine use of enzyme and its regulators as markers of prognosis and disease activity in rheumatoid arthritis 3.4.21.4 trypsin medicine trypsin is the chief culprit of severe acute pancreatitis-associated multiple organ dysfunction syndromes, the pancreatic tissue bleeding and necrosis is special pathological change in pancreas autodigestive effect from digestive enzymes such as trypsin in severe acute pancreatitis, the activated trypsin destroys the pancreas itself causing pancreatic tissue bleeding and necrosis, trypsin also destroys the vascular endothelial barrier leading to highly increased vascular permeability 3.4.21.4 trypsin medicine role of trypsin as inducer of inflammation in skin via secretion of inflammatory mediators. King crab trypsin enhances the secretion ofIL-8, MMP-2 and MMP-9 by human skin keratinocytes. Exposure to proteases from the seafood may lead to inflammatory reactions in skin 3.4.21.4 trypsin medicine role of trypsin as inducer of inflammation in skin via secretion of inflammatory mediators. Salmon trypsin enhances the secretion of IL-8 and MMP-2 by human skin keratinocytes. Exposure to proteases from the seafood may lead to inflammatory reactions in skin 3.4.21.4 trypsin medicine dental plaque is a causative factor for oral disease and a potential reservoir for respiratory infection in the elderly. Therefore, there is a critical need for the development of effective methods to remove oral biofilm. Proteases reduce oral biofilm in vivo in elderly subjects. Tablets containing actinidin remove tongue coating in elderly subjects. Oral Actinomyces biofilm is significantly reduced by the proteases papain, actinidin and trypsin. Papain and trypsin effectively digest the major fimbrial proteins, FimP and FimA, from Actinomyces. Actinidin, papain and trypsin reduce multispecies biofilm that is reconstructed in vitro. Papain and trypsin inhibit formation of multispecies biofilm in vitro 3.4.21.5 thrombin medicine the enzyme can be engineered to function in vivo as a potent anticoagulant that may possess a superior therapeutic profile with reduced potential for bleeding complications 3.4.21.5 thrombin medicine enzyme inhibitors are used in therapy and prevention of venous and arterial thrombosis, inhibition mode, efficiency and safety, overview 3.4.21.5 thrombin medicine enzyme is a target for development of inhibitors in antithrombotic therapy 3.4.21.5 thrombin medicine enzyme activation of factor VIII mutant R372H, occuring in patients with hemophilia A, is about 80fold decreased, resulting in generation of about 6.1 nM factor X4 per min compared to 13 nM for wild-type 3.4.21.5 thrombin medicine exposure to thrombin induces an increase in cytosolic calcium in both anterior and equatorial lens cells. Repeated exposure produces a significant increase in cell coverage in the capsular bag model and increased thymidine incorporation into FHL124 cells. In FHL124 cells, exposure to thrombin induces biphasic increases in the phosphorylation of p42/p44 3.4.21.5 thrombin medicine mechanism of high affinity fibrinogen binding and cleavage in Staphylococcus aureus mediated endocarditis 3.4.21.5 thrombin medicine affinity probe capillary electrophoresis/laser-induced fluorescence polarization assay for detection of human thrombin using a specific aptamer as probe. Monovalent and bivalent cations promoting the formation of a stable G quadruplex conformation in the aptamer may enhance the binding of the aptamer and thrombin, while cations like K+ and Mg2+ cannot stabilize the affinity complex. Without the use of typical cations, a highly sensitive assay of human thrombin was developed with the corresponding detection limits of 4.38×10?19 and 2.94×10?19 mol in mass for standard solution and human serum, respectively 3.4.21.5 thrombin medicine beta2-glycoprotein I may regulate thrombin inactivation by heparin cofactor II. The presence of anti-beta2-glycoprotein I antibodies potentiates the protective effect of beta2-glycoprotein I on thrombin and may explain the prothrombic tendency in patients with antiphospholipid syndrome 3.4.21.5 thrombin medicine comparison of anticoagulation response to thrombin inhibitors ximelagatran and warfarin in rats on a normal diet to those on a vitamin K deficient diet. Ximelagatran and warfarin increase prothrombin time, activated partial thromboplastin time and ecarin clotting time in rats on normal diet. Vitamin K deficient diet alone causes modest increases in prothrombin time, activated partial thromboplastin time and ecarin clotting time. The anticoagulant activity of both ximelagatran and warfarin is significantly greater in rats on vitamin K deficient diet compared to those on normal diet. Thrombin activity is reduced by both ximelagatran and warfarin to 58% and 44%, respectively, in rats on normal diet. Thrombin activity is virtually abolished by both drugs in rats on vitamin K deficient diet 3.4.21.5 thrombin medicine comparison of thrombin inhibitors dabigatran and enoxaparin in unilateral total knee arthroplasty patients after surgery. Dabigatran shows inferior efficacy to enoxaparin. Bleeding rates are similar, and no drug-related hepatic illness has been recognized 3.4.21.5 thrombin medicine comparison of thrombin inhibitors lepirudin and argatroban for treatment of heparin-induced thrombocytopenia. Adult subjects with a positive anti-heparin platelet factor 4 antibody test and more than 50% decrease in platelet count during the first 30 days of admission over a period of 2 years were included in the study. Subjects treated with a thrombin inhibitor are more likely to experience platelet count recovery, with 87.5% for the lepirudin group and 82.4% for the argatroban group, compared to those who do not receive antithrombin therapy. The thrombosis rate for subjects who do not receive antithrombin therapy after the diagnosis of heparin-induced thrombocytopenia is 26.8%, compared to 8.3% for the lepirudin group and 5.9% for the argatroban group 3.4.21.5 thrombin medicine development of a biosensor for thrombin detection using surface-enhanced Raman spectroscopy. The method utilizes the electrostatic interaction between capture thrombin aptamer and probe crystal violet molecules. Procedure shows a highly specific selectivity and a linear detection of thrombin in the range from 0.1 nM to 10 nM with a detection limit of about 20 pM and realizes the thrombin detection in human blood serum solution directly 3.4.21.5 thrombin medicine development of a modified electrochemical sandwich model for target protein detection using differential pulse voltammetry. With model target analyte thrombin, the sensor shows a linear response for thrombin in the range 1-60 nM with a detection limit of 0.5 nM 3.4.21.5 thrombin medicine development of an aptamer-based surface enhanced resonance Raman scattering sensor with high sensitivity, specificity, and stability for the detection of human alpha-thrombin. The sensor displays a limit of detection of 100 pM by monitoring the signal change upon the single-step of thrombin binding to immobilized thrombin binding aptamer and specifically discriminates thrombin from other proteins. The sensor can detect 1 nM thrombin in the presence of complex biofluids, such as 10% fetal calf serum, and is sufficiently robust for clinical diagnostic applications 3.4.21.5 thrombin medicine examination of the effect of thrombin on tumor cell cycle activation and spontaneous growth in synchronized serum-starved tumor cell lines and a model of spontaneous prostate cancer development in TRAMP mice expressing the SV40 Large T Antigen under the control of the prostate-specific probasin promoter, leading to the spontaneous development of prostate cancer and metastasis. Prostate LNCaP cells arrested in G0 and treated with thrombin or serum reveal a 48- and 29-fold increase in S phase cells, respectively, at 8 hours. Addition of thrombin, PAR-1 agonist TFLLRN, or serum down-regulates the inhibitory cell cycle regulator p27Kip1 with concomitant induction of Skp2, cyclin D1, and cyclin A with similar kinetics. LNCaP p27Kip1-transfected cells or Skp2 knockdown cells are refractory to thrombin-induced cell cycle activation. Repetitive thrombin injection enhances prostate tumor volume 6- to 8-fold. Repetitive hirudin injection, a specific potent antithrombin, decreases tumor volume 13- to 24fold 3.4.21.5 thrombin medicine exogenous oxidative stress, thrombin activation, progression of ageing and type 2 diabetes lead to protein carbonyls formation in platelets, and this modification can be attenuated by antioxidant enzymes 3.4.21.5 thrombin medicine in cell cultures of HUVEC and HPAEC cells, low concentrations of thrombin or of receptor PAR-1 agonist peptide induce significant anti-inflammatory activities. Relatively high concentration of thrombin or of PAR-1 agonist peptide show pro-inflammatory activities. The direct anti-inflammatory effects of low concentrations of thrombin are dependent on the activation of PAR-1 and PI3 kinase 3.4.21.5 thrombin medicine in patients with acute ST-segment elevation myocardial infarction who have received tenecteplase together with aspirin and heparin, thrombin-antithrombin complexes correlate with tissue factor activity associated with microparticles, and correlates with soluble platelet glycoprotein. Fibrinolysis failure in acute ST-segment elevation myocardial infarction is characterized by a higher procoagulant state associated with tissue factor activity associated with microparticles and lower plasmin generation 3.4.21.5 thrombin medicine in patients with first spontaneous venous thromboembolism, high endogenous thrombin potential confers an 1.6fold increased risk of recurrence, and risk of recurrence is 2.8fold higher among patients with both high endogenous thrombin potential and high fibrin D-dimer 3.4.21.5 thrombin medicine in patients with rheumatoid arthritis, citrullinated fibrin and fibrinogen are present in the synovium. Citrullinated fibrinogen is not a substrate for thrombin and may be associated with the pathophysiology of rheumatoid arthritis 3.4.21.5 thrombin medicine placentas from pregnancies complicated by preterm preeclampsia have a significantly higher frequency of strong receptor PAR-1 expression than placentas from women with spontaneous pre-term labour. Role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in preeclampsia. The effects of thrombin in preeclampsia are due to increased thrombin generation and higher expression of PAR-1 3.4.21.5 thrombin medicine rabbits receiving infusions with recombinant hirudin containing the RGD motif, which competitively inhibits the binding of fibrinogen to GP IIb/IIIa on platelets, have prolonged thrombin time, prothrombin time. and activated partial thromboplastin time which are similar to that of wild-type hirudin. In addition, recombinant RGD-hirudin is capable of inhibiting platelet aggregation and is two to three times more effective than wild-type hirudin in preventing thrombosis 3.4.21.5 thrombin medicine thrombin augments the contractility of uterine smooth muscle cell and immortalized myometrial smooth muscle cell collagen gels. The effect is inhibited by thrombin inhibitor hirudin. Thrombin-induced collagen contractility results in activation of thrombin receptor F2R 3.4.21.5 thrombin medicine thrombin inhibition by argatroban improves neurological outcomes and provides neuroprotection against acute events after subarachnoid hemorrhage such as blood-brain barrier disruption, brain edema, and cell death 3.4.21.5 thrombin medicine treatment of adults with one or more mild or moderate bleeding sites not manageable by conventional modalities during elective cardiovascular, neurologic, or general surgey procedures with human or bovine thrombin, applied topically with an absorbable gelatin sponge. The proportions of patients achieving hemostasis within 10 min, 6 min or 3 min were equivalent for human and bovine thrombin.12.7% of patients who received bovine thrombin demonstrated seroconversion compared with 3.3% of the patients who received human thrombin 3.4.21.5 thrombin medicine treatment of adults with one or more mild or moderate bleeding sites not manageable by conventional modalities during elective cardiovascular, neurologic, or general surgey procedures with human or bovine thrombin, applied topically with an absorbable gelatin sponge. The proportions of patients achieving hemostasis within 10 min, 6 min or 3 min were equivalent for human and bovine thrombin.12.7% of patients who received bovine thrombin demonstrated seroconversion compared with 3.3% of the patients who received human thrombin. None of the patients in the human thrombin group developed seroconversion for anti-human thrombin or anti-human factor V/Va antibodies 3.4.21.5 thrombin medicine treatment of iatrogenic pseudoaneurisms of the trunk by injection of 765 IU thrombin. Both percutaneous and endoluminal techniques are technically feasible and safe but the questioning of dosage and long-term results need further experiences 3.4.21.5 thrombin medicine treatment of pigs that underwent mid-left anterior descending coronary artery occlusion followed by reperfusion with saline vehicle or thrombin fragment TP508, i.e. chrysalin as a bolus into the ischemic period followed by continuous intravenous infusion. Endothelium-dependent coronary microvascular relaxation is greater in the TP508 group and associated with higher endothelial nitric oxide synthase phosphorylation. Both infarct size and TUNEL staining is decreased in the TP508 group compared with the saline control group. ession of cell survival proteins B-cell lymphoma and heat shock protein-73 is higher in the TB508 group. Expression of cell death-signaling proteins polyadenosine-diphosphate-ribose polymerase, cleaved polyadenosine-diphosphate-ribose polymerase, and B-cell lymphoma2/adenovirus E1B 19 kDa-interacting protein is significantly higher in the TB508 group in the ischemic territory 3.4.21.5 thrombin medicine when endothelial protein C receptor is ligated by protein C, the cleavage of receptor PAR-1 by thrombin initiates antiinflammatory responses, thus leading to activation of Rac I and inhibition of RhoA and nuclear factor kappaB signaling cascades 3.4.21.5 thrombin medicine thrombin activation is not related to the measured thrombus surface area or thrombus volume in patients with abdominal aortic aneurysms 3.4.21.5 thrombin medicine because of the essential role of thrombin in the coagulation cascade, achieving the ability to specifically modulate thrombin activity represents a major goal in the development of anticoagulant strategies. Thrombin-binding aptamer (TBA), is a single-stranded 15-mer DNA with the sequence (5'-GGT TGG TGT GGT TGG-3') that binds thrombin with high specificity and affinity. TBA specifically inhibits clot-bound thrombin and reduces arterial thrombus formation. Native TBA consisting of only natural bases is susceptible to nuclease digestion and has a very short half-life in vivo of 108/s. Its binding affinity and selectivity need to be optimized. These optimization efforts are of critical importance in both diagnostic and therapeutic applications. Chemical modification of the DNA aptamer can be used to significantly improve its binding affinity 3.4.21.5 thrombin medicine fibrinogenolytic properties make the enzyme applicable for biochemical research and drug development on thrombolytic therapy 3.4.21.6 coagulation factor Xa medicine enzyme is a target for antithrombotic agents 3.4.21.6 coagulation factor Xa medicine enzyme is a target for discovery, design of direct inhibitors and development of antithrombotic agents, overview 3.4.21.6 coagulation factor Xa medicine glycoprotein IIb/IIIa receptor antagonists in combination with heparin might contribute to improved therapy of acute coronary syndromes abd during percutaneous coronary interventions 3.4.21.6 coagulation factor Xa medicine enzyme inhibition by anticoagulants are recommended for numerous medical conditions, including the prevention and treatment of venous thromboembolism, stroke prevention in patients with atrial fibrillation, and secondary prevention in acute coronary syndromes 3.4.21.6 coagulation factor Xa medicine FXa is an attractive and potentially specific target for anticoagulant agents 3.4.21.B6 prostasin medicine blood-borne RT-PCR amplification of prostasin transcripts may provide an early diagnosis of disseminated disease in patients with organ-confined carcinoma 3.4.21.B6 prostasin medicine is a major regulator of epithelial Na+ channel-mediated Na+ current, airway prostasin is a target for therapeutic inhibition to normalize ion current in cystic fibrosis airway 3.4.21.B6 prostasin medicine promoter DNA methylation partly causes the prostasin down-regualtion in prostate cancer cell lines 3.4.21.B6 prostasin medicine genetic variation of the prostasin gene may be implicated in the development of hypertension in youths 3.4.21.B6 prostasin medicine prostasin is a tumor marker in ovarian cancer 3.4.21.B6 prostasin medicine exogenous expression of prostasin can protect suckling mice from life-threatening DENV-2 infection. Inhibition of DENV propagation by prostasin is due to reducing expression of epithelial growth factor receptor, leading to suppression of the Akt/NF-kappaB-mediated cyclooxygenase-2 signaling pathway 3.4.21.B6 prostasin medicine matriptase and prostasin mRNA levels are significantly reduced in colonic tissues from patients with both ulcerative colitis and Crohn's disease 3.4.21.B6 prostasin medicine mRNA and protein expression of both matriptase and prostasin are rapidly down-regulated in the initiating inflammatory phases of dextran sulfate sodium-induced experimental colitis, and the loss of these proteases precedes the appearance of clinical symptoms. Barrier disruption by the colitis-associated Th2-type cytokines, IL-4 and IL-13, down-regulates matriptase as well as prostasin through phosphorylation of the transcriptional regulator STAT6 3.4.21.B6 prostasin medicine patients with dengue fever show relatively low expression of prostasin and compared with healthy individuals and a high correlation of prostasin expression and DENV-2 RNA copy number. Dengue virus infection significantly decreases prostasin RNA levels of in vivo and in vitro models 3.4.21.B6 prostasin medicine prostasin, matriptase, hepatocyte growth factor activator inhibitor type 1 (HAI-1) and 2, and nexin-1 mRNA abundances are not different in placental tissue between patients with preeclampsia and healthy pregnant women. Prostasin mRNA in placenta correlates directly with nexin-1 and HAI-1 mRNA, but not with matriptase mRNA. Plasma prostasin and placental homogenate prostasin and nexin-1 protein levels do not differ between groups. Preeclamptic patients show significantly elevated levels of prostasin in urine that correlates with urine albumin 3.4.21.B6 prostasin medicine PRSS8 is expressed in ovarian cancer at levels more than 100fold greater than in normal or benign ovarian lesions. Overexpression is found in early stages of ovarian cancer and is maintained in higher stages and grades of ovarian cancer. The PRSS8 overexpression is specific for ovarian cancer and urinary bladder cancer among 18 human cancer types. The majority of ovarian cell lines overexpress PRSS8. Overexpression of prostasin is largely localized to tumor epithelium and is absent in neighboring stroma 3.4.21.7 plasmin medicine a reversibly acylated plasmin-staphylokinase complex might be protected from rapid irreversible inhibition by alpha2-antiplasmin in plasma, exhibits a prolonged plasma half-life and has altered pharmacodynamic properties 3.4.21.7 plasmin medicine a mutant, noninhibitory plasminogen activator inhibitor-type 1 reduces pathological ECM accumulation in anti-thy-1 nephritis, in large part through effectively competing with native plasminogen activator inhibitor-type 1, thereby restoring plasmin generation and increasing plasmin-dependent degradation of matrix components 3.4.21.7 plasmin medicine binding of inactive plasmin to annexin A2 inhibits plasmin induction of matrix metalloproteinase-1. Inactive plasmin may be useful in suppressing inflammatory diseases that involve a series of proteases (e.g., matrix metalloproteinases) 3.4.21.7 plasmin medicine blocking plasmin prevents the generation of active platelet-derived growth factor-C, which is the major platelet-derived growth factor isoform relevant for proliferative vitreoretinopathy. Thus, plasmin is a therapeutic target for patients with proliferative vitreoretinopathy 3.4.21.7 plasmin medicine exerts proinflammatory functions. Direct activation of RAW264.7 cell monocytes by plasmin 3.4.21.7 plasmin medicine less efficient proteolytic processing of the Pro370Leu protein by plasmin, coupled with the strong association of this variant with ethnicity, contributes to the differential prevalence of cardiovascular disease across ethnic groups 3.4.21.7 plasmin medicine plasmin activates transforming growth factor beta 2, which has a potential protective role in breast cancer by its inhibitory effect on epithelial cell growth 3.4.21.7 plasmin medicine plasmin can impair hemostasis by partially degrading fibrinogen to fragment X, a product that retains clottability but forms clots with reduced tensile strength that stimulate plasminogen activation by tissue-type plasminogen activator more than fibrin clots. Attenuation of thrombolytic therapy-induced fragment X formation may reduce the risk of bleeding 3.4.21.7 plasmin medicine plasmin generated in atherosclerotic lesion can induce macrophage activation 3.4.21.7 plasmin medicine plasmin generation system plays an important role in tissue repair/remodeling 3.4.21.7 plasmin medicine plasmin induces an endothelium-dependent NO-mediated vasorelaxation in the porcine coronary artery, whereas it inhibits the endothelium-dependent relaxation induced by thrombin 3.4.21.7 plasmin medicine processing of pro-brain-derived neurotrophic factor by plasmin stimulates neurite outgrowth on TrkB-transfected PC-12 cells to a similar extent than mature wild-type brain-derived neurotrophic factor 3.4.21.7 plasmin medicine role in the course of tissue repair. Plasmin directly influences ERK-mediated signaling leading to epithelial to mesenchymal transition 3.4.21.7 plasmin medicine the plasminogen/plasmin system decreases Bim(EL) expression and activation of caspase-3 via the ERK1/2 signaling pathway during liver regeneration, resulting in an enhancement of cell survival. Plasmin protects against starvation-induced apoptosis in primary hepatocytes of mice 3.4.21.7 plasmin medicine 11% of patients with systemic reactions to Hymenoptera stings display increased serum baseline plasmin level and 70% of these have a history of anaphylaxis. Indication of bone marrow examination for the diagnosis of clonal mast cell disease 3.4.21.7 plasmin medicine 16% of patients with a history of systemic reaction to Hymenoptera and Diptera venom show an elevated level of plasmin. These patients report fewer usual skin reactions, more flushing and frequently do not present skin reaction. Mastocytosis was diagnosed in 33% of patients with elevated plasmin level 3.4.21.7 plasmin medicine application of human plasminogen to plasminogen-deficient mice with bacterially induced arthritis. Plasmin protects against Staphylococcus aureus-induced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression 3.4.21.7 plasmin medicine comparison of serum plasmin levels and scoring mastocytosis index reveals a positive correlation. Use of scoring mastocytosis index as a tool for evaluating the severity of cutaneous mastocytosis 3.4.21.7 plasmin medicine in presence of plasmin on the bacterial surface, Streptococcus pneumoniae transmigration across epithelial A549 and endothelial EaHy layer increases 3.4.21.7 plasmin medicine induction of asthma by ovalbumin results in thickening of the airway wall, hypertrophy of smooth muscle cells, infiltration of inflammatory cells, subepithelial fibrosis, epithelial and endothelial lesions. Tissue plasminogen activator activity is significantly decreased in asthmatic animals, and activity of plasmin inhibitor PAI-1 is significantly higher as is alpha2-antiplasmin, consistent with the superiority of plasmin system inhibition over activation in plasma 3.4.21.7 plasmin medicine antifibrinolytic inhibitors, e.g. aprotinin, of the serine protease plasmin are commonly used to reduce bleeding during surgery 3.4.21.7 plasmin medicine localized immobilization of bioactive plasmin on stainless steel substrates, including stents, may attenuate metallic prosthesis-induced thrombus formation 3.4.21.B7 mannan-binding lectin-associated serine protease 1 medicine there is an association of higher MBL/MASP-1 complex activity with liver disease and an association with severity of fibrosis 3.4.21.B7 mannan-binding lectin-associated serine protease 1 medicine proteases MASP-1 and MASP-2 levels are significantly higher in children and adults with type 1 diabetes mellitus than in their respective control groups, whereas proteases MASP-3 and MAp44 levels do not differ between patients and controls. MASP-1 and MASP-2 levels correlate with hemoglobin HbA1c, and MASP levels decrease when glycaemic control improves 3.4.21.9 enteropeptidase medicine human TRAIL is a candidate for clinical application in cancer therapy, activity is lost in some forms of recombinant TRAIL, refolding of thioredoxin/TRAIL and cleavage by enteropeptidase yield a biological active anticancer agent 3.4.21.10 acrosin medicine acrosin activity positively correlates with normal sperm morphology and with fertilization rate. Use of enzyme assay to predict sperm fertilizing capacity in in vitro fertilization independently of sperm morphology 3.4.21.10 acrosin medicine egg-sperm interaction: proenzyme binds to bovine serum albumin-mannose, binding sites are stabilized by noncovalent bonds and disulfide linkages. Binding sites are located both at the N- and C-terminus of protein 3.4.21.10 acrosin medicine sperm-egg interaction: interaction of protein with zona pellucida glycoproteins, highest binding activity with glycoprotein ZPA. Interaction involves mannosyl, fucosyl, and sulfated glycans. Binding sites are located both on N- and C-terminus of proacrosin, revealing a key role of proenzyme in the interaction 3.4.21.10 acrosin medicine use of total enzyme activity as biochemical marker for clinical evaluation of unexplained infertility in males 3.4.21.10 acrosin medicine possible use as parameter for the determination of infertility 3.4.21.10 acrosin medicine acrosin represents a potential target for the design and development of male contraceptive agents 3.4.21.B10 neurosin medicine developoment of a monoclonal antibody to conform the high expression level of hK6 in ovarian tumor cells. The development of high-quality monoclonal antibodies will facilitate the evaluation of biomarkers and allow further screening tool development for early detection of avarian cancer 3.4.21.B10 neurosin medicine kallikrein 6 and other kallikreins have the potential as useful biomarker for salivary gland neoplasms 3.4.21.B10 neurosin medicine active hK6 is present in ovarian cancer ascites fluid, provides a rationale for the development of novel therapeutic strategies 3.4.21.B10 neurosin medicine Klk6 expression decreases E-cadherin levels at the membrane in concert with cytoplasmic and nuclear accumulation of beta-catenin. Klk6 transgene expression induces keratinocyte proliferation and migration during cutaneous wound healing 3.4.21.B10 neurosin medicine KLK6 is a biomarker for tumor diagnosis and management and a promising therapeutic target. KLK6 expression induces E-cadherin ectodomain shedding and reduces cell-cell adhesion. KLK6-induced E-cadherin ectodomain shedding requires proteolytic activity of matrix metalloproteinase and/or disintegrin and metalloproteinase 3.4.21.B10 neurosin medicine KLK6 is an unfavorable prognostic biomarker for ovarian cancer. KLK6 is transcriptionally upregulated in ovarian cancer, but probably not through alternative mRNA transcript expression, genomic mutation, or steroid hormone induction. Upregulation correlates with cancer stage 3.4.21.B10 neurosin medicine multiple co-operating mechanisms underlie the inactivation of KLK6 expression in breast cancer and provide ways for its pharmacological modulation with potential therapeutic implications 3.4.21.B10 neurosin medicine protease M in oligodendrocytes is closely associated with the expression of the myelin basic protein and the PLP gene. Maintenance of myelination is an important function of protease M in oligodendrocytes. The enzyme may be related to the oligodendroglial response to myelin disorders 3.4.21.B10 neurosin medicine tumor-associated overexpression of tissue kallikreins contributes to ovarian cancer progression. Possibily effects observed may be due to the activity of only some of the four kallikreins hK4, hK5, hK6, and hK7 under survey 3.4.21.B10 neurosin medicine the enzyme might be used as a potential biomarker and therapeutic target for gastric cancer 3.4.21.B10 neurosin medicine the enzyme might be useful as target for therapeutic intervention in case of intracranial tumors 3.4.21.B10 neurosin medicine Klk6 represents an important target for conditions in which pro-inflammatory responses play a critical role in disease development, including multiple sclerosis 3.4.21.B10 neurosin medicine possibility to exploit KLK6 as a novel therapeutic target for Parkinson disease and other synucleinopathies 3.4.21.B12 prostase medicine enzyme might be useful as diagnostic marker in ovarian cancer 3.4.21.B12 prostase medicine naturally occuring gene mutation G214A results in a truncated enzyme that lacks residue S207 of the catalytic triad. Mutation affects tooth enamel formation causing the enamel crystallites to grow incompletely in thickness or width but to normal length, i.e. autosomal recessive hypomaturation amelogenesis imperfecta 3.4.21.B12 prostase medicine no significant differences in enzyme protein content between healthy prostate tissue and malignant or benign prostate 3.4.21.B12 prostase medicine patients with epithelial ovarian carcinoma, carcinoma cells expressed enzyme in 80% of effusions and 82% of solid tumors, levels are highest in effusions. Enzyme expression does not predict survival 3.4.21.B12 prostase medicine expression of the various tissue kallikreins like KLK4 in the endometrium and conceptus during the estrous cycle and early pregnancy in the pig can serve in the activation of growth factors and tissue remodeling during the establishment of pregnancy 3.4.21.B12 prostase medicine K4 is not only expressed in prostate cancer cells, but also osteoblasts, in bone metastases. Thus, K4 may have proteolytic roles as a potential mediator of cellular interactions between prostate cancer and bone cells. Complex interactions may occur between prostate cancer and bone cells in the metastatic environment. Co-culture models are a crucial tool in evaluating cellular interactions 3.4.21.B12 prostase medicine KLK-4 proteinase is essential for the final crystallite growth of enamel but is not critical for crystallite orientation, prism formation or enamel thickness 3.4.21.B12 prostase medicine KLK4 initiates Ca2+ mobilization via PAR-1 and PAR-2 but not via PAR-4. KLK4 has greater efficacy for initiating Ca2+ signalling via PAR-2 than PAR-1. Signals induced by KLK4 via PARs may be important in prostate cancer 3.4.21.B12 prostase medicine KLK4 is a proliferative factor with effects on cell cycle-related gene expression. It may have an important role in prostate cancer development and progression 3.4.21.B12 prostase medicine tumor-associated overexpression of tissue kallikreins contributes to ovarian cancer progression. OV-MZ-6 ovarian cancer cells simultaneously expressing K4-7 display similar proliferative capacity as the vector-transfected control cells, but show significantly increased invasive behavior. Simultaneous expression of K4-7 in OV-MZ-6 cells and inoculated into the peritoneum of nude mice, results in a remarkable 92% mean increase in tumor burden compared to control cell line 3.4.21.B12 prostase medicine kallikrein 4 quantification serves as an independent biomarker for the discrimination between the malignant and the benign nature of prostate tumors 3.4.21.B12 prostase medicine KLK4 can serve as a potential therapeutic target in patients with oral cancer. Inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines 3.4.21.20 cathepsin G medicine JNJ-10311795 is an inhibitor of cathepsin G and chymase. The possibility to inhibit both cathepsin G and chymase with a single molecule suggests an exciting opportunity in the treatment of asthma and chronic obstructive pulmonary disease 3.4.21.20 cathepsin G medicine cathepsin G is a potentially novel therapeutic target in the treatment of breast cancer bone metastasis 3.4.21.20 cathepsin G medicine cathepsin G as potential therapeutic target 3.4.21.20 cathepsin G medicine enzyme inhibitors are used as drugs for psoriasis 3.4.21.21 coagulation factor VIIa medicine digoxigenin ester derivatives of factor VIIa facilitate staining studies to localize tissue factor activity in human atherosclerotic plaques. The product of factor VIIa obtained at 50fold digoxigenin excess is the best choice for pathologic staining because it retains full enzyme activity together with a large number of incorporated digoxigenin units 3.4.21.21 coagulation factor VIIa medicine the recombinant activated factor VII corrects the deficient thrombin generation seen in factor VII and factor IX deficiency, and in blood containing factor VIII inhibitors. As s consequence, platelet function is improved and clot structure is enhanced 3.4.21.21 coagulation factor VIIa medicine recombinant FVIIa constitutes an efficient substitution therapy for treatment of patients with haemophilia A and haemophilia B which lack or have dysfunctional FVIII and FIX, respectively, pharmacological mechanism of action of FVIIa, overview 3.4.21.21 coagulation factor VIIa medicine the enzyme is clinically used to treat hemophilia, clinical trials, overview 3.4.21.21 coagulation factor VIIa medicine the recombinant enzyme is useful as hemostatic agent in the treatment of hemorrhage in hemophiliacs with inhibitors, and in use as hemostatic agent in severe bleeding unresponsive to standard treatment, associated with disseminated intravascular coagulation, clinical trials, mode of action, overview 3.4.21.21 coagulation factor VIIa medicine recombinant coagulation factor VIIa is administered to control acute bleeding in a patient with Klippel-Trenaunay-Weber syndrome 3.4.21.21 coagulation factor VIIa medicine the efficacy of recombinant factor VIIa for the reversal of anticoagulation in patients with warfarin-associated intracranial hemorrhage is described in several case reports, case series, and retrospective cohort studies. Its use may be considered for as a viable alternative treatment to standard treatment with fresh-frozen plasma. Patients should be screened for increased risk of thrombosis before administration of the drug 3.4.21.21 coagulation factor VIIa medicine the therapeutic efficacy and safety of recombinant factor VIIa in haemophilia patients with inhibitors is established in a number of clinical trials which also forms the basis for regulatory approval 3.4.21.21 coagulation factor VIIa medicine to assess effects of rFVIIa on survival outcomes, rFVIIa cases are matched to controls on injury severity and age. 22 battle-injured patients from the Combat Trauma Registry received rFVIIa. Over two-thirds (68%) of the rFVIIa patients survived, an identical outcome seen for a matched control group of 22 patients 3.4.21.21 coagulation factor VIIa medicine gene-based FVIIa variants show improved hemostatic efficacy for the treatment of hemophilia. Factor VIIa variants VEAY7 and DVQ30 exhibit increased tissue factor-independent coagulant activity relative to the wild type 3.4.21.21 coagulation factor VIIa medicine recombinant factor-activated VII has safety and potential benefit for control and prevention of hemorrhage in pediatric patients without congenital hemophilia 3.4.21.B21 trepolisin medicine Treponema denticola exerts a pathogenic effect on periodontal tissue via local dysregulation of inflammatory cytokines by dentilisin 3.4.21.22 coagulation factor IXa medicine anti-thrombosis therapy 3.4.21.22 coagulation factor IXa medicine target of therapy in thrombotic disorders, application of a complementary oliconucleotide antidote to RB006, a aptamer-based inhibitor to factor IXa, return factor IX activity to its baseline levels 3.4.21.22 coagulation factor IXa medicine long-acting FIX microspheres are used in hemophilic prophylaxis 3.4.21.B24 proprotein convertase 4 medicine abnormal processing of insulin growth factor-II by PC4 is involved in the pathophysiology of fetoplacental growth restriction 3.4.21.B24 proprotein convertase 4 medicine manifold effects of proprotein convertases, influencing tumor cell proliferation, motility, adhesiveness, and invasiveness, should be exploited by further developing competitive or inhibitory therapeutic strategies that would be able to neutralize simultaneously the most salient cancer cell properties 3.4.21.B24 proprotein convertase 4 medicine PC4 inhibitors may find potential therapeutic and clinical applications in male fertility 3.4.21.B24 proprotein convertase 4 medicine PCSK4 appears to be a crucial enzyme for reproduction. Alterations of PCSK4 expression or activity could be the underlying cause of some unexplained cases of human infertility. Conversely, inactivation of this protease represents a potential strategy for non-hormonal contraception 3.4.21.B25 PACE4 proprotein convertase medicine PACE4 overexpression results in enhanced susceptibility to carcinogenesis and tumor progression pointing to a new target for blocking tumor cell invasiveness, PACE4 enhances induced epidermal proliferation, activates matrix metalloproteinases in vivo, disrupts basement membrane structure, increases susceptibility to skin cancer and induces higher levels of matrix metalloproteinases and tumors of advanced malignant phenotype 3.4.21.B25 PACE4 proprotein convertase medicine PACE4 represents a target for the development of osteoarthritis therapeutics 3.4.21.B25 PACE4 proprotein convertase medicine PACE4 siRNA may exert antitumor activity through the mitochondrial pathway and is expected to be a promising therapeutic strategy for the treatment of pancreatic cancer 3.4.21.B25 PACE4 proprotein convertase medicine the enzyme has an important role in prostate cancer cell proliferation and is a potential therapeutic target 3.4.21.B25 PACE4 proprotein convertase medicine the enzyme is a validated target for prostate cancer 3.4.21.B25 PACE4 proprotein convertase medicine the inhibition of the enzyme slows prostate cancer progression and is emerging as a promising therapeutic strategy 3.4.21.26 prolyl oligopeptidase medicine the inhibitors (-)-epigallocatechin gallate, (-)-epicatechin gallate and (+)-gallocatechin are expected to be useful for preventing and curing of Alzheimer‘s disease 3.4.21.26 prolyl oligopeptidase medicine coperfusion of enzyme into rat intestine with a highly digestive-resistant 33-mer peptide and partially proteolyzed gliadin. Enzyme supplementation helps in efficient processing of peptides resistant to proteolysis. Use of enzyme to treat patients with Celiac Sprue 3.4.21.26 prolyl oligopeptidase medicine enzyme at 20 mU/ml can partly degrade gliadin peptides in vitro and ex vivo and decreases the amount of intact peptides crosing the intestinal biopsy specimens of celiac disease patients but cannot prevent the intestinal passage of toxic or immunostimulatory metabolites. Enzyme concentrations of at least 500 mU/ml are required to achieve full detoxification 3.4.21.26 prolyl oligopeptidase medicine enzyme levels in postmortem brains of Alzheimer’s disease patients reveal significant increases in enzyme activity. Use of unsaturated fatty acids in preventing memory loss 3.4.21.26 prolyl oligopeptidase medicine treatment of proteolyzed gluten with enzyme decreases the number of potentially immunostimulatory peptides with rapid destruction of alpha-gliadin epitopes but less complete processing of gamma-gliadin epitopes. Use of enzyme in oral therapy of Celiac Sprue 3.4.21.26 prolyl oligopeptidase medicine use of enzyme in antibody-directed enzyme prodrug therapy strategy, ADEPT. Coupling of enzyme mutant E289G to human antibody specific to the EDB domain of fibronectin, conjugate retains antigen binding and enzymatic activity 3.4.21.26 prolyl oligopeptidase medicine inhibition of the enzyme may be a therapeutic approach to neurodegenerative disorders including Alzheimer and Parkinson diseases 3.4.21.26 prolyl oligopeptidase medicine positive effect of prolyl oligopeptidase inhibitors on learning and memory in animal models for amnesia, enzyme activity measurements in patient samples and (neuro)peptide degradation studies link the enzyme with neurodegenerative disorders 3.4.21.26 prolyl oligopeptidase medicine involvement in pathogenesis of sleeping sickness suggested 3.4.21.26 prolyl oligopeptidase medicine potential target in cognitive function, memory and neurodegenerative disorders 3.4.21.26 prolyl oligopeptidase medicine target for the treatment of neuropsychiatric diseases and cognitive disturbances 3.4.21.B26 proprotein convertase 5 medicine av endoproteolytic activation is necessary for integrin-mediated adhesion and migration as well as signaling and requires PC5 in vascular smooth muscle cells 3.4.21.B26 proprotein convertase 5 medicine carotid atherosclerotic lesions obtained by endaterectomy contain PC5, PC5 colocalizes with av integrin 3.4.21.B26 proprotein convertase 5 medicine crucial role in heart development and in endothelial cells, involved in embryonic bone morphogenesis 3.4.21.B26 proprotein convertase 5 medicine crucial role in prorenin activation within the adrenal cortex or in HIV gp160 processing in CD4+ cells, major impact on cellular proliferation and on sexual differentiation, involvement in food metabolism 3.4.21.B26 proprotein convertase 5 medicine PC5 is a potential contributor to the initiation, progression, and complications of atherosclerosis and restenosis, targeting PC5 will likely provide novel anti-atherosclerosis strategies 3.4.21.B26 proprotein convertase 5 medicine PC5/6 plays a key role for decidualization in human endometrium and its action is necessary for prolactin production from endometrial stromal cells 3.4.21.B26 proprotein convertase 5 medicine PC5/6A is involved in squamous differentiation of human nasal epithelial cells, possibly through up-regulation of the BMP-2/pSmad1/5/8/p38 signaling pathway, pointing to a potential therapeutic target for the prevention of chronic airway diseases that exhibit squamous metaplasia 3.4.21.27 coagulation factor XIa medicine anti-thrombosis therapy 3.4.21.27 coagulation factor XIa medicine antithrombosis therapy 3.4.21.27 coagulation factor XIa medicine blood coagulation 3.4.21.27 coagulation factor XIa medicine the enzyme may be a suitable target for the development of an antithrombotic therapy 3.4.21.27 coagulation factor XIa medicine diagnosis of FXI deficiency may be considered in patients with delayed postoperative bleeding and prolonged activated partial thromboplastin time, especially in a demographically high-risk population, such as Ashkenazi Jews. Women with severe FXI deficiency and prolonged activated partial thromboplastin time can be managed with fresh frozen plasma transfusion before neuraxial anesthesia 3.4.21.27 coagulation factor XIa medicine therapeutically targeting FXI may offer a strategy for preventing or treating arterial thrombosis that is not associated with the high rate of hemorrhage that accompanies many currently used anticoagulants. Pharmacological FXI inhibitors may be beneficial in septic disease 3.4.21.27 coagulation factor XIa medicine treatment options for FXI-deficient patients include virus-inactivated fresh frozen plasma, plasma-derived FXI concentrates, and activated recombinant FVII. Potential role of desmopressin for either treatment of bleeding episodes or the prevention of postoperative bleeding in patients with milder FXI defects. A single desmopressin infusion is sufficient to provide an efficient perioperative hemostasis 3.4.21.B27 proprotein convertase 7 medicine may have a role in immunity or in defence mechanisms 3.4.21.B27 proprotein convertase 7 medicine plays a role in Alzheimer´s disease by participating in the non-amyloidogenic pathway through the activation of alpha-secretase, can also contribute to pro-parathyroid hormone activation, could participate in the activation of viral surface glycoproteins including the HIV gp160 type I glycoprotein, seems likely that perturbance of the levels of PC7 could lead to cancer of lymphatic tissues, could be important in cell proliferation 3.4.21.B27 proprotein convertase 7 medicine PCSK7 rs236918 C allele is a risk factor for cirrhosis development in Italian patients with HFE-hemochromatosis 3.4.21.B28 fibroblast activation protein alpha subunit medicine expression of active seprase increases tumor growth and microvessel density 3.4.21.B28 fibroblast activation protein alpha subunit medicine protease complex consisting of seprase and dipeptidylpeptidase IV in endothelial cells that are activated to migrate and invade in the extracellular matrix in vitro and are coexpressed with the three major protease systems matrix metalloproteinase, plasminogen activator, and type II transmembrane serine protease, at the cell surface and organize as a complex at invadopodia-like protrusions 3.4.21.B28 fibroblast activation protein alpha subunit medicine role in the invasive and metastatic progression of gastric carcinoma, tendency towards a worse prognosis in patients whose tumors exhibit high levels of the 170000 Da seprase dimer 3.4.21.B28 fibroblast activation protein alpha subunit medicine selectively induced in fibrotic foci, but not in normal or emphysematous lung 3.4.21.B28 fibroblast activation protein alpha subunit medicine significant correlation between seprase expression and lymph node metastasis 3.4.21.B28 fibroblast activation protein alpha subunit medicine tumor suppressor that abrogates tumorigenicity through regulation of cell growth and survival, in vitro, FAP expression restores contact inhibition, leads to cell cylcle arrest at G0/G1 phase, increases susceptibility to stress-induced apoptosis, and leads to caspase activation 3.4.21.B28 fibroblast activation protein alpha subunit medicine fibroblast activation protein alpha has a high-risk correlation with the malignant level of clinical outcomes in gastric cancer patients 3.4.21.B28 fibroblast activation protein alpha subunit medicine targeting fibroblast activation protein and cancer-associated fibroblasts in combination with radiation is capable of enhancing anti-tumor T cell infiltrate and function, but does not result in sufficient tumor clearance to extend survival 3.4.21.B28 fibroblast activation protein alpha subunit medicine the limited expression of the enzyme in healthy tissues together with its presence in both transformed and stromal cells suggests that it may be a candidate target for specific delivery of therapeutic agents in glioblastoma 3.4.21.34 plasma kallikrein medicine DX-88 has a strong neuroprotective effect in the early phases of brain ischemia preventing reperfusion injury and indicates that inhibition of plasma kallikrein may be useful tool in the strategy aimed at reducing the detrimental effects linked to reperfusion 3.4.21.34 plasma kallikrein medicine porcine pancreatic kallikrein is absorbed after oral administration and to exert its pharmacological action via kinins produced by kininogen degradation in dogs 3.4.21.34 plasma kallikrein medicine targeting plasma kallikrein may offer a strategy for prevention or treatment of thrombosis 3.4.21.34 plasma kallikrein medicine enzyme inhibition can decrease blood-brain barrier damage and cell invasion during neuroinflammation and may offer a strategy for the treatment of multiple sclerosis 3.4.21.35 tissue kallikrein medicine enzyme complexed with prostate protease inhibitor-6 may be a naturally occuring marker of tissue damage and necrosis associated with neoplasia 3.4.21.35 tissue kallikrein medicine diagnostic marker for ovarian cancer 3.4.21.35 tissue kallikrein medicine enzyme is a diagnostic marker for prostate cancer 3.4.21.35 tissue kallikrein medicine For men with localized prostate cancer and moderate elevation of prostate-specific antigen in serum, addition of free prostate-specific antigen and enzyme data increase predictive accuracy 3.4.21.35 tissue kallikrein medicine the enzyme-activated prodrug Ac-GKAFRR-L12ADT, i.e. Ac-GKAFRR-thapsigarin, is stable in vivo. The maximally tolerated dose is 6 mg/kg, which produces a serum concentration of about 0.036 mM and has a half-life of 40 min 3.4.21.35 tissue kallikrein medicine tissue kallikreins may be causally involved in carcinogenesis, particularly in tumor metastasis and invasion, and thus, may represent attractive drug targets to consider for therapeutic intervention. Certain kallikreins are markers of favorable prognosis for cancer patients 3.4.21.35 tissue kallikrein medicine kallikrein may serve as new drug target for the prevention and treatment of heart failure, renal disease and stroke in humans 3.4.21.35 tissue kallikrein medicine protective effects against cardiac hypertrophy 3.4.21.35 tissue kallikrein medicine expression of tissue kallikrein exerts antihypertrophic and antifibrotic actions in the heart 3.4.21.35 tissue kallikrein medicine in the context of chronic unilateral reduction in renal blood flow, tissue kallikrein does not influence the trophicity of kidneys, the synthesis and secretion of rennin, blood pressure increase and cardiac remodelling due to rennin angiotensin system activation 3.4.21.35 tissue kallikrein medicine kallikrein improves cardiac function and reduces infarct size in kininogen-deficient rats, icatibant and N-alpha-nitro-L-arginine-methyl-ester block kallikrein's cardioprotective effects 3.4.21.35 tissue kallikrein medicine KLK1 plays a critical role in arterial function, KLK1 is also involved in the control of ionic transport in the renal tubule, there are cardio- and nephroprotective effects of KLK1 and kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes 3.4.21.35 tissue kallikrein medicine rhinovirus-induced human tissue kallikrein activation may contribute to airway inflammation and asthmatic exacerbations 3.4.21.35 tissue kallikrein medicine tissue kallikrein exerts a protective role in heart failure in mice, tissue kallikrein-deficient subjects may be at increased risk of mortality in heart failure 3.4.21.35 tissue kallikrein medicine tissue kallikreins, particularly KLK6, are considered potential candidates for epithelial antimetastatic therapy 3.4.21.35 tissue kallikrein medicine urinary kallikrein excretion is positively correlated to renal function, serum and urinary inflammatory mediator monocyte chemoattractant protein-1 in chronic kidney disease patients 3.4.21.35 tissue kallikrein medicine kallidinogenase may be efficacious for simple retinopathy including hyperpermeability in subjects with diabetes 3.4.21.35 tissue kallikrein medicine tissue kallikrein therapy is a promising regimen in the treatment of acute ischemic stroke in humans 3.4.21.35 tissue kallikrein medicine plasma tissue kallikrein levels are negatively associated with the risk of first-ever stroke and stroke recurrence and positively associated with event-free survival during 5 years of follow-up 3.4.21.35 tissue kallikrein medicine tissue kallikrein administration can remarkably alleviate hypoxia/reoxygenation-induced neuronal injury by reduction of lactate dehydrogenase release and promotion of neuron viability 3.4.21.35 tissue kallikrein medicine high KLK1 levels are an independent predictor for coronary artery disease 3.4.21.35 tissue kallikrein medicine KLK10 expression and stage are independent predictors of unfavorable DFS and overall survival in colorectal cancer 3.4.21.36 pancreatic elastase medicine molecular marker for detecting definite chronic pancreatitis 3.4.21.36 pancreatic elastase medicine pancreatic elastase-1 is a potential substitute for fecal fat for evaluating pancreatic function 3.4.21.36 pancreatic elastase medicine intratracheal administration of two doses of ELT induces a proinflammatory response in the lung that is characterized by significant infiltration of macrophages and an increased level of interleukin-1beta in lung homogenates 3.4.21.36 pancreatic elastase medicine fecal elastase-1 is a good marker of pancreatic exocrine secretion 3.4.21.36 pancreatic elastase medicine type I pancreatic elastase PRT-201 treatment of atherosclerotic peripheral arteries in patients can increase artery diameter, and thus luminal area, possibly alleviating some of the symptoms of peripheral artery disease 3.4.21.37 leukocyte elastase medicine the synthetic inhibitor 2,3-dihydro-6-[3-(2-hydroxymethyl)-phenyl-2-propenyl]5-benzofuranol may provide a new and useful therapeutic for the treatment of diseases characterized by polymorphonuclear elastase involvement 3.4.21.37 leukocyte elastase medicine imbalance between elastase and its endogenous inhibitors may result in several pathophysiological states such as chronic obstructive pulmonary disease, asthma, emphysema, cystic fibrosis and chronic inflammatory diseases. An orally active leukocyte elastase can be useful for the treatment of these diseases. SSR69071 is a selective, orally active, and potent inhibitor of leukocyte elastase with good penetration in respiratory tissues 3.4.21.37 leukocyte elastase medicine the enzyme has been implicated in the promotion or exacerbation of a number of diseases including pancreatitis acute respiratory distress syndrome, rheumatoid arthritis, atherosclerosis, pulmonary emphysema and cystic fibrosis. During the last decade, an intense effort has been directed towards the development of inhibitors to supplement the body elastase inhibitory capacity and thereby shift the proteinase/antiproteinase imbalance in pathogenic conditions. Several of these inhibitors have been produced by recombinant technology and formulations have been developed for aerosol and/or intravenous administration. The review focuses on low molecular-weight, synthetic inhibitors. A very small percentage of compounds possess all the necessary properties, including lack of toxicity, for progression into the clinic. ICI 200,880 has many of the desired characteristics of a drug to treat the diseases associated with human neutrophil elastase: chemical stability, in vitro and in vivo activity, a long duration of action and adequate metabolic stability. Currently ICI 200,880 is the only low molecular-weight inhibitor for neutrophil elastase known to be undergoing clinical trials, and may be the compound which finally demonstrates, the clinical utility of a synthetic neutrophil elastase inhibitor 3.4.21.37 leukocyte elastase medicine peptidyl trifluoromethyl ketone inhibitors can achieve high levels of oral activity and bioavailibility, and therefore they may prove useful as therapeutic agents in the treatment of diseases in which elastase is implicated 3.4.21.37 leukocyte elastase medicine the tosylalanine ester of 3-hydroxy-5-phenylpyrrole is localized on reagent strips and used diagnostically to test urine for the presence of human leukocyte elastase as an indication of urinary tract infection 3.4.21.37 leukocyte elastase medicine neutrophil elastase is a mediator of atherosclerotic plaque development and a therapeutic target in atherosclerosis 3.4.21.37 leukocyte elastase medicine neutrophil elastase is a target fot therapies in the treatment of cystic fibrosis 3.4.21.37 leukocyte elastase medicine neutrophil elastase is involved in the development of anti-Thy1.1 nephritis 3.4.21.37 leukocyte elastase medicine neutrophil elastase is needed for neutrophil emigration into lungs in ventilator-induced lung injury, neutrophil elastase is required for neutrophil egression from the vascular into the alveolar space, and interfering with this process leads to neutrophil-related endothelial cell injury 3.4.21.37 leukocyte elastase medicine neutrophil elastase may contribute to neuronal death in hippocampal CA1 following forebrain ischemia 3.4.21.37 leukocyte elastase medicine neutrophil elastase plays an important role in the progression of acute lung injury 3.4.21.37 leukocyte elastase medicine It is feasible to administer neutrophil elastase inhibitor Sivelestat as a preventive measure against lung dysfunction after cardiopulmonary bypass 3.4.21.37 leukocyte elastase medicine neutrophil elastase inhibitor sivelestat improves liver injury and prevents the increase of tissue malondialdehyde, MDA. Liver ischemia-reperfusion injury is one of the most serious complications of hepatic surgery 3.4.21.37 leukocyte elastase medicine targeting neutrophil elastase represents a useful approach for preventing liver ischemia/reperfusion injury and hence expanding the organ donor pool and improving the overall success of liver transplantation 3.4.21.37 leukocyte elastase medicine the enzyme inhibitor sivelestat sodium hydrate may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing a cardiopulmonary bypass and aortic valve replacement 3.4.21.37 leukocyte elastase medicine neutrophil elastase is a major target for the development of compounds that inhibit the progression of long-term lung function decline in chronic obstructive pulmonary disease patients 3.4.21.37 leukocyte elastase medicine enzyme activity is associated with predicted severity of acute pancreatitis and acute pancreatitis-associated respiratory failure 3.4.21.38 coagulation factor XIIa medicine activation of factor XIIa increase thrombin generation, which promotes thrombin-activated fibrinolysis inhibitor TAFIa-mediated attenuation of fibrinolysis 3.4.21.38 coagulation factor XIIa medicine after transient middle cerebral artery occlusion, the volume of infarcted brain in enzyme-deficient or enzyme-inhibitor treated mice is substantially less than in control, without an increase in infarct-associated hemorrhage 3.4.21.38 coagulation factor XIIa medicine factor XII levels are lower and high molecular weight kininogen levels and the prevalence of factor XII, prekallikrein and high molecular weight kininogen deficiency higher in a population of patients with a history of venous thrombosis than in a population of healthy blood donors 3.4.21.38 coagulation factor XIIa medicine folate-deficiency induced hyperhomocysteinemia reduces the functional activities of factors XII, X, and II. Folic acid supplementations restores 3.4.21.38 coagulation factor XIIa medicine impaired factor XIIa-dependent activation of fibrinolysis as a key mechanism related to late-pregnancy complications in patients with the antiphospholipid syndrome 3.4.21.38 coagulation factor XIIa medicine limited activation of factor XIIa is sufficient to promote plasma kallikrein activation, resulting in the conversion of high-molecular-weight kininogen and in bradykinin generation. Presence of platelets significantly promotes factor XIIa-initiated bradykinin formation and critically promotes factor XIIa-driven thrombin and fibrin formation 3.4.21.38 coagulation factor XIIa medicine plasma level of factor XIIa is related to plasma levels of cholesterol and triglycerides. No association of plasma level of factor XIIa with risk of coronary events 3.4.21.38 coagulation factor XIIa medicine influence of blood coagulation factors on blood pressure analyzed, blood pressure and heart rate of bioassay rats studied after intravenous bolus of the activated beta-fragment of human coagulation factor XIIa 3.4.21.38 coagulation factor XIIa medicine plasma variations of different types of XIIa following thrombolytic treatment analyzed 3.4.21.38 coagulation factor XIIa medicine decreased FXII activity may causally relate to reproductive failure 3.4.21.39 chymase medicine enzyme activity is significantly enhanced in vitreous fluid of patients wth idiopathic macular holes 3.4.21.39 chymase medicine number of cells positive for enzyme, tryptase, and kit receptor is markedly increased in skin of patients after irradiation therapy 3.4.21.39 chymase medicine target in vascular disease, chymase inhibition may represent a strategy for the treatment of vascular disease 3.4.21.39 chymase medicine carriers of the high-producer allele CMA/B A have increased risk of gastric cancer development, especially Helicobacter pylori-infected patients with non-cardia gastric cancer 3.4.21.39 chymase medicine chymase is involved in angiotnesin II-induced abdominal aortic aneurysm development in apolipoprotein E-deficient mice 3.4.21.39 chymase medicine chymase is upregulated in atherosclerotic conditions 3.4.21.39 chymase medicine chymase, is upregulated in atherosclerotic conditions 3.4.21.39 chymase medicine mast cell chymase may be involved in itch induction 3.4.21.39 chymase medicine mast cell-derived chymase plays an important role in juvenile crescentic glomerulonephritis 3.4.21.39 chymase medicine MCP-4 has a dual role in the development of autoimmune arthritis, first in the initiation phase of collagen-induced arthritis by stimulating the production of pathogenic immunglobulin G anti-collagen II antibodies, and second in the effector phase of arthritis by stimulating local joint inflammation 3.4.21.39 chymase medicine there is a positive association between the CMA1-1903 G/A single nucleotide polymorphism and asthma in children 3.4.21.39 chymase medicine chymase inhibitors have no blood pressure-lowering effect despite blocking angiotensin II formation. Thus, chymase inhibitors may be useful for preventing damage to various organs via multiple mechanisms without lowering blood pressure. Chymase inhibitors may be widely used for prevention of angiotensin II- and inflammation-related diseases 3.4.21.39 chymase medicine chymase is a potential target for pharmacotherapy for allergic conjunctivitis 3.4.21.39 chymase medicine the fibrinolytic enzyme with anticoagulative properties may aid in the clearance of fibrin from vessel walls in aged vasculitis lesions 3.4.21.B39 stratum corneum tryptic enzyme medicine regulation by protease inhibitors may have potential clinical applications 3.4.21.B39 stratum corneum tryptic enzyme medicine KLK5 mRNA, analyzed by quantitative PCR in prostate needle biopsies, could be an independent biomarker for the differential diagnosis and prognosis in prostate cancer 3.4.21.B39 stratum corneum tryptic enzyme medicine human kallikrein 5 is a potential target for the treatment of skin inflammation and cancer 3.4.21.41 complement subcomponent C1r medicine anti-inflammatory functions are exerted via inhibition of complement system proteases (C1r, C1s, MASP2) and the plasma kallikrein-kinin system proteases 3.4.21.B41 kallikrein 10 medicine kallikrein 10 may serve as a biomarker for uterine serous papillary carcinoma 3.4.21.B41 kallikrein 10 medicine high status KLK10 expression is a significant factor for disease-free survival and overall survival of colorectal cancer patients. KLK10 gene expression may be used as a marker of unfavorable prognosis for colorectal cancer 3.4.21.42 complement subcomponent C1s medicine C1s-INH-248 is a highly selective small molecule inhibitor of complement subcomponent C1s. Blocking the classical complement pathway with a highly specific and potent synthetic inhibitor of the classical C1 complex appears to be an effective mean to preserve ischemic myocardium from injury following reperfusion 3.4.21.42 complement subcomponent C1s medicine the enzyme represents a pivotal upstream point of control in the classical pathway of complement activation and is therefore likely to be a useful target in the therapeutic intervention of diseases like hereditary angioedema, ischemia-reperfusion injury and acute transplant rejection 3.4.21.42 complement subcomponent C1s medicine angioedema due to acquired C1 esterase deficiency is a rare condition and a non-inflammatory disease characterized by episodes of edema of the mucosa of the upper airway or gastrointestinal tract. Careful evaluation of the acute abdomen in acquired C1 esterase deficiency is very important in the emergency department to distinguish between medical and surgical causes of an acute abdomen 3.4.21.42 complement subcomponent C1s medicine drug combinations of C1 esterase inhibitor with coagulation factor XIII and N-acetylcysteine can reduce the leukocyte adherence in a sepsis model in rats indicating an anti-inflammatory effect of these combinations 3.4.21.42 complement subcomponent C1s medicine two patients with C1s deficiency or abnormality in a Japanese family that have distinct compound heterozygous genotypes derived from three distinct C1s gene mutations including a novel missense mutation in exon XII, and which share similar symptoms, but which are different from those of previously reported cases 3.4.21.42 complement subcomponent C1s medicine enzyme inhibition with sutimlimab rapidly stopps hemolysis in patients with cold agglutinin disease 3.4.21.B42 hippostasin medicine KLK11 mRNA may serve as a marker to discriminate between benign prostatic hyperplasia and prostate cancer 3.4.21.B42 hippostasin medicine K11 is a serum marker for the diagnosis of ovarian carcinoma 3.4.21.B42 hippostasin medicine overexpression of human kallikrein 11 is associated with poor prognosis in patients with low rectal carcinoma 3.4.21.B42 hippostasin medicine the down-regulation of KLK11 gene in advanced and more aggressive tumors opens the feasibility of being used as biomarker distinguishing the tumor aggressiveness and prognostic indicators for human prostate cancer 3.4.21.B42 hippostasin medicine negative kallikrein 11 expression is associated with nearly 5fold increased risk of distant metastasis after curative gastrectomy in gastric cancer patients. Kallikrein 11 expression is a significant independent prognostic factor for disease-free survival and overall survival in gastric cancer patients 3.4.21.43 classical-complement-pathway C3/C5 convertase medicine activation of complement via the lectin pathway may be a more prominent contributor to the pathology of inflammatory reactions as compared to activation of complement via the classical pathway 3.4.21.45 complement factor I medicine the process of factor I binding is a potential target for therapeutic intervention to facilitate host defense against Staphylococcus aureus 3.4.21.45 complement factor I medicine presence of factor I decreases phagocytosis efficiency 3.4.21.45 complement factor I medicine association of complement factor I with atypical hemolytic uremic syndrome analyzed 3.4.21.45 complement factor I medicine expression of complement factor I in lung cancer cells analyzed 3.4.21.45 complement factor I medicine expression of complement factor I in non-small lung cancer cells analyzed 3.4.21.45 complement factor I medicine expression of complement factor I in non-small lung cancer cells and complement-dependent lysis analyzed 3.4.21.45 complement factor I medicine studies on inflammatory kidney disease membranoproliferative glomerulonephritis type II (MPGN2) 3.4.21.45 complement factor I medicine studies on mutations of complement factor I 3.4.21.45 complement factor I medicine studies on mutations of complement factor I predisposing to atypical hemolytic uremic syndrome aHUS 3.4.21.45 complement factor I medicine a single nucleotide polymorphism just 3' of complement factor I on chromosome 4 shows significant association with risk of advanced age-related macular degeneration 3.4.21.45 complement factor I medicine amyloid beta activates the complement system within drusen by blocking the function of factor I leading to a low-grade, chronic inflammation in subretinal tissues 3.4.21.45 complement factor I medicine importance of screening patients with atypical hemolytic uremic syndrome for mutations in the CFI gene before renal transplantation, to avoid unsuccessful transplantation 3.4.21.45 complement factor I medicine the serine protease domain of pig factor I indicates that the serine protease functions not only in pig serum, but in human and other serum, as well. Therefore, pig factor I may be considered a substitute for human factor I for the function of serine protease during the treatment of hepatic failure 3.4.21.45 complement factor I medicine two Spanish families with complete factor I deficiency, suffering from meningitis. The two families have different mutations at exon 5 of the factor I gene, which codifies for module LDLr1. One mutation corresponds to a 772G-A change at the donor splice site that is originally found in a family from Northern England. The second is a new missense mutation 739T-G, that generates a Cys to Gly change. Homozygous factor I deficiency is associated with infectious and/or autoimmune diseases 3.4.21.45 complement factor I medicine case-control study of factor I gene involving 190 DNA samples from macular degeneration patients and 179 control samples genotypes six single nucleotide polymorphisms. Four single nucleotide polymorphisms are nominally significant in this initial analysis, and no single single nucleotide polymorphism maintains marginal significance after conservative Bonferroni correction for multiple testing. These four single nucleotide polymorphisms have very similar minor allele frequencies and are likely to be genetically hitchhiking with one another. Data implicate genomic variation in the region of the complement factor I gene with age-related macular disease susceptibility 3.4.21.45 complement factor I medicine high enzyme expression in in breast cancer tumor cells is correlated with significantly shorter cancer-specific survival and recurrence-free survival 3.4.21.B45 kallikrein 14 medicine KLK14 has the prognostic potential to recognize prostate cancer patients at higher risk of disease recurrence after radical prostatectomy. As an independent factor, KLK14 is expected to supplement postoperative prostate-specific antigen values for a more precise prognosis 3.4.21.B45 kallikrein 14 medicine normal salivary glands, pleomorphic adenoma, adenoid cystic carcinoma and mucoepidermoid carcinoma show strong expression of KLK14 in ductal and non-ductal cells. Both pleomorphic adenoma and adenoid cystic carcinoma show higher KLK14 levels than normal glands and mucoepidermoid carcinoma tissues. There are no statistically significant associations between levels of KLK14 and clinical parameters 3.4.21.B45 kallikrein 14 medicine study on the clinical value of seminal kallikreins in the evaluation of semen quality and differential diagnosis and etiology of abnormal liquefaction and/or viscosity. Combination of KLK2, 3, 13, and 14 and KLK1, 2, 5, 6, 7, 8, 10, 13, and 14 shows very strong discriminatory potential for semen liquefaction and viscosity, respectively. Liquefaction state is associated with several parameters of sperm motility. KLK14 is differentially expressed in asthenospermic cases 3.4.21.B45 kallikrein 14 medicine KLK14 and its receptor proteinase-activated receptor-2 represent therapeutic targets for colon tumorigenesis 3.4.21.46 complement factor D medicine intravitreal VEGF-D gene transfer causes blood-retina barrier breakdown but not neovessel formation in the rabbit eye. Inflammation-like alterations in the choriocapillaries are observed in the baculoviral VEGF-D-treated eyes, but not in adenoviral VEGF-D-treated eyes at 6 days after gene transfer 3.4.21.46 complement factor D medicine is linked to the control of lymphangiogenesis and lymphatic metastasis. Epigenetic control of histone acetylation represents an important determinant of vegf-D gene expression in cancer cells 3.4.21.46 complement factor D medicine PDGF-D is present in the neointima of the arteriopathy of chronic allograft nephropathy, where it can engage PDGF-Rbeta to promote mesenchymal cell migration, proliferation, and neointima formation. PDGF-D may engage the PDGF-Rbeta to promote interstitial injury in chronic allograft injury 3.4.21.46 complement factor D medicine VEGF-D plays an essential role in tumoral lymphangiogenesis and lymphatic spread, VEGF-D expression, and the intratumoral lymphatics may be clinically useful indicators for prognostic evaluation in patients with epithelial ovarian carcinoma 3.4.21.46 complement factor D medicine by downregulation of VEGF-D expression in a lung tumor mouse model using Deguielin, a rotenoid of the flavonoid family, tumor-associated lymphangiogenesis and lymphatic metastasis are suppressed 3.4.21.46 complement factor D medicine serum VEGF-D levels are a good biomarker for lymphatic involvement in patients with lympangioleiomyomatosis 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine intervention in complement-mediated pathologies by modulation of enzyme half-life through replacement of enzyme compoment C3 by the corresponding sequences of cobra venom factor from Naja kaouthia 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine patient with membranoproliferative glomerulonephritis, preparation of naturally occuring antibodies to enzyme exhibits nephritic factor activity 60fold stronger than total IgG. Antibodies promote enzyme generation, when added to the convertase precursor or during convertase assembly 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine therapeutic reduction of complement activity in vivo by use of engineered enzyme component C3 resulting in greatly improved half-life of C3 convertase 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine clinical significance of early complement stimulation in trauma patients analyzed, complement stimulation, particularly alternative pathway related to clinical outcomes in patients with severe trauma 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine studies on role of properdin in AP complement initiation for understanding the selective predisposition of properdin-deficient patients to meningococcal infection 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine activation of complement via the lectin pathway may be a more prominent contributor to the pathology of inflammatory reactions as compared to activation of complement via the classical pathway 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine mutation 923DELTADG in complement factor 3 gene is identified in patients with dense deposit disease. Mutant C3923DELTADG, which lacks 2 amino acids, cannot be cleaved to C3b by the alternative pathway C3-convertase and is therefore the predominant circulating C3 protein in the patients. Upon activation to C3b by proteases, or to C3(H2O) by spontaneous thioester hydrolysis, mutant C3 generates an active C3-convertase that is regulated normally by decay accelerating factor but is resistant to decay by factor H. Activated C3b923DELTADG and C3(H2O)923DELTADG are resistant to proteolysis by factor I in the presence of factor H, but are efficiently inactivated in the presence of membrane cofactor protein, causing a fluid phase-restricted alternative pathway dysregulation in the patients that continuously activates and consumes C3 produced by the normal C3 allele 3.4.21.47 alternative-complement-pathway C3/C5 convertase medicine Streptococcus pneumoniae induces increased gene expression of factor B of the alternative complement pathway and C3 in mouse middle ear epithelium. Activation of factor B and C3 in the middle ear lavage fluids is significantly greater than in simultaneously obtained serum samples. Complement C3 activation and opsonophagocytosis of Streptococcus pneumoniae are greatly attenuated in factor B- and factor B/C2-deficient mice. Local complement activation is an important host innate immune response and activation of the alternative complement pathway represents one of the innate immune defense mechanisms against pneumococcal infection during the early stage of acute otitis media 3.4.21.49 hypodermin C medicine dynamics of circulating hypodermin C in previously infested cattle resemble those in previously uninfested cattle. Development of a significant immune response during the primary infestation that is reflected in the rapid and substantial production of antibodies upon re-infestation, thus migrating first instars may induce significant reduction in host immune response 3.4.21.49 hypodermin C medicine the enzyme improves the survival of kidney allografts in mice 3.4.21.49 hypodermin C medicine the enzyme may be used as immunosuppressive agent for the inhibition of the xenotransplant rejection 3.4.21.50 lysyl endopeptidase medicine following infection with Pseudomonas aeruginosa, Ca2+ increase in the cornea can favor production of enzyme, which has been associated with corneal damage 3.4.21.B50 DegQ peptidase medicine the purified recombinant DegQVh is a protective immunogen that could confer protection upon fish against infection by Vibrio harveyi. In order to improve the efficiency of DegQVh as a vaccine, a genetic construct in the form of the plasmid pAQ1 is built, in which the DNA encoding the processed DegQVh protein is fused with the DNA encoding the secretion region of AgaV, an extracellular beta-agarase. The Escherichia coli strain harboring pAQ1 can express and secrete the chimeric DegQVh protein into the culture supernatant. Vaccination of fish with viable Escherichia coli expressing chimeric degQVh significantly enhanced the survival of fish against Vibrio harveyi challenge, which is possibly due to the relatively prolonged exposure of the immune system to the recombinant antigen produced constitutively 3.4.21.53 Endopeptidase La medicine lon and aconitase may be key players in the maintenance of mitochondrial homeostasis under conditions of stress, partial compromise of their function may contribute to both aging and degenerative diseases 3.4.21.53 Endopeptidase La medicine lon downregulates virulence, is involved in transcriptional regulation of type three secretion systems to translocate virulence proteins 3.4.21.53 Endopeptidase La medicine lon downregulates virulence, is involved in transcriptional regulation of type three secretion systems to translocate virulence proteins. Oppositely modulates infection stages (epithelial invasion and survival within murine macrophages) 3.4.21.53 Endopeptidase La medicine lon downregulation may contribute to the aging process 3.4.21.53 Endopeptidase La medicine lon is a target in the development of antibiotics 3.4.21.53 Endopeptidase La medicine lon is involved in eliminating misfolded proteins, may contribute to the virulence of Campylobacter jejuni 3.4.21.53 Endopeptidase La medicine lon mediates proteolysis for the expression of virulence genes that promote mammalian cell infection 3.4.21.53 Endopeptidase La medicine lon upregulates virulence, is involved in transcriptional regulation of type three secretion systems to translocate virulence proteins 3.4.21.53 Endopeptidase La medicine potential therapeutic antimicrobial target to combat fluoroquinolone resistance 3.4.21.53 Endopeptidase La medicine subinhibitory concentrations of antibiotics induce a set of genes, e.g. lon protease, that are likely to affect the interaction of Pseudomonas aeruginosa with host cells. lon protease is essential for biofilm formation and motility in Pseudomonas aeruginosa 3.4.21.53 Endopeptidase La medicine in muscle creatine kinase mouse heart model for Friedreich ataxia, a rare hereditary neurodegenerative disease characterized by progressive ataxia and cardiomyopathy, there is a clear progressive increase in protein levels of mitochondrial ATP-dependent proteases, Lon and ClpP, in the hearts of muscle creatine kinase mutants. Lon and ClpP upregulation, which is triggered at a mid-stage of the disease through separate pathways, is accompanied by an increase in proteolytic activity. There is a simultaneous and significant progressive loss of mitochondrial Fe-S proteins with no substantial change in their mRNA level 3.4.21.53 Endopeptidase La medicine lon single and cpxR and lon double mutants produce 2.0- and 3.2fold increases, respectively, of capsular polysaccharide, which is a major antigenic component. Approximately 104fold attenuation assessed by analysis of LD50 of BALB/c mouse is observed by deleting the lon/cpxR genes 3.4.21.B57 pernisine medicine potential application for the inactivation of abnormal prion protein PrPSc, a protease-resistant isoform of normal prion protein. PrPSc is largely unaffected by standard methods of sterilization, thus, contaminated neurosurgical instruments are the major cause of human transmissible spongiform encephalopathies 3.4.21.B57 pernisine medicine the abnormal prion protein (scrapie-associated prion protein, PrP(Sc)) is considered to be included in the group of infectious agents of transmissible spongiform encephalopathies. Since PrP(Sc) is highly resistant to normal sterilization procedures, the decontamination of PrP(Sc) is a significant public health issue. The hyperthermostable protease, Tk-subtilisin, can be an effective agent for medical decontamination of of PrP(Sc). Rather small amounts of Tk-subtilisin (0.3 U) are required to degrade PrP(Sc) at 100 °C and pH 8.0. In addition, Tk-subtilisin is observed to degrade PrP(Sc) in the presence of sodium dodecyl sulfate or other industrial surfactants. Basic information for the practical use of the proteolytic enzyme for PrP(Sc) degradation is provided 3.4.21.B57 pernisine medicine the enzyme may have potential application as a detergent additive to decrease the infectivity of abnormal prion protein PrPSc 3.4.21.B57 pernisine medicine Tk-SP-containing detergents can be developed to decrease the secondary infection risks of transmissible spongiform encephalopathies 3.4.21.59 Tryptase medicine development of tryptase inhibitors for the treatment of asthma 3.4.21.59 Tryptase medicine heparin antagonists potentially may be used in treatment of mast cell-mediated diseases, potent and selective inhibitor of tryptase will be an essential tool to determine the role of tryptase in inflammation and other processes, tryptase plays a role in asthma and other allergic and inflammatory skin diseases like psoriasis and atopic dermatitis 3.4.21.59 Tryptase medicine important in bacterial infections of the lung 3.4.21.59 Tryptase medicine potent and selective inhibitor of tryptase will be an essential tool to determine the role of tryptase in inflammation and other processes, tryptase plays a role in asthma and other allergic and inflammatory skin diseases like psoriasis and atopic dermatitis 3.4.21.59 Tryptase medicine tryptase is a potent activator of pro-uPA, the zymogen form of a protease asociated with tumor metastasis and invasion, viable drug target to create therapeutically useful inhibitors 3.4.21.59 Tryptase medicine viruses utilizes the enzyme to trigger their infectivity and multiplication in lungs, an inhibitor may regulate the enzyme activity and viral infections in vivo 3.4.21.59 Tryptase medicine serum mast cell tryptase level is significantly increased in untreated patients with mastocytosis 3.4.21.59 Tryptase medicine the concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased serum baseline tryptase levels strongly suggests that a bone marrow examination is indicated for the diagnosis of clonal mast cell disease 3.4.21.59 Tryptase medicine the number of both tryptase- and cathepsin-G-positive mast cells is significantly higher in cutaneous mastocytosis as compared to normal skin 3.4.21.59 Tryptase medicine the serum basal tryptase level can be the indirect link between systemic mastocytosis and Hymenoptera venom allergy 3.4.21.59 Tryptase medicine there is no correlation of serum tryptase level with either the severity of psoriasis or the severity of atopic dermatitis, serum total tryptase does not prove to be a useful tool in assessing severity of psoriasis or atopic dermatitis 3.4.21.59 Tryptase medicine tryptase is involved in the itch of chronic dermatitis 3.4.21.59 Tryptase medicine mast cell tryptase can be an indicator of type I hypersensitivity reaction and thus may serve as a surrogate marker of anaphylaxis 3.4.21.59 Tryptase medicine tryptase is a diagnostic marker of myeloid neoplasms and a useful test in clinical haematology 3.4.21.59 Tryptase medicine tryptase may represent a marker of sarcoidosis severity 3.4.21.59 Tryptase medicine tryptase serum concentrations can discriminate between the allergic and histamine fish poisoning syndromes 3.4.21.59 Tryptase medicine increased tryptase concentrations are a risk marker for the severity of reactions to Hymenoptera stings or venom immunotherapy 3.4.21.60 Scutelarin medicine the enzyme has potential therapeutic application in pathological conditions where the controlled activation of prothrombin is desirable 3.4.21.B60 transmembrane protease serine 2 medicine 17-beta-estradiol may reduce SARS-CoV-2 infection of lung epithelial cells 3.4.21.B60 transmembrane protease serine 2 medicine brief exposure to topical camostat, an orally available serine protease inhibitor, effectively restricts SARS-CoV-2 infection in differentiated primary human airway epithelial cells. Topical TMPRSS2 inhibition when delivered in a clinically relevant and achievable dose to differentiated airways cells markedly restricts SARC-CoV-2 cellular infection. Enzalutamide, an oral androgen receptor antagonist, has no impact on SARS-CoV-2 infection 3.4.21.B60 transmembrane protease serine 2 medicine expression of both ACE2 and TMPRSS2 genes is necessary to support SARS-CoV-2 infection and replication in DF1 cells and a nonpermissive sub-lineage of MDCK cells. Titers of SARS-CoV-2 in these cell lines are comparable to those observed in control Vero cells 3.4.21.B60 transmembrane protease serine 2 medicine expression of both ACE2 and TMPRSS2 genes is necessary to support SARS-CoV-2 infection and replication in DF1 cells and a nonpermissive sub-lineage of MDCK cells. Titers of SARS-CoV-2 in these cell lines are comparable to those observed in control Vero cells. Permissive replication of SARS-CoV-2 is not found in pig or horse. Cells expressing genes from either bat species tested demonstrate temporal replication of SARS-CoV-2 that peaks early and is not sustained 3.4.21.B60 transmembrane protease serine 2 medicine in lung tissues collected from mice that were sub-chronically exposed to air or 0.8 ppm ozone for three weeks, the TMPRSS2 protein and Tmprss2 transcripts are significantly elevated in the extrapulmonary airways, parenchyma, and alveolar macrophages. A significant proportion of additional known SARS-CoV-2 host susceptibility genes are upregulated in alveolar macrophages and parenchyma from ozone-exposed mice 3.4.21.B60 transmembrane protease serine 2 medicine in tumor and adjacent lung tissues from non-small cell lung cancer patients, lower TMPRSS2 expression in tumor compared to adjacent non-tumor tissues is linked to a poor overall survival in patients with adenocarcinoma and those who are current smokers. A slight negative correlation between full-length TMPRSS2 and alpha-1-antitrypsin in non-tumor tissues seems to be related to smoking status 3.4.21.B60 transmembrane protease serine 2 medicine lower levels of sTMPRSS2 are noted in patients below 70 years and those with eosinophilic asthma, while no association is found between inhaled corticosteroids use and serum TMPRSS2. The level of serum TMPRSS2 also differs according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity ratio 3.4.21.61 Kexin medicine antisense inhibition of PCSK9 is an attractive and novel therapeutic approach for treating hypercholesterolemia 3.4.21.61 Kexin medicine circulating concentrations of human PCSK9 are directly correlated with LDL and total cholesterol concentrations. PCSK9 is likely not associated with specific lipoprotein particles. Assay providing a means to tailor PCSK9-inhibitor therapy to patients most likely to respond to and benefit from pharmacologic inhibition of PCSK9 3.4.21.61 Kexin medicine PCSK9 is an attractive drug target for decreasing low density lipoprotein cholesterol levels. Addition of a PCSK9 inhibitor to statin therapy may result in even further low density lipoprotein cholesterol level decreases 3.4.21.61 Kexin medicine a discrete C-terminal protein fragment competes with full-length PCSK9 for binding to LDLR in vitro and attenuates PCSK9-mediated hypercholesterolemia in mice 3.4.21.61 Kexin medicine biologic-based strategies to inhibit proprotein convertase subtilisin/kexin type 9 show promise as anti-hypercholesterolemic and, therefore, anti-atherosclerotic therapies 3.4.21.61 Kexin medicine the enzyme is a prominent therapeutic target for reducing LDL-cholesterol 3.4.21.61 Kexin medicine the proprotein convertase subtilisin/kexin type 9 has emerged as a promising treatment target to lower serum cholesterol, a major risk factor of cardiovascular diseases 3.4.21.61 Kexin medicine PCSK6 may become a reasonable target for the development of drugs able to control high blood pressure by directly modulating pro-ANP cleavage and, therefore, increasing endogenous circulating alphaANP levels. Such a therapeutic approach may reveal beneficial also in the treatment of heart failure 3.4.21.B61 transmembrane protease serine 11D medicine both HAT expression and activity are upregulated in human idiopathic pulmonary fibrosis specimens 3.4.21.B61 transmembrane protease serine 11D medicine both TMPRSS11D mRNA and protein expression levels are significantly higher in non-small cell lung cancer tumorous tissues than in adjacent normal tissues. High TMPRSS11D protein expression is associated with high TNM stages, and high TMPRSS11D protein expression is an independent prognostic marker in non-small cell lung cancer 3.4.21.B61 transmembrane protease serine 11D medicine cotransfection of mammalian cells with plasmids encoding hemagglutinin of influenza viruses and protease TMPRSS2 or human airway trypsin-like protease HAT results in hemagglutinin cleavage in situ. Transient expression of either protease in MDCK cells enables multicycle replication of influenza viruses in these cells in the absence of exogenous trypsin 3.4.21.B61 transmembrane protease serine 11D medicine HAT can stimulate mucin5AC hypersecretion through a PAR2-mediated signaling pathway in 16HBE bronchial epithelial cells 3.4.21.B61 transmembrane protease serine 11D medicine MDCK cells with inducible expression of either TMPRSS2 or protease HAT cells support growth of human and avian influenza viruses of different subtypes in the absence of exogenous trypsin. Multicycle viral replication in both cell lines is markedly suppressed in the presence of serine protease inhibitors 3.4.21.62 Subtilisin medicine fibrinolytic activiy of strain DJ-4, develop the enzyme for its use as a thrombolytic agent 3.4.21.62 Subtilisin medicine expression during non-fatal human rhinoorbital mucormycosis 3.4.21.64 peptidase K medicine segment GGG of functionally important N-terminal octapeptide region of human prion protein, involved in spongifirm encephalopathy, strongly binds as a substrate at the substrate recognition site 3.4.21.64 peptidase K medicine PK activity in the presence of brain correlates precisely with the concentration of Cu2+ ions that prevent PK digestion of cellular prion protein and other brain proteins. Apparent resistance of cellular prion protein to proteolysis by PK appears to be directly attributable to the inhibition of PK activity by copper-(II) ions 3.4.21.64 peptidase K medicine PK magnetic reactor is a useful tool for prion protein digestion 3.4.21.64 peptidase K medicine proteinase K can be used in combination with antibiotics to enhance the dispersal/control of biofilms 3.4.21.68 t-Plasminogen activator medicine t-PA has been widely and successfully used as a therapeutic fibrinolytic agent to treat acute myocardial infarction and pulmonary embolism 3.4.21.68 t-Plasminogen activator medicine non-glycosylated TK1-2 useful for the treatment of cancer can be efficiently produced in Pichia, with retaining its activity 3.4.21.68 t-Plasminogen activator medicine the kringle domain of tissue-type plasminogen activator inhibits in vivo tumor growth by suppression of angiogenesis without interfering with fibrinolysis 3.4.21.68 t-Plasminogen activator medicine combining antithrombin III, R-TPA and supportive care is more advantageous in treating the clinical manifestations of disseminated intravascular coagulation in this neonatal pig model than either single modality or supportive care alone 3.4.21.68 t-Plasminogen activator medicine dogs with femoral artery thrombosis are given either M5, a single site mutant of prourkinase or tPA by i.v. infusion. Thrombolysis is comparably effective by both activators. Blood loss is 10-fold higher with t-PA than with M5 and occurred at more multiple sites. This effect is postulated to be related to differences in the mechanism of plasminogen activation by t-PA and M5 in which the latter is promoted by degraded rather than intact (hemostatic) fibrin 3.4.21.68 t-Plasminogen activator medicine effects of intravenous administration of tPA on serum levels of IGF-1 and IGF-binding protein-3 in patients with acute ischemic stroke are investigated by radioimmunoassay in 10 patients. During tPA treatment, total IGF-1 and IGFBP-3 serum levels do not change, but there was an 70% increase in free IGF-1 serum levels at the end of the 1-h infusion. Intravenous therapy with tPA enhances the bioavailability of IGF-1 3.4.21.68 t-Plasminogen activator medicine establishment of a global assay of overall haemostasis potential: coagulation cascade in platelet-poor plasma is triggered by adding a minimal dose of recombinant tissue factor together with purified phospholipids and calcium; fibrinolysis is initiated by adding recombinant tPA in a concentration similar to what can be obtained during thrombolysis. Numerical differentials of optical densities reflecting rates of fibrin formation and degradation are calculated, and the Coagulation Profile (Cp) and the Fibrinolysis Profile (Fp) are determined. The combined effect of these counteractive systems is expressed as a ratio of Cp to Fp, called the Overall Haemostasis Index 3.4.21.68 t-Plasminogen activator medicine it is shown that exogenous tPA or tPA/plasminogen promotes axonal regeneration, remyelination, and functional recovery after sciatic nerve injury in the mouse, probably through removal of fibrin deposition and activation of MMP-9-positive macrophages, which may be responsible for myelin debris clearance and preventing collagen scar formation. Therefore, tPA may be useful for treatment of peripheral nerve injury 3.4.21.68 t-Plasminogen activator medicine medical case report of a 14-year-old male with Down syndrome and acute myeloblastic leukemia, diagnosed with infective endocarditis characterized by two large vegetations on aortic and mitral valves, who is successfully treated with r-tPA 3.4.21.68 t-Plasminogen activator medicine the present data support a model in which amyloid deposition in Alzheimer's disease induces a decrease in tPA activity through the overproduction of PAI-1 by activated glial cells 3.4.21.68 t-Plasminogen activator medicine thromboelastography shows the clots formed from procine whole blood to be highly resistant to human tPA-catalyzed lysis, indicating a poor activation of porcine plasminogen by human rtPA. The results suggest caution in using the pig as an experimental model when studying the effects of various agents on fibrolysis 3.4.21.68 t-Plasminogen activator medicine although rtPA enhances ischemic damage, the dose of recombinant tPA used in clinics does not affect the powerful neuroprotection by the JNK inhibitor XG-102 3.4.21.68 t-Plasminogen activator medicine desmoteplase has additional advantages to human tPA, it is not neurotoxic and is unaffected by beta-amyloid. Desmoteplase antagonizes the neurotoxicity induced by vascular tPA possibly by competing with tPA for the low-density lipoprotein receptorrelated protein-1 binding at the BBB and thus preventing tPA access to the brain parenchyma. A phase III clinical trial of desmoteplase is halted since it has failed to demonstrate any beneficial effects in terms of neurological improvements and survival 3.4.21.68 t-Plasminogen activator medicine excellent outcome (remarkable recovery 6 h after onset of symptoms) after the use of intravenous t-PA approximately 4 h after onset of symptoms for vertebrobasilar stroke 3.4.21.68 t-Plasminogen activator medicine in comparison with t-PA, plasmin shows a distinct benefit-to-risk advantage. Plasmin is equally effective as t-PA in thrombolysis and may be superior for treating thrombi in totally-occluded vessels. Whereas t-PA causes bleeding from vascular trauma sites in animals when infused at dosages used for thrombolysis (0.5-1 mg/kg), plasmin exhibits safety at therapeutic dosages. Plasmin can be used at several fold higher concentrations than is needed for thrombolysis, thereby providing a significant safety margin that is not attainable for t-PA 3.4.21.68 t-Plasminogen activator medicine ischemic stroke patients weighing more than 100 kg seem to derive less benefit from IV t-PA than their lighter counterparts 3.4.21.68 t-Plasminogen activator medicine no evidence of hemorrhage or any adverse effect due to topical application of t-PA. Control and t-PA treated rats show fibrosis inhibition 6 weeks after surgery and show no significant difference in inflammation or with regard to necrosis and abscess formation 3.4.21.68 t-Plasminogen activator medicine plasmin is a suitable alternative to t-PA as it causes less bleeding but has equivalent or greater thrombolytic efficacy 3.4.21.68 t-Plasminogen activator medicine pregnancy is associated with major perturbations of endogenous fibrinolytic capacity with an overwhelming increase in plasma plasminogen activator inhibitor type 1 concentrations and an inadequate release of active t-PA, i.e., these prothrombotic effects may, in part, explain the increased risk of arterial and venous thrombosis in pregnant women 3.4.21.68 t-Plasminogen activator medicine t-PA therapy has a clinically important and statistically significant benefit in spite of subgroup imbalances in baseline stroke severity and an increased risk of symptomatic intracerebral hemorrhage in patients receiving t-PA 3.4.21.68 t-Plasminogen activator medicine tPA generation in wound epidermis is at least partially controlled by changes in local interleukin-1alpha activity 3.4.21.68 t-Plasminogen activator medicine tPA is used as a thrombolytic agent for treatment of ischemic stroke and is the only agent that has been shown to improve stroke outcome in clinical trials. Patients receive little or no benefit if tPA therapy is initiated more than 3 h after the onset of stroke, which excludes most stroke patients from tPA treatment due to the time required for transportation to medical facilities and proper diagnosis. tPA may damage the basal lamina of the blood vessels, resulting in edema, disruption of the blood-brain barrier, or hemorrhage, thus any patients with evidence of hemorrhage or who have been taking any anti-coagulant medication such as aspirin are not candidates for tPA therapy 3.4.21.68 t-Plasminogen activator medicine tPA-plasmin pathway dysfunction may play a role in the link between major depressive disorder and cardiovascular disease. Agents that modulate tPA-plasminogen activity may be potential drugs for the treatment of patients with both major depressive disorder and cardiovascular disease 3.4.21.68 t-Plasminogen activator medicine type 2 diabetes mellitus patients with periodontal disease and otherwise healthy periodontally diseased patients tend to exhibit higher total amounts of t-PA than systemically and periodontally healthy control subjects, thus type 2 diabetes seems not to increase gingival crevicular fluid levels of inflammatory mediators like t-PA 3.4.21.68 t-Plasminogen activator medicine vaccination with a nucleoprotein with a tPA signal sequence efficiently clears homologous H5N1 influenza virus in infected lungs and induces partial cross-protection against heterologous, highly pathogenic H5N1 strains in mice. IFN-gamma producing T cells are more efficiently induced and expanded in mice immunized with ptPAs/nucleoprotein vaccine 3.4.21.68 t-Plasminogen activator medicine working strategy for targeted delivery of recombinant tPA bound to magnetic nanoparticles with less than 20% of a regular dose under magnetic guidance, resulting in effective thrombolysis and restore of hemodynamics in the rat embolic model 3.4.21.68 t-Plasminogen activator medicine enzyme has important thrombolytic properties due to its high fibrin affinity, it is approved for treating acute myocardial infarction, or heart attacks, and later for acute ischemic stroke, and acute, massive pulmonary embolism 3.4.21.68 t-Plasminogen activator medicine in the rabbit small clot embolic stroke model, which is a useful translational model and possibly a predictor of treatments that may show efficacy in human clinical trials, in combination with the thrombolytic, tissue plasminogen activator using a standard intravenous dose of 3.3 mg/kg (20% bolus, 80% infused), simvastatin can be safely administered with tissue plasminogen activator to improve clinical scores 3.4.21.68 t-Plasminogen activator medicine it is used clinically to dissolve 3.4.21.68 t-Plasminogen activator medicine therapy for acute ischemic stroke 3.4.21.68 t-Plasminogen activator medicine tissue plasminogen activator is the first-line treatment for stroke patients 3.4.21.68 t-Plasminogen activator medicine putative interaction and cleavage of NR1 subunit of N-methyl-D-aspartate receptors by a tPA-dependent mechanism can be a relevant therapeutic target for stroke treatment in humans 3.4.21.68 t-Plasminogen activator medicine the kringle 2 plus serine protease domains, K2S, of human tissue plasminogen activator is an efficacious thrombolytic drug, which is used to treat heart attacks and strokes by breaking up the fibrin clots that cause them 3.4.21.68 t-Plasminogen activator medicine recombinant human t-PA is extensively used as a therapeutic agent for the treatment of thrombotic diseases owing to its greater safety and efficiency compared with other plasminogen activators like urokinase and streptokinase. CERTS132A-based secretion engineering can be an effective strategy for enhancing recombinant enzyme production in CHO cells 3.4.21.68 t-Plasminogen activator medicine intensive care medication of ischemic stroke, thrombus targeting nanosystems could serve as carriers for enhanced delivery of enzyme tPA to the thrombi in order to increase its effective local concentrations. Biocompatible magnetite drug carriers, stabilized by a dextran shell, are developed to carry tissue plasminogen activator (tPA) for targeted thrombolysis under an external magnetic field, method evaluation, overview. Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted great attention in many biomedical fields and are used in preclinical/experimental drug delivery, hyperthermia and medical imaging. All synthesized types of nanoparticles are well tolerated in cell culture experiments with human umbilical vein endothelial cells, indicating their potential utility for future therapeutic applications in thromboembolic diseases 3.4.21.68 t-Plasminogen activator medicine tissue plasminogen activator converts plasminogen into plasmin and is used clinically to treat thrombosis 3.4.21.69 Protein C (activated) medicine activated protein C might be useful as therapeutic agent in sepsis, clinical trials, overview 3.4.21.69 Protein C (activated) medicine low molecular weight activated protein C inhibitors might be useful as potential treatment for hemophilic disorders 3.4.21.69 Protein C (activated) medicine the activated protein C exhibits anti-inflammatory and cytoprotective properties, which may contribute to the beneficial effect of APC in treating severe sepsis patients, a higher incidence of bleeding because of its anticoagulant function is a major drawback of APC as an effective anti-inflammatory drug 3.4.21.69 Protein C (activated) medicine the enzyme is used for treatment of sepsis in humans, but the enzyme shows harmful side effects by causing life-threatening hemorrhage, clinical trials, overview 3.4.21.69 Protein C (activated) medicine the recombinant human activated protein C is useful for the postexposure treatment of Ebola hemorrhagic fever, clinical studies in rhesus monkeys, overview 3.4.21.69 Protein C (activated) medicine a low level of APC-protein C inhibitor complex in plasma may be associated with an increased risk of arteriovenous fistula/graft failure in hemodialysis patients 3.4.21.69 Protein C (activated) medicine activated protein C-protein C inhibitor complex correlates with abdominal aortic aneurysm diameter, body mass index, and age. Activated protein C-C-protein C inhibitor complex does not correlate with abdominal aortic aneurysm growth rate. Effect of the abdominal aortic aneurysm diameter on the protein C inhibitor complex concentration differs between men and women 3.4.21.69 Protein C (activated) medicine important role for the aPC/endothelial protein C receptor pathway in reducing metastasis via inhibition of tumor cell adhesion and transmigration 3.4.21.69 Protein C (activated) medicine leukocyte integrins are cellular receptors for recombinant activated protein C and the interaction decreases neutrophil recruitment into tissues, providing a potential mechanism by which recombinant human APC may protect against sepsis 3.4.21.69 Protein C (activated) medicine recombinant activated protein C-mediated upregulation of interleukin-10 reduces tissue factor in circulating monocytes. Part of the protective effect of recombinant activated protein C therapy may reflect the ability of recombinant activated protein C to dampen the proinflammatory and procoagulant potential of activated monocytes 3.4.21.69 Protein C (activated) medicine activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version is approved by the U.S. Food and Drug Administration to treat severe sepsis 3.4.21.69 Protein C (activated) medicine possible therapeutic applications of the enzyme mutant G216D, that has no catalytic activity but retains its antiseptic function without anticoagulant side effects 3.4.21.69 Protein C (activated) medicine the enzyme might have therappeutic potential in treatment of Alzheimer's disease 3.4.21.69 Protein C (activated) medicine enzyme mutant 3K3A-APC appears to be safe in ischemic stroke patients and reduced bleeding in the brain after tissue plasminogen activator therapy in a recent phase 2 clinical trial. Studies using human fetal neural stem and progenitor cells show that 3K3A-APC promotes neurogenesis in vitro as well as in vivo in the murine middle cerebral artery occlusion stroke model. 3K3A-APC appears to be safe in ischemic stroke patients and reduced bleeding in the brain after tissue plasminogen activator therapy in a recent phase 2 clinical trial. Enzyme mutant 3K3A-APC may potentially be used for late treatment of stroke in patients in ongoing phase 1 (NCT01151124) and phase 2 (NCT02117635) clinical trials that involve directly injecting manufactured NSCs into the brain of patients that remain moderately to severely disabled following an ischemic stroke 3.4.21.69 Protein C (activated) medicine possible effects of APC administration may include attenuation of the proinflammatory cytokine storm, re-balancing dysregulated haemostasis or degradation of cytotoxic extracellular histones that circulate during sepsis. Worldwide evaluation in severe sepsis (PROWESS) study demonstrated that recombinant APC (Xigris) administration reduces the relative risk of death compared with patients treated with a placebo (28 day mortality rate of 24.7% in individuals treated with recombinant APC, compared with 30.8% treated with placebo), prompting food and drug administration (FDA) approval for the application of Xigris in the treatment of severe sepsis. Subsequent concerns as to the efficacy and safety profile of Xigris prompted the PROWESS SHOCK trial that, in contrast with the original PROWESS study, indicated a lack of efficacy for Xigris in reducing the risk of death in severe sepsis patients, resulting in market withdrawal. The broad cytoprotective functions of APC on multiple cell types mean APC continues to lend itself to therapeutic applications, overview 3.4.21.69 Protein C (activated) medicine protective effect of recombinant APC administration in animals subject to Escherichia coli-induced sepsis. Possible effects of APC administration may include attenuation of the proinflammatory cytokine storm, re-balancing dysregulated haemostasis or degradation of cytotoxic extracellular histones that circulate during sepsis. Successful pre-clinical animal studies indicate that the neuroprotective effects of recombinant APC do not require anti-coagulant activity for therapeutic benefit to be achieved 3.4.21.69 Protein C (activated) medicine protective effect of recombinant APC administration in animals subject to Escherichia coli-induced sepsis. Possible effects of APC administration may include attenuation of the proinflammatory cytokine storm, re-balancing dysregulated haemostasis or degradation of cytotoxic extracellular histones that circulate during sepsis. Successful pre-clinical animal studies indicate that the neuroprotective effects of recombinant APC do not require anti-coagulant activity for therapeutic benefit to be achieved. The bleeding risk associated with the use of recombinant APC in the treatment of severe sepsis and apparent lack of requirement for APC anti-coagulant function for protective activity in murine endotoxemia and stroke models prompted the development of APC variants with selectively diminished anti-coagulant activity. APC variants that possess limited anti-coagulant function but normal cytoprotective signalling activity represent a potentially safer alternative to recombinant wild-type APC in disease settings in which APC has been shown to be protective 3.4.21.69 Protein C (activated) medicine Recombinant APC and/or its analogues with reduced by over 90% anticoagulant activity such as mutant 3K3A-APC (K191A/K192A/K193A), engineered to reduce APC-associated bleeding risk while retaining normal cell signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic/reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes, and lethal body radiation. Enzyme mutant 3K3A-APC stimulates neuronal production by human neural stem/progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate receptor 1-Akt pathway, suggesting the potential for APC-based treatment as a strategy for structural repair in the human central nervous system. Late post-ischemic treatment of C57BL/6J mice with 3K3A-APC stimulates neuronal production by transplanted human NSCs, promotes circuit restoration, and improves functional recovery 3.4.21.72 IgA-specific serine endopeptidase medicine causing agent of gonorrhoea 3.4.21.72 IgA-specific serine endopeptidase medicine inactivation of the enzyme has the potential to reduce bacterial colonisation at mucosal surrfaces 3.4.21.72 IgA-specific serine endopeptidase medicine the inactive mutant E1605A can be considered as a candidate vaccine component 3.4.21.72 IgA-specific serine endopeptidase medicine IgA1 protease may be an effective therapeutic candidate for IgAN by removing the mesangial deposited IgA1 in glomerular mesangium leading to immunoglobulin A nephropathy. The removal of IgA1 by IgA1 protease may separate the IgA1-containing immune complexes thereby eliminating its other components at the same time 3.4.21.72 IgA-specific serine endopeptidase medicine the IgA1 proteases may have the potential to cleave IgA1 complexes in the human host kidney and be a therapeutic agent for IgA1 nephropathy, a disease characterized by deposition of the IgA1 antibody in the glomerulus 3.4.21.72 IgA-specific serine endopeptidase medicine IgA protease-mediated degradation of agIgA1 and agIgA1 immune complexes is a potential therapy for IgA nephropathy 3.4.21.72 IgA-specific serine endopeptidase medicine immunization of animals with IgA1pr MA28-P1004LEH6 or proteins I, II, III provides the formation of immunological memory and can protect against both meningococcal and a number of pneumococcal fatal infections. Protective properties of meningococcal IgA1pr MA28-P1004LEH6 and proteins I, II, III against pneumococci may be attributed to their conformational epitopes close in structure to epitopes of pneumococcal surface proteins. In the model of passive animal protection, sera from rabbits immunized with Streptococcus pneumoniae of different serotypes are shown to be capable of animal protection from infection with Neisseria meningitidis, at least serogroup B. Pneumococcal and meningococcal infections can cause a crossprotective effect. This makes meningococcal IgA1 proteases and their recombinant derivatives the potential components of polyvalent vaccines 3.4.21.73 u-Plasminogen activator medicine associated with tumor metastasis and invasion, selective inhibitors of uPA may have potential as therapeutically useful drugs for prostate, breast and other cancers 3.4.21.73 u-Plasminogen activator medicine active enzyme promotes tumor progression, activation of enzyme appears as a key step in tumor progression. Inhibition of enzyme with natural or synthetic inhibitors diminishes high intravasating Matrigel invasion in vitro and intravasation and metastasis in vivo 3.4.21.73 u-Plasminogen activator medicine after infection with staphylococci, level of metabolically active enzyme is unaltered in plasma but significantly decreased in kidney homogenate. Enzyme acts as endogenous antibacterial substance. Decrease in enzyme level in infected organs may be due to dramatically increased production of plasminogen activator inhibitor type I 3.4.21.73 u-Plasminogen activator medicine amino-terminal fragment ATF of urokinase exerts an antitumor effect via dual mechanisms: essentially through targeting the uPA-uPAR system via the EGF-like domain and partially through targeting a uPAR-indepedent interaction via the kringle domain 3.4.21.73 u-Plasminogen activator medicine treatment of cancer with small-molecule active-site inhibitors with a C-terminal 4-amindinobenzylamide residue to prevent metastasis. Inhibitor dose of 2 x 1.5 mg/kg/day of inhibitor N-(benzylsulfonyl)-D-seryl-N-(4-carbamimidoylbenzyl)-L-serinamide reduces number of metastases to 4.6% in mice 3.4.21.73 u-Plasminogen activator medicine all patients examined with common variable immunodeficiency had increased plasma levels of soluble uPA receptor with particularly high levels in those with splenomegaly and thrombocytopenia. Plasma uPA levels were also raised in these patients, and both soluble uPA receptor and uPA levels correlated with the monocyte activation marker neopterin. Monocytes from patients with common variable immunodeficiency had increased expression of uPA receptor 3.4.21.73 u-Plasminogen activator medicine brain tissue of thermally injured rats displays an increase in the brain water content and the presence of Evans blue, temporally associated with an increased expression of endogenous tPA and uPA. Peripheral thermal injury does induce an increase in the permeability of the blood brain barrier 3.4.21.73 u-Plasminogen activator medicine either uPA/uPAR interaction, Mac-1 activation, or prevention of its association with uPAR triggers a signaling pathway leading to the inefficient release of HIV from monocytic cells 3.4.21.73 u-Plasminogen activator medicine expression of uPA, its receptor, and of inhibitor PAI-1 is increased in response to Helicobacter pylori, and for uPA, but not the receptor or PAI-1, requires the virulence factor CagE. Helicobacter pylori also stimulates soluble and cell surface-bound uPA activity. It stimulates epithelial cell proliferation, which is inhibited by uPA immunoneutralization and uPA receptor knock-down. Expogenous uPA also stimulates proliferation that is further increased after PAI-1 knock-down 3.4.21.73 u-Plasminogen activator medicine in a severe combined immunodeficient-human mouse model, PC-3 cells are the major source of uPA in the experimental bone tumor. Injection of uPA-silenced PC-3 cells in bone xenografts results in significant reduction of bone tumor burdens and protection of trabecular bones from destruction. The suppressed tumor growth is associated with the level of uPA expression but not with its activity. An increase in the expression of PAI-1, the endogenous uPA inhibitor, is found during in vitro tumor-stromal interactions. Up-regulation of PAI-1 in bone stromal cells and preosteoclasts/osteoblasts is due to soluble factor(s) released by PC cells, and the enhanced PAI-1 expression in turn stimulated PC cell migration 3.4.21.73 u-Plasminogen activator medicine in cancer cell, expression of uPA and uPA receptor underlies a mechanism of stem cell tropism to malignant tumors 3.4.21.73 u-Plasminogen activator medicine in mice model for kidney ischemia reperfusion injury, deficiency for uPA receptor, but not uPA protects from ischemia reperfusion injury. In the allogenic kidney transplant model, uPA receptor but not uPA deficiency of the allograft causes superior recipient survival and strongly attenuates loss of renal function. uPA receptor-deficient allografts show reduced generation of reactive oxygen species and apoptosis. Neutrophil and monocyte/macrophage infiltration is strongly attenuated and up-regulation of the adhesion molecule ICAM-1 is completely abrogated in uPA receptor-deficient allografts 3.4.21.73 u-Plasminogen activator medicine in patients with colorectal cancer, the protease antigen levels are significantly higher compared with other groups. At the time of clinical detection proteases cathepsin B, cathepsin L and urokinase-type plasminogen activator and its inhibitor are more sensitive indicators for colorectal cancer than commonly used tumor markers. Determination of cathepsin B, cathepsin L and urokinase-type plasminogen activator and its inhibitor have a major prognostic impact in patients with colorectal cancer 3.4.21.73 u-Plasminogen activator medicine in sputum derived from patients with house dust mite allergic asthma, the medium concentration of uPA is significantly greater than in healthy control patients. The sputum concentration of uPA correlates with sputum total cell count and with logarithmically transformed exhaled nitric oxide concentration, but not with FEV1 or bronchial reactivity to histamine. Tge effect of uPA seems to be independent of its fibrinolytic activity 3.4.21.73 u-Plasminogen activator medicine induction of lateral fluid percussion brain injury results in up-regulation of uPA and ERK mitogen-activated protein kinase. uPA contributes to the impairment of sodium nitroprusside and PGE2-mediated cerebrovasodilatation through activation of low-density lipoprotein receptor and ERK mitogen-activated protein kinase 3.4.21.73 u-Plasminogen activator medicine possible involvement of uPA in natural killer cell-mediated immune surveillance and tumor escape. Addition of uPA to natural killer cell receptor Ly49E positive adult and fetal natural killer cells inhibits interferon-gamma secretion and reduces their cytotoxic potential, respectively 3.4.21.73 u-Plasminogen activator medicine quantification of uPA and inhibitor PAI-1 mRNA expression in breast cancer cell lines as well as in tumor tissue of breast cancer patients by sensitive quantitative real-time PCR assays, based on the LightCycler technology. In breast cancer cell lines, mRNA and antigen values are highly correlated for both uPA and PAI-1 I. Correlations between uPA/PAI-1 mRNA and protein in the breast cancer samples were found to be distinctly weaker or not significant. Quantitative determination of mRNA expression for both factors does not mirror antigen levels in breast cancer tissue 3.4.21.73 u-Plasminogen activator medicine silencing of transmembrane protein Notch1 expression by siRNa inhibits invasion of human prostate cancer cells by inhibiting the expression of matrix metalloproteinase-9 and uPA 3.4.21.73 u-Plasminogen activator medicine study on cocaine-induced conditioned-place preference in rats with bilateral intra-accumbens injections of uPA-expressing lentiviral vectors. Overexpression of uPA in the nucleus accumbens significantly augments cocaine-induced place preference. Reinstatement with a low dose of cocaine produces significantly greater preference to the cocaine-associated context. Once cocaine-induced conditioned-place preference has been established, and the preference extinguished, reinstatement induced by a priming dose of cocaine is facilitated by uPA. Inhibition of tuPA expression abolishes the augmented acquisition produced by overexpression of uPA but not the expression of the cocaine-induced conditioned-place preference. When uPA is inhibited during the acquisition phase, animals no longer demonstrate place preference for the environment previously paired with cocaine. B428, a specific uPA inhibitor does not affect drug reinstatement after extinction if uPA has been activated during acquisition. Cocaine-induced conditioned-place preference and reinstatement may be dependent on active extracellular uPA 3.4.21.73 u-Plasminogen activator medicine the levels of uPA and uPA receptor in patients with acute or chronic hepatitis B significantly exceeds those in healthy controls. Patients with severe chronic hepatitis B have significantly higher levels of uPA and uPA receptor than those with moderate and mild chronic disease and those with acute hepatitis B. The plasma uPA and uPA receptor levels markedly increase in the acute stage and dramatically decrease in the remission stage, but in all stages levels exceede those in healthy subjects. The concentration of plasma uPA receptor is positively correlated with prothrombin and total bilirubin 3.4.21.73 u-Plasminogen activator medicine the overexpression of uPA in Quebec platelet disease emerges with megakaryocyte differentiation, without altering the expression of flanking genes. uPA is costored with-granule proteins prior to their proteolysis in Quebec platelet disease 3.4.21.73 u-Plasminogen activator medicine uPA promotes inward arterial remodeling by regulating oxidative stress and inflammation after arterial injury 3.4.21.73 u-Plasminogen activator medicine uPA, seprase and pipeptidylaminopeptidase IV immunoreactivity is found in dysplastic and cancer cells as well as in stromal cells adjacent to dysplasia and cancer sites, but not in normal epithelium. There is a significant association between uPA expression and sex, tumor size and histological classification in carcinomas. Squamous cell carcinoma lines display higher levels of uPA, seprase and dipeptidylaminopeptidase IV than normal esophageal epithelial cell lines 3.4.21.73 u-Plasminogen activator medicine macrophages, recruited into venous thrombi, can be used to target uPA gene constructs to the thrombus after systemic administration 3.4.21.73 u-Plasminogen activator medicine co-operation between TIMP-1 and host uPA suggests that therapies, simultaneously interfering with pro- and anti-proteolytic pathways may be beneficial for patients with metastatic disease 3.4.21.73 u-Plasminogen activator medicine inhibition of the enzyme might be beneficial in treating cancer 3.4.21.74 venombin A medicine ancrod currently under investigation for treatment of acute ischemic stroke, therapeutic doses results in the formation of soluble fibrin complexes that are degraded by plasmin 3.4.21.74 venombin A medicine high-level production of ancrod by Pichia pastoris has the potential to be used clinically 3.4.21.74 venombin A medicine potentially useful as antithrombotic defibrinating agent. Albofibrase effects can be rapidly reversed using commercial available antivenom. The enzyme shows anticoagulant activity, it progressively prolongs prothrombin time and activated partial thromboplastin time of normal human plasma in a time-dependent manner 3.4.21.74 venombin A medicine purified Autographa californica nuclear polyhedrosis virus-r-habutobin dose-dependently increases fibrin forming activity and inhibits collagen-induced aggregation of rabbit washed platelets. Thus, recombinant habutobin produced by baculoviral system is very useful for study on structure-function relationship, which is necessary for developing an antithrombotic drug from habutobin 3.4.21.74 venombin A medicine venom differences, e. g. content of metallproteases, among same snake species living in the same geographical area 3.4.21.74 venombin A medicine an initial controlled rapid ancrod infusion with mean post-9-h fibrinogen levels greater than 70 mg/dl may yield superior efficacy and safety. Modifications to ancrod dosing may substantially improve efficacy while reducing the rate of symptomatic intracranial hemorrhage 3.4.21.74 venombin A medicine a recombinant fusion protein with a pharmacodynamically inert large protein domain effectively prevents peritoneal adhesions without causing side effects, notably systemic fibrinogen depletion, bleeding, or impaired wound repair 3.4.21.74 venombin A medicine components of the intrinsic blood coagulation pathway, among them factor VIIIa (FVIIIa), have been recognized as suitable therapeutic targets to treat venous thromboembolism, pathological process behind two very serious cardiovascular diseases, deep vein thrombosis and pulmonary embolism. Enzyme VaaSPH-1 cab be a safe anticoagulant since it lacks proteolytic activity different from the contemporary drugs, which frequently induce excessive bleeding and other complications, during medical application. VaaSPH-1 is unlikely to be orally available for chronic usage as it has molecular mass of 35 kDa 3.4.21.74 venombin A medicine in standard experimental conditions VaF1 is not recognised by antiserum against the whole venom, so it can contribute to postserotherapy complications, such as ineffective blood coagulation, in the envenomed patient 3.4.21.74 venombin A medicine the identification and characterization of relevant epitopes recognized by B cells in snake venom toxins may provide valuable information for the preparation of immunogens that help in the production of improved therapeutic antivenoms 3.4.21.75 Furin medicine potential therapeutic value of furin inhibitors, alpha1-PDX is able to block in vivo maturation of pro-gB, the cytomegalovirus envelope glycoprotein 3.4.21.75 Furin medicine copper and zinc complexes of terpyridine derivatives are stable under various conditions and are not expected to pose delivery problems, qualities vital for the development of a wide-scope anti-bioterror agent for civil and military uses 3.4.21.75 Furin medicine cell-to-cell spread of Borna disease virus requires neither the expression of cellular receptors involved in virus primary infection, nor the furin-mediated processing of Borna disease virus glycoprotein 3.4.21.75 Furin medicine furin is predominantely expressed in tumors from patients surviving less than five years. Furin may constitute a marker for ovarian tumor progression and may contribute to predict the outcome of the disease 3.4.21.75 Furin medicine furin-like protease activity may be involved in mediating host-parasite interactions. Inhibition of infection is due to an effect on the parasite-derived furin activity rather than the host cell furin 3.4.21.75 Furin medicine inhibiting furin-like proprotein convertases protects the host from the distinct furin-dependent infections and lay a foundation for novel, host cell-focused therapies against acute diseases 3.4.21.75 Furin medicine interleukin 12 induction of furin plays a role in interferon gamma protein regulation and control of T helper 1 cell differentiation 3.4.21.75 Furin medicine introduction of a prototypic furin recognition motif at R667 of the SARS coronavirus spike glycoprotein allows for efficient cleavage of the mutant glycoprotein and increases cell-cell fusion activity but shows no effect on virion infectivity 3.4.21.75 Furin medicine massive vaccination of host poultry results in an influenza variant Fujian-like H5N1 strain with two mutations at the furin-processing site of hemagglutinin, which is resistant to immunization 3.4.21.75 Furin medicine pivotal role for furin, MT1-MMP, and MMP2 in tumor necrosis factor alpha-induced sphingolipid signaling. This system may be a possible target to inhibit smooth muscle cell proliferation in vascular diseases 3.4.21.75 Furin medicine some mutations of H5N1 H5 cleavage sequence fit less well into furin and hence may reduce the high pathogenicity of the H5N1 virus 3.4.21.75 Furin medicine specific and opposing roles of furin and PACE4 in the regulation of MMP-9/TIMP-1 mediated cell motility and invasion. Furin prosegment inhibits cell migration and invasion as well as MMP-9 activity without affecting TIMP-1. It prevents adequate repair of scratch wounds 3.4.21.75 Furin medicine furin expression is detected in all rhabdomyosarcoma cell lines tested at high levels, while myoblasts and fibroblasts show low levels of furin transcripts. Peptide CMGTINTRTKKC has strong affinity for rhabdomyosarcoma cells in vitro and in vivo, by binding to furin 3.4.21.75 Furin medicine hypoxia triggers relocalization of furin from the trans-Golgi network to endosomomal compartments and the cell surface in cancer cells. Exposing these cells back to normoxic conditions reverses furin redistribution, suggesting that the tumor microenvironment modulates furin trafficking in a highly regulated manner. Both Rab4GTPase-dependent recycling and interaction of furin with the cytoskeletal anchoring protein, filamin-A, are essential for the cell surface relocalization of furin. Interference with the association of furin with filamin A, prevents cell surface relocalization of furin and abolishes the ability of cancer cells to migrate in response to hypoxia 3.4.21.75 Furin medicine increased replication of heaptitis C virus RNA in hepatitis C-infected cells is significantly reduced in the presence of transforming growth factor TGF-beta1 siRNA, thrombospondin-1 siRNA or furin siRNA 3.4.21.75 Furin medicine peptide CMGTINTRTKKC has strong affinity for rhabdomyosarcoma cells in vitro and in vivo, by binding to furin. Treatment of rhabdomyosarcoma cells in mice with doxorubicin coupled to the targeting peptide results in a two-fold increase in therapeutic efficacy compared to doxorubicin treatment alone. Surface-furin binding may be used as novel mechanism for therapeutic cell penetration 3.4.21.76 Myeloblastin medicine major target autoantigen in patients with Wegener's granulomatosis, a systemic vasculitis 3.4.21.76 Myeloblastin medicine specific inhibition of PR3 activity to process IL-32 or neutralization of IL-32 by inactive PR3 or its fragments may reduce the consequences of IL-32 in immune regulated diseases 3.4.21.76 Myeloblastin medicine down-regulation of anticoagulation during inflammation by rapid endothelial cell protein C receptor proteolysis by PR3 3.4.21.76 Myeloblastin medicine in patients with Wegener’s granulomatosis, epitope recognition by anti-neutrophil cytoplasmic antibodies (ANCA) is affected by the glycosylation status of PR3 3.4.21.76 Myeloblastin medicine involved in autoimmune small vessel vasculitides, e. g. Wegener´s granulomatosis. PR3 is the main target autoatigen of antineutrophilic cytoplasmic antibodies (ANCA). Structure(charge)-based binding interactions between PR3-ANCA and conformational epitopes of PR3. Binding of PR3 to physiological molecules as well as to autoantibodies may induce and promote proinflammatory responses 3.4.21.76 Myeloblastin medicine PR3 induces DC maturation via protease-activated receptor-2. Wegener’s autoantigen PR3 interacts with a “gateway” receptor (protease-activated receptor-2) on iDCs in vitro, triggering their maturation and licenses them for a Th1-type response potentially favoring granuloma formation in Wegener’s granulomatosis. PR3-anti-neutrophil cytoplasmic antibodies are strongly associated with Wegener’s granulomatosis. PR3-anti-neutrophil cytoplasmic antibodies opsonization of apoptotic neutrophils results in effective phagocytosis by human monocyte-derived macrophages and leads to up-regulation of proinflammatory mediator production. An animal model for PR3-anti-neutrophil cytoplasmic antibodies-associated vasculitis that shows characteristics similar to human Wegener’s granulomatosis is not yet available 3.4.21.76 Myeloblastin medicine PR3- and CD177-expressing neutrophils constitute a subpopulation of neutrophils with an unknown role in the innate immune system, which may play an important role in diseases such as Wegener’s granulomatosis and polycythemia vera 3.4.21.76 Myeloblastin medicine PR3-anti-neutrophil cytoplasmic antibodies from Wegener’s granulomatosis patients do not recognize the natively folded murine PR3 3.4.21.76 Myeloblastin medicine proinflammatory role of membrane PR3 expression may involve interference with macrophage clearance of apoptotic neutrophils 3.4.21.76 Myeloblastin medicine responsible for eliminating intracellular pathogens and breaking down tissues at inflammatory sites. Possible molecular target for anti-inflammatory agents. Involved in degradation of ECM components and cleavage of inflammatory mediators, platlet activation, induction of endothelial cells and apoptosis, negative feedback regulation of granulopoiesis. Shows bactericidal properties. Is a target of auto-antibodies in Wegener’s granulomatosis 3.4.21.76 Myeloblastin medicine extra-intestinal pulmonary complications of ulcerative colitis with elevated proteinase-3 anti-neutrophil cytoplasmic antibody resembling Wegener’s granulomatosis and spontaneous improvement 3.4.21.76 Myeloblastin medicine novel anti-proteinase-3-human native-human recombinant enzyme-linked immunosorbent assay (ELISA) with a very high sensitivity for the detection of proteinase-3-antineutrophil cytoplasmic antibodies (ANCA) in patients with ANCA-associated vasculitis with C-ANCA 3.4.21.76 Myeloblastin medicine classic symptoms and clinical findings, together with serology titres positive for anti-neutrophil cytolplasmic antibody against proteinase 3 confirm the diagnosis of Wegener's Granulomatosis, which can occasionally involve other organs as the respiratory and renal tracts and in such cases a differential diagnosis of Wegener's Granulomatosis must be considered, as early recognition and treatment of this potentially fatal disease is paramount 3.4.21.76 Myeloblastin medicine neutrophil-activating potential of cANCAs can vary in patients, depending on the association rates, target specificities, and titers of antibodies, as well as on local concentrations of human PR3 inhibitors 3.4.21.76 Myeloblastin medicine only therapies based on the dual inhibition of caspase 1 and serine proteases will be successful in the management of complex inflammatory diseases in humans 3.4.21.76 Myeloblastin medicine PRTN3 is a promising antigen for immunotherapy of myeloid leukemia 3.4.21.76 Myeloblastin medicine the substrate N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) may be used for the construction of a very reliable, inexpensive, and easy to use diagnostic test for PR3 determination 3.4.21.76 Myeloblastin medicine affinity chromatography of neutrophil lysates using epoxy beads coated with Streptococcus sanguinis reveals involvement of PR3 in phagocytosis of Streptococcus sanguinis. Enzymatic cleavage of the glycosylphosphatidylinositol linker of NB1, a co-receptor for membrane-bound PR3, significantly reduces the phagocytosis. The neutralization of membrane-bound PR3 with antibody reduces both binding and phagocytosis of Streptococcus sanguinis. Protease activity is required for phagocytosis, and protease-activated receptor PAR2 is involved in signal transmission from PR3 during this process 3.4.21.76 Myeloblastin medicine in all individuals tested, neutrophils are either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils is increased significantly in anti-neutrophil cytoplasmic antibodies-associated systemic vasculitis and systemic lupus erythematosus patients. The proportion of mPR3+/CD177+ cells is not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. The increased membrane expression of PR3 found in anti-neutrophil cytoplasmic antibodies-associated systemic vasculitis is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene 3.4.21.77 semenogelase medicine enzyme is a marker for prostatic disease 3.4.21.77 semenogelase medicine the size of the fraction of free enzyme in serum is a marker to distinguish benign hyperplasia from malignant carcinoma 3.4.21.77 semenogelase medicine enzyme is a marker for cancer 3.4.21.77 semenogelase medicine used in the diagnosis of prostate cancer 3.4.21.77 semenogelase medicine enzyme may modulate the tumor-associated urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor-system activity by either activating the pro-enzyme form of plasminogen activator or cleaving the cell surface-associated receptor 3.4.21.77 semenogelase medicine before treatment, prostate specific antigen kinetics may provide valuable prognostic information regarding the risk of treatment failure and subsequent death from cancer. Prostate specific antigen velocity is easier to calculate but prostate specific antigen doubling time may have greater biological justification. Precise cutoff levels require further investigation 3.4.21.77 semenogelase medicine biomarker used in the diagnosis of prostate cancer and to monitor therapeutic response. Design and development of potent and specific inhibitors of PSA 3.4.21.77 semenogelase medicine important marker for the diagnosis and management of prostate cancer 3.4.21.77 semenogelase medicine purified active PSA has a potential use in prostate cancer diagnostics and/or therapeutics 3.4.21.77 semenogelase medicine splice variant PSA-SV5 may have applications as a biomarker in clinical diagnosis of prostate cancer based on its expression in a much higher percentage of prostate cancers compared to benign prostate hyperplasia 3.4.21.77 semenogelase medicine kinetics of prostate-specific antigen are indicative of tumour progression and are therefore used in clinical decision-making in men on active surveillance for early prostate cancer. A high prostate-specific antigen velocity or short prostate-specific antigen doubling time are related with an unfavourable outcome and should lead to performing an additional prostate biopsy or to deferred radical treatment during follow-up of active surveillance. A low prostate-specific antigen velocity or a long prostate-specific antigen doubling time is associated with a nonaggressive course of the disease and may justify a more conservative attitude. A prostate-specific antigen doubling time more than 10 years, a static course of the prostate-specific antigen values, or a negative prostate-specific antigen doubling time are generally associated with a good prognosis. A prostate-specific antigen doubling time of less than 3-4 years should lead to the advice to switch to radical treatment 3.4.21.77 semenogelase medicine low frequency of positive results in patients with prostatic cancer and a high frequency of positive results in those with benign prostatic hyperplasia seems to discourage the use of prostate-specific antigen-positive circulating cells in the search for a clinical diagnosis of prostate cancer 3.4.21.77 semenogelase medicine prostate-specific antigen is identified as a useful serum marker for assessing patients with prostate cancer during their follow-up. It is approved as a tool for detecting the disease in men aged over 50 years. There are limitations of a single prostate-specific antigen measurement, i.e. its low sensitivity and specificity in detecting prostate cancer, which may lead to the over-detection of cancers that pose little threat to health and/or life. Prostate-specific antigen kinetics (prostate-specific antigen velocity, doubling-time, half-time and progression) may be used to predict the outcome in both localized and advanced prostate cancer. Limitations of all prostate-specific antigen kinetics is the choice of many methods for calculation that can result in considerable variation in prediction and even in errors in patient management 3.4.21.77 semenogelase medicine prostate-specific antigen kinetics provide unique prognostic information to patients with prostate cancer. Pretreatment prostate-specific antigen velocity plays an important role in risk assessment of men treated by radical prostatectomy and external beam radiation therapy. Prostate-specific antigen doubling time at relapse predicts time to metastasis 3.4.21.77 semenogelase medicine prostate-specific antigen velocity is more accurate than prostate-specific antigen doubling time for predicting adverse histology on repeat biopsies, suggesting that prostate-specific antigen velocity shall be used in preference to PSA doubling time to describe prostate-specific antigen kinetics in untreated, localized prostate cancer 3.4.21.77 semenogelase medicine the predictive performance for prostate cancer using genetic variants and family history is similar to that of prostate-specific antigen. Such genetic markers may be used to supplement prostate-specific antigen to improve its predictive value 3.4.21.77 semenogelase medicine a novel method using molecular, polymerase chain reaction-based detection of cancer cell clusters, which is applied for predicting prostate cancer and to assess the effect of radical prostatectomy on reducing cancer cell clusters and for prognostication of relapse-free survival, as serum total prostate-specific antigen has limited specificity at 4-10 ng/ml 3.4.21.77 semenogelase medicine according to partial AUC-ROC (full-range area under the curve of receiver operating characteristics) analyses, pro/free PSA and pro/free/total ratio may be excellent predictive markers for prostate cancer, allowing unnecessary biopsy to be avoided while maintaining high sensitivity at 90% or 95%, in the PSA range 4-20 ng/mL. Not only pro/free PSA, but also age, findings on digital rectal examination and PSA density are independent parameters for predicting biopsy outcomes 3.4.21.77 semenogelase medicine although benign prostatic hyperplasia-associated as single marker or ratio to total PSA does not improve the diagnostic performance of percent free PSA or total PSA, the incorporation of benign prostatic hyperplasia-associated/total PSA into an artificial neural network model increases the specificity compared with percent free PSA by 13% and 17% at 90% and 95% sensitivity, respectively. Thus, automated benign prostatic hyperplasia-associated research assay may improve prostate cancer detection when incorporating this new marker into an artificial neural network 3.4.21.77 semenogelase medicine decreases in prostate volume over time and the resultant change in prostate-specific antigen performance characteristics may have contributed a bias toward the detection of high-grade disease in the finasteride arm of the Prostate Cancer Prevention Trial. Performance of prostate specific antigen for the detection of any cancer and high-grade cancer is affected by prostate size: prostate-specific antigen performance is significantly better in men with smaller prostates for both the detection of low-grade and high-grade disease 3.4.21.77 semenogelase medicine detection rates of nonpalpable prostate cancer in Korean men do not differ significantly in two groups of patients with a lower and a higher PSA range, thus a lower PSA level (2.5 ng/mL may be a more appropriate cutoff point than 4.0 ng/mL) may be considered as an indication for prostate biopsy 3.4.21.77 semenogelase medicine development of a nomogram to predict the probability of clinically significant cancers before biopsy, which is most likely to be useful in the management of patients with moderate to elevated PSA 3.4.21.77 semenogelase medicine development of an electrochemical immunosensor for PSA with a self-assembled 4-(2-(4-(acetylthio)phenyl)ethynyl)benzoic acid as a bioreceptor. To enhance the electrochemical activity of PSA detection, poly(amidoamine) dendrimer is linked on the 4-(2-(4-(acetylthio)phenyl)ethynyl)benzoic acid self-assembled monolayer 3.4.21.77 semenogelase medicine early detection and treatment of prostate cancer is critical to prognosis, with an initial PSA reading being important to the patients management plan. There is limited evidence that the additional use of prostate-specific antigen velocity compared with a single PSA measurement increases sensitivity and specificity of cancer detection. But PSAV remains a useful practical tool in the management of men with prostate cancer: PSA kinetics are also useful in monitoring men on active surveillance in assessing the status of their disease and the presence of cancer progression 3.4.21.77 semenogelase medicine effects of isoflavones and curcumin on PSA production in prostate cells, particularly in combination, may have therapeutic advantages in patients with high PSA level who has negative prostate biopsies. Isoflavones and curcumin may improve the asymptomatic inflammation in prostates with high serum PSA levels 3.4.21.77 semenogelase medicine free PSA performs significantly better than total PSA at predicting thresholds of prostate volume: free PSA may be used to estimate prostate volume and can be a useful tool in making therapeutic decisions in Chinese men with benign prostatic hyperplasia 3.4.21.77 semenogelase medicine generation of stable hybridomas producing specific monoclonal antibodies of the IgG class against PSA from fusions of splenocytes from immunized mice with myeloma cells, which can be used to develop radioimmunodiagnostic, radioimaging, and immunohistochemistry techniques for the early detection and treatment of prostate cancer 3.4.21.77 semenogelase medicine PSA appears to be a useful screening tool for detecting prostate cancers with significant volume 3.4.21.77 semenogelase medicine PSA kinetics at the initiation of androgen-deprivation therapy can predict overall survival in patients with metastatic hormone-sensitive prostate cancer 3.4.21.77 semenogelase medicine PSA kinetics differ significantly following different radiotherapy methods. A higher radiobiological efficiency of brachytherapy in comparison to external-beam radiotherapy (with a total dose of 70.2 Gy) in respect of normal prostate tissue (lower PSA nadir for patients without biochemical failure) and malignant prostate cells (lower PSA failure rate). PSA bounces occur predominantly in the first three years after treatment, particularly after low-dose-rate-brachytherapy 3.4.21.77 semenogelase medicine PSA may serve as a sensitive biomarker of Hsp90 inhibition and may aid in selecting new chemotherapeutics 3.4.21.77 semenogelase medicine serum PSA is a very useful biomarker for prostate cancer. PSA at the same time stimulates tumor cell invasion and inhibits the formation of metastatic tumors by inhibiting angiogenesis. High PSA expression in the prostate is associated with low microvessel density, whereas low PSA expression is associated with poor prognosis. PSA is a potential target for prostate cancer treatment and imaging, it may be possible to control tumor angiogenesis and, thus, prostate cancer growth by modulating the proteolytic activity of PSA 3.4.21.77 semenogelase medicine urine detection of the PSA activation peptide may represent a clinically sensitive measure of PSA production/secretion and may prove to be a viable alternative/addition to current PSA assays 3.4.21.77 semenogelase medicine using changes in PSA-related parameters after antibacterial therapy DELTAPSA, DELTAPSA density, and DELTA free/total PSA improve the prostate cancer detection rate and decrease unnecessary prostate biopsies in patients with asymptomatic prostatitis 3.4.21.77 semenogelase medicine analysis of values of serum prostate-specific antigen PSA in American Veterans during the time before their diagnosis of prostate cancer. The values appear to follow an exponential model with respect to time. The model comprises a sum of two exponential functions, one for an early, slowly rising component of PSA and a second for a later, faster rising component. The relative velocity of the slow component is significantly associated with the volume of benign tissue, both the amplitude and relative velocity of the fast component are significantly associated with the volume of tumor. At the time of diagnosis of prostate cancer the level and velocity of PSA reflect the combination of slow and fast components. The model provides insight into how benign and malignant tissues in the prostate determine the dynamics of PSA 3.4.21.77 semenogelase medicine development of a water-soluble paclitaxel prodrug that is activated specifically by PSA. epsilon-Maleimidocaproyl-Arg-Ser-Ser-Tyr-Tyr-Ser-Leu-p-aminobenzyloxycarbonyl-paclitaxel is water-soluble and is bound to endogenous and exogenous albumin. The albumin-bound form of the prodrug is cleaved rapidly at the P1-P1' scissile bond releasing the paclitaxel-dipeptide Ser-Leu-p-aminobenzyloxycarbonyl-paclitaxel. Due to the incorporation of a p-aminobenzyloxycarbonyl self-eliminating linker, this dipeptide is rapidly degraded to liberate paclitaxel as a final cleavage product within a few hours in prostate tumour tissue homogenates 3.4.21.77 semenogelase medicine evaluation of the use of proPSA, free PSA, and PSA to enhance specificity for detecting overall and high-grade prostate cancer. Study on men in a prospective multi-institutional trial with no history of prostate cancer shows that prostate health index Phi may be useful in prostate cancer screening to reduce unnecessary biopsies in men age over 50 years with PSA values of 2-10 ng/ml and negative digital rectal examination findings, with minimal loss in sensitivity 3.4.21.77 semenogelase medicine evaluation of the use of PSA isoforms p2PSA and benign prostatic hyperplasia-associated PSA, BPHA, in prostate cancer predictive value. The p2PSA and Beckman Coulter Prostate Health Index levels differ significantly between men with and without prostate cancer. No difference in BPHA levels is observed. there are significant increases in prostate cancer predictive value and specificity of Beckman Coulter Prostate Health Index and percent free prostate-specific antigen compared to total prostate-specific antigen tPSA and percent free prostate-specific antigen. p2PSA has limited additional value in identifying aggressive prostate cancer 3.4.21.77 semenogelase medicine in breast cancer tissue, about 40% of samples express PSA. The immunoexpression of PSA is significantly correlated only with the length of CA polymorphic tandem repeats in the 3'-untranslated region of estrogen receptor beta, genotypes with longer CA repeats being associated with PSA negativity. CAG and TA repeats are not associated with PSA expression 3.4.21.77 semenogelase medicine mass spectrometry-based analytical method to measure different glycosylated forms of glycoproteins from complex biological samples by coupling glycopeptide extraction strategy for specific glycosylation with selected reaction monitoring SRM. Using this method, glycosylated and sialylated prostate-specific antigen PSA in prostate cancer and noncancer tissues can be monitored. The relative abundance of glycosylated PSA isoforms is not correlated with total PSA protein levels measured in the same prostate cancer tissue samples by clinical immunoassay. The sialylated PSA is differentially distributed in cancer and noncancer tissues, and elevated in cancer tissues compared to noncancerous tissues 3.4.21.77 semenogelase medicine PSA may be involved in a signal transduction-dependent feedback loop, whereby it promotes a more aggressive behavior by human prostate cancer cells. Ligation of prostate cancer cell surface protein GRP78 by its natural ligand, activated alpha2-macroglobulin, results in a 2-3-fold upregulation in the synthesis of PSA. The PSA is secreted into the medium as an active proteinase, where it binds to native alpha2-macroglobulin. The resultant alpha2-macroglobulin-PSA complexes bind to GRP78, causing a 1.5-2fold increase in the activation of MEK1/2, ERK1/2, S6K, and Akt, which is coupled with a 2-3-fold increase in DNA and protein synthesis 3.4.21.77 semenogelase medicine with prostate specific antigen included in progression criteria, prostate specific antigen at confirmatory biopsy and positive confirmatory biopsy are independent predictors of progression. When prostate specific antigen is excluded from progression criteria, 2- and 5-year progression-free probability is 91% and 76%, respectively. Prostate specific antigen greater than 10 ng/ml was excluded as a criterion 3.4.21.78 granzyme A medicine diagnosis tool, patients with various viral diseases or with rheumatic arthritis have elevated levels of circulating granzyme A 3.4.21.78 granzyme A medicine cytolytic T-lymphocytes from enzyme or granzyme B deficient mice similarly induce early proapoptotic features such as phosphatidyl serine exposure on plasma membrane, or reactive oxygen radical generation, though with distinct kinetics. Cytolytic T-lymphocytes from granzyme A, but not granzyme B deficient animals activate caspase 3 and 9. All granzyme-induced apoptotic features depend critically on perforin 3.4.21.78 granzyme A medicine granzyme A is located in intracellular granules of rectal CD8+ T cells in healthy and HIV-1-positive individuals, while similar amounts of perforin RNA are detected in both groups, but perforin protein is absent in rectal tissue of HIV-1-positive individuals 3.4.21.78 granzyme A medicine investigation of glucocorticoid-induced expression of granzyme A as a potential early biomarker for personalized therapy of acute lymphoblastic leukemia patients 3.4.21.78 granzyme A medicine involvement of granzyme A in development of chronic obstructive pulmonary disease (COPD) shown, increased expression of granzyme A in type II pneumocytes indicated 3.4.21.78 granzyme A medicine involvement of granzyme A in development of chronic obstructive pulmonary disease shown 3.4.21.78 granzyme A medicine involvement of granzyme A in development of chronic obstructive pulmonary disease shown, increased expression of granzyme A in type II pneumocytes 3.4.21.78 granzyme A medicine role of extracellular granzymes in disease reviewed 3.4.21.78 granzyme A medicine studies on the role of granzyme A in polymorphonuclear neutrophils (PMNs) in defence against invading pathogens 3.4.21.78 granzyme A medicine studies on the role of granzyme A-mediated cell death in the pathogenesis of familial chilblain lupus 3.4.21.78 granzyme A medicine both GzmA and GzmB levels are significantly increased in serum of patients with patients with amyotrophic lateral sclerosis 3.4.21.78 granzyme A medicine construction of a chimeric protein IGA, consisting of interleukin IL-2 and granzyme A, using IL-2 as a targeting moiety and granzyme A as a killing moiety to overcome multidrug resistance MDR in anticancer therapy. The IGA chimeric protein enters the target sensitive and MDR cancer cells overexpressing IL-2 receptor and induces caspase 3-independent cell death. After its entry, IGA causes a decrease in the mitochondrial potential, and triggers translocation of nm23-H1, a granzyme A-dependent DNase, from the cytoplasm to the nucleus, where it causes single-strand DNA nicks, thus causing cell death. IGA is able to overcome MDR and kill cells resistant to chemotherapeutic drugs 3.4.21.78 granzyme A medicine proinflammatory gzmA and anti-inflammatory gzmB are novel modulators of the Th1/2 balance and defense in helminth infection 3.4.21.78 granzyme A medicine the protease may be a therapeutic target for the prevention of bacterial sepsis without affecting immune control of the pathogen 3.4.21.79 granzyme B medicine cytolytic T-lymphocytes from enzyme or granzyme A deficient mice similarly induce early proapoptotic features such as phosphatidyl serine exposure on plasma membrane, or reactive oxygen radical generation, though with distinct kinetics. Cytolytic T-lymphocytes from granzyme A, but not granzyme B deficient animals activate caspase 3 and 9. All granzyme-induced apoptotic features depend critically on perforin 3.4.21.79 granzyme B medicine A streptolysin-O/GrB combination results in the induction of p53 accumulation and transcriptional activity associated with strong induction of apoptotic cell death in T1 cells 3.4.21.79 granzyme B medicine activated mast cells contribute, via secreted gzmB, to cell death, increased vascular permeability, leukocyte extravasation and subsequent inflammatory processes in affected tissues. GzmB-induced detachment of adherent mouse embryonic fibroblasts leads to anoikis. GzmB induces a disorganization of endothelial cell-cell contacts 3.4.21.79 granzyme B medicine can induce rapid apoptosis of target cells, which is dependent on caspase activation and mitochondrial damage. GzmH-induced death is characterized by phosphatidylserine externalization, nuclear condensation, DNA fragmentation, caspase activation and cytochrome c release. GzmH may play an essential role in caspase-dependent pathogen clearance in the innate immunity that may complement the proapoptotic function of GzmB in human natural killer cells 3.4.21.79 granzyme B medicine detection of target GzB activity followed by caspase 3 activation provides a unique readout of a potentially lethal injury delivered by cytotoxic lymphocytes 3.4.21.79 granzyme B medicine ELISPOT measurements of granzyme B permit the identification of actively ongoing CD8+ cell responses. Importance for immune diagnostic of infections, transplantation, allergies, autoimmune diseases, tumors and vaccine development 3.4.21.79 granzyme B medicine expression of granzyme B by peripheral CD8+ T lymphocytes does not vary between emphysematous smokers, smokers and non-smokers with normal lung function 3.4.21.79 granzyme B medicine extension of the present standard of IFN-gamma measurements to the analysis of GzB and perforin release in functional T cell assays will provide new insights into CD8+ effector T cell function in HIV infection 3.4.21.79 granzyme B medicine granzyme B may play a key role in ateromatous diseases. Role in cardiac allograft vasculopathy and atherosclerosis 3.4.21.79 granzyme B medicine granzyme B plays a role in the cytotoxic response in lichen planus. It is a probable target for future immunomodulator therapy 3.4.21.79 granzyme B medicine granzyme H participates in the anti-adenovirus response by both inhibiting virus replication directly and simultaneously re-sensitizing infected cell to granzyme B-induced cell death 3.4.21.79 granzyme B medicine granzymes can mediate antiviral activity through direct cleavage of viral substrates. Different granzymes have synergistic functions to outflank viral defenses that block host antiviral activities 3.4.21.79 granzyme B medicine GrB proteolysis of Hsc70/Hsp70-interacting protein is important to the efficiency of death induction 3.4.21.79 granzyme B medicine GzmH induces cell death, it is nearly as potent as GzmB. Exhibits an alternative cell death pathway in innate immunity. In contrast to GzmB, GzmH achieves cell death by acting on mitochondrial and nuclear targets but not through the activation of hallmark apoptotic substrates 3.4.21.79 granzyme B medicine Hsp70/Hsp90-organizing protein per se does not set the threshold for susceptibility to GzmB-induced apoptosis 3.4.21.79 granzyme B medicine key role of plasticity in the granzyme B mediated cell death pathway in the killing of changed tumor cells, resulting in keratoacanthoma regression through apoptosis or direct damage of tumor cells. Insufficient activation of cytotoxic T lymphocytes and decreased release or activity of granzyme B may be responsible for squamous cell-carcinoma progression and occasional aggressive behavior in keratoacanthomas. Targeted delivery of granzyme B to squamous cell, carcinoma cells may be a new agent that may have an additive or synergic effect with conventional therapeutic modalities, since there are still no known cellular resistance mechanisms capable of protecting cells against all granzyme B mediated pathways 3.4.21.79 granzyme B medicine pleiotropic pro-apoptotic function of gzmB presumably to counteract evasion strategies of pathogens and to control tumors 3.4.21.79 granzyme B medicine Treg cells derived from the tumor environment can induce NK and CD8(+) T cell death in a granzyme B- and perforin-dependent fashion. Granzyme B and perforin are relevant for Treg cell-mediated suppression of tumor clearance in vivo 3.4.21.79 granzyme B medicine extracellular granzyme B may help control localized coagulation during inflammation 3.4.21.79 granzyme B medicine granzyme B level may contribute to a diagnosis of immune-mediated epilepsy including Rasmussen syndrome 3.4.21.79 granzyme B medicine granzyme B may be the limiting factor in adaptive regulatory T cell-mediated K562 target cell killing 3.4.21.79 granzyme B medicine plasma granzyme B level on day 14 is a significant predicting factor for left ventricular remodeling after acute myocardial infarction 3.4.21.79 granzyme B medicine platelets are lymphotoxic effectors in sepsis via granzyme B 3.4.21.79 granzyme B medicine potential role for granzyme B in the process of initiation of myasthenia gravis 3.4.21.79 granzyme B medicine the release of granzyme B through two routes from unconjugated cytotoxic lymphocytes suggests that it functions outside the cell and may contribute to pathology in cases of immune dysregulation, such as familial hemophagocytic lymphohistiocytosis 3.4.21.79 granzyme B medicine granzyme B GrB labels a subpopulation of effector cells involved in ongoing cytotoxic action should be considered as a specific marker showing the extent of the direct local cytotoxic damage in patients with lupus erythematosus 3.4.21.79 granzyme B medicine modified versions of GzmB with lower isoelectric points can be utilized without loss of apoptosis-inducing potential but fewer side activities 3.4.21.79 granzyme B medicine since GzmB is very effective in killing human tumor cell lines that are resistant against cytotoxic drugs GrzmB is used as an effector domain in potential immunoconjugates 3.4.21.79 granzyme B medicine both GzmA and GzmB levels are significantly increased in serum of patients with patients with amyotrophic lateral sclerosis. There is a significant correlation of serum GzmB levels with severity of clinical state of amyotrophic lateral sclerosis patients 3.4.21.79 granzyme B medicine granzyme B-deficient mice, and to a lesser extent perforin-deficient mice, exhibit a significant increase in the number of Ag-specific CD8+ T cells in the lungs and draining lymph nodes of virally infected animals. Viral titers in granzyme B-deficient mice are similar to wild-type mice and significantly less than perforin-deficient mice. Regulatory T cells from wild-type mice express high levels of granzyme B in response to infection, and depletion of regulatory T cells from these mice results in an increase in the number of Ag-specific CD8+ T cells, similar to that observed in granzyme B-deficient mice. Granzyme B-deficient regulatory T cells display defective suppression of CD8+ T cell proliferation in vitro 3.4.21.79 granzyme B medicine human neurons are selectively susceptible to granzyme B isolated from cytotoxic T cell granules. In vitro, purified human GrB induces neuronal death to the same extent as the whole activated T cell population. Following internalization through various parts of neurons, GrB accumulates in the neuronal soma. Within the cell body, GrB diffuses out of endosomes possibly through a perforin-independent mechanism and induces subsequent activation of caspases and cleavage of a-tubulin. Inhibition of caspase-3, a substrate for GrB, significantly reduces GrB-mediated neurotoxicity. Treatment of neurons with mannose-6-phosphate prevents GrB entry and inhibits GrB-mediated neuronal death 3.4.21.79 granzyme B medicine internalization of grB by membrane Hsp70 positive tumor cells is dependent on mammalian glycosylation of GrB. Neuraminic acid blocks binding of GrB to CT26 tumor cells 3.4.21.79 granzyme B medicine ischemic brain samples after stroke contain significantly higher levels of Gra-b and interferon-gamma inducible protein-10 than non-ischemic controls. In stroke, poly(ADP-ribose) polymerase-1 and heat shock protein-70 are cleaved to canonical proteolytic signature fragments by Gra-b. Gra-b also binds to Bid and caspase-3 and colocalizesw with Annexin-V+/TUNEL+ in degenerating neurons. Gra-b inhibition protects both normal and ischemia-reperfused neurons against in vitro neurotoxicity mediated by activated CG-SH cells and supernatants. Increased leukocyte infiltration and elevated Gra-b levels in the post-stroke brain can induce contact-dependent and independent post-ischemic neuronal death to aggravate stroke injury 3.4.21.79 granzyme B medicine proinflammatory gzmA and anti-inflammatory gzmB are novel modulators of the Th1/2 balance and defense in helminth infection 3.4.21.79 granzyme B medicine the precursor frequency and cytotoxic lymphocyte activity of HLA-A2-restricted transaldolase 168-176-specific CD8+ T cells is increased in multiple sclerosis patients. The major C-terminal GrB cleavage product of transaldolase, residues 28-337, has no enzymatic activity but retains the antigenicity of full-length transaldolase, effectively stimulating the proliferation and cytotoxic lymphocyte activity of peripheral blood mononuclear cells and of CD8+ T cell lines from patients with multiple sclerosis. Sera of multiple sclerosis patients exhibit similar binding affinity to wild-type and GrB-cleaved transaldolase 3.4.21.79 granzyme B medicine The soluble granzyme B levels are higher in systemic lupus erythematosus patients and associated with various clinical features like reduced complement components, C3 and C4, and skin lesion. The soluble granzyme B levels are also sturdily related with severity of the disease. Excessive secretion of soluble granzyme B and enhanced activity of cytotoxic T lymphocyte may play a vital role in the pathogenesis of systemic lupus erythematosus and organ damage 3.4.21.79 granzyme B medicine the protease may be a therapeutic target for the prevention of bacterial sepsis without affecting immune control of the pathogen 3.4.21.83 Oligopeptidase B medicine involved in host cell invasion, important target for drug design 3.4.21.83 Oligopeptidase B medicine potential theraputic target in infectious disease 3.4.21.89 Signal peptidase I medicine developing of medication designed to arrest tissue damage during Pseudomonas infection, opportunistic pathogen causes morbidity and mortality in patients with burns, cystic fibrosis, pneumonia, urinary tract infections, skin infections, cancer, acquired immunodeficiency syndrome, and ocular disease 3.4.21.89 Signal peptidase I medicine inhibition of enzyme by arylomycin A-C16 results in an insufficient flux of proteins through the secretion pathway leading to mislocalization of proteins. Inhibition results in synergistic sensitivity of cells when combined with an aminoglycoside. Antibiotics tetracycline, erythromycin, and vancomycin each interact additively with arylomycin A-C16, while rifampin and trimethoprim show pronounced antagonism 3.4.21.89 Signal peptidase I medicine inhibition of enzyme by arylomycin A-C16 results in an insufficient flux of proteins through the secretion pathway leading to mislocalization of proteins. Inhibition results in synergistic sensitivity of cells when combined with an aminoglycoside. No significant interactions are observed between arylomycin A-C16 and erythromycin, polymyxin B, trimethoprim, or ciprofloxacin. Arylomycin A-C16 shows mild synergism with cephalexin, pronounced synergism with rifampin and gentamicin, and antagonism with the translational inhibitor tetracycline 3.4.21.91 Flavivirin medicine to validate NS2B as a potential target in allosteric inhibitor development, a cNS2B specific human monoclonal antibody (3F10) is used. 3F10 disrupts the interaction between cNS2B and NS3 in vitro and reduces DENV viral replication in HEK293 cells 3.4.21.92 Endopeptidase Clp medicine C. jejuni is the principal cause of bacterial food-borne gastroenteritis in humans. ClpP may be a suitable target of new intervention strategies aimed at reducing C. jejuni in poultry production. The growth of the ClpP mutant is impaired at high temperature and at conditions that are known to increase the level of misfolded proteins 3.4.21.92 Endopeptidase Clp medicine ClpP as antibacterial drug target 3.4.21.92 Endopeptidase Clp medicine ClpP proteolytic activity is strongly involved in the pathogenicity of S. aureus and adaptation of the pathogen to several stresses 3.4.21.92 Endopeptidase Clp medicine induction of Bacillus subtilis genes controlled by the extracytoplasmic function alternative sigma factor W is strongly impaired in a strain deleted for the ClpP peptidase gene 3.4.21.92 Endopeptidase Clp medicine ClpP is expressed in vivo during mild and paucibacillary paratuberculosis infection in sheep 3.4.21.92 Endopeptidase Clp medicine correlative effect of Lon and ClpP upregulation on loss of mitochondrial Fe-S proteins during the progression of Friedreich ataxia suggesting that Fe-S proteins are potential targets of Lon and ClpP proteases in Friedreich ataxia 3.4.21.92 Endopeptidase Clp medicine immunizing mice intranasally with a mixture of ClpP and CbpA (choline binding protein A) elicites better protection than that of immunizing either single ClpP or CbpA 3.4.21.92 Endopeptidase Clp medicine protective efficacy of mucosal immunization with ClpP as a promising pneumococcal protein antigen 3.4.21.92 Endopeptidase Clp medicine ClpP activation is an effective means of controlling the replication of Mycobacterium tuberculosis 3.4.21.92 Endopeptidase Clp medicine ATP-dependent Clp protease proteolytic subunit 2 displays potent immunogenicity. In tuberculosis patients, both the levels of ClpP2 antigen and antibody are increased. ClpP2 antigens may be used as a biomarker in tuberculosis pathogen­esis 3.4.21.92 Endopeptidase Clp medicine treatment with ClpP inhibits cell growth and induces apoptosis in SK-N-SH neuroblastoma cells. Treatment results in hypodiploid DNA contents, increased Bax/Bcl-2 ratio and induction of reactive oxygen species production. The release of cytochrome c from mitochondria into the cytosol, is not observed in ClpP-treated cells. Pretreatment with Z-Val-Ala-Asp-fluoromethylketone, a broad spectrum caspase inhibitor, cannot rescue apoptotic cells from ClpP toxicity. Caspase-3 and -8 activation and cleavage of PARP are not detected. Caspase independent apoptosis-inducing factor is released from mitochondria and translocated to the nucleus in response to ClpP. ClpP treatment results in the increase of p53 activity, and cytoplasmic p53 levels are increased by ClpP 3.4.21.92 Endopeptidase Clp medicine reducing the levels of mitochondrial ClpP or ClpX renders human cancer cells more sensitive to cisplatin. ClpP levels are elevated in cervical carcinoma cells (KB-CP20) and hepatoma cells (BEL-7404-CP20) independently selected for cisplatin resistance 3.4.21.93 Proprotein convertase 1 medicine extension of the clinical and molecular spectrum of human congenital PC1/3 deficiency 3.4.21.93 Proprotein convertase 1 medicine Pc1 N222D homozygous mice are obese and mimic humans with mutations in PC1. This mutation will be a valuable resource in understanding the role of prohormone processing in energy homeostasis 3.4.21.93 Proprotein convertase 1 medicine transplantation of PC1/3-expressing alpha-cells prevents streptozotocin-induced hyperglycemia by preserving beta-cell area and islet morphology, possibly via stimulating beta-cell replication. Expression of PC1/3 rather than PC2 in alpha-cells induces glucagon-like peptide 1 and glucagon-like peptide 2 production and converts the alpha-cell from a hyperglycemia-promoting cell to one that lowers blood glucose levels. Alteration of proglucagon processing in the alpha-cell may be therapeutically useful in the context of type 1 diabetes 3.4.21.93 Proprotein convertase 1 medicine downregulation of prohormone convertase 1/3 by short-term morphine and upregulation by long-term morphine treatment may be a signal mediating the switch from drug use to drug abuse 3.4.21.93 Proprotein convertase 1 medicine significant activation of PC1/3 in the alpha-cells of pancreatic islet is observed in mouse models of insulin resistance such as pregnant, obese, diabetic and prediabetic NOD mice. Data suggest a role of alpha-cells for beta-cell proliferation and further for the endocrine cell network within an islet 3.4.21.93 Proprotein convertase 1 medicine prohormone convertase 1/3 activity is significantly lower in type 2 diabetic patients than in the control group. Decreased activity of prohormone convertase 1/3 rather than prohormone convertase 2 in pancreatic beta-cells is involved in the impaired proinsulin processing, resulting in elevated intact proinsulin levels in type 2 diabetic patients 3.4.21.93 Proprotein convertase 1 medicine UVB irradiation to the eye and stress loading increase the expression of prohormone convertase 1/3 and prohormone convertase 2 in the pituitary gland. The increase in expression of pituitary prohormone convertase 2 is greater in animals subjected to UVB eye irradiation than to stress, whereas no difference is seen between the two groups for the increase in PC1/3 3.4.21.93 Proprotein convertase 1 medicine role of prohormone convertase 1/3 in the transformation of corticotroph cell adenomas into Cushing's disease. Prohormone convertase 1/3 expression is negative or weak in the three patients in the initial phase of corticotroph cell adenoma, while a strong expression is observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as Cushing's disease 3.4.21.94 proprotein convertase 2 medicine defects in processing, sorting, and/or secretion of (pro)IAPP associated with beta-cell dysfunction in type 2 diabetes and insulinomas may result in production and secretion of elevated levels of proIAPP and its NH(2)-terminally unprocessed form, leading to intracellular and/or fibril formation and beta-cell apoptosis. Restoration of intact IAPP processing may be a potential therapeutic approach to prevent or slow (pro)IAPP-induced beta-cell apoptosis and maintain beta-cell mass in type 2 diabetes 3.4.21.94 proprotein convertase 2 medicine PCSK2 is a strong functional candidate for type 2 diabetes. Association with type 2 diabetes among four single nucleotide polymorphisms in an African American population. None of the single nucleotide polymorphisms are associated with age at type 2 diabetes diagnosis. A variant in the PCKS2 gene (rs2021785) appears to play a role in susceptibility to type 2 diabetes-end stage renal disease in this African American population 3.4.21.94 proprotein convertase 2 medicine transplantation of PC2-expressing alpha-cells increases plasma glucagon levels and causes mild fasting hyperglycemia, impairs glucose tolerance, and alpha-cell hypoplasia. PC2-expressing alpha-cells neither prevent streptozotocin-induced hyperglycemia nor increased beta-cell proliferation in the context of type 1 diabetes 3.4.21.94 proprotein convertase 2 medicine in a rat model of transient focal cerebral ischemia by performing 100 min of middle cerebral artery occlusion, proprotein convertase 2 activity gradually decreases in the ischemic cortex with increasing duration of reperfusion. In an in vitro model of experimental oxygen-glucose deprivation using cultured rat cortical neuron, the number of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive neurons significantly increases and proprotein convertase 2 activity also decreases gradually with increasing duration of oxygen-glucose deprivation 3.4.21.94 proprotein convertase 2 medicine UVB irradiation to the eye and stress loading increase the expression of prohormone convertase 1/3 and prohormone convertase 2 in the pituitary gland. The increase in expression of pituitary prohormone convertase 2 is greater in animals subjected to UVB eye irradiation than to stress, whereas no difference is seen between the two groups for the increase in PC1/3 3.4.21.95 Snake venom factor V activator medicine potential use of snake venom proteases as diagnostic and thrombolytic agents 3.4.21.95 Snake venom factor V activator medicine small peptides derived from factor V activator destabilize the beta-amyloid aggregate. Peptide CTNIF and a mixture of six peptides are most potent in converting the aggregates to the monomeric state and thus, preventing cytotoxicity in SH-SY5Y human neuroblastoma cells. Some of the peptides are stable in blood for 24 h 3.4.21.97 assemblin medicine targeting prodrugs for activation by a specific protease encoded by the infectious HCMV pathogen may be achievable. Dipeptide prodrug of ganciclovir, acetyl-L-Gln-L-Ala-ganciclover, is a potential selective prodrug candidate 3.4.21.98 hepacivirin medicine natural substrate of enzyme is the mitochondrial antiviral signaling protein. Blocking the cleavage of mitochondrial antiviral signaling protein as means for prevention and treatment of hepatitis C 3.4.21.98 hepacivirin medicine NS3 protease blunts the ability of hepatitis C virus to induce IFN-alpha promoter activity by proteolytically cleaving MAVS/IPS-1. Hepatitis C virus blocks the synthetic dsRNA-induced signaling pathway at a point upstream of MAVS/IPS-1 by an NS3-independent mechanism 3.4.21.98 hepacivirin medicine NS3-4A protease has an essential role in the generation of the viral RNA replication machinery. One of the major means by which the virus antagonizes the host cell innate immune response. Viral resistance to most of the NS3-4A inhibitors is going to arise rapidly, at least in the course monotherapy treatment 3.4.21.98 hepacivirin medicine NS3/4A-mediated trans-activation assay can be used to monitor Hepatitis C virus expression in different cell lines. NS3/4A-dependent chimera can be used to monitor hepatitis C virus infection and to perform the purification of hepatitis C virus-infected cells 3.4.21.98 hepacivirin medicine presence of the A156T mutation in close to 1% of NS3 sequences within the liver quasispecies of a chronic Hepatitis C patient never treated with anti-NS3-protease inhibitors 3.4.21.98 hepacivirin medicine inhibitor shows selective and potent in vitro anti-HCV activity, the potential for combination with other anti-HCV agents, and a favorable pharmacokinetic profile 3.4.21.98 hepacivirin medicine inhibitory effects of NS3-4A on antiviral signaling pathways are limited to the Cardif-mediated pathway in human hepatocytes 3.4.21.98 hepacivirin medicine cleavage of T cell protein tyrosine phosphatase by NS3/4A induces a shift of the intrahepatic immune response toward a nonantiviral Th2-dominated immunity 3.4.21.100 sedolisin medicine potential importance as a virulence factor and in the industrial hydrolysis of protein source 3.4.21.104 mannan-binding lectin-associated serine protease-2 medicine it is investigated whether the concentration of mannose-binding lectin and MASP-2 is associated with prognosis in pediatric patients with cancer. In the 372 patients studied, median serum concentration of mannose-binding lectin (MBL) is 2.808 mg/l and 391 mg/l for MASP-2. The estimated 4-year event-free survival is 0.60. In the entire, heterogeneous sample, MBL and MASP-2 are not significantly associated with overall survival or event-free survival. In patients with hematologic malignancies, higher MASP-2 is associated with better event-free survival in a significant and clinically relevant way. This is due to patients with lymphoma, but less for those with acute leukemia 3.4.21.104 mannan-binding lectin-associated serine protease-2 medicine evaluation of the role of MASP-2 in HIV infection. The MASP-2 .126L variant is associated with MASP-2 levels <200 ng/ml and increases the susceptibility to HIV infection and to HIV plus hepatitis B virus positive status. p.126L in addition to other variants associated with low MASP-2 levels such as p.120G, p.377A and p.439H, presents a protective effect against AIDS, independently of age, sex, hepatic function andviral load. MASP-2 serum levels are lower in HIV positive and HIV plus hepatitis B virus positive patients than in controls. Among patients, MASP-2 levels are higher in patients with opportunistic diseases and AIDS. MASP-2 levels correlate positively with MBL/MASP2-mediated complement component C4 and negatively with CD4+ cell counts 3.4.21.104 mannan-binding lectin-associated serine protease-2 medicine MASP-2 serum levels vary between younger children (12 years and less) and older children (above 12 years) and adults. Younger children with a patent infection with with Schistosoma haematobium have significantly lower MASP-2 serum levels than uninfected children. Older children and adults with a current infection have higher serum MASP-2 levels than controls. mannose-binding lectin serum levels correlate positively with MASP-2 serum levels. MASP2 secretor haplotypes are associated with MASP-2 serum levels in healthy subjects. The heterozygous MASP2 P126L variant is associated with reduced serum MASP-2 levels 3.4.21.104 mannan-binding lectin-associated serine protease-2 medicine proteases MASP-1 and MASP-2 levels are significantly higher in children and adults with type 1 diabetes mellitus than in their respective control groups, whereas proteases MASP-3 and MAp44 levels do not differ between patients and controls. MASP-1 and MASP-2 levels correlate with hemoglobin HbA1c, and MASP levels decrease when glycaemic control improves 3.4.21.105 rhomboid protease medicine TgROM5 is able to cleave MIC adhesins. It likely provides the key protease activity necessary for invasion. The enzyme TgROM5 offers a target for therapeutic intervention against invasion by the deadly pathogen Toxoplasma gondii 3.4.21.105 rhomboid protease medicine variation in rhomboid protease PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome 3.4.21.105 rhomboid protease medicine chicken vaccination with a recombinant Mycobacterium bovis BCG strains carrying the Eimeria tenella rhomboid gene delivered by an extrachromosomal vector and integrative vector, respectively, demonstrate significant protection against Eimeria tenella challenge 3.4.21.105 rhomboid protease medicine introduction of positively charged amino acid residues in the transmembrane sequence of the substrate redirects the RHBDL4-mediated cleavage of amyloid precursor protein from its ectodomain closer towards the transmembrane sequence, possibly inducing an ER-associated degradation of the substrate. The cytoplasmic tail and proposed palmitoylation sites in the ectodomain of amyloid precursor protein are not essential for the RHBDL4-mediated amyloid precursor protein processing 3.4.21.106 hepsin medicine expression of the non-transmembrane isoform in vivo does not exert any apparent inhibitory effect on cell growth 3.4.21.106 hepsin medicine hepsin expression in tumours is dysregulated and may influence tumorigenesis through inappropiate activation and/or regulation of hepatocyte growth factor receptor functions 3.4.21.106 hepsin medicine hepsin is a potent activator of pro-hepatocyte growth factor, thus contributing to tumor progression 3.4.21.106 hepsin medicine hepsin is significantly decreased in pT2 or greater tumor samples, while expression does not differ between the normal and cancerous tissue of pT1 tumors, survival in patients bearing tumors with hepsin expression below the 10th percentile expression of hepsin in noncancerous tissue is poorer than that in patients with tumors with expression above that cutoff, the level of hepsin is found to be a significant predictor of death from renal cell carcinoma 3.4.21.106 hepsin medicine hepsin significantly inhibits cell growth in the monolayer, anchorage-independent cell growth in soft agar in vitro, and tumorigenicity in vivo in ovarian cancer cell lines, through up-regulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations 3.4.21.106 hepsin medicine human hepsin interacts directly with X protein of human hepatitis B virus both in vitro and in vivo, their interaction appears to play a role in both promoting cell proliferation and blocking apoptosis in human liver tumor cell and normal liver cell lines, promotes expression of viral protein HBeAg in Hep-G2.2.1.5 cells, thus stimulating viral replication 3.4.21.106 hepsin medicine overexpression of hepsin in a mouse model of nonmetastasizing prostate cancer has no impact on cell proliferation, but causes disorganization of the basement membrane and promotes primary prostate cancer progression and metastasis to liver, lung and bones 3.4.21.106 hepsin medicine association of five of eleven single nucleotide polymorphisms on the hepsin gene HPN with susceptibility to prostate cancer among men of European descent. Association of one of the single nucleotide polymorphisms with Gleason score, which suggests a role of HPN in tumor aggressiveness 3.4.21.106 hepsin medicine hepsin has a potential therapeutic effect that inhibits through upregulation of p53-dependent apoptosis and caspase-3, -6, and -7 activations. Hepsin may be useful in ovarian cancer treatment 3.4.21.106 hepsin medicine hepsin is not necessary for embryonic development of mice and postnatal survival and is dispensable for normal hemostasis and liver function 3.4.21.106 hepsin medicine hepsin is one of the most upregulated genes in prostate cancer. Upregulation appears to correlate with disease progression. Role of hepsin is more important in cancer cell migration/invasion than cell proliferation. Hepsin mRNA expression appears to be lower in hormone-refractory prostate cancer compared to clinically localized prostate cancer. Single nucleotide polymorphisms are associated with prostate cancer susceptibility. In contrast, prostate cancer cell lines stably transfected with a hepsin expressing plasmid grow slower and are less invasive in culture. Similarly, stable transfection of hepsin cDNA in ovarian cancer cell lines promotes apoptosis and inhibits tumor cell growth 3.4.21.106 hepsin medicine hepsin may initiate plasmin-mediated proteolytic pathways at the tumor/stroma interface that lead to basement membrane disruption and tumor progression 3.4.21.106 hepsin medicine hepsin protein expression may be an important indication for high risk of endometrial cancer 3.4.21.106 hepsin medicine TMPRSS1 is required for normal auditory function 3.4.21.106 hepsin medicine direct cleavage of Laminin-332 may be one mechanism by which hepsin promotes prostate tumor progression and metastasis, possibly by up-regulating prostate cancer cell motility 3.4.21.106 hepsin medicine germline genetic variation of HPN does not seem to contribute to risk of prostate cancer or prognosis 3.4.21.106 hepsin medicine alpha-methylacyl-CoA racemase and hepsin are unable to diagnose prostate cancer with better true positive and false negative rates than prostate-specific antigen. There are no correlations between alpha-methylacyl-CoA racemase levels, hepsin levels, tumor stage of benign prostate hyperplasia and prostate cancer, and Gleason score 3.4.21.107 peptidase Do medicine aroC aroD HtrA mutant shows promise as a typhoid vaccine in humans 3.4.21.107 peptidase Do medicine htrA mutants can act as vaccines 3.4.21.107 peptidase Do medicine HtrA is important both for adherence to and invasion of human INT407 epithelial cells 3.4.21.107 peptidase Do medicine HtrA1 is developmentally regulated in the uterus and trophoblast during placental establishment 3.4.21.107 peptidase Do medicine increased expression of HtrA1 in the human placenta in the third trimester of gestation, especially in the outer layer forming the syncytiotrophoblast 3.4.21.107 peptidase Do medicine HtrA is an antigen for serum immunglobulin G during Chlamydia trachomatis sexually transmitted infection, but is not associated with pathology 3.4.21.107 peptidase Do medicine HTRA1 is involved in osteoarthritis 3.4.21.107 peptidase Do medicine purified recombinant DegP is a protective immunogen that can induce the production of specific serum antibodies and elicit strong protective immunity in fish vaccinated with recombinant DegP 3.4.21.107 peptidase Do medicine cigarette smoke–induced methylation of HtrA3 can contribute to the etiology of chemoresistant disease in smoking-related lung cancer 3.4.21.107 peptidase Do medicine human isoform HTRA1 degrades aggregated and fibrillar tau, a protein that is critically involved in various neurological disorders. Neuronal cells and patient brains accumulate less tau, neurofibrillary tangles, and neuritic plaques, respectively, when HTRA1 is expressed at elevated levels. HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated tau concentrations 3.4.21.107 peptidase Do medicine late stage Lyme disease patients, as well as infected mice and rabbits develop a robust antibody response to HtrA, indicating that it is a B-cell antigen 3.4.21.108 HtrA2 peptidase medicine amyloid beta, a pivotal factor implicated in the pathogenesis of Alzheimer´s disease interacts with HtrA2/Omi 3.4.21.108 HtrA2 peptidase medicine heterozygous G399S mutation in Parkinson's disease patients, which is absent in healthy controls, a A141S polymorphism is associated with Parkinson's disease, both mutations result in defective activation of Omi/HtrA2 and mitochondrial dysfunction associated with altered mitochondrial morphology 3.4.21.108 HtrA2 peptidase medicine HtrA2 knockout mice display features characteristic of a Parkinson syndrome, deletion of HtrA2 results in increased susceptibility to cell death stimuli, Smac/DIABOLO can compensate for the removal of HtrA2 in terms of neutralizing inhibitor of apoptosis proteins 3.4.21.108 HtrA2 peptidase medicine involvement of HtrA2 in the etiology of Alzheimer's disease 3.4.21.108 HtrA2 peptidase medicine myocardial ischemia/reperfusion significantly increases cytosolic Omi/HtrA2 content and markedly increases apoptosis, ucf-101 can inhibit apoptosis 3.4.21.108 HtrA2 peptidase medicine transfecting cells with siRNA molecules against Omi effectively eliminate Omi/HtrA2 protein expression 3.4.21.108 HtrA2 peptidase medicine way to limit renal injury by specifically inhibiting its proteolytic activity 3.4.21.108 HtrA2 peptidase medicine critical role of HtrA2 in a cytokine-induced cell death response. Inhibition by a viral protein 3.4.21.108 HtrA2 peptidase medicine HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. HtrA2 interacts with PINK1 and that both are components of the same stress-sensing pathway 3.4.21.108 HtrA2 peptidase medicine link between HtrA2/Omi and Parkinson’s disease or Alzheimer’s disease 3.4.21.108 HtrA2 peptidase medicine Omi/HtrA2 is involved in neuronal cell death following focal cerebral ischemia/reperfusion. Blocking the proteolytic activity of Omi/HtrA2 with specific inhibitors, such as the ucf-101, may be a way to afford neuroprotection and minimize cellular damage in cerebral ischemia/reperfusion 3.4.21.108 HtrA2 peptidase medicine protease activity of HtrA2 is essential for the production of C161. Processing of amyloid precursor protein into C161 by HtrA2 is a natural event occurring under normal physiological conditions. Direct cleavage of mitochondrial beta-amyloid precursor protein by HtrA2 may prevent mitochondrial dysfunction caused by accumulation of amyloid precursor protein. Regulation of HtrA2 protease activity may be a therapeutic target in Alzheimer disease 3.4.21.108 HtrA2 peptidase medicine role for HtrA2/Omi in apoptosis 3.4.21.108 HtrA2 peptidase medicine HtrA2 is linked to cancer and neurodegeneration, like Alzheimers disease, Parkinsons disease, Huntingtons disease, and brain, kidney and myocardial ischemia, reperfusion 3.4.21.108 HtrA2 peptidase medicine HtrA2 is linked to Parkinsons disease 3.4.21.108 HtrA2 peptidase medicine loss of HtrA2 function might contribute to the activation of a stress response of mitochondrial origin in the brain that promotes neurodegeneration 3.4.21.108 HtrA2 peptidase medicine mutations in the OMI/HTRA2 gene are linked to Parkinsons disease 3.4.21.108 HtrA2 peptidase medicine mutations of the OMI/HTRA2 gene are linked to Parkinsons disease 3.4.21.108 HtrA2 peptidase medicine the function of Omi/HtrA2 is linked to selective vulnerability of striatal neurons in Huntingtons disease 3.4.21.108 HtrA2 peptidase medicine the identification of the role of HtrA2 in neurodegeneration will lead to an improved understanding of the pathogenesis of Parkinsons disease 3.4.21.108 HtrA2 peptidase medicine the relation between p73 and HtrA2 may help to understand the behavior of the p73 protein in the responses of cancer cells to chemotherapy 3.4.21.108 HtrA2 peptidase medicine the study does not support a role of HtrA2 variants in the pathogenesis of Parkinsons disease 3.4.21.108 HtrA2 peptidase medicine therapeutic interventions that inhibit HtrA2 expression, translocation, or protease activity may provide attractive therapeutics in the treatment of cardiovascular diseases 3.4.21.108 HtrA2 peptidase medicine therapeutic interventions that inhibit HtrA2/Omi expression, translocation, or protease activity may represent novel therapeutic strategies for retinal pigment epithelial cells and retinal pigment epithelial cells-related diseases 3.4.21.108 HtrA2 peptidase medicine HtrA2/Omi is associated with the pathogenesis of amyotrophic lateral sclerosis 3.4.21.108 HtrA2 peptidase medicine HtrA2-mediated proteolysis of WT1 may directly contribute to the effect of cytotoxic drugs warrants 3.4.21.108 HtrA2 peptidase medicine HtrA2 under several different stress conditions induces cleavage of vimentin in wild-type as well as SH-SY5Y cells transfected with amyloid precursor protein with the Alzheimer disease-associated Swedish mutation. After stress treatment, inhibition of HtrA2 protease activity by the specific inhibitor, Ucf-101, reduces the cleavage of vimentin in wild-type cells 3.4.21.109 matriptase medicine expression of serine protease SNC19/matripase and hepatocyte growth factor is decreased in gastrointestinal cancer tissues compared to their normal counterparts, decreased expression may correlate with invasion and lymph node metastasis 3.4.21.109 matriptase medicine matripase mediates cell invasion through activation of receptor-bound pro-urokinase-type plasminogen activator 3.4.21.109 matriptase medicine multiple roles for hepatocyte growth factor activator inhibitor-1 to regulate matripase, including its proper expression, intracellular trafficking, activation and inhibition 3.4.21.109 matriptase medicine possibly controlls epithelial-cell turnover by regulating cell-cell and/or cell-substratum adhesions 3.4.21.109 matriptase medicine prolonged stabilization of matripase is stabilized by UDP-N-acetylglucosamine: alpha-mannoside beta-1,6-N-acetylglucosminyltransferase-mediated glycosylation in vivo, thus extending its halftime and permitting it to play role in the early phases of papillary carcinoma, but not in its later progression 3.4.21.109 matriptase medicine inhibition of matriptase appears to suppress both primar tumor growth and metastasis, leading to considerable interest in the development of potent matriptase inhibitors as anti-cancer drugs 3.4.21.109 matriptase medicine matriptase is identified as a cancer-associated protease 3.4.21.109 matriptase medicine matriptase may be considered to be a potential target for the development of anti-cancer drugs 3.4.21.109 matriptase medicine matriptase may play an important role in the metastasis of prostate cancer 3.4.21.109 matriptase medicine matriptase-2 plays a putative role as a tumor suppressor enzyme in human breast cancer 3.4.21.109 matriptase medicine upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo 3.4.21.109 matriptase medicine time-domain near infrared fluorescence (NIRF) imaging is applied to characterize expression and activity of matriptase in vivo in an orthotopic AsPC-1 pancreatic tumor model in nude mice. Strong expression and tumor-specific binding of intravenously injected antimatriptase antibody only to primary AsPC-1 tumors and their metastases is shown. Using a synthetic substrate it is shown that matriptase is proteolytically active in vitro as well as in vivo in tumor-bearing mice, and that application of synthetic active-site inhibitors can efficiently inhibit its proteolytic activity for at least 24 h 3.4.21.109 matriptase medicine coexpression of matriptase with amyloid precursor protein APP695 results in site-specific cleavagesof amyloid precursor protein. Replacement of Arg-601 (Arg-5 in Abeta1-42) by Ala in APP695 prevents matriptase cleavage at this site. Overexpression of matriptase in M17 cells results in a significant reduction of the endogenous amyloid precursor protein quantity 3.4.21.109 matriptase medicine in breast cancer cells, a significant amount of the 30-40-kDa serine protease inhibitor HAI-2 can translocate to and inhibit matriptase on the cell surface, followed by shedding of the matriptase-HAI-2 complex 3.4.21.109 matriptase medicine loss of cell surface protease inhibitor HAI-2 in intestinal epithelial cells leads to unrestrained matriptase activity and efficient cleavage of epithelial cell adhesion molecule EPCAM. Congenital tufting enteropathy-associated HAI-2 mutant proteins exhibit reduced ability to inhibit matriptase and also fail to efficiently stabilize claudin-7 in intestinal epithelial cells 3.4.21.109 matriptase medicine mRNA and protein expression of both matriptase and prostasin are rapidly down-regulated in the initiating inflammatory phases of dextran sulfate sodium-induced experimental colitis, and the loss of these proteases precedes the appearance of clinical symptoms. Barrier disruption by the colitis-associated Th2-type cytokines, IL-4 and IL-13, down-regulates matriptase as well as prostasin through phosphorylation of the transcriptional regulator STAT6 3.4.21.110 C5a peptidase medicine acts as a potential invasin of group A streptococcus and promotes invasion independent of fibronectin 3.4.21.110 C5a peptidase medicine immunization with C5a peptidase protein from either group A or group B streptococci provides protection against group A streptococcus infections in mice, moreover, mice immunized with antibodies directed against protein from group B streptococci also cleared streptococci from their lungs more efficiently than those immunized with tetanus toxoid 3.4.21.110 C5a peptidase medicine inactivates recombinant chemotaxin C5a by destroying its capacity to interact with the C5a receptor on human polymorphonuclear leukocytes 3.4.21.110 C5a peptidase medicine intranasal immunization with SCPA prevents colonization and infection of human tonsils, thereby eliminating potential reservoirs that maintain endemic disease 3.4.21.110 C5a peptidase medicine SCPA is highly immunogenic in children infected with group A streptococcal pharyngitis 3.4.21.110 C5a peptidase medicine encapsulated C5a peptidase elicites significant immune responses and protection against group B streptococci challenge. C5a peptidase microsphere encapsulation has potential as a group B streptococci vaccine 3.4.21.110 C5a peptidase medicine fibronectin adhesin activity of scpB plays a role in virulence 3.4.21.110 C5a peptidase medicine increased anti-SCPA IgG levels in rheumatic fever, rheumatic heart disease and acute glomerulo nephritis cases. The rise of anti-SCPA IgG observed in patients is irrespective of different emm types of group A streptococci strains isolated from these patients. Indian females show higher concentration of anti-SCPA antibodies than male patients. Anti-SCPA IgG1 and anti-SCPA IgG3 are the predominant subclasses of anti-SCPA antibody and clearly distinguish individuals with acute rheumatic fever from those free of streptococcal disease 3.4.21.110 C5a peptidase medicine encapsulated C5a peptidase elicits significant immune responses and protection against a group B Streptococcus challenge. C5a peptidase poly(lactide-coglycolide) microsphere encapsulation has potential as a group B Streptococcus vaccine 3.4.21.110 C5a peptidase medicine the enzyme is used for vaccine development against group B Streptococcus 3.4.21.110 C5a peptidase medicine the enzyme can be useful for development of subunit vaccine against the pathogen Streptococcus zooepidemicus 3.4.21.110 C5a peptidase medicine inactive mutant H193A elicits high titers of antigen-specific IgG1 antibodies and robust T cell-mediated immunities in mice showing potential as a Streptococcus vaccine. Cconjugating the trisaccharide repeating unit of Streptococcus polysaccharide with mutant H193A converts the nonimmunogenic oligosaccharide into a highly active and T cell-dependent antigen 3.4.21.112 site-1 protease medicine S1P plays an integral role in skeletal development. S1P activity is necessary for a specialized endoplasmic reticulum stress response required by chondrocytes for the genesis of normal cartilage and thus endochondral ossification 3.4.21.112 site-1 protease medicine SKI-1/S1P processing is strictly required for incorporation of viral glycoproteins. SKI-1/S1P may represent a promising antiviral target 3.4.21.112 site-1 protease medicine useful role of SKI-1/S1P in controlling cholesterol synthesis, particularly in the presence of endoplasmic reticulum stress. SKI-1/S1P inhibition may be a potential tool for the treatment of alcohol-induced liver steatosis 3.4.21.112 site-1 protease medicine small-molecule S1P inhibitors are capable of reducing cholesterol and fatty acid synthesis in vivo and, therefore, represent a potential new class of therapeutic agents for dyslipidemia and for a variety of cardiometabolic risk factors associated with diabetes, obesity, and the metabolic syndrome 3.4.21.112 site-1 protease medicine glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies 3.4.21.112 site-1 protease medicine the enzyme is a potential target for melanoma therapy 3.4.21.112 site-1 protease medicine a female patient with a heterozygous missense mutation in the transmembrane domain of S1P (Pro1003Ser) displays episodic, activity-induced, focal myoedema and myalgias with hyperCKemia. The clinical phenotype includes gastrointestinal hypomotility, ocular migraines, and polycystic ovary syndrome. The mutation leads to increased activation of protein response and lipid and cholesterol regulatory pathways and localization of S1P Pro1003Ser in the Golgi 3.4.21.112 site-1 protease medicine in fibroblasts of mucolipidosis type II mice and Niemann-Pick type C patients characterized by aberrant cholesterol accumulation, the proteolytic cleavage of the alpha/beta-subunit precursor of N -acetylglucosamine-1-phosphotransferase is not impaired 3.4.21.112 site-1 protease medicine S1P is a potential target for indirect-acting pan-serotypic anti-dengue virus agents 3.4.21.113 pestivirus NS3 polyprotein peptidase medicine NS3 protease domain is essential for the process of viral RNA replication and, given its electrostatic contribution to RNA binding, it may also assist in packaging of the viral RNA 3.4.21.117 stratum corneum chymotryptic enzyme medicine because the enzyme appears only in abundance in tumor tissue and contains a secretion signal sequence, suggesting that the enzyme is secreted, it may prove to be a useful diagnostic/prognostic tool for the detection of metastatic or recurrent disease or as a novel molecular target for cervical cancer therapy 3.4.21.117 stratum corneum chymotryptic enzyme medicine breast cancer patients with KLK7 positive tumors have relatively shorter disease-free survival and overall survival than patients with KLK7 negative tumors. KLK7 gene expression may be used as a marker of unfavorable prognosis for breast cancer patients 3.4.21.117 stratum corneum chymotryptic enzyme medicine expression of full-length KLK7 mRNA may represent a new prognostic marker in breast cancer disease 3.4.21.117 stratum corneum chymotryptic enzyme medicine kallikrein 7 may be useful in clinics as biomarkers for the detection and monitoring of non-small cell lung cancer 3.4.21.117 stratum corneum chymotryptic enzyme medicine ectopic expression of KLK7 in pancreatic cancer cells leads to a reduction in cell adhesion to vitronectin that may result from the cleavage of uPAR from the cell surface. KLK 7 expression, plays an important role in the dissemination of tumor cells through the production of soluble uPAR in pancreatic cancer 3.4.21.117 stratum corneum chymotryptic enzyme medicine the KLK7 polymorphism does not confer a risk for eczema 3.4.21.117 stratum corneum chymotryptic enzyme medicine study on KLK7 expression in prostate cancer. A total of 64 of 92 (69.57%) benign cases show positive staining for KLK7 and 23 of 116 (19.83%)malignant cases show positive staining. The expression level of kallikrein-related peptidase 7 mRNA is significantly decreased in prostate cancer tissues compared with that in benign prostate hyperplasia tissues and normal prostate tissue. The protein expression levels of KLK7 is lower in prostate cancer than in benign prostate hyperplasia tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are downregulated in prostate cancer and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level 3.4.21.118 kallikrein 8 medicine TAGD14 may be a useful molecular target for therapy or a diagnostic tool as tumor marker due to its overexpression in ovarian carcinoma 3.4.21.118 kallikrein 8 medicine patients with ovarian cancer, women with enzyme-positive tumors most often have lower-grade tumors, no residual tumor after surgery, optimal debulking success, and significantly longer progression-free survival and overall survival. Use of enzyme as independent marker of favorable prognsis in ovarian cancer 3.4.21.118 kallikrein 8 medicine in psoriatic lesion, KLK8 modulates hyperproliferation and prevents excessive hyperkeratosis by shedding the corneocytes 3.4.21.118 kallikrein 8 medicine KLK8 overexpression suppresses tumor growth and cancer cell invasion in a mouse model in vivo. Early-stage non-small cell lung cancer patients with high KLK8 expression have a lower recurrence rate than patients with low KLK8 expression. KLK8 can be used as a prognostic marker in early-stage non-small cell lung cancer patients 3.4.21.118 kallikrein 8 medicine occurrence of two synaptic capture mechanisms for a weakly stimulated synapse to acquire persistency (i.e., neuropsin dependent and independent). Neuropsin-dependent late associativity may serve in the acquisition of nonaversive memory (e.g., inquisitive behavior) 3.4.21.118 kallikrein 8 medicine clinical value of 11 members of the tissue kallikrein family as potential biomarkers for lung cancer diagnosis are evaluated: Serum specimens from 51 patients with non-small cell lung cancer and from healthy volunteers are collected. Compared with sera from normal subjects, sera of patients with non-small cell lung cancer have lower levels of KLK5, KLK7, KLK8, KLK10, and KLK12, and higher levels of KLK11, KLK13, and KLK14. Expression of KLK11and KLK12 is positively correlated with stage. A multiparametric panel of kallikrein markers for lung cancer diagnosis is provided with relatively good accuracy 3.4.21.118 kallikrein 8 medicine imiquimod-treated skin of wild-type mice shows characteristic neutrophil microabscess formation in the epidermis, which is markedly reduced in Klk8 knockout mice. Klk8 is crucial for microabscess formation in the upper epidermis, where Klk8 is significantly involved in IL-36 expression 3.4.21.118 kallikrein 8 medicine in hepatitis B patients, both serum KLK8 protein and estimated glomerular filtration rate increase significantly after long-term telbivudine treatment. No direct correlation is found between KLK8 increase and estimated glomerular filtration rate change. Estimated glomerular filtration rate change is positively associated with post-treatment KLK8 levels following adjustment for body height 3.4.21.119 kallikrein 13 medicine gene may be involved in the pathogenesis and/or progression of breast cancer and may find applicability as cancer biomarker 3.4.21.119 kallikrein 13 medicine most salivary gland tumors show high levels of enzyme expression. Pleomorphic adenoma shows less staining than normal tissue, adenoid cystic carcinomas, polymorphous low grade adenocarcinomas and adenocarcinomas not otherwise specified stain significantly more than normal salivary gland tissue 3.4.21.119 kallikrein 13 medicine patients with ovarian carcinoma, women with enzyme-positive tumors most often have early stage disease, no residual tumor after surgery and optimal debulking success. Patients with enzyme-positive tumors have a significantly longer progression-free survival and overall survival. Use of enzyme as biomarker for ovarian carcinoma 3.4.21.119 kallikrein 13 medicine treatment of ovarian cancer cell lines secreting enzyme with an enzyme neutralizing antibody results in less migration of cells 3.4.21.119 kallikrein 13 medicine hK13 is one of the important kallikreins in skin physiology 3.4.21.119 kallikrein 13 medicine a multiparametric panel of kallikrein markers for lung cancer diagnosis with relatively good accuracy is provided 3.4.21.119 kallikrein 13 medicine although marginally significant, patients with high KLK13 expression at the mRNA or protein level have lower overall survival 3.4.21.122 transmembrane protease serine 2 medicine clinical isolates of coronaviruses HCoV-OC43 and -HKU1 prefer the cell-surface protease TMRRSS2 over endosomal cathepsins for host cell entry. Virus adaptation in cultured cells after isolation alters the route of cell entry and such modified isolates might not reflect the HCoVs of the natural world 3.4.21.122 transmembrane protease serine 2 medicine clinical isolates of human coronavirus HCoV-229E are less likely to utilize cathepsin L for host cell entry. rather, they show a preference for TMPRSS2. Amino acid substitutions R642M and N714K in the S protein of HCoV-229E clinical isolates alter their sensitivity to a cathepsin L inhibitor. After 20 passages in HeLa cells, the ability of the isolate to use cathepsin increases, caused by amino acid substitution I577S in the S protein 3.4.21.122 transmembrane protease serine 2 medicine cotransfection of mammalian cells with plasmids encoding hemagglutinin of influenza viruses and protease TMPRSS2 or human airway trypsin-like protease HAT results in hemagglutinin cleavage in situ. Transient expression of either protease in MDCK cells enables multicycle replication of influenza viruses in these cells in the absence of exogenous trypsin 3.4.21.122 transmembrane protease serine 2 medicine in Vero cells expressing TMPRSS2, large syncytia are induced by SARS-CoV infection. Lysosome-tropic reagents fail to inhibit, whereas the heptad repeat peptide efficiently inhibits viral entry into cells. Production of virus in TMPRSS2-expressing cells does not result in S-protein cleavage or increased infectivity of the resulting virus. TMPRSS2 needs to be expressed in the opposing (target) cell membrane to activate S protein rather than in the producer cell 3.4.21.122 transmembrane protease serine 2 medicine MDCK cells with inducible expression of either TMPRSS2 or protease HAT cells support growth of human and avian influenza viruses of different subtypes in the absence of exogenous trypsin. Multicycle viral replication in both cell lines is markedly suppressed in the presence of serine protease inhibitors 3.4.21.122 transmembrane protease serine 2 medicine primary prostate cancer and prostate cancer metastases. TMPRSS2 expression is significantly higher in both neoplastic prostate and in the epithelium of prostatic hyperplasia compared to normal epithelium. TMPRSS2 expression is further elevated in higher Gleason grade cancers (patterns 4 and 5) compared to pattern 3. In most high-grade cancers, TMPRSS2 is mislocalized, being expressed in the cytoplasm as well as in the cell membrane 3.4.21.122 transmembrane protease serine 2 medicine SARS spike (S) protein cleavage by TMPRSS2 decreases viral sensitivity to inhibition by neutralizing antibodies, and TMPRSS2-dependent SARS S shedding confers resistance against antibody-mediated neutralization. TMPRSS2 cleaves and activates SARS S in trans. TMPRSS2 on target cells allows efficient SARS S-driven virus-cell fusion in the presence of a lysosomotropic agent and a cathepsin inhibitor 3.4.21.122 transmembrane protease serine 2 medicine the ability of TMPRSS2 to promote prostate cancer tumor growth and metastasis is associated with increased matriptase activation and enhanced degradation of extracellular matrix nidogen-1 and laminin beta1 in tumor xenografts 3.4.21.122 transmembrane protease serine 2 medicine the spike protein of the human coronavirus EMC does not use known coronavirus receptors for host cell entry. TMPRSS2 activates the spike protein of human coronavirus EMC for cathepsin B/L-independent host cell entry. The serum from a human coronavirus EMC-infected patient contains neutralizing antibodies 3.4.21.122 transmembrane protease serine 2 medicine TMPRSS2 is necessary for the functional activation, in vitro, of both the hemagglutinin of human seasonal influenza and other Group 2 HA influenza strains 3.4.21.122 transmembrane protease serine 2 medicine TMPRSS2 protease is highly expressed in metastatic prostate cancers and promotes cancer invasion and metastasis 3.4.21.122 transmembrane protease serine 2 medicine TMPRSS2-ERG gene fusion status with prostate cancer patients is significantly associated with higher Gleason scores, higher major Gleason scores, higher minor Gleason scores, higher percentage of lethal class, more tumor area, and poor prognosis. TMPRSS2-ERG fusion status is significantly associated with an increased relative risk for prostate cancer death 3.4.21.122 transmembrane protease serine 2 medicine TMPRSS2-ERG is the most common gene fusion in prostate cancer. 74% (117/158) of the prostate adenocarcinomas analyzed were positive for the TMPRSS2-ERG and/or telomerase TERT expression. Significantly higher expression of ERG is detected in TMPRSS2-ERG-positive tumors, whereas more intense expression of SPINK1 is characteristic for the TMPRSS2-ERG negative tumors. The cases negative for both transcripts, TMPRSS2-ERG and TERT, rarely recurr and show significantly longer biochemical recurrence-free period as compared to the TMPRSS2-ERG and/or TERT-positive cases 3.4.21.122 transmembrane protease serine 2 medicine treatment of LNCaP cells with a cellular immunopurified TMPRSS2 protease induces a transient increase in intracellular calcium. This calcium mobilization is inhibited by cellular pretreatment with a specific PAR-2 antagonist and also by cellular pretreatment with suramin or 2-APB (2-aminoethoxydiphenyl borate) 3.4.21.122 transmembrane protease serine 2 medicine Vero cells constitutively expressing TMPRSS2 show larger syncytia at 18 h after infection with Middle East respiratory syndrome coronavirus MERS-CoV than after infection with other coronaviruses. The susceptibility of Vero-TMPRSS2 cells to MERS-CoV is 100fold higher than that of non-TMPRSS2-expressing parental Vero cells. Simultaneous treatment with inhibitors of cathepsin L and TMPRSS2 completely blocks virus entry into Vero-TMPRSS2 cells. A single camostat treatment suppresses MERS-CoV entry into human bronchial submucosal gland-derived Calu-3 cells by 10fold and virus growth by 270fold 3.4.22.1 cathepsin B medicine accumulation of undegraded macromolecules in lysosomes after oxidative damage are caused in part by direct protease inactivation by adduct formation with lipid peroxidation products 3.4.22.1 cathepsin B medicine enzyme is involved in neuronal cell death, particularly following ischemia 3.4.22.1 cathepsin B medicine involvement of cathepsins in the diminution of the lung antiprotease screen possibly leading to lung destruction in emphysema 3.4.22.1 cathepsin B medicine cathepsin B inhibitors have a potential in cancer chemotherapy 3.4.22.1 cathepsin B medicine cathepsin B inhibitors are effective therapeutic agents in treatment of Alzheimer's disease reducing the amyloid beta plaque load in brain regions by up to 55%, reducing the formation of amyloid beta 40 and amyloid beta 42 by 45% and 40%, and improving the memory function, overview 3.4.22.1 cathepsin B medicine cathepsin B inhibitors are expected to be useful for the treatment of inflammatory joint disease, invasion of cancer, and other diseases related to cathepsin B disorder 3.4.22.1 cathepsin B medicine inhibition of cathepsins B and L may provide a unique mechanism for selectively inducing death of neuroblastoma with limited toxicity to normal cells and tissues 3.4.22.1 cathepsin B medicine pharmacologic modulation of cathepsin activity diminishes reovirus disease severity 3.4.22.1 cathepsin B medicine cathepsin B is a target for anti-cancer therapy. RNA interference oligonucleotide shRNA-CTSB2 is the most efficient inhibition of cathepsin B at both mRNA and protein levels and results in suppressing endometrial cancer growth and development in vivo 3.4.22.1 cathepsin B medicine engineering of a mouse T7 trypsinogen mutant (D22A,K24G), which is robustly activated by cathepsin B but cannot undergo autoactivation. These studies set the stage for the generation of a preclinical mouse model of CTSB-dependent pancreatitis 3.4.22.1 cathepsin B medicine the control of cathepsin B expression may be a target for the treatment of metabolic disorders associated to an inflammatory background 3.4.22.1 cathepsin B medicine the enzyme has good antigenicity, and elicits high protection in Trichinella-infected mice, especially in the intestinal stage, a key stage for controlling infection. Therefore, TsCPB2 might be a promising vaccine candidate for controlling trichinellosis 3.4.22.1 cathepsin B medicine the enzyme is involved in tumour progression and represents a potential therapeutic target in cancer 3.4.22.1 cathepsin B medicine three dimensional structure of cathepsin B from Hordeum vulgare is predicted by using a homology modeling technique. The sequence and structure analysis reveal that the active site residues of cathepsin B from Hordeum vulgare are exactly the same to human cathepsin B. Probable involvement in the cleavage of amyloid beta peptide. Hence, the structure of cathepsin B from Hordeum vulgare can be useful to study Abeta peptide degradation in detail at the atomic level. Thus, this study might be useful to understand amyloid beta peptide degradation as well as to design alternative strategies to control Alzheimer's disease 3.4.22.2 papain medicine used for wound debridement, the removal of necrotic tissue 3.4.22.2 papain medicine used in external treatment of hard tissue, wart and scar tissue removal, acne treatment, depilation, skin cleansing treatment, inclusing in toothpaste. Papain is used in preparation of Tyr derivatives which are used for treatment of Parkinsonism and for the preparation of tetanus vaccines and immunoglobulin samples for intravenous injection 3.4.22.2 papain medicine enzyme is used for a number of biomedical applications 3.4.22.2 papain medicine papain is widely used for many medical and para-medical purposes such as to assist protein digestion in chronic dyspepsia, gastric fermentation, gastritis, removal of necrotic tissue, preparation of tyrosine derivatives for the treatment of Parkinsonism, preparation of tetanus vaccines, skin cleansing agents and acne treatment 3.4.22.2 papain medicine effects of papain and neuraminidase enzyme treatment on electrohydrodynamics and IgG-mediated agglutination of type A red blood cells. Papain treatment results in a significant reduction of the hydrodynamic permeability of the external soft glycoprotein layer of the cells, reflecting a significant decrease in soft surface layer thickness and a loss in cell surface integrity/rigidity 3.4.22.2 papain medicine entrapment of papain into a polymeric matrix in order to obtain a drug delivery system that can be used as medical device after sterilization by gamma radiation. Papain release and its activity in membranes containing 2% w/w papain in a silicone dispersion is not significantly affected by gamma irradiation 3.4.22.2 papain medicine method for internalization of monoclonal antibodies based on papain digestion followed by flow cytometry. This method can identify whether the binding monoclonal antibody has internalized into the cell, with an additional advantage of accurately quantifying the internalized monoclonal antibody without altering cell morphology after papain digestion. The methodology can facilitate understanding of the efficiency of monoclonal antibody internalization and evaluation of the targeted killing capacity of the monoclonal antibody 3.4.22.2 papain medicine study wether glucosamine modulates the immune and inflammatory responses to joint injury in organs proximal to glucosamine absorption using a papin-injected knee mouse model. Papain significantly degrades the proteoglycans in the injected knees by 2 days. Cartilage proteoglycan content is significantly higher in glucosamine-treated, papain-injected knees at Day 14. The peak concentration of serum pro-inflammatory cytokines occurrs earlier and decreases sooner in the injected, glucosamine-supplemented mice 3.4.22.2 papain medicine a potential new self-emulsifying drug delivery system with mucolytic features for oral administration is developed. Using hydrophobic ion pairing, papain can be successfully included in the system. Within all formulations papain exhibits a mucolytic effect and accelerates a higher permeation in porcine intestinal mucus. Additionally a prolonged mucosal residence confirms that upon incorporation of enzyme, self-emulsifying drug delivery systems are awarded with the ability to overcome the intestinal barrier more easily. This system can be presented as a promising carrier capable to transport a therapeutic ingredient across the mucus barrier and finally improve its bioavailability 3.4.22.2 papain medicine dental plaque is a causative factor for oral disease and a potential reservoir for respiratory infection in the elderly. Therefore, there is a critical need for the development of effective methods to remove oral biofilm. Proteases reduce oral biofilm in vivo in elderly subjects. Tablets containing actinidin remove tongue coating in elderly subjects. Oral Actinomyces biofilm is significantly reduced by the proteases papain, actinidin and trypsin. Papain and trypsin effectively digest the major fimbrial proteins, FimP and FimA, from Actinomyces. Actinidin, papain and trypsin reduce multispecies biofilm that is reconstructed in vitro. Papain and trypsin inhibit formation of multispecies biofilm in vitro 3.4.22.3 ficain medicine ficin is a potent tool for staphylococcal biofilm treatment and fabrication of novel antimicrobial therapeutics for medical and veterinary applications 3.4.22.B5 CPB protease medicine amastigote-specific cysteine peptidases of Leishmania mexicana are central to the ability of the parasite to modulate signaling vie NF-kapaB and consequently inhibit IL-12 production by mouse bone marrow-derived macrophages 3.4.22.B5 CPB protease medicine CPB isoenzymes with a few negative charge modifications provide the parasite with an array of hydrolytic activity and enzymatic adaptation to pH, salinity, and temperature that may be needed for its interaction with the mammalian host 3.4.22.B5 CPB protease medicine large preference for Pro in the P2' position for the hydrolytic activity of CPB3, which may be relevant to a role in the activation mechanism of th Leishmania mexicana 3.4.22.B5 CPB protease medicine Leishmanial cysteine protease is implicated in modulation of the host immune system to favor parasite survival and proliferation, the enzyme has vaccine potential and is involved in effecting a cell death process in the parasite 3.4.22.B5 CPB protease medicine the hybrid CPA/B is able to elicit a protective immune response against Leishmania major in the mice model 3.4.22.B5 CPB protease medicine Leishmania chagasi recombinant cysteine proteinase is potentially useful for diagnosis of canine visceral leishmaniasis, as well as for the discrimination of clinical and subclinical forms of the disease 3.4.22.B5 CPB protease medicine coupling of CPB and CPA to nanoparticles in combination with coupling of poly D,L-lactide-co-glycolic acid enhances Th1 immune response. Immunization of mice leads to significant induction of nitric oxide production by peritoneal macrophages and increase in splenocyte IFN-gamma production 3.4.22.6 chymopapain medicine is used for chemonucleolysis of damaged human intervertebral spinal discs 3.4.22.6 chymopapain medicine significantly more nucleus can be removed from a disc using a bilateral rather than a unilateral approach. A unilateral approach using rongeurs alone leads to removal of only about one-third of the nucleus. Rongeurs, followed by chymopapain, lead to removal of significantly more nucleus than when rongeurs are used alone. The most effective method is a bilateral approach using rongeurs followed by chymopapain where about three-quarters of the nucleus can be removed. This approach can create sufficient space for the implant insertion. A brush, which can be inserted through a trocar, assists in the removal of strands of nucleus that are loosened by chymopapain. Experiments are carried out on sheep spines since they are increasingly being used as models for human spines 3.4.22.6 chymopapain medicine enzyme is used for a number of biomedical applications 3.4.22.6 chymopapain medicine used for pain relief in treatment of herniated invertebral disc 3.4.22.B6 cathepsin B-like protease medicine TcoCBc1 elicits an important immune response in experimentally infected cattle. The protein is a potential therapeutic target and is a plausible antigen for Trypanosoma congolense diagnosis 3.4.22.8 clostripain medicine influence of protease inhibitors aprotinin, phenylmethylsulfonyl fluoride, L-1-chloro-3-[4-tosylamido]-7-amino-2-heptanone, and chymostatin on toxicity of Clostridium histolyticum supernatant towards HeLa cells. Aprotinin has no effect, while the other inhibitors potentiate the cytotoxic activity of Clostridium histolyticum probybly by hindering the natural defense of cells. In addition, phenylmethylsulfonyl fluoride and L-1-chloro-3-[4-tosylamido]-7-amino-2-heptanone block clostripain enzymic activity 3.4.22.8 clostripain medicine it is possible to isolate significant numbers of human islets combining collagenase only with clostripain. The supplementation with clostripain is an effective means to substantially reduce neutral protease activity, which significantly decreases survival and viability after culture 3.4.22.8 clostripain medicine neutral protease derived from Clostridium histolyticum and clostripain, in combination with collagenase derived from the same bacteria, may effectively increase the isolation efficiency of pancreatic islet without affecting the quality of islets 3.4.22.8 clostripain medicine the addition of clostripain to the enzyme blend soundly improves islet yields and transplantation rates. It gently aids pancreas digestion and maintained proper islet functionality. The addition of clostripain to the enzyme blend is implemented into standard isolation protocols at the isolation centers in Uppsala and in Oslo 3.4.22.14 actinidain medicine to isolate major kiwifruit allergens a large group of kiwi-sensitized patients with different clinical symptoms are investigated. The three major IgE-binding proteins from kiwifruit extracts are isolated and characterized. The isolated kiwifruit allergens are: actinidin Act d 1, glycosylated thaumatin-like Act d 2 and a novel 40 kDa glycoprotein designated as Act d 3.02. Specific IgE to each of the three allergens is found in over 60% of sera from kiwi-sensitized patients, and Act d 1 and Act d 2 induces positive SPT responses in over 50% of the tested patients. A significant link between IgE levels to Act d 1 and Act d 3 and anaphylaxis is uncovered. Act d 1, Act d 2 and Act d 3 are major allergens in the population studied. Severe symptoms after kiwi ingestion are associated with high IgE levels to Act d 1 and Act d 3 3.4.22.14 actinidain medicine actinidin is a biomarker of kiwifruit allergy 3.4.22.14 actinidain medicine dental plaque is a causative factor for oral disease and a potential reservoir for respiratory infection in the elderly. Therefore, there is a critical need for the development of effective methods to remove oral biofilm. Proteases reduce oral biofilm in vivo in elderly subjects. Tablets containing actinidin remove tongue coating in elderly subjects. Oral Actinomyces biofilm is significantly reduced by the proteases papain, actinidin and trypsin. Papain and trypsin effectively digest the major fimbrial proteins, FimP and FimA, from Actinomyces. Actinidin, papain and trypsin reduce multispecies biofilm that is reconstructed in vitro. Papain and trypsin inhibit formation of multispecies biofilm in vitro 3.4.22.14 actinidain medicine the enzyme increases intestinal permeability in both in vivo (mice) and in vitro (Caco-2 cell culture) models. The food allergen with intrinsic proteolytic activity can compromise the gut epithelial barrier, contributing to the sensitization process in food allergy pathogenesis 3.4.22.15 cathepsin L medicine activation of the Nipah virus fusion protein depends on a low pH value and the activity of cathepsin L in host cells 3.4.22.15 cathepsin L medicine cathepsin L expression in cardiomyocytes blunts cardiac hypertrophy through blocking of Akt/GSK3beta signaling. Constitutive cardiac over-expression of cathepsin L in mice attenuates the hypertropic response, markedly reduces apoptosis, and fibrosis 3.4.22.15 cathepsin L medicine endothelial progenitor cells of patients with type 2 diabetes reveal profoundly decreased cathepsin L expression and activity 3.4.22.15 cathepsin L medicine expression of lysosomal cathepsin L is significantly increased in atherosclerotic plaques with formation of the necrotic core and rupture of the cap. In those plaques, cathepsin L is associated mainly with CD68-positive macrophages, whereas significant lower levels of smooth muscle cell actin are detected. The expression of cathepsin L in these plaques is also correlated with apoptosis and the stress protein ferritin. Plaques from symptomatic patients show greater increased levels of cathepsin L than those from asymptomatic patients. Human monocyte-derived macrophages from coronary artery disease patients show significantly higher levels of cathepsin L, cellular lipids and apoptosis versus cells from matched healthy donors. 7beta-hydroxycholesterol significantly enhances cathepsin L in cells from healthy donors but not in cells from coronary artery disease patients. Macrophage apoptosis is significantly correlated with expression of cathepsin L in cell nuclei and membranes 3.4.22.15 cathepsin L medicine in patients with colorectal cancer, the protease antigen levels are significantly higher compared with other groups. At the time of clinical detection proteases cathepsin B, cathepsin L and urokinase-type plasminogen activator and its inhibitor are more sensitive indicators for colorectal cancer than commonly used tumor markers. Determination of cathepsin B, cathepsin L and urokinase-type plasminogen activator and its inhibitor have a major prognostic impact in patients with colorectal cancer 3.4.22.15 cathepsin L medicine in vivo a tumor hypoxic environment up-regulates cathepsin L expression which promotes tumor progression 3.4.22.15 cathepsin L medicine infection of HL-60 cells with Anaplasma phagocytophilum results in elevated cathepsin L activity and the proteolysis of CDP. Blocking the action of cathepsin L with a chemical inhibitor or siRNA causes a marked reduction in the degree of Anaplasma phagocytophilum infection. Increasing cathepsin L activity is a strategy used by Anaplasma phagocytophilum to alter CDP activity and thereby globallly influence neutrophil function 3.4.22.15 cathepsin L medicine mice lacking the activity of cathepsin B, cathepsin L, or cathepsin S are similar to wild-type in their ability to control the growth and dissemination of Mycobacterium tuberculosis 3.4.22.15 cathepsin L medicine serum cathepsin L levels are significantly higher in patients with coronary heart disease than in those without coronary heart disease. Patients with unstable angina pectoris have higher serum cathepsin L levels than those with stable angina pectoris. Of patients with acute coronary syndrome, those with acute myocardial infarction have higher serum cathepsin L levels than those with unstable angina pectoris, and patients with previous myocardial infarction have the highest levels. Serum cathepsin L associates positively with number of coronary branch luminal narrowings, Gensini scores, high-sensitivity C-reactive protein, fasting glucose, and cigarette smokers, but inversely with high-density lipoprotein and apolipoprotein A1 3.4.22.15 cathepsin L medicine survival of patients with colorectal cancer is inversely associated with staining intensity in the epithelial cytoplasm and stromal nuclei. In different colorectal cell lines and in vivo tumors, pro- and active cathepsin L isoforms are present in both the cytoplasm and nuclear samples, with pro-cathepsin L at 50 kDa and active cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions show cathepsin L activity 3.4.22.15 cathepsin L medicine treatment of isolated bovine coronary arteries with cathepsin L markedly attenuates endothelium-dependent vasodilator responses to bradykinin or A23187 by 56% and 69%, respectively. The inhibitory effect of cathepsin L on endothelium-dependent vasodilator responses can be significantly reversed by pre-incubation of the arteries with O2- scavenger, Tiron, or neutralizing anti-endostatin antibody. Cathepsin L dose-dependently increases endostatin production in coronary arteries. Cathepsin L decreases bradykinin- and A23187-induced NO levels in the intact endothelium, but it has no effect on Ca2+ response to these vasodilators. Cathepsin L-induced reduction of NO is restored by the pretreatment of an anti-endostatin antibody. Cathepsin L increases O2- production which can be markedly attenuated by the NAD(P)H oxidase inhibitors, apocynin or anti-endostatin antibody 3.4.22.15 cathepsin L medicine cathepsin L inhibition in combination with conventional chemotherapy is a promising therapy in cancer treatment 3.4.22.15 cathepsin L medicine cathepsin L inhibition not only reverses but also prevents the development of drug resistance to doxorubicin, tamoxifen, imatinib, trichostatin A, and flutamide 3.4.22.15 cathepsin L medicine cathepsin L is a potential biomarker for prognosis of nasopharyngeal carcinoma and contributes to nasopharyngeal carcinoma metastasis. Patients with overexpression of cathepsin L in tumor tissue have worse 5-year survival than those without such expression patter 3.4.22.15 cathepsin L medicine cathepsin L is a target in the treatment of patients with metastatic bone disease 3.4.22.15 cathepsin L medicine targeted expression of the cytotoxic cathepsin L splice variant DELTActsl is useful in management of cancer 3.4.22.15 cathepsin L medicine the cathepsin L/total protein ratio is a useful index of the skin conditions in humans 3.4.22.15 cathepsin L medicine subcutaneous injections of recombinant pro-enzyme of Fasciola gigantica in mice elicit high levels of protection against challenge infections with the Fasciola gigantica metacercariae 3.4.22.15 cathepsin L medicine the enzyme is a target for vaccine and chemotherapy for controlling Fasciola gigantica infection 3.4.22.15 cathepsin L medicine treatment with cathepsin L inhibitors significantly reduces the replication of caliciviruses 3.4.22.16 cathepsin H medicine tumor specific increase in cathepsin H antigen may be useful marker of tumor progression in central nervous system neoplasms 3.4.22.16 cathepsin H medicine enzyme activity, immunoreactivity, and mRNA in most basal cell carcinomas are higher than in normal skin. Reactive cells are located between and around tumor nodules, but not in tumor nests. Enzyme in peritumoral cells may either promote invasion of the tumor cells by degradation of the extracellular matrix or may reflect an elevated activity of the surrounding immunological cells 3.4.22.16 cathepsin H medicine enzyme from meningogioma shows a 3.5fold increased vmax-value compared to normal tissue, and a 1.3fold decrease in KM-value. Molecular weight of tumor enzyme is decreased 3.4.22.B24 calpain 4 medicine Capn4 significantly correlates with invasive phenotype of hepatocellular carcinoma (HCC). Univariate and multivariate analyses indicates that Capn4 is an independent prognostic factor for recurrence and survival of HCC patients 3.4.22.B24 calpain 4 medicine calpain-4 expression in tumor samples of 174 gastric cancer patients. Calpain-4 is generally increased in gastric cancer cell lines and primary tumor tissues. High expression of calpain-4 is positively associated with vessel invasion, lymph node metastasis, and advanced tumor node metastasis stage. Calpain-4 is an independent prognostic factor for poor prognosis 3.4.22.B25 calpain 5 medicine CAPN5 plays a role in polycystic ovary syndrome susceptibility in humans. The haplotypes H (GGCA) and I (GGTG) are overrepresented in patients when compared with controls. The presence of familial antecedents of obesity and essential hypertension in polycystic ovary syndrome women is associated with a non-random distribution of CAPN5 haplotypes. Association between CAPN5 gene and polycystic ovary syndrome patients with amenorrhoea and aggregation of diabetes mellitus 3.4.22.B25 calpain 5 medicine hepatitis C uses the membrane protein CD81 to invade human liver cells. Calpain-5 and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene CBLB form a complex with CD81 and support hepatitis C virus entry. Calpain-5 and CBLB are required for a post-binding and pre-replication step in the hepatitis C virus life cycle. Knockout of calpain-5 and CBLB reduces susceptibility to all tested hepatitis C virus genotypes 3.4.22.26 cancer procoagulant medicine enzyme has potential as a sensitive and early tumor marker 3.4.22.26 cancer procoagulant medicine cancer proagulant plays an important role in tumour progression, so immunisation with cancer proagulant can reduce the risk of development of malignant disease 3.4.22.B26 calpain 6 medicine calpain-6 is a therapeutic target in chemoresistant osteosarcoma 3.4.22.B26 calpain 6 medicine calpain-6 is a possible therapeutic target in chemoresistant osteosarcoma 3.4.22.B26 calpain 6 medicine calpain-6 expression is associated with cancer stem cell features. Calpain-6 levels are especially high in tumors that have been successfully propagated in mouse to establish patient-derived xenografts. Calpain-6 levels are increased by hypoxia in vitro and calpain-6 is detected within hypoxic areas in tumors. Calpain-6 expression depends on the stem cell transcription network that involves Oct4, Nanog, and Sox2 and is activated by hypoxia. Calpain-6 expression in sarcomas inversely correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia-dependent prevention of senescence entry and also promotion of autophagic flux 3.4.22.B26 calpain 6 medicine calpain-6 expression is associated with cancer stem cell features. In mouse models of bone sarcoma, calpain-6-expressing cells have unique tumor-initiating and metastatic capacities. Calpain-6 levels are especially high in tumors that have been successfully propagated in mouse to establish patient-derived xenografts. Calpain-6 levels are increased by hypoxia in vitro and calpain-6 is detected within hypoxic areas in tumors. Calpain-6 knockdown blocks tumor development in mouse and induces depletion of the cancer stem cell population. Calpain-6 expression depends on the stem cell transcription network that involves Oct4, Nanog, and Sox2 and is activated by hypoxia. Calpain-6 expression in sarcomas inversely correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia-dependent prevention of senescence entry and also promotion of autophagic flux 3.4.22.27 cathepsin S medicine - 3.4.22.27 cathepsin S medicine cathepsin S is a potential therapeutic target for regulation of major histocompatibility complex class II immune responses, possibly resulting in treatments for autoimmune diseases and allergic asthma 3.4.22.27 cathepsin S medicine the inhibitor JNJ 10329670 is a candidate for immunosuppressive therapy of allergies and autoimmune diseases, completely reversible inhibition 3.4.22.27 cathepsin S medicine tear cathepsin S serves as a candidate biomarker for Sjögren's Syndrome 3.4.22.27 cathepsin S medicine Cat-S or PAR2 inhibition might be a strategy to prevent microvascular disease in diabetes and other diseases 3.4.22.27 cathepsin S medicine cathepsin S activation of PAR-2 may represent a potential therapeutic target for amelioration of ocular surface inflammation in Sjögren's syndrome patients 3.4.22.28 picornain 3C medicine the enzyme is essential for viral replication and infectivity and represents a target for the development of antiviral drugs 3.4.22.28 picornain 3C medicine 3Cpro as an attractive target for antiviral drugs 3.4.22.28 picornain 3C medicine attractive target for antiviral drugs 3.4.22.28 picornain 3C medicine conservation of critical amino acid residues in 3C protease and the potent, broad-spectrum activity of rupintrivir highlight the advantage of 3C protease as an antiviral target 3.4.22.28 picornain 3C medicine enteroviruses use a dual strategy for host translation shutoff, requiring cleavage of poly(A)-binding protein by 3Cpro and of translation iniation factor 4GI by 2Apro, inhibition of endogenous mRNA translation by 3Cpro in HeLa cells is independent of translation iniation factor 4GI or translation iniation factor 4GI cleavage 3.4.22.28 picornain 3C medicine foot-and mouth disease virus 3Cpro plays a vital role in virus replication, the enzyme is an attractive target for antiviral drugs 3.4.22.28 picornain 3C medicine poliovirus-encoded nonstructural polypeptide 2C can negatively regulate the viral protease 3Cpro-mediated cleavage of transcription factor cyclic AMP-responsive element binding protein in vitro 3.4.22.B28 calpain 8 medicine calpain-9 is generally decreased in gastric cancer cell lines and primary tumor tissues, while calpain-8 expression is not significantly altered. Calpain-9 induces cell cycle arrest in the G1 phase and cellular apoptosis in vitro, and it attenuates the growth of subcutaneous tumor xenografts in vivo. Low expression of calpain-9 is positively associated with male sex, late T stage, lymph node metastasis, and advanced TNM stage (tumor, node, metastasis). Calpain-9 is an independent prognostic factor for poor prognosis, and combining calpain-9 with TNM stage generates a better predictive model for patient outcomes 3.4.22.B28 calpain 8 medicine calpain-9 is generally decreased in gastric cancer cell lines and primary tumor tissues, while calpain-8 expression is not significantly altered. Calpain-9, but not calpain-8, induces cell cycle arrest at the G1 phase and cellular apoptosis in gastric cancer cells 3.4.22.B29 calpain 9 medicine differential regulation of calpain 9 plays a role in hypertensive target organ damage 3.4.22.B30 calpain 10 medicine calpain-10 is the first diabetes gene that can be identified through a genome scan 3.4.22.B30 calpain 10 medicine glucose-tolerant but not glucose-intolerant individuals upregulate their CAPN10 mRNA levels in response to prolonged exposure to fat 3.4.22.B30 calpain 10 medicine calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians 3.4.22.B30 calpain 10 medicine type 2 diabetes mellitus patients with the SNP-43 G-allele have 4.6fold more CAPN10 transcripts compared to subjects with the A-allele. The mRNA half-life of this transcript in 293T cells (SNP-43 G/G) and Jurkat cells (SNP-43 A/A) is of 8 h. In type 2 diabetes mellitus subjects the G-allele increases the CAPN10 mRNA levels. It is proposed that a defective CAPN10 pre-mRNA processing is responsible for the decreased levels of SNP-43 A-allele transcripts in peripheral white cells of healthy and T2D individuals 3.4.22.B30 calpain 10 medicine 111/121 diplotype of calpain-10 is associated with the risk of polycystic ovary syndrome in Korean women 3.4.22.B30 calpain 10 medicine CAPN10 gene variants rs3792267, rs3749166 and rs5030952 may affect type 2 diabetes mellitus susceptibility in the Irish population 3.4.22.B30 calpain 10 medicine genetic variation in calpain 10 (the minor allele of single nucleotide polymorphism-43 (rs3792267) in intron 3) is associated with increased risk of pancreatic cance among smokers 3.4.22.B30 calpain 10 medicine the 2111 haplotype of calpain-10 with gene polymorphisms SNP-44 (rs2975760), -43 (rs3792267), -19 (rs3842570), and -63 (rs5030952) is associated with type 2 diabetes mellitus in an Asian Indian population in Southern India 3.4.22.B30 calpain 10 medicine the calpain-10 single nucleotide polymorphism-63 (rs5030952C>T) and 1-1-2-haplotype (derived from SNP-43, SNP-19 and SNP-63) are associated with posttransplant diabetes mellitus 3.4.22.B30 calpain 10 medicine the CAPN10 gene may play an important role in the pathogenesis of impaired fasting glucose/impaired glucose tolerance in essential hypertension patients 3.4.22.B30 calpain 10 medicine there is no association between single nucleotide polymorphisms of the CAPN10 gene and susceptibility to polycystic ovary syndrome or related traits in Turkish adolescent girls 3.4.22.B30 calpain 10 medicine the enzyme is a potential target for the development of drug therapies for the treatment of hypertension 3.4.22.32 Stem bromelain medicine oral bromelain may potentially modify inflammation within the gastrointestinal tract via local proteolytic activity within the colonic microenvironment 3.4.22.32 Stem bromelain medicine the complex between stem bromelain and polyclonal Fab* monomer can serve as a model with potential in vivo and industrial application especially in homogenous reaction phases and development of subunit vaccines owing to preponderance of hydrophobic interaction and better diffusion potential of Fab' than of intact IgG 3.4.22.32 Stem bromelain medicine bromelain has antitumoral activity 3.4.22.32 Stem bromelain medicine bromelain shows antitumorigenic potential by inducing apoptosis-related proteins along with inhibition of nuclear factor-kappa B driven cyclooxygenase-2 expression by blocking the mitogen-activated protein kinase and Akt/protein kinase B signaling in 7,12-dimethylbenz(a)anthracene-12-O-tetradecanoylphorbol-13-acetate-induced mouse skin tumors 3.4.22.32 Stem bromelain medicine stem bromelain triggers an Akt-dependent survival pathway in the heart, revealing a mechanism of cardioprotective action and a potential therapeutic target against ischemia/perfusion injury 3.4.22.32 Stem bromelain medicine bromelain from pineapple stem shows therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease, mechanism, overview. Bromelain primary long-term effect is abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion are correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 3.4.22.32 Stem bromelain medicine bromelain possesses anti-inflammatory activity and reduces blood viscosity, prevents the aggregation of blood platelets, and improves ischemia-reperfusion injury, I/R, in a skeletal muscle model in adult Sprague-Dawley rats. The enzyme increases phosphorylation of Akt in rat heart both in the cytosolic and the nuclear fraction following I/R 3.4.22.32 Stem bromelain medicine effects of orally administered bromelain in an ovalbumin-induced murine model of acute allergic airway disease in female C57BL/6J mice, bromelain causes decreased methacholine sensitivity, reduction in bronchoalveolar lavage eosinophils and interleukin-13 concentrations, as well as of CD19+ B cells and CD8+ T cells, as compared with controls, overview. Bromelain modulates lung lymphocytes during acute asthma 3.4.22.32 Stem bromelain medicine bromelain has anti-cancer activity, as well as antithrombotic, fibrinolytic, antiedematous, and burn debridement properties 3.4.22.32 Stem bromelain medicine the nonnative form of SBM shows only a fraction of the native protein's enzymatic activity but is more effective at inhibiting cell growth and displays better antitumorigenic properties than native SBM 3.4.22.32 Stem bromelain medicine bromelain relieves osteoarthritis. Bromelain is used as an adjuvant therapeutic approach in the treatment of chronic inflammatory, malignant, and autoimmune diseases. Bromelain prevents or minimizes the severity of angina pectoris and transient ischemic attack. Bromelain influences blood coagulation by increasing the serum fibrinolytic ability and by inhibiting the synthesis of fibrin. Bromelain counteracts some of the effects of certain intestinal pathogens like Vibrio cholera and Escherichia coli, whose enterotoxin causes diarrhea. The anticancerous activity of bromelain is due to its direct impact on cancer cells and their microenvironment, as well as on the modulation of immune, inflammatory, and haemostatic systems. Bromelain is used for treating acute inflammation and sports injuries. Bromelain applied as a cream (35% bromelain in a lipid base) can be beneficial for debridement of necrotic tissue and acceleration of healing 3.4.22.32 Stem bromelain medicine bromelain exhibits various fibrinolytic, anti-edematous, anti-thrombotic, and anti-inflammatory activities supporting its application for many therapeutic benefits. Effects of bromelain on the pro-wound healing activities and the regenerative properties of mesenchymal stem cells. The combined use of bromelain and dexamethasone sodium phosphate stimulated the pro-wound healing activities and the regenerative properties of mesenchymal stem cells better than bromelain and dexamethasone alone 3.4.22.32 Stem bromelain medicine bromelain has gained wide acceptance and compliance as a phytotherapeutical drug. Cysteine proteases in pineapple (Ananas comosus) plants are phytotherapeutical agents that demonstrate anti-edematous, anti-inflammatory, anti-thrombotic and fibrinolytic activities 3.4.22.32 Stem bromelain medicine potential of the stem bromelain to be developed as an active compound for lung cancer therapy because of its high anti-proliferation and apoptosis-induction activity in A549 cells 3.4.22.B32 calpain 12 medicine in a patient with a paternal missense mutation (c.1511C>A; p.P504Q) and a maternal deletion due to activation of a cryptic splice site in exon 9 of the gene (c.1090_1129del; p.Val364Lysfs*11), filaggrin expression is almost absent in the skin 3.4.22.33 Fruit bromelain medicine bromelain can be used as a phytotherapy agent in several aspects, overview 3.4.22.33 Fruit bromelain medicine bromelain exhibits various fibrinolytic, anti-edematous, antithrombotic, and anti-inflammatory activities supporting its application for many therapeutic benefits. Effects of bromelain on the pro-wound healing activities and the regenerative properties of mesenchymal stem cells. The combined use of bromelain and dexamethasone sodium phosphate stimulated the pro-wound healing activities and the regenerative properties of mesenchymal stem cells better than bromelain and dexamethasone alone 3.4.22.33 Fruit bromelain medicine bromelain has gained wide acceptance and compliance as a phytotherapeutical drug. Cysteine proteases in pineapple (Ananas comosus) plants are phytotherapeutical agents that demonstrate antiedematous, anti-inflammatory, anti-thrombotic and fibrinolytic activities 3.4.22.34 Legumain medicine studies on a functional role of legumain in atherogenesis 3.4.22.34 Legumain medicine since recombinant legumain-1 needs trans-activation through a cathepsin, it is probably involved in an enzyme cascade and therefore remains interesting as a candidate in a multi-component vaccine 3.4.22.B35 calpain 15 medicine biomarkers proposed for stroke diagnosis include tissue leakage metalloproteins such as calpain-15, titin (isoform 3), and tropomyosin alpha-4 chain. Metalloproteins, such as selenoprotein P or glutathione peroxidase, are identified in all stroke type groups 3.4.22.36 caspase-1 medicine ICE activity is a possible target for fighting excessive inflammatory conditions 3.4.22.36 caspase-1 medicine the caspase-1/IL-1beta signaling pathway plays an important role in diabetes-induced retinal pathology, and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy 3.4.22.37 gingipain R medicine development of structure-based inhibitors for treatment of periodontal diseases 3.4.22.37 gingipain R medicine development of potent, gingipain-specific inhibitors might be a helpful tool in a therapeutic strategy to prevent or treat periodontal disease 3.4.22.38 cathepsin K medicine cathepsin K immunodetection may be a valuable adjunct in the correct classification of pulmonary adenocarcinomas, especially in small sclerosing bronchioloalveolar carcinomas, especially in small sclerosing bronchioloalveolar carcinomas and mixed adenocarcinoma subtypes with minimal infiltrative growth 3.4.22.38 cathepsin K medicine cathepsin K is an attractive target for the development of therapies to treat osteoporosis 3.4.22.38 cathepsin K medicine the serum level of cathepsin K could serve as a marker for fracture preduction and bone mineral density. The correlation between cathepsin K concentration in subjects without fractures and in those with multiple nontraumatic fractures are statistically significant. The cathepsin K levels of controls and patients with osteoporosis are significantly different 3.4.22.38 cathepsin K medicine cathepsin K is linked to the pathogenesis of osteoporosis, arthritis, cardiovascular and respiratory diseases 3.4.22.38 cathepsin K medicine cathepsin K is shown to play an essential role in rheumatoid arthritis, osteoarthritis, atherosclerosis, lung inflammation, amyloidosis, gaucher disease and obesity 3.4.22.38 cathepsin K medicine catK plays an important role in melanoma invasion and metastasis by mediating intracellular degradation of matrix proteins after phagocytosis. Clinical use of catK inhibitors may be promising for the treatment of melanoma 3.4.22.38 cathepsin K medicine it is shown that cathepsin K acts as a potent kinin-degrading enzyme in bloodstream. Contrary to cathepsin L, cathepsin K attenuates kallikrein-induced decrease of rat blood pressure, and reduces the hypotensive effect of bradykinin in a dose-dependant manner 3.4.22.38 cathepsin K medicine it is suggested that cathepsin K plays an important role in the homeostasis of the dermal extracellular matrix and the dynamic equilibrium between matrix synthesis and proteolytic degradation, by counteracting deposition of matrix proteins during scar formation with its matrix-degrading activity 3.4.22.38 cathepsin K medicine one genetic disorder is traced to cathepsin K: peridontopathia. Osteoblasts from these patients accumulate undigested collagen fibrils. Nonsense, missense and stop codon mutations have been shown in patients 3.4.22.38 cathepsin K medicine the results suggest that cathepsin K plays an important role in the immune system and serves as a valid therapeutic target in autoimmune diseases 3.4.22.38 cathepsin K medicine inhibition of CTSK activity may decrease the risk of breast tumor progression 3.4.22.38 cathepsin K medicine introduction of the enzyme, influencing the bone resorption, into bones might be helpful to stimulate and/or induce bone formation mechanisms, overview 3.4.22.38 cathepsin K medicine because excessive bone remodeling is a key element in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders, cathepsin K is a potential target for therapeutic intervention 3.4.22.38 cathepsin K medicine cathepsin K is a marker of osteoclastic activity in periodontal disease 3.4.22.38 cathepsin K medicine cathepsin K is a target for the pharmacological treatment of osteoporosis 3.4.22.38 cathepsin K medicine cathepsin K is associated with skeletal and cardiovascular disorders, cathepsin K is a pharmaceutical industry target for treatment of osteoporosis 3.4.22.38 cathepsin K medicine CTSK inhibitors are a potential novel therapeutic option to decrease squamous cell carcinoma progression 3.4.22.38 cathepsin K medicine determination of cathepsin K and Cystatin C concentrations has no clinical significance in the prognosis of the survival time in lung cancer 3.4.22.38 cathepsin K medicine serum cathepsin K is a marker of bone metabolism in postmenopausal women treated with alendronate 3.4.22.38 cathepsin K medicine treatment with the potent cathepsin K inhibitor relacatib preserves cortical and trabecular bone mass in ovariectomized monkeys 3.4.22.38 cathepsin K medicine cathepsin K inhibitors may aid in the management of canine osteosarcoma-related malignant osteolysis 3.4.22.38 cathepsin K medicine human cathepsinK is a major drug target for the treatment of osteoporosis 3.4.22.38 cathepsin K medicine activation of cathepsin K may be a promising strategy to prevent homing of therapy-resistant glioma stem-like cells (GSLCs) in niches and thus render these cells sensitive to chemotherapy and radiation 3.4.22.38 cathepsin K medicine cathepsin K is a drug target for skeletal disorders 3.4.22.38 cathepsin K medicine selective inhibition of cathepsin K has a therapeutic potential for diseases associated with bone loss and osseous inflammation, such as osteoarthritis, periodontitis, and osteoporosis. Cathepsin K inhibition may have anabolic effects on bone and cartilage regeneration that may be explained as a feedback response to cathepsin K depletion. The use of cathepsin K inhibition to reduce inflammation and associated bone resorption in equine osseous disorders may offer advantages to other therapeutics 3.4.22.39 adenain medicine NO may be a useful antiadenovirus agent, inhibits adenovirus replication by targeting the adenovirus proteinase. Treatment of infectious virus by 2,2'-(hydroxynitrosohydrazono)bis-ethaneamine dramatically decreases viral infectivity 3.4.22.39 adenain medicine required for the synthesis of infectious virus and is a target for antiviral therapy 3.4.22.40 bleomycin hydrolase medicine - 3.4.22.40 bleomycin hydrolase medicine is thought to be the major cause of tumor cell resistance to bleomycin chemotherapy 3.4.22.40 bleomycin hydrolase medicine ectopic expression of enzyme alters processing of amyloid precursor protein and increases significantly release of beta-amyloid 3.4.22.40 bleomycin hydrolase medicine ectopic expression of enzyme increases the secretion of amyloid precursor protein, increase is blocked in mutant C73S 3.4.22.40 bleomycin hydrolase medicine patient study, patients with testicular germ-cell cancer treated with bleomycin-containing chemotherapy, response to chemotherapy determined by gene polymorphisms involved in metabolism of cytotoxic drugs analyzed, importance for risk classification and selection for alternative treatment strategies suggested 3.4.22.40 bleomycin hydrolase medicine the bleomycins (BLMs) are widely used in combination therapies for the treatment of various cancers. Dose-dependent and cumulative pulmonary toxicity is the major cause of BLM-associated morbidity, limiting the broad uses of BLMs as anticancer drugs. Opportunities to overcome bleomycin-induced pulmonary toxicity in chemotherapies, potentially by exploring BLM B2 as the preferred congener, engineering designer bleomycins with optimized activity for recombinant human bleomycin hydrolase (rhBLMH), or co-administrating rhBLMH directly into the lung as a potential protein therapeutic 3.4.22.41 cathepsin F medicine the enzyme is immunogenic and a possible target for development of vaccines for teladorsagiosis 3.4.22.43 cathepsin V medicine studies on the role of cathepsin V and cystatin C in the pathophysiology aortic stenosis 3.4.22.43 cathepsin V medicine mammalian protease cathepsin V is a therapeutic target to inhibit TLR4-mediated inflammation induced by extracellular high-mobility group box 1 (HMGB1) (disulfide form). HMGB1 (disulfide form), via activation of toll-like receptor 4 (TLR4)-dependent signaling, is a strong driver of pathologic inflammation in both acute and chronic conditions. The mechanism of action involves a direct interaction between cathepsin V with TLR4 and its adaptor protein MyD88 3.4.22.47 gingipain K medicine development of structure-based inhibitors for treatment of periodontal diseases 3.4.22.47 gingipain K medicine results indicate that degradation of apoB-100 by Rgp but not Kgp plays a crucial role in the promotion of atherosclerosis by Porphyromonas gingivalis infection 3.4.22.47 gingipain K medicine development of potent, gingipain-specific inhibitors might be a helpful tool in a therapeutic strategy to prevent or treat periodontal disease 3.4.22.48 staphopain medicine studies on ability of staphopain B of Staphylococcus aureus to elicit and maintain a chronic inflammatory state, staphopain B suggested to mediate recruitment of specialized host cells, including immunoregulatory plasmacytoid dendritic cells and/or macrophages 3.4.22.49 separase medicine the results show that separase might be a tumor supressor gene 3.4.22.49 separase medicine due to the oncogenic activity of cohesin protease, separase in human cancer cells, modulation of separase enzymatic activity could constitute a new therapeutic strategy for targeting resistant, separase-overexpressing aneuploid tumors 3.4.22.B49 cathepsin L1 medicine potential in the development of first generation liver fluke vaccines. Vaccine trials in both sheep and cattle with purified native FheCL1 and FheCL2 show that the enzymes can induce protection, ranging from 33-79%, to experimental challenge with metacercariae of Fasciola hepatica, and very potent anti-embryonation/hatch rate effects that would block parasite transmission 3.4.22.B49 cathepsin L1 medicine diagnostic ability to detect human IgG antibodies against Fasciola gigantica cathepsin L1 by peptide-based ELISA, serodiagnosis of human fascioliasis, which is rapid, cheap and easy to produce 3.4.22.B49 cathepsin L1 medicine the cathepsin L1 gene may be used for DNA vaccination, recombinant protein derived from the gene can be used for serological diagnostics against Fasciola hepatica in Turkey 3.4.22.B49 cathepsin L1 medicine enteral vaccination of rats against Fasciola hepatica using recombinant cysteine proteinase (cathepsin L1). The mature CPFhW protein is the enzyme secreted by Fasciola hepatica with which the host organism has contact. This can explain why immunisation with this antigen resultes in best protection in challenged animals, especially in comparison to the immature form of the CPFhW protein. Substantial protection can be obtained when the antigen is given with food. Oral administration of the antigen does not lead to decreasing of the level of protection compared with intragastric administration 3.4.22.B49 cathepsin L1 medicine cattle can be protected against a natural infection of Fasciola hepatica by vaccination with recombinant cathepsin L1 3.4.22.B49 cathepsin L1 medicine mice immunized with recombinant CL1 show a decrease of 21.8% in Schistosoma mansoni burden 3.4.22.B49 cathepsin L1 medicine recombinant cathepsin L1 is a vaccine for fasciolosis in goats 3.4.22.B49 cathepsin L1 medicine a leucine aminopeptidase-cathepsin L1 chimeric protein may be used as a diagnostic tool for detection of antibodies against Fasciola hepatica in bovine sera and as an immunogen to induce protection against bovine fasciolosis 3.4.22.B49 cathepsin L1 medicine a monoclonal antibody (MoAb) against recombinant Fasciola gigantica cathepsin L1H (rFgCatL1H) is produced by hybridoma technique using spleen cells from BALB/c mice immunized with recombinant proFgCatL1H (rproFgCatL1H). This MoAb is an immunoglobulin (Ig)G1 with kappa light chain isotype. The MoAb reacts specifically with rproFgCatL1H, the native FgCatL1H at a molecular weight (MW) 38-48 kDa in the extract of whole body (WB) of metacercariae and newly excysted juvenile (NEJ) and cross-reacted with rFgCatL1 and native FgCatLs at MW 25 to 28 kDa in WB of 2- and 4-week-old juveniles, adult, and adult excretory-secretory (ES) fractions by immunoblotting and indirect ELISA. It does not cross-react with antigens in WB fractions from other parasites. FgCatL1H and its MoAb may be used for immunodiagnosis of both early and late fasciolosis in ruminants and humans 3.4.22.B49 cathepsin L1 medicine recombinant proFgCatL1H protein expressed from Pichia pastoris is mixed with Freund's adjuvants and used to subcutaneously immunize mice, the mice are then challenged with metacercariae of Fasciola gigantica. The percentage of worm protection in the rproFgCatL1H-vaccinated mice compared to the non-immunized and adjuvant control mice are approximately 62.7% and 66.1%, respectively. The levels of IgG1 and IgG2a in the immune sera are shown to be strongly correlated with the numbers of worm recovery, and the correlation coefficient is higher for IgG1. The levels of serum aspartate amino-transferase and alanine transaminase are significantly lower in the sera of rproFgCatL1H-vaccinated mice than in the infected control mice indicating a lower degree of liver damage 3.4.22.B49 cathepsin L1 medicine vaccination of mice by subcutaneous injection with recombinant proFgCatL1 and recombinant mature FgCatL1 combined with Freund's adjuvant. Two weeks after the second boost, mice are infected with 15 metacercariae by the oral route. The level of protection of rproFgCatL1 and rmatFgCatL1 vaccines is estimated to be 39.1-41.7% and 44.9-47.2% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. Antibodies in the immune sera of vaccinated mice are shown by immunoblotting to react with the native FgCatL1 in the extract of newly excysted juveniles (NEJ), 4-week-old juveniles, and the excretory-secretory products of 4 week-old juveniles. rFgCatL1 has a potential as a vaccine candidate against Fasciola gigantica in mice, and might also be effective in ruminants 3.4.22.B50 papain-like proteinase 2 medicine antiviral therapy 3.4.22.B50 papain-like proteinase 2 medicine PLpro is an important target for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV 3.4.22.B50 papain-like proteinase 2 medicine viral strategy to modulate the host cell ubiquitination machinery to its advantage 3.4.22.B50 papain-like proteinase 2 medicine the enzyme is a potential targets for antiviral drug development 3.4.22.B50 papain-like proteinase 2 medicine vaccination of Shetland mares, either with deubiquitinase DUB-positive or DUB-negative recombinant equine arteritis virus. Upon challenge with the virulent KY84 strain of equine arteritis virus, both vaccine viruses proved to be replication competent in vivo. The DUB-negative virus provides a similar degree of protection against clinical disease as its DUB-positive parental counterpart. A possible improvement due to inactivation of PLP2 DUB activity could not be detected under these experimental conditions 3.4.22.51 cruzipain medicine CatL-like sequences are excellent targets for diagnosis and genotyping of Trypanosoma rangeli by PCR 3.4.22.51 cruzipain medicine cruzain is a primary cysteine protease expressed by the protozoan parasite Trypanosoma cruzi during Chagas disease infection, and thus, the development of inhibitors of this protein is a promising target for designing an effective therapy against the disease 3.4.22.51 cruzipain medicine cruzipain inhibition is a chemotherapeutic approach for Chagas disease because of its trypanocidal activity and due to the inhibitory effect on TGF-beta activation 3.4.22.52 calpain-1 medicine protein phosphatase 2A functions as a physiological calpain phosphatase to directly dephosphorylate mu-calpain, which leads to decreased calpain activity and suppression of migration and invasion of human lung cancer cells. Therapeutic activation of protein phosphatase 2A to dephosphorylate calpain by enhancing ceramide production may have clinical relevance for the treatment of cancer metastasis 3.4.22.52 calpain-1 medicine role for the mu-calpain isoform in the hypermeability of the diabetic endothelium. mu-calpain is the molecular target of the endothelial protective action of pharmacological calpain inhibition in vivo 3.4.22.52 calpain-1 medicine calpain and calpain inhibition is a therapeutic tool in Parkinson’s disease 3.4.22.52 calpain-1 medicine calpain inhibition attenuates endotoxin-induced diaphragm weakness, suggesting that such inhibitors may be a potential treatment to improve respiratory function in infected patients 3.4.22.52 calpain-1 medicine calpain-1 activation is important in the development of diabetic cardiomyopathy and thus represents a potential therapeutic target for diabetic heart diseases 3.4.22.52 calpain-1 medicine calpain1 is a therapeutic target in HER2-positive breast cancer 3.4.22.52 calpain-1 medicine manipulating calpain activity by calpain inhibitor SNJ-1945 is a therapy for management of pathological angiogenesis, such as that occurring in proliferative retinopathy and age-related macular degeneration with neovascularization 3.4.22.52 calpain-1 medicine mu-calpain can serve as an predictor of muscle injury 3.4.22.52 calpain-1 medicine mu-calpain is a marker of tumor aggressiveness and is apotential target for limiting development of rhabdomyosarcoma tumor as well as their metastatic behavior 3.4.22.52 calpain-1 medicine the inhibition of calpain is a potential therapeutic intervention for lissencephaly 3.4.22.52 calpain-1 medicine calpain-1 regulates platelet hyperactivity in sickle mice, and may offer a viable pharmacological target to reduce platelet hyperactivity in sickle cell disease 3.4.22.52 calpain-1 medicine inhibition of the mitochondrial calpain 1 could be a potential strategy to decrease cardiac injury during ischemia-reperfusion 3.4.22.52 calpain-1 medicine since calpain inhibition prevents diabetes-induced endothelial dysfunction in mesenteric arteries. Calpains represent an interesting therapeutic target for the prevention of cardiovascular complication of diabetes 3.4.22.53 calpain-2 medicine m-calpain inhibition at the time of reperfusion is a potentially useful strategy to limit infarct size 3.4.22.53 calpain-2 medicine m-calpain is a marker of tumor aggressiveness and is apotential target for limiting development of rhabdomyosarcoma tumor as well as their metastatic behavior 3.4.22.53 calpain-2 medicine calpain 2 represents a potential therapeutic target in breast cancer 3.4.22.53 calpain-2 medicine a selective calpain-2 inhibitor could prevent acute glaucoma-induced retinal ganglion cell death and blindness 3.4.22.55 caspase-2 medicine caspase-2 mediates death in a proportion of retinal ganglion cells but not photoreceptors at the site of blunt ocular trauma. Thus, intravitreally delivered siCASP2 is a possible therapeutic for the effective treatment of retinal ganglion cell death to prevent traumatic optic neuropathy 3.4.22.56 caspase-3 medicine during glutamte-induced apoptotic cell death, at least two mechanisms are involved: a caspase-3-dependent pathway and an enzyme-independent pathway using calpain and apoptosis inducing factor 3.4.22.56 caspase-3 medicine during glutamte-induced apoptotic cell death, glutamate induces activation of calpain, enzyme and translocation of mitochondrial apoptosis inducing factor AIF to cytosol and nuclei. These processes are inhibited/reversed by 17beta-estradiol and DELTA8,17beta-estradiol with the latter being more potent 3.4.22.56 caspase-3 medicine in macrophages from arteriosclerotic carotid artery, presence of proapoptotic markers such as enzyme, poly(ADP-ribose) polymerase, apoptosis-inducing factor, c-Jun/AP-1, and proinflammatory markers such as macrophage migration inhibitory factor and cyclooxygenase-2. Colocalization of proapoptic markers and proinflammatory markers and oxidized low-density lipoproteins 3.4.22.56 caspase-3 medicine induction of apoptosis with mitomycin-c in presence or absence of general caspase inhibitor benzoyl-Val-Ala-Asp-fluoromethylketone. Benzoyl-Val-Ala-Asp-fluoromethylketone prevents mitomycin-c-induced cell death. In contrast, specific inhibition of enzyme or caspase-7 in presence of mitomycin-c induces necrotic-like or paraptotic-like morphological changes but does not prevent cell death 3.4.22.56 caspase-3 medicine PANDER-induced downregulation of cyclin-dependent kinase inhibitor 1A expression coupled with induced CASP3-activation may serve a central role in islet cell death and offers further insight into the mechanisms of cytokine-induced beta-cell apoptosis 3.4.22.56 caspase-3 medicine caspase 3-dependent apoptosis contributes to the pathogenesis of lethal West Nile virus encephalitis and suggests possible novel therapeutic targets to restrict injury of central nervous system 3.4.22.56 caspase-3 medicine geldanamycin limits caspase-3 expression and protects from organ injury by suppressing inducible nitric oxide synthase expression and apoptosome formation. Geldanamycin, therefore may prove useful as an adjuvant in fluids used to treat patients suffering blood loss 3.4.22.56 caspase-3 medicine light-activated caspase-3 can be used for precise ablation of neurons in vivo 3.4.22.57 caspase-4 medicine caspase-4 represents a target for the treatment of (auto)inflammatory diseases 3.4.22.57 caspase-4 medicine regulation of the expression, activation, or activity of caspase-4 represents targets for systemic inflammatory response syndrome, sepsis, septic shock, and related disorders 3.4.22.59 caspase-6 medicine caspase 6 expression remains elevated long after the occurrence of acute cell death during epileptogenesis and epilepsy, indicating that the enzyme has functions other than execution of programmed cell death in epileptogenic hippocampus 3.4.22.59 caspase-6 medicine caspase-6 is active early in the pathogenesis of Alzheimer´s disease, the enzyme is strongly implicated in human neuronal degeneration and apoptosis, its inhibition may be an efficient treatment 3.4.22.59 caspase-6 medicine caspase-6 is phosphorylated by AMP-activated protein kinase related kinase 5 at Ser257 in colorectal cancer cells, leading to inactivation of caspase-6 and resulting in resistance to cell death via cFLIPs protection and leading to resistance to the FAS ligand/Fas system 3.4.22.59 caspase-6 medicine caspase-6 is upregulated in response to p53 overexpression, induction of caspase-6 expression lowers the cell death threshold in response to apoptotic signals that activate caspase-6, potential mechanism of lowering the death threshold, which could be important for chemosensitization 3.4.22.59 caspase-6 medicine critical role of caspase-6 and its cleavage of lamin A in apoptotic signaling triggered by resveratrol in the colon carcinoma cells 3.4.22.59 caspase-6 medicine difference between normal fiber cell differentation and apoptosis and the capacity of the lens to differentially regulate these two processes 3.4.22.59 caspase-6 medicine role for caspase-6 and N-terminal truncation of tau during neurovibrillary tangle evolution and the progression of Alzheimer´s disease 3.4.22.59 caspase-6 medicine Streptococcus pneumoniae induces apoptosis of human alveolar and bronchial epithelial cells, programmed cell death is excecuted by caspase 6, and can be blocked by overexpression of Bcl2 3.4.22.59 caspase-6 medicine the loss of caspase-6 does not appear to impair the ability of any anticancer agents to induce apoptosis 3.4.22.59 caspase-6 medicine compared to caspase-3 there is a siginificant correlation between caspase-6 protein and necrosis and proliferation index of the analysed tumors 3.4.22.59 caspase-6 medicine lamin A/C cleavage by caspase-6 is crucial for apoptotic induction by photodynamic therapy with hexaminolevulinate in human B-cell lymphoma cells 3.4.22.59 caspase-6 medicine caspase-6 inhibition is a promising strategy to stop early stage neurodegenerative events 3.4.22.59 caspase-6 medicine caspase-6 might be a key nod molecule to regulate immunological steady-state and be a therapeutic candidate for tumor immunotherapy 3.4.22.60 caspase-7 medicine Actinobacillus actinomycetemcomitans cytolethal distending toxin acts as an immunosuppressive factor, it possesses the ability to induce human T-cell apoptosis through activation of caspase-7 3.4.22.60 caspase-7 medicine acute hemorrhagic conjunctivitis, Enterovirus 70 infection induces caspase-7-mediated apoptosis 3.4.22.60 caspase-7 medicine cleavage of claspin by caspase-7 inactivates the Chk1 signaling pathway, this mechanism may regulate the balance between cell cycle arrest and induction of apoptosis during response of genotoxic stress 3.4.22.60 caspase-7 medicine hydrophobic P5 residue has a favorable contribution to the recognition and hydrolysis of substrates but not by caspase-7, this information helps to design specific inhibitors for each caspase 3.4.22.60 caspase-7 medicine low-dosage topoisomerase II inhibitor etoposide effectively inhibits proliferation rate 3.4.22.60 caspase-7 medicine strong correlation between caspase-7 activity, normal brain development, and apoptotic DNA fragmenation in Casp3-/-mice 3.4.22.60 caspase-7 medicine strong correlation between caspase-7 activity, normal brain development, and apoptotic DNA fragmenation in Casp3-/-mice, caspase-7 is a caspase-3 surrogate in Casp3-/-mice 3.4.22.60 caspase-7 medicine substitution in the P1' position could be used in synergy with other elements to obtain highly potent and isozyme-selective caspase inhibitors 3.4.22.60 caspase-7 medicine SUMO-1 modification in caspase-7 may contribute to the cleavage of nuclear substrates during neuronal apoptosis 3.4.22.60 caspase-7 medicine caspase-7 may play a role in ataxin-7 proteolysis and pathology of spinocerebellar ataxia type 7. Inhibition of this protease may be therapeutically important 3.4.22.60 caspase-7 medicine involvement of the CASP7 gene in the susceptibility to rheumatoid arthritis. The higher production of the no functional variant of CASP7 by individuals with a particular genotype could be the basis of this association 3.4.22.61 caspase-8 medicine caspase-8 may be a potentially useful target for a new class of antiinflammatory and immunosuppressive therapeutics 3.4.22.61 caspase-8 medicine caspase-8 activation mediates p53-independent apoptosis of glioma cells 3.4.22.61 caspase-8 medicine caspase-8 activity prevents type 2 cytokinine responses and is required for protective T cell-mediated immunity against Trypanosoma cruzi infection 3.4.22.61 caspase-8 medicine caspase-8 is potentially metastasis promoting in other tumor types than neuroblastoma because it stimulates cell migration 3.4.22.61 caspase-8 medicine caspase-8 is required for T cell activation 3.4.22.61 caspase-8 medicine caspase-8 mediates NF-kappa-B-dependent inflammatory responses in antiviral signaling 3.4.22.61 caspase-8 medicine caspase-8 plays an important role in Pseudomonas aeruginosa Exotoxin A-induced mast cell apoptosis 3.4.22.61 caspase-8 medicine caspase-8 regulates innate immunity conferred by B cells 3.4.22.61 caspase-8 medicine clinical therapies involving caspase inhibitors may arrest apoptosis, but also have the effect of promoting autophagic cell death 3.4.22.61 caspase-8 medicine HER-2 cleavage contributes to the TNF-alpha-induced apoptosis pathway 3.4.22.61 caspase-8 medicine aberrant methylation of caspase 8 apoptotic signaling gene results in acquired resistance to therapy in cervical cancer 3.4.22.61 caspase-8 medicine CASP8 is a candidate gene for multiple sclerosis risk. CASP8 polymorphisms are associated with increased risk for disease susceptibility in primary progressive multiple sclerosis patients and act as genetic modifiers of the progression of multiple sclerosis in patients with this clinical form 3.4.22.61 caspase-8 medicine caspase-8 protein expression fails to independently predict survival in parotid cancer patients 3.4.22.61 caspase-8 medicine compound 6'-benzyloxy-4-bromo-2'-hydroxychalcone displays potent cytotoxic properties against human leukaemia cells U-937, HL-60, K-562, NALM-6 and MOLT-3. Application results in significant activation of caspase-8 after 24 h of treatment 3.4.22.61 caspase-8 medicine infection by Trypanosoma cruzi induces caspase-8 activity and caspase-8 inhibition increases trophoblast cells infection while decreases parasite-induced cellular differentiation and apoptotic cell death, but not cellular proliferation 3.4.22.61 caspase-8 medicine levels of caspase-8 and caspase-9 in sperm and plasma are significantly negatively correlated with sperm concentration, motility and A % (motility grade A). The level of caspase-8 in plasma is significantly negatively correlated with sperm concentration. Compared with the healthy fertile controls, only the oligoasxadthenoteratozoospermia group exhibited significantly increased level of caspase-8 in sperm 3.4.22.B61 cathepsin L5 medicine cathepsin L5 antibody titre correlates well with actual Fasciola worm burdens 3.4.22.B61 cathepsin L5 medicine cathepsin L5, cathepsin L1g and cathepsin B are expressed in yeast from cDNA clones isolated from adult, metacercariae and newly excysted juvenile flukes respectively. Each is used solely or in combination to vaccinate rats that are subsequently challenged with Fasciola hepatica metercercariae. Each protein induces an immune response, and all groups vaccinated with recombinant protein yield significantly fewer and smaller flukes than the control group. Maximal protection of 83% is seen in the group vaccinated with cathepsin B and cathepsin L5 in combination 3.4.22.B61 cathepsin L5 medicine Fasciola hepatica infection continues to be a major problem in the agriculture sector, particularly in sheep and cattle. Cathepsin L and B proteases are major components of the excretory/secretory material of the parasite, and their roles in several important aspects of parasite invasion and survival has led to their use as targets in rational vaccine design. Recombinant versions of cathepsin L5 and cathepsin B2 produced in yeast are used in combination in a commercial adjuvant preparation to vaccinate sheep. Intramuscular and intranasal forms of administration are applied, and sheep are subsequently challenged with 150 Fasciola hepatica metacercariae. Intramuscular vaccination is able to induce a strong systemic antibody response against both antigens, but fails to confer significant protection. Conversely, no elevated antibody response is detected against the vaccine antigens following nasal vaccination, but a reduction in parasite egg viability (above 92%) and a statistically significant, predominantly adjuvant-mediated reduction in worm burdens is observed 3.4.22.62 caspase-9 medicine inhibition of the caspase-9 activity would render opportunity to treat patients suffering from neurological diseases such as stroke, neurodegenerative diseases or brain injury caused by hypoxia 3.4.22.62 caspase-9 medicine caspase-9 is a target for development of therapeutic approaches for histamine-related diseases 3.4.22.62 caspase-9 medicine analysis of a single nucleotide polymorphism (SNP) in the caspase-9 gene in relation to susceptibility to multiple sclerosis (MS) 3.4.22.62 caspase-9 medicine dysregulation of the apoptotic response in differentiating neurons participates in the neuropathology of diseases that display with an imbalance of DYRK1A gene-dosage 3.4.22.62 caspase-9 medicine effectiveness and specificity of an inducible caspase 9-based safety switch system, to halt an ongoing immune attack, reduction of the risk of severe graft-vs-host disease, murine model for cell therapy-induced type I diabetes 3.4.22.62 caspase-9 medicine mechanisms of adenosine-induced apoptosis in human colonic cancer cells 3.4.22.62 caspase-9 medicine there is a weak correlation between activated caspase-9 and poor neurologic outcome after severe traumatic brain injury 3.4.22.62 caspase-9 medicine B cell lymphoid malignancies are treated with T cells expressing the chimeric antigen receptor (CAR) specific for the CD19 antigen (CD19.CAR-Ts). The inducible caspase-9 safety switch, i.e. a modified human caspase-9 fused to the human FK506 binding protein, can eliminate CD19.CAR-Ts in a dose-dependent manner, allowing either a selective containment of CD19.CAR-T expansion in case of cytokine release syndrome or complete deletion on demand granting normal B cell reconstitution 3.4.22.62 caspase-9 medicine levels of caspase-8 and caspase-9 in sperm and plasma are significantly negatively correlated with sperm concentration, motility and A % (motility grade A). Only in healthy fertile controls sperm concentration is significantly negatively correlated with caspase-9 in sperm. Caspase-8 and caspase-9 in sperm and plasma are correlated with sperm motility, and can reflect the quality of sperm in vitro 3.4.22.63 caspase-10 medicine two patients that are combined heterozygous for single nucleotide substitutions in the Fas and caspase-10 genes. The first patient carries a splice site defect suppressing allele expression in the Fas gene and the P501L substitution in caspase-10. The second has a mutation causing a premature stop codon (Q47X) in the Fas gene and the Y446C substitution in caspase-10. Fas expression is reduced and caspase-10 activity is decreased in both patients. In both patients, the mutations are inherited from distinct healthy parents. Co-transmission of these mutation is responsible for autoimmune lymphoproliferative syndrome 3.4.22.63 caspase-10 medicine silencer of death domain and caspase-10 are frequently over-expressed in ALL. Interfering with these proteins may provide another strategy for the treatment of this and potentially other cancers 3.4.22.63 caspase-10 medicine in HL-60 cells that are treated with chemotherapy drugs combined with a caspase-10 inhibitor, the rate of survival decreases significantly compared with HL?60 cells treated with chemotherapy drugs alone. The rate of survival of Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor increases significantly compared with Jurkat cells treated with chemotherapy drugs alone. Caspase-10 may be associated with autophagy in acute myeloid leukemia cells, but not in acute lymphatic leukemia cells 3.4.22.63 caspase-10 medicine the apoptosis-inducing complex FADDosome is driven by ATR-dependent caspase-10 upregulation. During FADDosome-induced apoptosis, FLICE-inhibitory protein cFLIPL is ubiquitinated by TRAF2, leading to its degradation and subsequent adaptor protein FADD-dependent caspase-8 activation. Cancer cells lacking caspase-10, TRAF2 or ATR switch from this cell-autonomous suicide to a more effective, autocrine/paracrine mode of apoptosis initiated by a different complex, the FLIPosome. It leads to processing of cFLIPL to cFLIPp43, TNF-alpha production and consequently, contrary to the FADDosome, p53-independent apoptosis 3.4.22.64 caspase-11 medicine caspase-11 has a regulatory role in ethanol-induced apoptosis. Suppression of caspase-11 may be a mechanism by which Scutellariae radix (Chineses herbal medicine) exerts its cytoprotective effect 3.4.22.65 peptidase 1 (mite) medicine the efficient system to prepare active recombinant enzyme is useful for diagnosis and standardized allergen-specific immunotherapy for house dust mite allergy. The system would by a tool for analysis of IgE epitopes, determination of tertiary structure, allergen engineering for safer and more effective allergen-specific immunotherapy 3.4.22.65 peptidase 1 (mite) medicine affects individuals with allergy, resulting in rhinitis, asthma and/or atopic dermatitits 3.4.22.65 peptidase 1 (mite) medicine allergen is associated with allergic diseases such as bronchial asthma, rhinitis, and atopic dermatitis 3.4.22.65 peptidase 1 (mite) medicine induces biological responses in a human airway-derived epithelial cell line 3.4.22.65 peptidase 1 (mite) medicine involved in the pathogenesis of allergy 3.4.22.65 peptidase 1 (mite) medicine proteolytic activity in pathogenesis of allergens 3.4.22.65 peptidase 1 (mite) medicine contribution of Der f 1 is particularly relevant in the mattresses and much less so in floor dust from the bedroom or living room, mattress covers (Goratex bedding system) seem to be an obvious option for lowering allergen exposure in sensitized individuals, geographical differences in prevelance of Dermatophagoides farinae in the Netherlands 3.4.22.65 peptidase 1 (mite) medicine cystatin A produced by keratinocytes is the dominant biochemical skin barrier against mite cysteine proteases 3.4.22.65 peptidase 1 (mite) medicine Der f 1 is one of the most potent indoor allergens from house dust mites, shows IgE-eliciting activity in mice, recombinant DER f 1-N53Q will be a useful tool as alternatives to the natural Der f1 for in vitro and in vivo analyses 3.4.22.65 peptidase 1 (mite) medicine prodomains of Der f 1 reduce allergenicity, decreased activity of the proforms in inhibiting IgE binding, proforms exhibit different secondary structures than the mature forms, major conformational IgE epitopes commonly found in a broad population of patients exist within the 2 regions blocked by the prosegments, results basis for allergen standardization and design of safer and more effective allergen vaccines 3.4.22.65 peptidase 1 (mite) medicine upholstered seats in workplaces in Italy may constitue a significant reservoir of Der f1, significant correlation between indoor temperature and Der f 1 levels on floors, expressed per surface (no correlation when levels were expressed per weight), no correlation between concentration of mite allergen and geographical location, floor above ground, type of ventilation and indoor humidity, exposure to this allergen in workplaces may represent a risk factor for elicitation of symptoms and/or induction/maintenance of inflammation in allergic individuals and for sensitization 3.4.22.65 peptidase 1 (mite) medicine mimotopes identify conformational B-cell epitopes on the house dust mite allergen Der p 1. These mimotopes are potential candidates for the directed induction of blocking antibodies and epitope-specific immunotherapy of mite allergy 3.4.22.65 peptidase 1 (mite) medicine chimeras assembling Der p 1 and Der p 2 allergens are potential candidate vaccines against house dust mite allergy. But significant solubility and stability issues can limit the application of such chimeras for immunotherapy or diagnostic 3.4.22.65 peptidase 1 (mite) medicine production of recombinant enzyme for allergen-specific immunotherapy 3.4.22.66 calicivirin medicine calicivirus 3CLpro mediates the cleavage of poly(A)-binding protein as part of its strategy to inhibit cellular translation 3.4.22.66 calicivirin medicine establishment of a mammalian cell-based system for analysis of human norovirus replication and, thus makes it feasible to investigate antiviral agents in mammalian cells 3.4.22.66 calicivirin medicine nonbacterial acute gastroenteritis and other diseases associated with viruses expressing 3Cpro, knowledge of the structure and previous mutagenesis study allows to correlate proteolysis and structure 3.4.22.66 calicivirin medicine norovirus precursor comprised of both the proteinase and polymerase (released from 3C-like proteinase) is a bifunctional enzyme during virus replication, which might be useful in the development of antiviral drugs of the noroviruses associated with acute gastroenteritis 3.4.22.66 calicivirin medicine Norwalk virus is the major cause of acute, epidemic, viral gastroenteritis 3.4.22.66 calicivirin medicine poliovirus 3Cpro mediates the cleavage of poly(A)-binding protein as part of its strategy to inhibit cellular translation 3.4.22.B66 caspase-12 medicine endoplasmic reticulum stress may be associated with apoptosis of lens epithelial cells, resulting in cataract formation in diabetic patients. The expression of calpain and caspase-12 is in highest diabetic cataract patients with proliferative diabetic retinopathy, followed by diabetic cataract patients with nonprolifeative diabetic retinopathy, cataract patients with diabetes mellitus and without diabetic retinopathy, and finally cataract patients without diabetes mellitus 3.4.22.68 Ulp1 peptidase medicine there may be a connection between a defect in SUMO-1 conjugation to the PML protein and acute promyelocytic leukemia (ALP). Specific Ulp inhibitors can therefore have therapeutic value for ALP 3.4.22.69 SARS coronavirus main proteinase medicine SARS-3CLpro is a viral cysteine protease critical to the life cycle of the pathogen and hence a therapeutic target of importance 3.4.22.69 SARS coronavirus main proteinase medicine this enzyme is a target for the design of potential anti-SARS drugs 3.4.22.69 SARS coronavirus main proteinase medicine patients infected with a SARS-Cov-2 sub-lineage (B.1.1.284) carrying the Pro108Ser mutation in 3CLpro tend to have a comparatively milder clinical course than patients infected with the same sub-lineage of virus not carrying the mutation 3.4.22.70 sortase A medicine substrate-derived irreversible inhibitors of SrtA that might find application in delineating the role of the cysteine protease-transpeptidase in cell surface protein sorting and adherence of Gram-positive organisms 3.4.22.70 sortase A medicine in principle the purified SrtA protein can be used to screen for compounds that inhibit cell wall sorting, a strategy that may lead to new therapies for human infections caused by Gram-positive bacteria 3.4.22.70 sortase A medicine potential of inhibitors for the treatment of Staphylococcus aureus infections: (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, beta-sitosterol-3-O-glucopyranoside, berberine chloride and psammaplin A1 3.4.22.70 sortase A medicine SrtA activity is a prime target for inhibition of Staphylococcus aureus colonization 3.4.22.70 sortase A medicine Bacillus anthracis SrtA anchors surface proteins bearing LPXTG motif sorting signals to the cell wall envelope of vegetative bacilli, srtA gene of Bacillus anthracis is not required for the development of acute anthrax disease in A/J mice 3.4.22.70 sortase A medicine SrtA contributes to pneumococcal nasopharyngeal colonization in the chinchilla model 3.4.22.70 sortase A medicine 4-vinylsulfonyl 5-phenyl prolinates inhibit Staphylococcus aureus sortase SrtA irreversibly by modification of the enzyme Cys184 and could be used as hits for the development of antibacterials and antivirulence agents 3.4.22.70 sortase A medicine the mutant strain TBY-1DELTAsrtA is used as a live vaccine, which is administered via intraperitoneal injection. It provides the relative percent survival value of 95.5% in Nile tilapia, thereby demonstrating its high potential as an effective attenuated live vaccine candidate 3.4.22.B70 SENP1 peptidase medicine diagnostic value of measuring the urinary content of SENP1 mRNAs for detection of tumor recurrence 3.4.22.B70 SENP1 peptidase medicine SENP1 is overexpressed in most of colon cancer tissues. SENP1 regulates the in vitro and in vivo growth of colon cancer cells with the upregulated expression of CDK inhibitors 3.4.22.B70 SENP1 peptidase medicine SENP1 overexpression induces transformation of the normal prostate gland and gradually facilitates the onset of high-grade prostatic intraepithelial neoplasiade. SUMOylation plays a critical role in prostate pathogenesis through induction of HIF1alpha-dependent angiogenesis and enhanced cell proliferation 3.4.22.B70 SENP1 peptidase medicine SENP1, can transform normal prostate epithelia to a dysplasic state and directly modulate several oncogenic pathways in prostate cells, including AR, c-Jun, and Cyclin D1 3.4.22.B70 SENP1 peptidase medicine SENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. In the subgroup of ERG positive, PTEN undeleted cancers, the prognostic role of SENP1 expression is independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection 3.4.22.B70 SENP1 peptidase medicine the expression of SENP1 is positively correlated with the malignant grades of astrocytoma. The NF-kappaB and Akt signaling pathways in glioblastoma multiforme tissues are activated. Knock-down of endogenous SENP1 promotes cell apoptosis. Downregulation of SENP1 expression can inhibit the phosphorylation of IkappaBalpha and Akt, and also the expression of its downstream regulation factors Bcl-xL and cyclinD1 3.4.22.71 sortase B medicine potential to be used as inhibitors for the treatment of Staphylococcus aureus infections: (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, beta-sitosterol-3-O-glucopyranoside, berberine chloride and psammaplin A1 3.4.22.B71 SENP2 peptidase medicine muscle enzyme SENP2 can be a therapeutic target for the treatment of obesity-linked metabolic disorders 3.4.22.B71 SENP2 peptidase medicine in bladder cancer cells, SENP2 inhibits MMP13 expression through deSUMOylation of TBL1/TBLR1, which inhibits nuclear translocation of beta-catenin 3.4.22.B71 SENP2 peptidase medicine SENP2 expression is significantly downregulated in clinical osteosarcoma tissues compared with adjacent normal samples. Ectopic expression of SENP2 results in the suppression of proliferation, migration and invasion in osteosarcoma cells, whereas SENP2 knockdown has the opposite effect. SENP2 is associated with the proteaxadsome-dependent ubiquitination and degradation of SRY-box-9 (SOX9). SOX9 silencing impairs SENP2-depletion-induced accelerated cell growth and migration 3.4.22.B71 SENP2 peptidase medicine SENP2 is frequently downregulated in bladder cancer, especially in metastatic bladder cancer. SENP2 downregulation is associated with more aggressive phenotypes and poor patient outcomes. SENP2 suppresses bladder cancer cell invasion in vitro and tumor metastasis in vivo, acts as a tumor suppressor gene in bladder cancer 3.4.22.B73 SENP5 peptidase medicine the SENP5 expression status is associated with differentiation of oral squamous cell carcinoma and not with any other clinicopathological parameters. No detected correlation between SENP5 expression and the degree of epithelial dysplasia in the paracarcinoma epithelium. No expression difference between primary tumors and lymph node metastatic lesions. SENP5 expression is not associated with lymph node metastasis and cumulative survival 3.4.22.B73 SENP5 peptidase medicine Senp5 is significantly repressed in clinical acute myeloid leukemia when compared to healthy neutrophil samples 3.4.22.B75 SENP7 peptidase medicine increased degradation of SENP7 by overexpression of SPOP decreases vimentin levels, which in turn may attenuate hepatocellular carcinoma cell metastasis 3.4.22.B75 SENP7 peptidase medicine SENP7 is significantly up-regulated in patients with systemic lupus erythematosus 3.4.22.B75 SENP7 peptidase medicine SENP7S is the predominant SENP transcript in human mammary epithelia but is significantly reduced in precancerous ductal carcinoma in situ and all breast cancer subtypes 3.4.22.B76 Allium alpha-fibrinogenase AFTEII medicine AFTEII may be useful as thrombolytic agent 3.4.22.B79 nsP2 protease medicine plays an essential role in virus propagation 3.4.22.B79 nsP2 protease medicine the nsp2pro N-terminal domain is a novel cysteine protease fold. the C-terminal domain displays structural similarity to S-adenosyl-L-methionine-dependent RNA methyltransferases. This structure will significantly aid drug discovery and development efforts to combat Venezuelan equine encephalitis alphavirus and related viruses 3.4.22.B79 nsP2 protease medicine SINV nsP2 is an important factor in viral RNA replication and modification of cell biology 3.4.22.B79 nsP2 protease medicine ubiquitin-like protein ISG15 overexpression inhibits porcine reproductive and respiratory syndrome virus replication in cell culture and the antiviral activity of interferon is reduced by inhibition of ISG15 conjugation. Nonstructural protein nsp2 is a key factor in counteracting the antiviral function of ISG15 3.4.22.B79 nsP2 protease medicine minimal linear Nsp2 B cell epitopes, 188ELSDDSNRPV197, 42HLKRYSPPAE51, and 54CGWHCISA61, are identified by the monoclonal antibodies 4A12, 4G8, and 8H11, respectively. 42HLKRYSPPAE51 and 188ELSDDSNRPV197 are located separately in hypervariable region 1 and hypervariable region 2 of Nsp2. 54CGWHCISA61 is located in the PL2 region, which is highly conserved in all arteriviruses. 54CGWHCISA61 is located in the inner region of the expected 3D structure of Nsp2 3.4.23.1 pepsin A medicine correlation of protein allergen digestion in simulated gastric fluid with that in actual gastric fluid. Digestion of peanut allergen Ara h 1 with pepsin and porcine gastric fluid results in virtually identical hydrolysis patterns 3.4.23.1 pepsin A medicine for elucidation and diagnosis of the allergic potential of egg white ovomucoid, the combination of digestibility studies by simulated gastric fluid and human IgE-binding experiments is useful 3.4.23.1 pepsin A medicine the enzyme is a biomarker of gastric reflux into the esophagus, airways, and lungs 3.4.23.B1 napsin medicine enzyme is a specific marker in diagnosis of primary lung adenocarcinoma and to distinguish it from metastatic adenocarcinoma 3.4.23.B1 napsin medicine napsin A is useful to distinguish primary lung adenocarcinoma from adenocarcinomas of other organs 3.4.23.B1 napsin medicine observation that napsin A is expressed in more than 90% of primary lung adenocarcinomas but not in other malignancies shows that napsin A might be a marker for this type of carcinoma. Potential use as a marker for kidney dysfunction 3.4.23.B1 napsin medicine immunocytochemical markers for lung adenocarcinoma, identification of malignancy in effusions 3.4.23.B1 napsin medicine studies on differentiation of primary from secondary effects in the pathogenesis of juvenile and adult forms of Pulmonary alveolar proteinosis 3.4.23.B1 napsin medicine napsin A is a sensitive marker for pulmonary adenocarcinoma 3.4.23.B1 napsin medicine napsin-A is a marker for lung adenocarcinoma, napsin-A is useful as a surrogate marker when encountering a poorly differentiated lung adenocarcinoma or an unknown primary tumor 3.4.23.B1 napsin medicine napsin-A is useful for stages IA and IIIA and also related to regional lymph node metastasis, napsin-A contents correlate with better prognosis in stage IA 3.4.23.B1 napsin medicine among 10 probes of surgically resected sclerosing haemangioma, all tumours have diffuse and intense expression of napsin A in cuboidal superficial cells, whereas the round interstitial component is completely negative in four cases, and shows focal granular cytoplasmic positivity in six cases 3.4.23.B1 napsin medicine use of napsin A to distinguish between metastatic pulmonary and non-pulmonary adenocarvcinomas in cell blocks prepared from malignant pleural effusions. Napsin A is positive in 83% of pulmonary adenocarcinomas tested, while thyroid transcription factor TTF-1 is positive in 57% of pulmonary adenocarcinomas. All non-pulmonary adenocarcinoas tested are negative for napsin A and TTF-1. Napsin A shows a reactivity in more than 75% of the tumor cells in 82% of the positive cases, whereas TTF-1 shows a reactivity in more than 75% of the tumor cells only in 20% of the positive cases 3.4.23.B1 napsin medicine napsin A is expressed in a wider variety of metastatic nonpulmonary carcinomas than thyroid transcription factorTTF-1, and the monoclonal antibody is more specific. Napsin A is a useful adjunct to TTF-1, because occasional lung adenocarcinomas are TTF-1 negative but napsin A positive 3.4.23.B1 napsin medicine napsin A is frequently expressed in ovarian clear cell carcinomas and endometrian clear cell carcinomas, rarely in ovarian endometroid carcinomas and endometrian endometroid carcinomas, and never in high-grade serous carcinoma cases. Findings confirm the importance of using a panel of antibodies that includes napsin A, TTF-1, and PAX8 when evaluating metastatic carcinomas of unknown origin 3.4.23.B1 napsin medicine napsin A staining occurs commonly in the surface cells and less commonly in the round cell component of sclerosing hemangioma, supporting a respiratory epithelial (specifically type II pneumocyte) origin for this tumor. Cytokeratin and TTF-1 staining in surface cells and TTF-1 staining with only weak and inconsistent cytokeratin staining in round cells confirms studies suggesting primitive or incompletely differentiated respiratory epithelium as the likely cell of origin for stromal round cells 3.4.23.3 gastricsin medicine potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies 3.4.23.3 gastricsin medicine the tissue expression of progatricsin represents a powerful tool for the diagnosis of prostate cancer. The enzyme is also a biomarker for gastric carcinoma and plays a direct role in the development of breast tumor progression 3.4.23.3 gastricsin medicine high level enzyme expression indicates better prognosis and longer survival in prostate cancer, breast cancer, ovary cancer and endometrial cancer 3.4.23.3 gastricsin medicine overexpressed pepsinogen C is associated with poor prognosis in human hepatocellular carcinoma 3.4.23.B4 Feline immunodeficiency virus protease medicine PR is an important target for antiviral therapies since PR is reponsible for the processing of viral Gag and Gag-Pol polyproteins into individual structural and enzymatic proteins during assembly and maturation. This proteolytic step is highly specific, ordered and essential for producing mature and infectious retrovirus particles 3.4.23.5 cathepsin D medicine the enzyme may have important implications in the pathophysiology and treatment of thrombotic disorders 3.4.23.5 cathepsin D medicine enzyme contributes to antigen-dependent processing defect in DELTA9-tetrahydrocannabinol-exposed macrophages 3.4.23.5 cathepsin D medicine enzyme is a key mediator in staurosporine-induced apoptosis 3.4.23.5 cathepsin D medicine enzyme secreted from prostate carcinoma cells is responsible for generation of angiostatin, pro-enzyme from breast cancer cells shows significantly lower angiostatin-generating activity than that from prostate carcinoma cells 3.4.23.5 cathepsin D medicine inhibition of enzyme by pepstatin A inhibits early apoptotic events and delays cell death in T lymphocytes exposed to apoptotic stimuli targeting mitochondria 3.4.23.5 cathepsin D medicine inhibitors CEL5-A, CEL5-G, EA-1, block production of known precursors to neurofibrillary tangles in hippocampal slices, link of enzyme lysosomal disfunction to the etiology of Alzheimers disease 3.4.23.5 cathepsin D medicine mice deficient in enzyme show progressive atrophy of intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin 3.4.23.5 cathepsin D medicine pretreatment with pepstatin A inhibits apoptosis in cells exposed to naphthazarin (5,8-dihydroxy-1,4-naphthoquinone), naphthazarin releases enzyme from lysosomes to cytosol, later, enzyme reappears in granules of increased size, and activity is restored 3.4.23.5 cathepsin D medicine significant correlation between age and enzyme immunoreactivity in cytoplasm of parahippocampal glial cells 3.4.23.5 cathepsin D medicine a new proapoptotic pathway is shown in which caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation 3.4.23.5 cathepsin D medicine beta-secretase activity in brain is mainly due to cathepsin D. As cathepsin D shows poor activity towards the wild-type beta-site of the amyloid precursor protein it is necessary to continue the search for additional beta-secretase candidates 3.4.23.5 cathepsin D medicine cathepsin D is involved in the postsecretory processing of the antimicrobial peptide DCD-1L in human sweat 3.4.23.5 cathepsin D medicine cathepsin D might serve as a biomarker for lung cancer 3.4.23.5 cathepsin D medicine it is shown that BmCatD is critically involved in the programmed cell death of the larval fat body and larval gut in silkworm metamorphosis 3.4.23.5 cathepsin D medicine results identify the lysosome as a novel target of polyphenol resveratrol activity and demonstrate a hierarchy of the proteolytic pathways involved in its cytotoxic mechanism in which the lysosomal cathepsin D acts upstream of the cytosolic caspase activation. Any metabolic, pharmacologic or genetic conditions affecting cathepsin D expression and/or activity can reflect on the sensitivity of cancer cells to polyphenol resveratrol 3.4.23.5 cathepsin D medicine the activity of cathepsin D in saliva of cystic fibrosis patients is significantly higher than in healthy controls before the stimulation of excretion with paraffin pledgets 3.4.23.5 cathepsin D medicine the results demonstrate an important role for CTSD in intracellular cholesterol trafficking and ABCA1-mediated efflux. Decreased CTSD expression may contribute to low plasma HDL-C levels 3.4.23.5 cathepsin D medicine cathepsin D is a marker for the detection of cellular senescence induced by ionizing radiation of xenografted tumors 3.4.23.5 cathepsin D medicine cathepsin D is an independent marker of poor prognosis in breast cancer as it is correlated with the incidence of clinical metastasis 3.4.23.5 cathepsin D medicine application of cathepsin D gel can increase the stratum corneum cathepsin D content and repair the epidermal barrier in chronic photodamaged skin 3.4.23.5 cathepsin D medicine the enzyme is an independent prognostic marker in breast cancer associated with metastatic risk and in colorectal cancer 3.4.23.B8 human T-cell leukemia virus type 1 protease medicine currently employed HIV protease inhibitors can not be used to treat HTLV infections 3.4.23.B8 human T-cell leukemia virus type 1 protease medicine HTLV-1 is associated with a number of human diseases. HTLV-1 is a potential target for chemotherapy 3.4.23.B8 human T-cell leukemia virus type 1 protease medicine the enzyme is an attractive target for inhibitor design 3.4.23.B14 plasmepsin IV medicine plasmepsin IV appears to be a potential target for the development of new antiparasitic drugs. Plasmepsin I, II and IV might act in concert. While this might suggest that inhibition of individual enzymes might be insufficient to kill the parasite, the broad similarities between the plasmepsins may permit the development of compunds able to inhibit all three enzymes to produce a drug capable of imposing a multiple blockade on the pathway of haemoglobin digestion 3.4.23.B14 plasmepsin IV medicine plasmepsin 4 is the food vacuole plasmepsin present in all four Plasmodium spp. infecting man, and the only food vacuole plasmepsin in three of the four species. For this reason it represents a potential antimalarial drug target against which one drug may control infections by any of the four species 3.4.23.15 renin medicine depending on incubation conditions, circulating renin inhibitors interfere with the recognition of active renin molecules by the monoclonal antibodies used in commercial available assays. Careful considerations must therefore by given to the methodology used for quantifying immunoreactive plasma active renin when patients are treated with renin inhibitors, to avoid an overestimation of the magnitude of active renin release attributable to conformational changes in plasma prorenin 3.4.23.15 renin medicine hypertension is a pathophysiologically heterogeneous condition in which renin-angiotensin system activity is an important determinant of the blood pressure response to antihypertensive drug treatment. The pretreatment plasma renin activity level is a significant predictor of treatment efficacy despite the different experimental designs employed and the ethnically diverse populations evaluated. These observations support the case that pathophysiologic markers such as plasma renin activity should be incorporated into the design of studies that assess antihypertensive treatment strategies 3.4.23.15 renin medicine plasma active renin concentration is superior to plasma renin activity and a high plasma active renin concentration is an independent prognostic predictor in heart failure patients who are already receiving angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers 3.4.23.15 renin medicine renin angiotensin system inhibition improves diabetic nephropathy at several levels, independently of its effects on blood pressure and glycemic control, via mechanisms depending of renal oxidative stress 3.4.23.15 renin medicine in patients with biopsy-confirmed post-transplant glomerulonephritis, statins and renal reini-angiotensin system blockers prolong graft survival. The effect persists after adjustment for presentation with nephrotic syndrome, graft dysfunction, mean arterial pressure, immunosuppression enhancement with mycophenolate mofetil 3.4.23.15 renin medicine renin inhibition improves systemic insulin sensitivity, insulin metabolic signaling and glucose transport, along with normalization of angiotensin II, angiotensin type I receptor and mineralocorticoid receptor levels, oxidative stress markers, fibrosis and mitochondrial structural abnormalities 3.4.23.15 renin medicine blockade of renin activation is a therapeutic target to prevent glomerular injury and associated proteinuria 3.4.23.15 renin medicine direct renin inhibition with aliskiren represents an effective option for the long-term treatment of essential hypertension 3.4.23.15 renin medicine inhibition of the renin-angiotensin-aldosterone system plays a pivotal role in preventing and treating diabetic nephropathy. Inhibition of renin with aliskiren decreases blood pressure in patients with hypertension. Direct renin inhibition with aliskiren has antiproteinuric effects in type 2 diabetic patients with nephropathy and additive proteinuric effects when used in diabetic patients already treated with the maximal dose of angiotensin type 1 receptor blockers 3.4.23.15 renin medicine plasma renin activity is an independent predictor of morbidity and mortality in patients with hypertension 3.4.23.15 renin medicine renin inhibition is the preferred pharmacologic approach to blockade of the renin-angiotensin system. Renin inhibition offers substantial promise for cardioprotection and renoprotection 3.4.23.15 renin medicine renin inhibition with aliskiren is useful for antihypertensive treatment in patients with severe arterial hypertension, in patients with an already long-lasting course of disease, and in the presence of comorbidities such as diabetes mellitus 3.4.23.15 renin medicine renin is a target to prevent hypertension 3.4.23.15 renin medicine renin-angiotensin system inhibition is used as treatment for the primary and secondary prevention of atrial fibrillation 3.4.23.15 renin medicine there is an association of polymorphisms of renin-angiotensin-aldosterone system genes with the risk of non-control of hypertension in angiotensin-converting enzyme inhibitor drugs-treated patients 3.4.23.16 HIV-1 retropepsin medicine the enzyme is responsible for the processing of gag and gag-pol polyprotein precursors to produce structural proteins and enzymes for the mature virus. Hence it is essential for the maturation and infectivity of the virus and is thus a major target for the development of inhibitor drugs 3.4.23.16 HIV-1 retropepsin medicine HIV-1 protease is the target of some of the most effective antiviral AIDS therapy, as it facilitates viral maturation by cleaving ten asymmetric and nonhomologous sequences in the Gag and Pol polyproteins 3.4.23.16 HIV-1 retropepsin medicine drugs against protease and reverse transcriptase form the basis for Highly Active Anti-Retroviral Theraphy that has been successful in improving survival rates and quality of life for HIV infected individuals 3.4.23.16 HIV-1 retropepsin medicine the enzyme is an attractive target for antiviral drugs of HIV-1 3.4.23.16 HIV-1 retropepsin medicine insertions at positions 33 and 35 contribute to the viral resistance to most of the tested protease inhibitors. The structural analysis reveals local structural rearrangements in the flap region and in the substrate binding pockets. The enlargement of the HIV proteinase substrate binding site together with impaired flap dynamics could account for the weaker inhibitor binding by the insertion mutants. Amino acid insertions in the vicinity of the binding cleft represent a mechanism of HIV resistance development 3.4.23.16 HIV-1 retropepsin medicine construction of chimeric viruses using patient-derived gag-protease sequences amplified from plasma HIV RNA and inserted into an NL4-3 backbone. The chimeric viruses generated from elite controllers display lower replication capacity than viruses from chronic progressors. Human leukocyte antigen system allele HLA-B*57 is associated with lower replication capacity than other alleles in both elite controllers and chronic progressor groups. Chimeric viruses from allele B*57 elite controllers demonstrate lower replication capacity than viruses from allele B*57 chronic progressors. Cytotoxic T-lymphocyte selection pressure on gag-protease alters virus replication capacity, and HIV-specific cytotoxic T-lymphocytes inducing escape mutations with fitness costs in this region may be important for strict viremia control in elite controllers of HIV 3.4.23.16 HIV-1 retropepsin medicine isolation of subtype G viruses from patients with diverse amino acid combinations at codons 71, 74, 89 and 90. In isolates displaying 89I/V in combination with A71 or T74, a reversal to subtype G wild-type 89M is observed after growth in the absence of protease inhibitor. The presence of 71T in one isolate and 74S in another allows the persistence of 89I. Mutation 90M confers intermediate but significant degrees of drug resistance to ritonavir and nelfinavir in subtype G viruses. The combination of 71T or 74S, 89I and 90M results in higher levels of resistance to those protease inhibitors. 71T or 74S may stabilize 89I in the protease of subtype G 3.4.23.16 HIV-1 retropepsin medicine the HIV proteases are effective therapeutic targets for treating HIV infection because of the essential role in hydrolysing the viral Gag and Gag-Pol precursor polyprotein during infectious viral particle maturation 3.4.23.20 Penicillopepsin medicine design of inhibitors with enhanced potency against proteolytic enzymes has many applications for treatment of human diseases 3.4.23.21 Rhizopuspepsin medicine design of a selective and potent inhibitor is crucial since aspartic proteinases known to be involved in many diseases such as cancer and malaria 3.4.23.22 Endothiapepsin medicine aspartic proteinases play major roles in amyloid disease and malaria, implicated in tumourigenesis, design of inhibitors to this class of enzymes as potential therapeutic agents 3.4.23.22 Endothiapepsin medicine inhibitor design to discover novel therapeutic agents 3.4.23.24 Candidapepsin medicine biochemical target for drug development against clinically important fungal infections 3.4.23.24 Candidapepsin medicine protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2 3.4.23.24 Candidapepsin medicine recombinant truncated Sap2 is a candidate vaccine to fight vaginal candidiasis 3.4.23.B24 signal peptide peptidase medicine herpes simplex virus type 1 glycoprotein specifically binds to signal peptide peptidase SPP. SPP dominant negative mutants and shRNA against SPP significantly reduce herpes simplex virus type 1 replication in vitro. SPP also affects lysosomes and endoplasmic reticulum responses to herpes simplex virus type 1 infection 3.4.23.B24 signal peptide peptidase medicine malaria heat shock protein 101 is a substrate, and partial inhibition of Plasmodium falciparum signal peptide peptidase correlates with the emergence of gametocytes 3.4.23.B24 signal peptide peptidase medicine signal peptide peptidase SPP catalyzes the intramembrane cleavage of heme oxygenase HO-1. Coexpression of HO-1 with wild-type SPP promotes the nuclear localization of HO-1 in cells. Two adjacent intramembrane cleavage sites are located after S275 and F276 within the trans membrane segment. Mutations of S275F276 to A275L276 significantly hinder SPP-mediated cleavage and nuclear localization. Nuclear heme oxygenase-1 is detected in A549 and DU145 cancer cell lines expressing high levels of endogenous HO-1 and SPP. SPP knockdown or inhibition significantly reduces nuclear HO-1 localization in A549 and DU145 cells. The positive nuclear HO-1 stain is also evident in lung cancer tissues expressing high levels of HO-1 and SPP. Overexpression of a truncated HO-1 lacking the trans membrane segment in HeLa and H1299 cells promotes cell proliferation and migration/invasion 3.4.23.B24 signal peptide peptidase medicine specific inhibition of distinct SPP/SPPL proteases is proposed as a therapeutic concept e.g. for the treatment of autoimmunity and viral or protozoal infections 3.4.23.B24 signal peptide peptidase medicine specific inhibition of distinct SPP/SPPL proteases is proposed as a therapeutic concept e.g. for the treatment of autoimmunity and viral or protozoal infections. Scheme for potential applications of SPPL2a inhibitors, overview 3.4.23.B24 signal peptide peptidase medicine the signal peptide peptidase hSPP is a biomedically important protease implicated as therapeutic target for hepatitis C 3.4.23.B24 signal peptide peptidase medicine the signal peptide peptidase pSPP is a biomedically important protease implicated as therapeutic target for treatement of Plasmodia and malaria 3.4.23.B24 signal peptide peptidase medicine the signal peptide peptidase SPPL2a is a biomedically important protease implicated as therapeutic target for B-cell immunomodulation and neoplasia 3.4.23.25 saccharopepsin medicine important in a number of pathological processes, including gastric ulcers, Alzheimer's disease, hypertension, malaria, and AIDS 3.4.23.25 saccharopepsin medicine participates in a variety of physiological processes, and the onset of pathological conditions such as hypertension, gastric ulcers, and neoplastic diseases may be related to changes in the level of activity 3.4.23.34 cathepsin E medicine cathepsin E is a specific marker of dysplasia in APC(Min/+) mouse intestine. Potential utility for catE as a marker for the inception and progression of intestinal cancers 3.4.23.34 cathepsin E medicine antitumor activity of cathepsin E in human prostate carcinoma tumor cell lines 3.4.23.34 cathepsin E medicine combination of cathepsin E and doxorubicin is sufficient to overcome resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in chemoresistant prostate cancer PPC-1 cells 3.4.23.34 cathepsin E medicine pancreas-bearing pancreatic intraepithelial neoplasia lesions and pancreatic tumours show an elevated expression of cathepsin E, allowing selective in-vivo detection of human pancreatic ductal adenocarcinoma xenografts and imaging of pancreas with pancreatic intraepithelial neoplasia lesions and pancreatic tumours in genetically engineered mouse models of pancreatic cancer 3.4.23.36 Signal peptidase II medicine important role of the enzyme in the pathogenicity of Legionella pneumophila, making it a promising target for therapeutic intervention 3.4.23.39 plasmepsin II medicine inhibitors of plasmepsin II are potential antimalarial agents 3.4.23.39 plasmepsin II medicine plasmepsin is an important target for the development of antimalarial drugs, since its inhibition leads to the starvation of Plasmodium falciparum 3.4.23.41 yapsin 1 medicine yapsin 1 displays specific immunoreactivity in the alpha-cells of human pancreatic islets 3.4.23.43 prepilin peptidase medicine the pathogenicity island PAPI-1 may have evolved by acquisition of a conjugation system but because of its dependence on an essential chromosomal determinant, its transfer is restricted to Pseudomonas aeruginosa or other species capable of providing a functional prepilin peptidase 3.4.23.45 memapsin 1 medicine samples from frontal cortex of both Alzheimer's disease-affected individuals and age-matched controls show substantial total amounts of BACE2 protein and enzymatic activity. BACE2 activity does not change significantly in the brain of patients with Alzheimer's disease, and is not related to amyloid beta-peptide concentration 3.4.23.45 memapsin 1 medicine in patients with preclinical to late-stage Alzheimer's disease, including amnestic mild cognitive impairment, and age-matched controls, cases of frontotemporal dementia, and Down's syndrome, BACE2 protein and enzymatic activity increase as early as preclinical Alzheimer's disease and are found in neurons and astrocytes. Although the levels of total BACE2 mRNA are unchanged, the mRNA for BACE2 splice form C (missing exon 7) increases in parallel with BACE2 protein and activity. BACE1 and BACE2 are strongly correlated with each other at all levels. BACE2 is also elevated in frontotemporal dementia but not in Down's syndrome, even in patients with substantial amyloid beta deposition 3.4.23.45 memapsin 1 medicine enzyme inhibition is a treatment of type 2 diabetes 3.4.23.46 memapsin 2 medicine strategies for inhibitor design 3.4.23.46 memapsin 2 medicine development of beta-secretase inhibitors as anti-Alzheimer's disease drugs 3.4.23.46 memapsin 2 medicine roles of BACE1 in regulation postmenopausal memory effects analyzed 3.4.23.46 memapsin 2 medicine screening of natural products for anti-dementia agents 3.4.23.46 memapsin 2 medicine studies on early pathogenesis of Alzheimers disease, investigation of metal homoeostasis in relation to accumulation of amyloid beta-peptides 3.4.23.46 memapsin 2 medicine a small cohort of human subjects displays age-dependent increase in cerebrospinal fluid beta-secretase-1 activity. In Alzheimer's disease subjects, a significant decline in age-adjusted cerebrospinal fluid beta-secretase-1 activity is observed 3.4.23.46 memapsin 2 medicine BACE-1 activity is a potential biomarker in human Alzheimer's disease 3.4.23.46 memapsin 2 medicine BACE1 polymorphisms do not influence platelet membrane beta-secretase activity or genetic susceptibility for Alzheimer's disease in the Northern Irish population 3.4.23.46 memapsin 2 medicine beta-secretase is a therapeutic target for Alzheimer's disease 3.4.23.46 memapsin 2 medicine cholesterol depletion within the cellular context inhibits both beta-secretase and gamma-secretase additively and independently from each other. The parallel and additive inhibition may indicate an intrinsic cross-talk between Alzheimer disease-related amyloid precursor protein processing, amyloid precursor protein function, and lipid biology 3.4.23.46 memapsin 2 medicine common BACE1 polymorphisms and putatively functional variants have no significant influence on genetic susceptibility to Alzheimer's disease, or platelet beta-secretase activity, in the Caucasian Northern Irish population 3.4.23.46 memapsin 2 medicine genotyping of 11 single nucleotide polymorphisms covering the complete BACE1 gene reveals no single-marker or haplotypic association with Alzheimer's disease. Neither ADAM10 coding for alpha-secretase nor BACE1 present with any evidence to suggest that they are major candidate genes involved in conferring risk for Alzheimer's disease 3.4.23.46 memapsin 2 medicine in Alzheimer's disease patients displaying abnormally high BACE1 protein the microRNA miR-29a/b-1 cluster is significantly and Alzheimer's disease-dementia-specific decreased. There is a potential causal relationship between miR-29a/b-1 expression and amyloid beta generation in a cell culture model 3.4.23.46 memapsin 2 medicine membrane cholesterol significantly influences membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with Alzheimer's disease or mild cognitive impairment are significantly more likely to lie within the negative correlation zone than control platelets. Pharmacological inhibition of SH-SY5Y beta-secretase activity results in increased membrane cholesterol levels 3.4.23.46 memapsin 2 medicine the BACE1-antisense transcript regulates BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo. Upon exposure to various cell stressors including amyloid-beta 1-42 , expression of BACE1-antisense becomes elevated, increasing BACE1 mRNA stability and generating additional amyloid beta 1-42 through a post-transcriptional feed-forward mechanism. BACE1-antisense concentrations are elevated in subjects with Alzheimer's disease 3.4.23.46 memapsin 2 medicine the BACE1-antisense transcript regulates BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo. Upon exposure to various cell stressors including amyloid-beta 1-42 , expression of BACE1-antisense becomes elevated, increasing BACE1 mRNA stability and generating additional amyloid beta 142 through a post-transcriptional feed-forward mechanism. BACE1-antisense concentrations are elevated in amyloid precursor protein transgenic mice 3.4.23.46 memapsin 2 medicine BACE1 is potential drug target for the treatment of Alzheimer’s disease and Notch-driven cancer types 3.4.23.46 memapsin 2 medicine common or potentially functional genetic variation in BACE1 interacting proteins (reticulon 3 and peptidylprolyl isomerase (cyclophilin)-like 2) does not affect platelet membrane beta-secretase activity or contributes to risk of Alzheimer's disease in the northern Irish population 3.4.23.46 memapsin 2 medicine the proteolytic nanobody Asec-1A engineered to cleave amyloid-beta at its alpha-secretase site has potential therapeutic value in the treatment of Alzheimer's disease 3.4.23.46 memapsin 2 medicine BACE1 knock-out mice have markedly enhanced clearance of axonal and myelin debris from degenerated fibers, accelerated axonal regeneration, and earlier reinnervation of neuromuscular junctions, compared with littermate controls. data suggest BACE1 inhibition as a therapeutic approach to accelerate regeneration and recovery after peripheral nerve damage 3.4.23.46 memapsin 2 medicine samples from frontal cortex of both Alzheimer's disease-affected individuals and age-matched controls. BACE1 activity shows a significant positive correlation with the amount of extractable amyloid beta-peptide, and BACE1 protein and activity are significantly increased in cases of alzheimer's disease 3.4.23.46 memapsin 2 medicine activated double-stranded RNA dependant protein kinase PKR and activated eukaryotic translation initiation factor eIF2alpha and BACE1 levels are increased in Alzheimer's disease cortices and BACE1 correlates with phosphorylated eIF2alpha levels. BACE1 protein levels are increased in response to oxidative stress in SH-SY5Y cells and specific inhibitions of PKR-eIF2alpha attenuate BACE1 protein levels in this model 3.4.23.46 memapsin 2 medicine BACE1 but not gamma-secretase inhibition leads to significant lowering of plasma soluble amyloid precursor protein beta with concurrent elevation of plasma soluble amyloid precursor protein alpha. Alzheimer's disease subjects show a significant increase in plasma BACE1 activity, soluble amyloid precursor proteins alpha and beta, and amyloid beta42 compared with age-matched controls 3.4.23.46 memapsin 2 medicine the enzyme is a major drug target in Alzheimer's disease 3.4.23.47 HIV-2 retropepsin medicine - 3.4.23.47 HIV-2 retropepsin medicine potential target for chemotherapy of virus infection and associated diseases, essential for maturation of infectious virions, development of drugs against the protease should be effective against HIV-2 3.4.23.47 HIV-2 retropepsin medicine the poly(A)-binding protein is known to be cleaved by several picornaviruses and caliciviruses. The results indicate that retroviruses such as HIV share the capacity to proteolyse poly(A)-binding protein 3.4.23.47 HIV-2 retropepsin medicine the role of natural polymorphisms in the PR gene on the time to the development of resistance to proteinase inhibitors using an HIV-2 tissue culture model are examined. Natural polymorphisms in HIV-2 facilitate the selection of proteinase inhibitor resistance 3.4.23.47 HIV-2 retropepsin medicine the HIV proteases are effective therapeutic targets for treating HIV infection because of the essential role in hydrolysing the viral Gag and Gag-Pol precursor polyprotein during infectious viral particle maturation 3.4.23.48 plasminogen activator Pla medicine the Lpp Pla double mutant of Yersinia pestis CO92 is highly attenuated and it retains the ability to elicit innate and subsequent acquired immune responses in the host similar to that of wild-type CO92, which are highly desirable in a live-attenuated vaccine candidate 3.4.23.48 plasminogen activator Pla medicine the enzyme is a target for vaccine development. B-cell epitope mapping with Human Sera, three-dimensional modeling, omptins allergenicity and antigenicity prediction, overviw 3.4.23.49 omptin medicine use in therapeutic peptide production, efficient cleavage of substrates with basic amino acids at the P4 and P6 positions, able to cleave efficiently a fusion protein carrying human glucagon-like peptide I, releases mature protein from an Escherichia coli expressed fusion protein carrying human atrial natriuretic peptide, a drug for acute congestive heart failure 3.4.23.49 omptin medicine the different contributions of EHEC and EPEC strains OmpT to the degradation and inactivation of antimicrobial peptide LL-37 may be due to their adaptation to their respective niches within the host, the colon and small intestine, respectively, where the environmental cues and abundance of antimicrobial peptides are different 3.4.23.49 omptin medicine the enzyme is a target for vaccine development. B-cell epitope mapping with human sera, three-dimensional modeling, omptins allergenicity and antigenicity prediction, overview 3.4.23.50 human endogenous retrovirus K endopeptidase medicine in the present study HIV-1 and HCV-1-positive plasma samples are screened for the presence of HERV-K(HML-2) RNA in an RT-PCR using HERV-K pol specific primers. Type 1 and type 2 HERV-K(HML- 2) viral RNA genomes are found to coexist in the same plasma of HIV-1 patients suggesting that HERV-K(HML-2) viral particles are induced in HIV-1-infected individuals 3.4.24.1 atrolysin A medicine recombinant protease inhibits platelet adhesion to fibrinogen with an estimated IC50 of 1 nM. It inhibits collagen- (IC50 is 18 nM) and ADP-induced (IC50 is 6 nM) platelet aggregation, and also inhibits platelet function on clot retraction 3.4.24.1 atrolysin A medicine disintegrins found in Crotalus atrox venom may have therapeutic potential for reducing hemorrhagic transformation after ischemic stroke 3.4.24.3 microbial collagenase medicine preparations containing clostridiopeptidase A are used topically for the debridement of dermal ulcers, burns and other necrotic lesions to facilitate the formation of granulationtissue and subsequent epithelization, allergic contact dermatitis with clostridiopeptidase A contained in an ointment used for treatment of dermal ulcers may occur 3.4.24.3 microbial collagenase medicine Clostridium histolyticum collagenase can effectively digest collagen isoforms that are present in necrotic wound tissues. Collagenase treatment enhances cell migration mediated by collagenase itself and by collagen degradation products 3.4.24.3 microbial collagenase medicine construction of fusion proteins between the collagen-binding domain (CBD) and polycystic kidney disease (PKD) domain of Clostridium histolyticum class II collagenase and basic fibroblast growth factor. Both fusion proteins bFGF-CBD and bFGF-PKD-CBD promote the in vitro proliferation of periosteal mesenchymal cells. Both bFGF-CBD and bFGF-PKD-CBD induce periosteal bone formation at higher rates than collagen sheet alone and bFGF. bFGF-PKD-CBD markedly enhances bone formation and has higher collagen-binding ability than bFGF-CBD in in vitro protein release assays 3.4.24.3 microbial collagenase medicine use of collagenase from Clostridium histolyticum for management of Dupuytren's contracture providing better outcomes in patients with mild-moderate joint contracture, with lower complications and side effects than open fasciectomy, overview 3.4.24.B3 matrix metalloproteinase-11 medicine ST-3+/TIMP-2- (stromelysin-3+/matrix metalloproteinase TIMP-2)-phenotype is an adverse prognosticator in esophageal cancer patients 3.4.24.B3 matrix metalloproteinase-11 medicine ST-3 is capable of enhancing tumourigenesis in breast cancer cell lines 3.4.24.B3 matrix metalloproteinase-11 medicine stromelysin-3 is a positive marker for dermatofibroma 3.4.24.B3 matrix metalloproteinase-11 medicine MMP11 expression level is correlated with poor prognosis in advanced gastric cancer. MMP11 has great potential to be a new tumor marker in serum 3.4.24.B3 matrix metalloproteinase-11 medicine MMP11 is a novel broadly expressed tumor associated antigen and a target candidate for cancer immunotherapy. Possible use of murine MMP11 as tumor-associated antigen for vaccination of human cancer patients. MMP11 vaccine induces cell-mediated and antibody immune response and exerts significant antitumoral protection in mice with colon cancer in prophylactic and therapeutic settings 3.4.24.B3 matrix metalloproteinase-11 medicine being selectively expressed in tumor tissues, MMP-11 is a promising target for immunotherapy against tumors 3.4.24.B3 matrix metalloproteinase-11 medicine enzyme MMP-11 is an antigen target for immunotherapy 3.4.24.B4 matrix metalloproteinase-13 medicine abundant expression of enzyme and of matrix metalloproteinase 10 in keratoacanthoma. Frequent expression of transformation-specific enzyme suggests that keratoacanthomas are incomplete squamous cell carcinomas 3.4.24.B4 matrix metalloproteinase-13 medicine cartilaginous growth plate abnormalities result from enzyme deficiency in mice phenocopy defects observed in human hereditary chondrodysplasis 3.4.24.B4 matrix metalloproteinase-13 medicine change of enzyme expression in response to caries attack. Extremely high enzyme mRNA expression in pooled pulp samples of sound and carious teeth, downregulation of enzyme expression during caries progression 3.4.24.B4 matrix metalloproteinase-13 medicine during gastric ulcer healing, enzyme expression as well as matrix metalloproteinase MMP-2 and MMP-3 are induced in stromal cells of the gastric mucosa bordering the ulcer. Enzyme mRNA is confined to the upper layers of the granulation tissue 3.4.24.B4 matrix metalloproteinase-13 medicine expression of enzyme and tissue inhibitor of matrix metalloproteinase, TIMP-1, is regulated by Wnt signaling combined with bone morphogenic protein BMP-2 in osteoblastic differentiation 3.4.24.B4 matrix metalloproteinase-13 medicine high level of enzyme expression by fibroblasts achieved by adenoviral gene delivery results in potent enhancement of remodeling and contraction of 3D collagen 3.4.24.B4 matrix metalloproteinase-13 medicine percentage of enzyme-positive cutaneous malignant melanomas correlates significantly and positively with the mitotic index in invasive cutaneous malignant melanoma. No significant association between tumoral enzyme expression and relapse-free survival in patients with invasive cutaneous malignant melanoma 3.4.24.B4 matrix metalloproteinase-13 medicine selective inhibition of enzyme to inhibit cleavage of fibromodulin as a treatment for patients suffering from arthritis 3.4.24.B4 matrix metalloproteinase-13 medicine selective inhibitors for enzyme for potential use in treatment of osteoarthritis 3.4.24.B4 matrix metalloproteinase-13 medicine mRNA expressions of matrix metalloproteinase-13 is significantly enhanced in osteoarthritis subchondral bone osteoblasts compared to subchondral bone osteoblasts without osteoarthritis. The expressions of this gene is greater in patients with severe cartilage damage than in those with mild cartilage damage 3.4.24.B4 matrix metalloproteinase-13 medicine orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Two series, quinazolinones and pyrido[3,4-d]pyrimidin-4-ones, that are potent and specific MMP-13 inhibitors, some of which are orally bioavailable. These specific MMP-13 inhibitors, occupying the unique S1'-specificity pocket, do not bind to the Zn2+ ion, effectively preventing cartilage damage in animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats 3.4.24.B4 matrix metalloproteinase-13 medicine tumor-derived, but not stromal fibroblast-derived, MMP-13 correlates with aggressive tumor phenotypes, and inversely correlated with the overall survival of breast cancer patients. MMP-13 may serve as an independent prognostic factor for invasive breast cancer patients. MMP-13 may be particularly useful as a prognostic marker when evaluated along with Her-2/neu and lymph node status 3.4.24.B4 matrix metalloproteinase-13 medicine MMP13 is a potential therapeutic target for breast cancer bone metastasis 3.4.24.B4 matrix metalloproteinase-13 medicine in a collagen-induced arthritis model, MMP-12 and MMP-13 activity probes based on derived from substrates Y(NO2)GPLG-LEEAK(Abz)G-NH2 and Y(NO2)GPAG-LYEK(Abz)G-NH2, respectively, discriminate between the activities of the 2 enzymes. In the disease model, MMP13 activity probe activation increases gradually after disease onset and correlates with disease severity over a longer period of 15 days 3.4.24.B4 matrix metalloproteinase-13 medicine patients with alcoholic liver cirrhosis (stage A, B, C) display increased blood serum levels of MMP13 and reduced concentrations of glutamic acid and glutamine compared to the control group. No significant differences are observed in the activity of MMP1 in alcoholics with or without liver cirrhosis or in controls 3.4.24.B5 matrix metalloproteinase-15 medicine MMP-15 can protect cells of various cancer types from cell death in vitro, connects metastasis and apoptosis resistance by an unknown regulatory mechanism 3.4.24.B5 matrix metalloproteinase-15 medicine MMP-15 is downregulated in experimental autoimmune encephalomyelitis, expression of MMP-15 correlates with disease course 3.4.24.B5 matrix metalloproteinase-15 medicine significant positive correlation between transcript expression and tumour grade for MMP-15 3.4.24.B6 matrix metalloproteinase-20 medicine critical role of MMPs in the processing and maturation of the dental matrix 3.4.24.B6 matrix metalloproteinase-20 medicine first report of a homozygous mutation in the MMP-20 gene, the mutation destroys the splice acceptor sequence at the 3' end of intron 6 encoding the hemopexin domain, the enamel of the subjects' teeth is pigmented, its surface mottled and rough and the enamel layer more opaque than the underlying dentine 3.4.24.B6 matrix metalloproteinase-20 medicine study on the hypothesis that MMP-20 is overexpressed in the dentin-enamel junction, dentin-pulp complex components, and carious dentin of patients that head-and-neck radiotherapy. No apparent damage to the dentin-enamel junction microstructure or other dentin-pulp complex components is observed and no statistically significant differences are detected in MMP-20 expression between the irradiated and control groups 3.4.24.7 interstitial collagenase medicine glycine-extended gastrin renders colon cancer cells more invasive by increasing MMP-I expression via the putative glycine-extended gastrin receptor and would thus be a good molecular target in a clinical setting 3.4.24.7 interstitial collagenase medicine high level expression of MMP-14 and MMP-2 are observed in ovarian clear cell carcinoma relative to other histotypes 3.4.24.7 interstitial collagenase medicine in leg ulcer tissue from patients with chronic venous insufficiency, matrix metalloproteinases MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 protein levels are elevated. Following compression therapy, reduction of MMP-1, MMP-2, and MMP-3 levels is associated with significantly higher rates of ulcer healing at 4 weeks 3.4.24.7 interstitial collagenase medicine in ovariectomized rats, during the first 1-4 weeks there is a significant increase in collagen accumulation and an increase MT1-MMP expression. Although active-form matrix metalloproteinase MMP-2 and collagen progressively return to normal levels, the markedly increased collagen deposition appears again at 8 weeks and persists until 12 weeks, followed by induction of MMP-2 and MT1-MMP at 12 weeks 3.4.24.7 interstitial collagenase medicine in tear samples of vernal keratoconjunctivitis patients, matrix metalloproteinase-1, matrix metalloproteinase-2, matrix metalloproteinase-3, matrix metalloproteinase-9 and matrix metalloproteinase-10 are highly present in all samples 3.4.24.7 interstitial collagenase medicine investigation on the relation of serum matrix metalloprotease MMP-1 and vascular endothelial growth factor VEGF-A concentrations to cardiac allograft rejection. Mean week 1 and week 2 serum MMP-1 concentrations predict rejection. At the optimal cutoff level of >7.5 ng/ml, MMP-1 predicts rejection with 82% sensitivity and 72% specificity. Initial serum MMP-1 <5.3 ng/ml is associated with rejection-free outcome in 80% of patients. Both MMP-1 and VEGF-A predict rejection on the next endomyocardial biopsies, while rejection at endomyocardial biopsy is identified only by VEGF-A. Patients receiving combined cyclosporine-A and everolimus have the lowest serum MMP-1 concentrations. While serum MMP-1 predicts rejection-free outcome and VEGF-A identifies rejection on endomyocardial biopsy, both markers predict rejection in follow-up of cardiac transplant recipients 3.4.24.7 interstitial collagenase medicine MMP-8, MMP-9, and to a lesser extent, MMP-2, MMP-3, MMP-11 and MMP-12 are present at higher levels in lung secretions of pediatric acute lung injury patients compared with controls. Almost all MMP-8 detected at later disease course is constitutively active, while in subjects who remain intubated for >10 days, MMP-9 activity decreases 3.4.24.7 interstitial collagenase medicine patients who underwent direct current electrical cardioversion for persistent atrial fibrillation have increased levels of C-reactive protein and lower levels of MMP-1 compared with controls. There are no differences in baseline levels of C-reactive protein, MMP-1, TIMP-1 and carboxyterminal telopeptide of collagen type I between those where electrical cardioversion was unsuccessful, compared to those with immediate EC success. Patients who maintain sinus rhythm at 30 days' follow-up have lower levels of C-reactive protein 3.4.24.7 interstitial collagenase medicine protease activity is localized at the polarized leading edge of migrating tumor cells rather than further back on the cell body. Activity is essential for cell migration in native cross-linked but not pepsin-treated collagen matrices 3.4.24.7 interstitial collagenase medicine MMP-1 suppressor Costaria costata fucoidan is a potential therapeutic agent for the prevention and treatment of photoaging of the skin 3.4.24.7 interstitial collagenase medicine MMP-1-mediated fragmentation of dermal collagen fibrils alters the morphology and function of dermal fibroblasts, linking collagen fibril fragmentation to age-related decline of fibroblast function 3.4.24.B7 matrix metalloproteinase-26 medicine expression of matrilysin-2 is significantly correlated with nuclear beta-catenin expression and MMP-9 expression. Patients with matrilysin-2-positive cancer have significantly shorter overall and disease-free survival periods than those with matrilysin-2 negative cancer. Matrilysin-2 expression retains its significant predictive value for overall and disease-free survival in multivariate analysis. Patients with concomitant expression of matrilysin-2 and MMP-9 have the worst prognosis 3.4.24.B7 matrix metalloproteinase-26 medicine MMP-26 is a valuable cancer marker, that contributers favorably to the survival of the estrogen receptor alpha/beta-positive cohort of breast cancer patients 3.4.24.B7 matrix metalloproteinase-26 medicine MMP-26 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as marker for early prostate cancer diagnosis 3.4.24.B7 matrix metalloproteinase-26 medicine matrix metalloproteinase-26 is a marker of melanomas and estrogen-dependent carcinomas 3.4.24.B7 matrix metalloproteinase-26 medicine matrix metalloproteinase MMP26 level is significantly higher in the resected chondrosarcoma than in the adjacent healthy chondral tissue from patients. Overexpression of MMP26 in SW-1353 cells increases cell invasiveness, while inhibition of MMP26 decreases cell invasiveness. Inhibition of Wnt signaling significantly decreases the effect of MMP26 on cancer cell invasion. A strong correlation is detected between MMP26 levels and the ratio of phosphorylated/total beta-catenin in chondrosarcoma from the patients 3.4.24.B7 matrix metalloproteinase-26 medicine slight, but significant, downregulation of MMP-26 in more degenerated intervertebral discs (Thompson grades III, IV and V) compared to healthier discs, while both TGF-beta and latent transforming growth factor-beta binding protein 2 are significantly and strongly upregulated 3.4.24.B7 matrix metalloproteinase-26 medicine all umbilical cord tissues, both control and preeclamptic, express MMP-26 and issue inhibitor of matrix metalloproteinase TIMP-4 in macromolecular complexes. Preeclampsia induces a significant increase in the content and actual activity of MMP-26 in umbilical cord vein and Wharton's jelly. The content of TIMP-4 in preeclamptic umbilical cord vein and Wharton's jelly is reduced. The content of MMP-26 mRNA is lower in umbilical cord arteries and veins, whereas higher in Wharton's jelly in preeclampsia 3.4.24.B7 matrix metalloproteinase-26 medicine in astrocytic glioma, MMP-26 expression is significantly associated with the World Health Organization grade. MMP-26 expression is an independent factor for evaluating the prognosis of astrocytic glioma patients 3.4.24.B7 matrix metalloproteinase-26 medicine MMP-26 expression levels in androgen-repressed human prostate cancer cells, transfected with sense or anti-sense MMP-26 cDNA, and in benign, neoplastic, and invasive prostate cancer tissues are directly correlated with those of the pro-apoptotic marker Bax. The MMP-26 protein levels are upregulated in high grade prostate intraepithelial neoplasia and decrease during the course of disease progression 3.4.24.B8 ADAM1 endopeptidase medicine crucial role of ADAM1b/ADAM2 fertilin not in the sperm/egg fusion, but in the appearance of these two ADAMs on the sperm surface 3.4.24.B8 ADAM1 endopeptidase medicine loss of ADAM1a results in male infertility due to severely impaired ability of sperm to migrate from the uterus into the oviduct through the uterotubul junction 3.4.24.B9 ADAM9 endopeptidase medicine all three enzymes ADAM9, ADAM12, and ADAM15 are significantly upregulated in gastric cancer compared to non-neoplastic foveolar epithelium. Anti-ADAM9 and anti-ADAM15 antibodies inhibit cell growth 3.4.24.B9 ADAM9 endopeptidase medicine elevated level of enzyme in malignant compared to benign prostate tissue. Increase in enzyme protein and mRNA upon exposure of prostate cells to stress conditions. Inhibition of stress-induction of enzyme by actinomycin D and cycloheximide. Decrease of enzyme expression results in apoptotic cell death in prostate cancer cells 3.4.24.B9 ADAM9 endopeptidase medicine enzyme overexpression in A-549 and EBC-1 cells results in increased invasive capacity in response to nerve growth factor, increased adhesion to brain tissue, and increased expression of integrin alpha3 and beta1 subunits. Administration of enzyme overexpressing A-549 cells to mice results in micrometastatic foci in brain and multiple metastatic colonies in the lungs 3.4.24.B9 ADAM9 endopeptidase medicine in melanoma, enzyme expression is restricted to the melanoma cells within the invading front. Enzyme is detected in melanoma cells and in peritumoral stromal fibroblasts, but absent in fibroblasts distal to the tumor site. In melanoma cell lines, enzyme is expressed in varying amounts in all cell lines studied. Downregulation of enzyme expression upon culture of cells within 3-dimensional latticies of fibrillar type I collagen, but not in the polysaccharide alginate 3.4.24.B9 ADAM9 endopeptidase medicine lung cancer cell line EBC-1, enzyme mRNA levels are significantly higher in highly brain-metastatic sublines than in the parent or highly bone-metastatic sublines 3.4.24.B9 ADAM9 endopeptidase medicine secreted form of enzyme promotes carcinoma invasion through tumor-stromal interactions 3.4.24.B9 ADAM9 endopeptidase medicine significantly higher level of enzyme expression in malignant plasma cells than in other cell populations present in bone marrow 3.4.24.B9 ADAM9 endopeptidase medicine injection of murine melanoma cells into the flank of ADAM-9-/- animals resultsin the development of significantly larger tumors than in wild-type animals as a result of increased proliferation and decreased apoptosis of melanoma cells 3.4.24.B9 ADAM9 endopeptidase medicine aberrant overexpression of ADAM9 is found in both gastric cancer tissues and cell lines. The expression of ADAM9 is significantly correlated with patient clinicopathological features including tumor size, local invasion, lymph node metastasis and tumor-node-metastasis stage. Knockdown of ADAM9 in gastric cancer SGC-7901 cells, which present the highest ADAM9 expression among the cell lines, induces a dramatic suppression of cell proliferation along with the arrest of the cell cycle in the G0/G1 phase. The 3' untranslated region of ADAM9 mRNA may be bound by miR-126, a suppressor in gastric cancer. Overexpression of miR-126 significantly downregulates ADAM9 in the gastric cancer cells 3.4.24.B9 ADAM9 endopeptidase medicine ADAM9 enhances the expression of the pro-migratory protein CDCP1 to promote lung metastasis. Endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 is associated with high migration ability in lung cancer cells 3.4.24.B9 ADAM9 endopeptidase medicine ADAM9 staining is increased in lung epithelial cells and macrophages in smokers and even more so in patients with chronic obstructive pulmonary disease COPD. ADAM9 staining correlates directly with pack-year smoking history and inversely with airflow obstruction and/or FEV1 percent predicted. Bronchial epithelial cell ADAM9 mRNA levels are higher in patients with COPD than control subjects and correlate directly with pack-year smoking history 3.4.24.B9 ADAM9 endopeptidase medicine cells lacking ADAM9 show a significant reduction in infection efficiency by encephalomyocarditis virus EMCV. Pharmacological inhibition of the metalloproteinase activity of ADAM9 does not affect virus infection. Reconstitution of inactive ADAM9 in knockout cells restores susceptibility to EMCV. ADAM9 facilitates attachment of EMCV to the cell surface 3.4.24.B10 ADAM12 endopeptidase medicine implication in Alzheimer's disease, arthritis, and cancer 3.4.24.B10 ADAM12 endopeptidase medicine tumor development and progression 3.4.24.B10 ADAM12 endopeptidase medicine tumor progression 3.4.24.B10 ADAM12 endopeptidase medicine tumor progression, cell apoptosis 3.4.24.B10 ADAM12 endopeptidase medicine ADAM12 represents a potential therapeutic target in breast cancer 3.4.24.B10 ADAM12 endopeptidase medicine low serum levels of the enzyme are associated with spontaneous pre-term delivery and IUGR 3.4.24.B10 ADAM12 endopeptidase medicine specific isoform ADAM12-L inhibition can optimize 5-fluorouracil-based chemotherapy of breast cancer 3.4.24.B10 ADAM12 endopeptidase medicine the enzyme is a predictor of chemoresistance in estrogen receptor-negative tumors 3.4.24.11 neprilysin medicine neprilysin can reduce the size and number of Abeta deposits in a transgenic mouse model. Neprilysin gene transfer therapy or other methods to increase endogenous neprilysin activity have the potential to prevent the accumulation of the amyloid Abeta peptide and as such may be able to prevent or delay the onset of Alzheimer#s disease 3.4.24.11 neprilysin medicine CD10, i.e. beta-secretase, expression is detected in 62.2% of prostate cancer samples and occurs preferentially in higher Gleason pattern. CD10 expression positively correlates with adverse tumor features such as elevated preoperative prostate-specific antigen, higher Gleason score, and advanced stage. Prostate-specific antigen recurrence is significantly associated with the staining pattern of CD10 expression. Outcome significantly declines from negative over membranous, membranous-cytoplasmic, to exclusively cytoplasmatic CD10 expression. In multivariate analysis, CD10 expression is an independent predictor for prostate-specific antigen failure 3.4.24.11 neprilysin medicine expression of neprilysin on the surface of leukocytes in mouse model of Alzheimer's disease reduces soluble brain amyloid beta peptide levels by 30% and lowers the accumulation of amyloid beta peptides by 50-60% when transplantation is performed at both young and early adult age. Peripheral neprilysin expression reduces amyloid-dependent performance deficits as measured by the Morris water maze test. Neprilysin expression results in the catabolism of amyloid beta to small, innocuous peptide fragments 3.4.24.11 neprilysin medicine impaired cardiopulmonary vagal reflex control of heart rate is a feature of normal aging, and this deficit may be ameliorated by either atrium natriuretic peptide infusion or chronic neutral endopeptidase inhibition 3.4.24.11 neprilysin medicine in the Flemish variant of amyloid beta, resistance to degradation by nepriylsin may underlie the pathogenicity associated with the A21G mutantion in amyloid beta 3.4.24.11 neprilysin medicine overexpression neprilysin at low levels in transgenic mouse affects primarily the levels of neuropeptide Y compared with other neuropeptides. Neprilysin cleaves neuropeptide Y in C-terminal fragments, whereas silcencing neprilysin reduces neuropeptide Y processing. Infusion of the most abundant neuropeptide Y fragments 21-36 and 31-36 into the brain of amyloid precursor protein transgenic mice ameliorates the neurodegenerative pathology in this model. The amidated neuropeptide Y fragments protect human neuronal cultures from the neurotoxic effects of amyloid beta 3.4.24.11 neprilysin medicine overexpression of human neprilysin for 4 months in young amyloid precursor protein//DeltaPS1 double-transgenic mice results in reduction in amyloid beta peptide levels, attenuation of amyloid load, oxidative stress, and inflammation, and improved spatial orientation. The overall reduction in amyloidosis and associated pathogenetic changes in the brain results in decreased memory impairment by about 50% 3.4.24.11 neprilysin medicine sustained expression of a lentiviral vector carrying the neprilysin gene in amyloid precursor protein transgenic mice for up to 6 months lowers not only the amyloid plaque load but also reduces the levels of intracellular amyloid beta immunoreactivity. This is associated with improved behavioral performance in the water maze test and ameliorates the dendritic and synaptic pathology in the amyloid precursor protein transgenic mice 3.4.24.11 neprilysin medicine engineered neprilysin can be a therapeutic for Alzheimer's disease due to its ability to degrade the peptide amyloid beta 3.4.24.11 neprilysin medicine since accumulation of neurotoxic amyloid beta peptide aggregates in the brain appears to be a causative agent in the pathophysiology of Alzheimer's disease, increased clearance of amyloid beta peptide resulting from overexpression of the enzyme exhibits therapeutic potential for Alzheimer's disease 3.4.24.11 neprilysin medicine the enzyme is a potential therapeutic source for degradation of deposited amyloid beta in Alzheimer's disease 3.4.24.11 neprilysin medicine NEP is a target for Entresto used in treatment of heart failure 3.4.24.11 neprilysin medicine upregulation of neprilysin (NEP) to reduce amyloid-beta (Abeta) accumulation in the brain is a promising strategy for the prevention of Alzheimer's disease (AD) 3.4.24.B11 ADAMTS1 endopeptidase medicine tumor growth inhibitor 3.4.24.B11 ADAMTS1 endopeptidase medicine in men not on pravastatin, those homozygous for the 227Pro allele of ADAMTS1 have a nearly 2-fold increased risk of coronary heart disease events compared with noncarriers. In this high-risk group, treatment with pravastatin is highly efficacious, reducing the odds of fatal coronary disease or nonfatal myocardial infarction by approximately 75%, as compared with 25% in noncarriers or heterozygotes 3.4.24.B11 ADAMTS1 endopeptidase medicine ADAMTS1, ADAMTS5 and follicle stimulating hormone receptors are expressed 2.56, 2.10, and 2.66fold less in Sertoli cells of NOA patients, than those of obstructive azoospermia. After recombinant follicle stimulating hormone is added onto Sertoli cell cultures of patients with nonobstructive azoospermia, their expression does not increase significantly and does not reach to levels of control group. Expression of ADAMTS1 and ADAMTS5 are insignificantly 1.03 and 1.1fold higher in obstructive azoospermia group, respectively. In the nonobstructive azoospermia group, their expressions are 1.70 and 1.96fold lower, respectively, when compared with the fertile control 3.4.24.B11 ADAMTS1 endopeptidase medicine expression of a majority of the investigated ADAMTS members ADAMTS-1, 4,5,6,8,9,10,13,17 on mRNA level is decreased in aneurysm compared to control aorta. ADAMTS-1 is one of the members that is reduced most. ADAMTS-1 is present predominantly in areas of smooth muscle cells and macrophages in aneurysmal aorta and higher expressed in abdominal aortic aneurysm compared to control aortas 3.4.24.B11 ADAMTS1 endopeptidase medicine mean serum ADAMTS-1 level is increased in adolescents and younger-aged females with polycystic ovary syndrome (PCOS) compared to ovulatory controls. An elevated ADAMTS-1 level is positive predictive of the diagnosis of PCOS with the best cut-off value of 2.5 ng/ml. A positive predictive role of ADAMTS-1 on the development of cardiovascular disease risk and insulin resistance is found among all patients. Serum ADAMTS-1 and aggrecan levels are significantly and positively correlated with each other 3.4.24.B11 ADAMTS1 endopeptidase medicine strong, diffuse staining is observed throughout myocardial tissue for ADAMTS1 both in individuals who died of myocardial infarction and a group who died of trauma. Among patients who died of myocardial infarction, no expression for ADAMTS1 is observed around fibrotic areas but slight staining in coagulative and necrotic zones 3.4.24.B11 ADAMTS1 endopeptidase medicine syngeneic B16F1 melanoma model in wild type and ADAMTS1 knockout mice. Genetic deletion of ADAMTS1 in the host microenvironment results in a drastic decrease of tumor growth and metastasis. Reduced tumors in ADAMTS1 KO mice display a paradoxical increase in vascular density and vascular-related genes with an impaired vasculature, along with a minor infiltration of macrophages. ADAMTS1is involved in vascular sprouting, and melanoma xenografts show a relevant induction of its expression in stroma compartments 3.4.24.B12 ADAMTS5 endopeptidase medicine potential target for treatment of osteoarthritis 3.4.24.B12 ADAMTS5 endopeptidase medicine the first thrombospondin type 1 repeat domain of ADAMTS5, unlike the second, has anti-angiogenic activities, ADAMTS5 is therefore an anti-angiogenic peptide and may serve as a prototype for future development into anti-cancer drugs 3.4.24.B12 ADAMTS5 endopeptidase medicine therapeutic target in osteoarthritis 3.4.24.B12 ADAMTS5 endopeptidase medicine stop progression of cartilage degradation in osteoarthritis by prevention of aggrecan cleavage via inhibition of aggrecanase 3.4.24.B12 ADAMTS5 endopeptidase medicine a single injection of ADAMTS5 siRNA induces the suppression of degradation in nucleus pulposus tissues 3.4.24.B12 ADAMTS5 endopeptidase medicine ADAMTS5 is a biomarker for prediction of response to Infliximab in patients with rheumatoid arthritis 3.4.24.B12 ADAMTS5 endopeptidase medicine design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5, which may be required for chronic osteoarthritis therapy 3.4.24.B12 ADAMTS5 endopeptidase medicine ADAMTS-5 is the main aggrecanase in laryngeal squamous cell carcinoma presenting a stage-related increase up to stage III (8fold higher expression compared to normal), and thereafter decreased in stage IV. ADAMTS-5 is highly expressed by carcinoma cells. Within the cancerous and their corresponding macroscopically normal laryngeal tissues, an altered distribution and organization of multiple molecular forms (latent, activated and fragmented forms) of the enzymes is found 3.4.24.B12 ADAMTS5 endopeptidase medicine overexpression of full-length ADAMTS5 suppresses B16 melanoma growth in mice. The reduced tumor growth is correlated with diminished tumor angiogenesis, together with reduced tumor cell proliferation and increased tumor cell apoptosis 3.4.24.B12 ADAMTS5 endopeptidase medicine the enzyme is a diagnostic marker in azoospermia 3.4.24.13 IgA-specific metalloendopeptidase medicine bacterial IgA proteases are potential candidates as vaccine 3.4.24.13 IgA-specific metalloendopeptidase medicine three of the igA gene restriction types, which appear to represent 98% of the Haemophilus influenzae serotype b population, encode IgA1 proteases that are inhibited by antisera to any one of theses types and therefore could form the basis for the development of a vaccine against Haemophilus influenzae meningitis 3.4.24.13 IgA-specific metalloendopeptidase medicine enzyme is a major Streptococcus pneumoniae antigen in humans 3.4.24.13 IgA-specific metalloendopeptidase medicine enzyme, as well as pneumococcal proteins alpha-enolase, immunoglobulin streptococcal lipoprotein rotamase A, and putative proteinase maturation protein A are immunogenic proteins that elicit antibody response early in life. No significant correlation between antibody titers to these proteins and pneumococcal carriage or infection 3.4.24.13 IgA-specific metalloendopeptidase medicine the broad and specific recognition of the epiA polypeptide by human sera demonstrate that the pneumococcal IgA1 protease contains an immunodominant B-cell epitope 3.4.24.13 IgA-specific metalloendopeptidase medicine systemically administered IgA protease is able to remove glomerular IgA immune complexes, both the antigen and antibody components, in a passive mouse model of IgA nephropathy. IgA protease decreases the amount of injected human IgA immune complexes deposited in the kidneys in vivo. The quantity of deposited complexes is reduced by digestion of IgA1 at a single site, the peptide bond between amino acid residues 231-232 in each alpha chain 3.4.24.13 IgA-specific metalloendopeptidase medicine IgA1 protease may be an effective therapeutic candidate for IgAN by removing the mesangial deposited IgA1 in glomerular mesangium leading to immunoglobulin A nephropathy. The removal of IgA1 by IgA1 protease may separate the IgA1-containing immune complexes thereby eliminating its other components at the same time 3.4.24.13 IgA-specific metalloendopeptidase medicine IgA1 protease is a surface protective antigen of Streptococcus suis serotype 2 (SS2), immunization with purified recombinant IgA1 protease (amino acid residues 600-1926) induces high IgG antibody titers and confers complete protection against a challenge with a lethal dose of SS2 in a mouse model. rIgAP emulsified with a Marcol 52-based adjuvant can induce high titers of specific IgG antibodies, including high levels of antibodies with bactericidal activity in the presence of phagocytes, as well as confer good protection against SS2 infection. The virulence-associated protein IgA1 protease is a protective antigen and one of promising and effective vaccine candidates against SS2 3.4.24.13 IgA-specific metalloendopeptidase medicine immunization of animals with IgA1pr MA28-P1004LEH6 or proteins I, II, III provides the formation of immunological memory and can protect against both meningococcal and a number of pneumococcal fatal infections. Protective properties of meningococcal IgA1pr MA28-P1004LEH6 and proteins I, II, III against pneumococci may be attributed to their conformational epitopes close in structure to epitopes of pneumococcal surface proteins. In the model of passive animal protection, sera from rabbits immunized with Streptococcus pneumoniae of different serotypes are shown to be capable of animal protection from infection with Neisseria meningitidis, at least serogroup B. Pneumococcal and meningococcal infections can cause a crossprotective effect. This makes meningococcal IgA1 proteases and their recombinant derivatives the potential components of polyvalent vaccines 3.4.24.B14 neprilysin-2 medicine altered NEP2 expression in mild cognitive impaired patients may potentially serve as preclinical markers for Alzheimer's disease and reduced NEP2 activity may be associated with the development of Alzheimer's disease 3.4.24.15 thimet oligopeptidase medicine enzyme is involved in extracellular activation of CPI-0004Na prodrug 3.4.24.B15 PHEX peptidase medicine alterations in the PHEX expression underlie X-linked hypophosphatemia 3.4.24.B15 PHEX peptidase medicine both male and female hypophosphatemic mice at 9 months of age have a mineral phenotype that is corrected by osteoblast-specific expression of the hPHEX gene. The morphometric phenotype and the serum chemistry, however, are not fully corrected 3.4.24.B15 PHEX peptidase medicine PHEX is the key enzyme in the pathogenesis of X-linked hypophosphatemic rickets. Mutational analysis of the PHEX gene reveals three point mutations and two amino acid changes which may be rare polymorphisms, as well as a small deletion, found as a mosaic in the affected patient. Early diagnosis of possibly affected children by molecular genetic analysis is of great importance because it allows early therapeutic intervention before manifestation of skeletal deformities occurs, thereby improving the clinical outcomes 3.4.24.B15 PHEX peptidase medicine the present genetic study of a large cohort of hypophosphatemic patients (209 patients representing 118 pedigrees) highlights the major role played by mutations in the PHEX gene as the cause of familial hypophosphatemic rickets. PHEX mutations are found in 79% of all proband 3.4.24.B15 PHEX peptidase medicine X-linked hypophosphatemia is a dominant disorder of phosphate homeostasis characterized by growth retardation, rachitic and osteomalacic bone disease, hypophosphatemia, and renal defects in phosphate reabsorption and vitamin D metabolism. The gene responsible for XLH is identified by positional cloning and designated PHEX (formerly PEX) to depict a phosphate regulating gene with homology to endopeptidases on the X chromosome 3.4.24.B15 PHEX peptidase medicine a PHEX splice acceptor mutation is found in intron 9 (c.1080-3C>A) in a family with 3 affected individuals with hypophosphatemic rickets. A sporadic case with hypophosphatemic rickets from the Indian subcontinent revealed PHEX mutation (c.1211_1215delACAAAinsTTTACAT, p.Asp404Valfs*5, de novo) located in exon 11. Analysis of all human splice sites adjacent to all 327293 exons across 81814 transcripts among 20345 human genes revealed that cytosine is, with 64.3%, the most frequent nucleobase at the minus 3 splice acceptor position, followed by thymidine with 28.7%, adenine with 6.3%, and guanine with 0.8% 3.4.24.B15 PHEX peptidase medicine identification of mutations c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887+-22,395,767del (179880 bp deletion including exon 16+-22 and ZNF645) in patients with hypophosphatemia. Patients with de novo PHEX mutations often have delayed diagnosis and significantly shorter in height than those who have inherited PHEX mutations. Compound heterzygous mutations in SLC34A3 are found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14 3.4.24.16 neurolysin medicine plays an important role in endothelium-mediated vasoregulation 3.4.24.B16 protease lasA medicine LasA protease is effective in the treatment of experimental Staphylococcus aureus keratitis in rabbits, in both early- and late-treatment protocols the clinical scores for eyes treated with LasA protease are significantly lower than those for the eyes of corresponding controls 3.4.24.B16 protease lasA medicine staphylolysin is effective in the treatment of experimental methicillin-resistant Staphylococcus aureus-induced endophthalmitis in rats, and causes no morphological adverse effects to ocular tissues. Staphylolysin may be beneficial in the treatment of Staphylococcus aureus endophthalmitis in humans 3.4.24.B16 protease lasA medicine LasA protease is an effective therapeutic agent for Staphylococcus aureus experimental keratitis. The enzyme provides long-lasting protection against several strains of Staphylococcus aureus (MSSA, MRSA COL, MRSA 02/48406, and MRSA 02/48103) with IC50 values of 0.0018-0.005 mg/ml 3.4.24.B16 protease lasA medicine presence of Pseudomonas aeruginosa alters Staphylococcus aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner. LasA endopeptidase potentiates lysis of Staphylococcus aureus by vancomycin. Vancomycin treatment of a Staphylococcus aureus mouse burn infection is potentiated by the presence of a LasA-producing Pseudomonas aeruginosa population 3.4.24.B16 protease lasA medicine the expression of LasA and LasB genes is decreased by Satureja khuzistanica essential oil extract. The MICs of the extract for different multidrug resistant isolates are 8-12 microg/ml 3.4.24.17 stromelysin 1 medicine attractive target for pharmaceutical design, implicated in diseases such as arthritis and cancer 3.4.24.17 stromelysin 1 medicine important target for inhibitor design and synthesis because of the widespread implications in arthritis, cancer, and cardiovascular disease 3.4.24.17 stromelysin 1 medicine MMP inhibitor development is the target of considerable effort within the pharmaceutical industry, MMP activity can contribute to the pathologies of cancer invasion and metastasis, arthritis, autoimmune disease, tissue ulceration, or cardiovascular disease 3.4.24.17 stromelysin 1 medicine MMP proteolysis contributes to tissue degeneration and inflammation in osteo and rheumatoid arthritis and may also play a role in the spread of such diseases, abnormally high concentrations of MMPs have been identified in human tissue surrounding invasive carcinomas, indicating a local imbalance in the MMP-TIMP equilibrium which directly enables tumor metastasis through EMP degradation and blood vessel formation 3.4.24.17 stromelysin 1 medicine overexpression of MMps is associated with a variety of diseases ranging from periodontal disease and arthritis to tumor invasion and metastasis 3.4.24.17 stromelysin 1 medicine proteolytic activity of the enzyme is precisely regulated by endogenous tissue inhibitors, disruption of this balance results in diseases such as arthritis, atherosclerosis, tumour growth and metastasis 3.4.24.17 stromelysin 1 medicine development of natural pharmacological inhibitors of enzyme: Proenzyme is proteolytically activated by plasmin. C18 unsaturated fatty acids are inhibitory, with elaidic acid totally abolishing the activation. Inhibitory effect result from binding of unsaturated fatty acids to kringle 5 3.4.24.17 stromelysin 1 medicine during gastric ulcer healing, enzyme expression as well as matrix metalloproteinase MMP-2 and MMP-13 are induced in stromal cells of the gastric mucosa bordering the ulcer. Enzyme mRNA is confined to the upper layers of the granulation tissue 3.4.24.17 stromelysin 1 medicine enzyme may be involved in the pathogenesis of endometriosis. Endometrial expression of enzyme, matrix metalloproteinases MMP-2 and MMP-11 and tissue inhibitor metalloproteinases TIMP-1 and TIMP-2 are similar in women with endometriosis and in those with peritoneal endometriosis. Expression of enzyme and matrix metalloproteinases MMP-2 and MMP-11 is higher in colorectal endometriosis than in ovarian and peritoneal endometriosis 3.4.24.17 stromelysin 1 medicine enzyme overexpression im lymphoma transfectants significantly improves their ability to migrate through the matrix. Animals injected with lymphoma cells expressing enzyme constitutively develop thymic lymphoma more rapidly than those injected with control cells. Local expression of enzyme promotes lymphoma progression 3.4.24.17 stromelysin 1 medicine no significant elevation in serum levels of enzyme and tissue inhibitor proteinase TIMP-1 of patients with malignant melanoma compared to control. Enzyme levels are significantly different in sera of males and females 3.4.24.17 stromelysin 1 medicine significantly higher levels of enzyme, soluble Fas and soluble Fas ligand are found in sera from patients with active untreated adult onset Still’s disease compared to healthy control. Serum levels of enzyme, soluble Fas and soluble Fas ligand fluctuate and are parallel to disease activity 3.4.24.17 stromelysin 1 medicine wild-type and enzyme null mutant animals, chemical carcinogenesis by 1-methyl-3-nitro-1-nitroso-guanidine or by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. No difference in tumor onset or incidence between wild-type and enzyme null mutant animal, but tumors originating on mutant mice have enhanced initial tumor growth coupled with with an elevated proliferative index and reduced vasculature density 3.4.24.17 stromelysin 1 medicine topical treatment of chronic dermal ulcers 3.4.24.17 stromelysin 1 medicine the 5A/6A polymorphism of the MMP3 gene influences arterial remodeling of the common carotid artery in healthy subjects, but not in patients with diabetes mellitus. Therefore, the significance of the 5A/6A polymorphism as a marker of risk in this high cardiovascular risk population seems to be somehow blunted 3.4.24.17 stromelysin 1 medicine serum MMP-3 is significantly elevated in ankylosing spondylitis patients with active disease 3.4.24.18 meprin A medicine animals treated with streptozocin, representing a model of type 1 diabetes mellitus, show inverse relationship between renal enzyme content and the severity of the renal injury 3.4.24.18 meprin A medicine db/db mice lacking the hypothalamic leptin receptor, representing a model of type 2 diabetes mellitus, manifest decreased enzyme and meprin-beta gene and protein expression before the development of overt kidney disease. Inverse relationship between renal enzyme content and the severity of the renal injury. Treatment with an inhibitor of angiotensin-converting enzyme is more effective than ANG II receptor type I blocker therapy in ameliorating diabetic nephrosis 3.4.24.18 meprin A medicine no significant differences in the overall excretion patterns among patients with diabetes mellitus compared with the nephrotic-range proteinuria group and control 3.4.24.18 meprin A medicine genetic association of gene MEP1A encoding the alpha-subunit of meprin A with inflammatory bowel disease in patients with ulcerative colitis. Meprin-alpha mRNA is decreased in inflamed mucosa of patients with ulcerative colitis 3.4.24.18 meprin A medicine meprin A subunit alpha knock-out mice exhibit a more severe intestinal injury and inflammation than their wild-type counterparts following oral administration of dextran sulfate sodium 3.4.24.18 meprin A medicine meprin alpha is a therapeutic target in cardiovascular diseases or in tumor growth inhibition 3.4.24.18 meprin A medicine meprin inhibition is therapeutically useful in atherosclerosis prevention 3.4.24.B18 m-AAA protease medicine all of the autosomal dominant mutations, such as N432T and R468C, localize to intersubunit interfaces of the hexamer, including the lateral interface between adjacent ATPase subunits where the nucleotide binding pocket is formed, the tightly interconnected helices that dominate the lateral interface of the protease domain, and the central protrusion of the AFG3L2 protease ring that is involved in substrate transfer to the protease domains 3.4.24.19 procollagen C-endopeptidase medicine procollagen C-proteinase inhibition may be a suitable target for the reduction of hypertrophic scarring 3.4.24.19 procollagen C-endopeptidase medicine secreted Frizzled-related protein sFRP2 serves as a direct enhancer of procollagen C proteinase activity of tolloid-like metalloproteinases. The level of fibrosis, in which procollagen processing by tolloid-like proteinases has a rate-limiting role, is markedly reduced in Sfrp2-null mice subjected to myocardial infarction. This reduced level of fibrosis is accompanied by significantly improved cardiac function 3.4.24.19 procollagen C-endopeptidase medicine the serum procollagen C-proteinase enhancer 1 glycopattern is associated with the physiological and pathological states of bone 3.4.24.22 stromelysin 2 medicine enzyme overexpression promotes tumor development 3.4.24.22 stromelysin 2 medicine melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer. Immunostaining for both melanoma inhibitory activity, MIA, and enzyme is correlated with poor prognosis in advanced gastric cancer. Patients with gastric cancer show high levels of enzyme in sera 3.4.24.23 matrilysin medicine developing and searching for effective inhibitors of matrilysin for cancer diagnosis and therapy 3.4.24.23 matrilysin medicine development of effective inhibitors useful for cancer therapy 3.4.24.23 matrilysin medicine matrilysin is overexpressed in cancer cells of variuos organs including prostate, colorectum, brain, and stomach, important role in tumor invasion and metastasis 3.4.24.23 matrilysin medicine enzyme is involved in cell dissociation and the subsequent invasion of pancreatic cancer cells. It induces the disruption of tight junction structure and forms a positive feedback loop with activation of the epidermal growth factor receptor mediated MEK-ERK signalling pathway 3.4.24.23 matrilysin medicine overexpression of enzyme correlates with breast cancer in vitro invasiveness, enzyme may promote invasion by increasing the secretion and activation of matrix metalloproteinases proMMP-2 and pro-MMP-9 3.4.24.23 matrilysin medicine MMP-7 promotes tolerance of incompatibel allografts and may help in development of strategies to improve long-term graft outcome in transplantation 3.4.24.23 matrilysin medicine among patients with pT3 rectosigmoid cancer, fortyfive percent of the rectosigmoid cancers show strong expression of MMP-7. Membranous or cytoplasmic beta-catenin expression is significantly related to E-cadherin and MMP-7 expression. No significant association is seen between E-cadherin, beta-catenin, or MMP-7 expression and some clinicopathologic features 3.4.24.23 matrilysin medicine induction of specific natural killer cells using monocyte-derived dendritic cells electroporated with MMP-7-mRNA. The induced CTLs elicit an antigen-specific and HLA-restricted cytolytic activity against tumor cells endogenously expressing the MMP-7 protein. MMP-7-specific natural killer cells could be induced using peripheral blood mononuclear cells from a patient with acute lymphoblastic leukemia capable of recognizing the autologous leukemic blasts while sparing nonmalignant cells 3.4.24.23 matrilysin medicine MMP-7 genetic polymorphisms are significant determinants of survival among Chinese women with breast cancer 3.4.24.23 matrilysin medicine serum matrilysin level predicts recurrence in curatively resected colorectal cancer patients. Patients with matrilysin level higher than the median 4.3 ng/ml are more likely to relapse. Median time to progression in relapsed patients is 8 months if matrilysin is above 4.3 ng/ml and 18 months if matrilysin is below 4.3 ng/ml. Node-negative patients with low matrilysin level have a predicted probability of relapse-free survival at 4 years of 88%; if the matrilysin level is higher than the median value, this probability is 77% 3.4.24.24 gelatinase A medicine attractive therapeutic target for cancer invasion and metastasis, morbidity and mortality of cancer patients are directly related to the ability of tumor cells to metastasize, gelatinase A is required by metastazing tumor cells to traverse basement membrane at tissue bounaries and in blood vessels, therefore this enzyme is a promising target for the development of antitumor drugs 3.4.24.24 gelatinase A medicine inhibitors for use as potential therapeutic agents 3.4.24.24 gelatinase A medicine understanding the detailed molecular structures and the comformational changes of MMP-2 in its zymogen, active, and inhibited states can aid in the rational design of anti-cancer drugs 3.4.24.24 gelatinase A medicine during gastric ulcer healing, enzyme expression as well as matrix metalloproteinase MMP-3 and MMP-13 are induced in stromal cells of the gastric mucosa bordering the ulcer. Gelatinolytic activity is increased during the healing and is associated with extracellular matrix of the healing mucosa and newly formed vessels. Enzyme mRNA is homogenously distributed in all layers of the ulcer bed 3.4.24.24 gelatinase A medicine endogenous urokinase plasminogen activator from cultured hepatic stellate cells significantly induces the active forms of enzyme and matrix metalloproteinase MMP-9 in cirrhotic tissue slices. Transfection of hepatic stellate cells with urokinase plasminogen activator gene results in overactivation of enzyme and matrix metalloproteinases MMP-3 and MMP-9 3.4.24.24 gelatinase A medicine enzyme is the main enzymatic activity of gelatinolysis in oral squamous cell carcinomas. The enzyme form/proform ratio obtained by zymography is significantly higher in T3 and T4 stages than in T1 and T2 stages 3.4.24.24 gelatinase A medicine only a minority of urine samples from patients with bladder cancer show enzyme activity 3.4.24.24 gelatinase A medicine ratio of matrx metalloproteinases MMP-9/MMP-2 is enhanced in cancer patients compared with benign diseases and healthy individuals. No correlation between gelatinolytic activity and high tumoral marker values is found 3.4.24.24 gelatinase A medicine topical treatment of chronic dermal ulcers 3.4.24.26 pseudolysin medicine 2-mercaptoacetyl-L-phenylalanyl-L-leucine represents a class of potent elastase inhibitors that might prove useful in the management of Pseudomonas aeruginosa infections 3.4.24.26 pseudolysin medicine application of the inhibitors may be helpful in the management of corneal infections with Pseudomonas aeruginosa 3.4.24.26 pseudolysin medicine Inflammation and consequent lung dysfunction are hallmarks of recurrent Pseudomonas aeruginosa infections in cystic fibrosis lungs. The continued presence of bacterial components, including PE, can evoke an ongoing host inflammatory response by induction of inflammatory cytokinines and chemokinines such as interleukin-8. Although this cytokinine is essential for an effective host defense, continuous neutrophil transmigration and degranulation will damage the lung tissue through neutrophil-derived proteases. Therefore, the use of specific antibody against Pseudomonas elastase as adjuvant therapy along with antibacterial agents can prove an effective approach in the treatment of chronic Pseudomonas aeruginosa infection. 3.4.24.26 pseudolysin medicine phosphoramidon, the inhibitor of the enzyme, may prove beneficial in the treatment of Pseudomonas aeruginosa corneal infections 3.4.24.26 pseudolysin medicine the inhibitor may have a therapeutic application by delaying the progression of corneal destruction in Pseudomonas keratitis 3.4.24.26 pseudolysin medicine the inhibitor of the enzyme, 2-mercaptoacetyl-L-phenyalanyl-L-leucine, has therapeutic potential as an adjunct to antibiotics treatment of Pseudomonas keratitis in rabbits 3.4.24.26 pseudolysin medicine the protective activity of elastase mutants against Pseudomonas infections may be useful in producing vaccines 3.4.24.26 pseudolysin medicine enzyme can silence the function of proteinase-activated receptor-2 in the respiratory tract, thereby altering the host innate defense mechanisms and respiratory functions, and thus contributing to the setting of a disease like cystic fibrosis 3.4.24.26 pseudolysin medicine Pseudomonas aeruginosa cytotoxic elastase is enhanced in the presence of the filamentous fungi Aspergillus fumigatus, suggesting that this may have a role to play in the damaging pathology associated with the lung tissue in this disease. This indicates that patients who have a co-colonisation with these two organisms may have a poorer prognosis 3.4.24.26 pseudolysin medicine the enzyme is a promising target for the development of new anti-virulence compounds 3.4.24.B26 myroilysin medicine construction of a nerve regeneration acellular nerve graft with homologous dental pulp stem cells: Xenogeneic acellular nerve graft Is processed by Myroilysin to completely remove cells and myelin sheath, while preserving extracellular matrix microstructure of the natural nerve. The acellular nerve graft can support cell attachment and proliferation and does not stimulate a vigorous host rejection response. 1 cm purebred New Zealand White Rabbits sciatic nerve defects are repaired using this nerve graft construction 3.4.24.27 thermolysin medicine thermolysin degrades cellular prion protein while preserving both proteinase K-sensitive and proteinase K-resistant isoforms of disease-related prion protein in both rodent and human prion strains. In variant Creutzfeldt-Jakob disease, up to 90% of total prion protein present in the brain resists degradation with thermolysin, whereas only about 15% of this material resists digestion by proteinase K 3.4.24.28 bacillolysin medicine the dry dog food infested with Tyrophagus putrescentiae and associated bacterium Bacillus cereus represents serious health risks that arise mainly from mite allergens and toxins of bacterium. Bacillolysins of Bacillus cereus symbiont can contribute to the protease activity of the mite extract 3.4.24.B28 ADAM15 medicine ADAM15 ranks in the top 5% of amplified genes and its mRNA is significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. In metastatic samples, increased ADAM15 immunoreactivity is associated with increasing cancer stage and exhibits significantly stronger staining. The knockdown of ADAM15 mRNA expression significantly inhibits bladder tumor cell migration and reduces the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibits tumor growth by 45% compared to controls 3.4.24.B28 ADAM15 medicine high expression of ADAM15 is associated with decreased overall survival and disease-free survival in non-small cell lung cancer (NSCLC) patients. shRNA-mediated knockdown of ADAM15 attenuates cell migration and invasion. ADAM15 upregulates MMP9 expression in lung cancer cells via activation of the MEK-ERK pathway. ADAM15 proteolytically cleaves and activates pro-MMP9 in vitro and interacts with MMP9 in vivo. Overexpression of ADAM15 in A-549 cells promotes cell invasion, while knocking down MMP9 attenuates cell invasive ability 3.4.24.29 aureolysin medicine enzyme does not act as a virulence factor. Staphylococcus aureus strains lacking enzyme, or serine protease, or cysteine protease, show similar frequency or severity of joint disease as wild-type in a mouse model 3.4.24.30 coccolysin medicine coccolysin is a virulence factor 3.4.24.B33 Vipera ammodytes ammodytes metalloproteinase VaH3 medicine snake venom metalloproteinases are important targets in antivenom therapy 3.4.24.34 neutrophil collagenase medicine design of anticancer or other drugs which should be highly selective for their particular MMP targets 3.4.24.34 neutrophil collagenase medicine implicated in cancer, arthritis, joint destruction and Alzheimer's disease 3.4.24.34 neutrophil collagenase medicine elevated MMP-8 in bronchoalveolar lavage fluid is a marker of acute lung inflammation, and perhaps a contributor to acute lung injury, but is not necessarily an indicator of a poor outcome 3.4.24.34 neutrophil collagenase medicine breast cancer cell lines MCF-7, SKBR-3, and MDA-MB-231 expressing wild-type MMP-8 reveal elevated levels of interleukins IL-6 and IL-8. This increase is mirrored at the mRNA level and is dependent on MMP-8 catalytic activity. Sustained expression of wild-type MMP-8 by breast cancer cells is non-permissive for long-term growth.In long-term culture of transfected MDA-MB-231 cells, expression of wild-type but not E198A mutant MMP-8 is lost, with IL-6 and IL-8 levels returning to base line 3.4.24.34 neutrophil collagenase medicine MMP-8 is critical for dexamethasone therapy in alkali-burned corneas under dry eye conditions. The anti-inflammatory effects of Dex are mediated through increased MMP-8 expression 3.4.24.B34 Vipera ammodytes ammodytes metalloproteinase VaF1 medicine in standard experimental conditions, enzyme VaF1 is not recognised by antiserum against the whole venom, so it can contribute to postserotherapy complications, such as ineffective blood coagulation, in the envenomed patient 3.4.24.35 gelatinase B medicine MMP-9 is suggested as a regulator of the angiogenic switch in tumor development 3.4.24.35 gelatinase B medicine abundant expression of enzyme by synovial tissue mast cells in patients with rheumatoid arthritis but not in normal control 3.4.24.35 gelatinase B medicine cells resistant to protein kinase C potentiated, transcription factor p53 mediated apoptosis express a higher level of matrix metalloproteinases MMP-9 and MMP-10. Matrix metalloproteinases function confers protection from protein kinase C/p53 induced apoptosis and are implicated in tumor cell resistance 3.4.24.35 gelatinase B medicine endogenous urokinase plasminogen activator from cultured hepatic stellate cells significantly induces the active forms of enzyme and matrix metalloproteinase MMP-2 in cirrhotic tissue slices. Transfection of hepatic stellate cells with urokinase plasminogen activator gene results in overactivation of enzyme and matrix metalloproteinases MMP-3 and MMP-2 3.4.24.35 gelatinase B medicine enzyme and leucocyte elastase are essential for granulocyte-mediated proteolysis resulting in dermal-epidermal separation in epidermolysis bullosa acquisita and bullous pemphigoid patient’s skin. Selective inhibition of enzyme by single-chain variable fragment of a monoclonal antibody results in suppression of blistering 3.4.24.35 gelatinase B medicine enzyme is present in extracts from leaking bleb tissue of glaucoma patients, but not in bleb leak fluid or aqueous humor samples 3.4.24.35 gelatinase B medicine enzyme levels are significantly elevated in cerebrospinal fluid of patients with vascular dementia compared to those with Alzheimer disease and to control 3.4.24.35 gelatinase B medicine enzyme, as well as monocyte chemotactic protein-1 and stromal cell-derived factor-1 may have a pathogenic role in the recruitment of leukocytes into the eye in sympathetic ophthalmia 3.4.24.35 gelatinase B medicine expression of enzyme is significantly higher in malignant than in nonmalignant prostate tissues. Significant difference in enzymatic activity among normal prostate, benign prostate hyperplasia, localized and metastatic tissue, and serum 3.4.24.35 gelatinase B medicine in children with aseptic and bacterial meningitis, both enzyme and collagenase MMP-8 show increased levels in cerebrospinal fluid. In patients with clinical signs of meningitis, but without cerebrospinal fluid pleocytosis, enzyme and MMP-8, MMP-13 are highly sensitive markers for intrathecal inflammation 3.4.24.35 gelatinase B medicine incubation of lenses with enzyme leads immediately to cataract 3.4.24.35 gelatinase B medicine majority of urine samples from patients with bladder cancer show enzyme activity. Enzyme content is enhanced in the urine from patieints with high-grade and advanced-stage bladder tumors. Urinary values of biomarkers tissue polypeptide-specific antigen and protein 22 of nuclear matrix correlate with the increase in enzyme activity in high-grade and advanced-stage bladder tumors 3.4.24.35 gelatinase B medicine neutrophils of patients with rheumatoid arthritis release considerable amounts of enzyme. Enzyme acts on fragments of collagen type II obtained by cleavage with collagenases MMP-1, MMP-8, or MMP-13. Enzyme produces small remnant peptides with still intact immunodominant epitopes. Lysines in the main immunodominant epitope are modified by partial hydroxylation and partial glycosylation 3.4.24.35 gelatinase B medicine proenzyme and enzyme levels are significantly increased in patients with proliferative diabetic retinopathy. Additionally, levels of tissue inhibitor of metalloproteinases-1 are significantly increased and functionally inhibit activation of enzyme in vitreous samples. Enzyme levels in vitreous samples of patients with hemorrhage are significantly higher than those in proliferative diabetic retinopathy patients and strongly correlate with hemoglobin levels 3.4.24.35 gelatinase B medicine ratio of matrx metalloproteinases MMP-9/MMP-2 is enhanced in cancer patients copared with benign diseases and healthy individuals. No correlation between gelatinolytic activity and high tumoral marker values is found 3.4.24.35 gelatinase B medicine a positive correlation between MMP-9 values and gestational age is observed in normal pregnant women 3.4.24.35 gelatinase B medicine brain levels of matrix metalloproteinase-9 are a marker of neuroinflammation, MMP-9 appears to be upregulated in microvessels within ischemic brain, MMP-9 levels are markedly lower in CD47 knockout brains compared to wild type brains 3.4.24.35 gelatinase B medicine cervicovaginal MMP-9 correlates with cervical ripening before labor at term, however, cervicovaginal MMP-9 does not change with spontaneous labor or rupture of membranes at term and does not predict success of labor induction 3.4.24.35 gelatinase B medicine higher levels of MMP-9 mRNA expression in the apical periodontitis when compared to healthy periapical ligaments, suggest that MMP-9 can be directly involved in tissue remodeling/destruction during lesion development 3.4.24.35 gelatinase B medicine matrix metalloproteinase is an independent predictor of the reduced nitrate-mediated dilatation in the type 1 diabetes mellitus 3.4.24.35 gelatinase B medicine matrix metalloproteinase-9 is an independent prognostic marker in laryngeal and hypopharyngeal cancer 3.4.24.35 gelatinase B medicine MMP-9 expression positively correlates with prognosis of oral squamous cell carcinoma 3.4.24.35 gelatinase B medicine MMP-9 genotype polymorphisms are primary predictors for oral squamous cell carcinoma risk 3.4.24.35 gelatinase B medicine MMP-9 is a marker of endothelial activation and dysfunction 3.4.24.35 gelatinase B medicine MMP-9 is an inflammatory marker in the tears of patients with ocular surface disease, pro-MMP-9 levels are significantly elevated in blepharitis, in allergic eye disease, in dry eye, and in conjunctivochalasis in comparison to controls 3.4.24.35 gelatinase B medicine serum MMP-9 level is related to FEV1 decline 3.4.24.35 gelatinase B medicine the expression of the mRNA of MMP-9 is not significantly elevated with the progression of biliary-associated liver fibrosis 3.4.24.35 gelatinase B medicine the functional polymorphism C1562T in the promoter of matrix metalloproteinase-9 gene is associated with susceptibility to knee osteoarthritis in the Turkish population 3.4.24.35 gelatinase B medicine the reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia 3.4.24.35 gelatinase B medicine there is an association of the allele distribution at the TIMP-1 +372 T/C locus, the levels of TIMP-1, -2, and MMP-9 in noninflamed tissue, and smoking habit with diagnostic and/or surgical recurrence of Crohn's disease 3.4.24.35 gelatinase B medicine controlling MMP-9 expression has therapeutic potential in Parkinson's disease 3.4.24.35 gelatinase B medicine down-regulation of the expression and activity of MMP-9 is a treatment alternative for plaque stabilization by inhibiting the nuclear factor-kappaB activation 3.4.24.35 gelatinase B medicine higher circulating MMP-9 concentrations are associated with abdominal aortic aneurysm presence 3.4.24.35 gelatinase B medicine imbalance between total MMP-9 and TIMP-1 may contribute to the pathogenesis of lupus nephritis 3.4.24.35 gelatinase B medicine MMP-9 is a nontraditional cardiovascular risk factor 3.4.24.35 gelatinase B medicine MMP-9 is a potential target for cerebral ischemic treatment in human stroke therapy 3.4.24.35 gelatinase B medicine MMP-9 is a potential therapeutic target for gastric adenocarcinomas 3.4.24.35 gelatinase B medicine MMP-9 is a potentially useful biomarker for diagnosing, classifying, and monitoring dysfunctional tear syndrome 3.4.24.35 gelatinase B medicine MMP-9 is a promising target for a neuroprotective approach to preventing seizure-induced hippocampal damage 3.4.24.35 gelatinase B medicine MMP-9 overexpression is an early marker of breast carcinogenesis preceding tumor invasion 3.4.24.35 gelatinase B medicine MMP-9 plasma levels are predictive of cognitive performance following carotid endarterectomy 3.4.24.35 gelatinase B medicine pharmacological inhibition of MMP-9 activity ameliorates skeletal muscle pathogenesis and enhanced myofiber regeneration in mdx mice. MMP-9 represents as one of the most promising therapeutic targets for the prevention of disease progression in Duchenne muscular dystrophy 3.4.24.35 gelatinase B medicine pretreatment serum levels of MMP-9 are powerful prognostic markers in patients with oral squamous cell carcinoma, patients with MMP-9 serum levels higher than median have significantly shorter overall survival than those with levels lower than median 3.4.24.35 gelatinase B medicine the serum levels of MMP-9 significantly correlate with the occurrence and severity of acute graft-versus-host disease 3.4.24.35 gelatinase B medicine MMP-9 induces TGF-beta1 production in the airway epithelium through the cleavage of EGF and EGF-like ligands and activating EGFR, suggesting potential targets of therapeutic intervention in airway fibrotic disorders 3.4.24.35 gelatinase B medicine matrix metalloproteinase-9 expression in glioma is an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of astrocytic glioma 3.4.24.35 gelatinase B medicine serum MMP9 levels are significantly associated with hyperlipidaemia 3.4.24.B35 Vipera ammodytes ammodytes metalloproteinase VaH4 medicine the enzyme displays a cytotoxic effect on cancer cells in culture, which makes it interesting for further medically-oriented studies 3.4.24.36 leishmanolysin medicine enzyme plays a key role during infection of humans with Leishmania parasites, inhibitors may aid the development of drugs 3.4.24.36 leishmanolysin medicine parasite virulence is not simply correlated with the activity of enzyme. Enzyme plays a significant role in association with other surface molecules, especially lipophosphoglycan. Overexpression of enzyme can compensate lipophosphoglycan defect in the vertebrate host but in sand flies both molecules fulfill quite different functions 3.4.24.36 leishmanolysin medicine DNA/DNA, DNA/protein and protein/protein based vaccination using gp63 against Leishmania donovani inducing immune responses and conferred protection against challenge infection, humural responses, quantitative overview 3.4.24.36 leishmanolysin medicine the endoplasmic reticulum and the Golgi hinderes the exit of GP63 metalloprotease from the parasitophorous vacuole and dampens the cleavage of host proteins by GP63 3.4.24.36 leishmanolysin medicine the monitoring of host MMPs levels and GP63 in Leishmania isolated from host samples can be used on the laboratory routine to predict the prognostic and treatment efficacy of American tegumentary leishmaniasis 3.4.24.B37 mutalysin II medicine mutalysin II has the potential to be an effective thrombolytic agent 3.4.24.B39 metallo-alpha-fibrinogenase medicine the enzyme has a clinical application for the therapy of thrombosis disease 3.4.24.B39 metallo-alpha-fibrinogenase medicine in an lipopolysaccharide-induced endotoxemia mice model, fibrinogenase treatment significantly increases the survival rate, remarkably protects liver and kidney from lipopolysaccharide damage as well as decreasing TNF-alpha level. In vitro, fibrinogenase significantly decreases LPS-induced TNF-alpha production and the expression of P-NF-kappaB 3.4.24.40 serralysin medicine enzyme is one of the virulence factors of the opportunistic pathogen which causes severe and lethal infections in patients with underlying diseases, implicated in the hydrolysis of many biologically active proteins 3.4.24.40 serralysin medicine anti-coagulant activity in human plasma 3.4.24.40 serralysin medicine inhibition of tumor necrosis factor-alpha-induced RANTES secretion 3.4.24.40 serralysin medicine inhibits IFN-gamma antiviral and immunomodulatory activity 3.4.24.41 atrolysin B medicine less potent hemorrhagic toxin, degradation of the basement membrane structure surrounding capillaries in muscle tissue 3.4.24.43 atroxase medicine no necrosis or hemorrhage, thrombolysis 3.4.24.44 atrolysin E medicine one of the most hemorrhagic metalloproteinases of the P-II class in the venom, causes extensive hemorrhage in muscle tissue and extensive degeneration of capillaries, degradation of basement membrane proteins and surrounding stroma, its free disintegrin domain possesses platelet-aggregation inhibitory activity 3.4.24.45 atrolysin F medicine second-most potent hemorrhagic toxin of all the atrolysins, systemic hemorrhage in lung, kidney, liver, heart, destruction of muscle tissue 3.4.24.46 adamalysin medicine recombinant disintegrin domain of enzyme, shows inhibitory activities on endothelial cell proliferation and adhesion on the integrin substrates fibronectin, vitronectin, and fibrinogen.The domain totally abrogates endothelial cell migration and blocks most capillary formation in a three-dimensional fibrin gel. Athymic mice bearing electrotransferred domain exhibit strong inhibition of tumor angiogenesis 3.4.24.47 horrilysin medicine horrilysin possesses hemorrhagic and lethal activities 3.4.24.48 ruberlysin medicine HT-2 has hemorrhagic and lethal activity 3.4.24.49 bothropasin medicine local tissue damage after snakebite, causes hemorrhage followed by myonecrosis and arterial necrosis after intramuscular injection of doses of 0.02 mg in mice, myonecrosis is still observed with lower doses down to 0.001 mg 3.4.24.49 bothropasin medicine secretory cells of venom gland can be a good in vitro apparatus to produce venom, assemblage of isolated cells into acini that grow in size up to 21 days, instead of adhering to the substrate, source for all pharmacological and biotechnological studies, as well as providing an improved avenue for treatments of snakebites, venom detection and quantification after 2 weeks only in culture devoid of Bothrops jararaca serum 3.4.24.52 trimerelysin I medicine causes localized hemorrhage through the degradation of basement membrane 3.4.24.53 trimerelysin II medicine completely free from hemorrhagic activity 3.4.24.54 mucrolysin medicine mucrolysin possesses lethal and hemorrhagic activities, induces coagulation necrosis, bleeding into various organs, especially the heart and stomach 3.4.24.56 insulysin medicine IDE represents a target for the development of a new class of drugs for the treatment of Alzheimer's disease that lowers amyloid beta-peptide levels by increasing ist rate of catabolism 3.4.24.56 insulysin medicine inverse correlation between insulysin activity levels and brain Abeta peptide levels suggest that modulation of insulysin activity may alter the risk for Alzheimer's disease 3.4.24.56 insulysin medicine stimulation of enzyme activity can provide a useful therapeutic approach in treatment of diseases caused by amyloidosis, like Alzheimer's disease, type2 non-insulin-dependent diabetes and the spongiform encephalopathies such as Creutzfeldt-Jakob disease 3.4.24.56 insulysin medicine substrate amyloid beta-protein is an essential factor in the pathogenesis of Alzheimer's disease 3.4.24.56 insulysin medicine the Alzheimer's beta-amyloid peptide is degraded by the enzyme 3.4.24.56 insulysin medicine enzyme is a cellular receptor for both cell-free and cell-associated Varicella-zoster virus. Enzyme interacts with Varicella-zoster virus glycoprotein E through its extracellular domain. Downregulation of enzyme by siRNA, or blocking with antibody inhibited Varicella-zoster infection. Transfection of cell lines impaired for infection with a plasmid expressing human enzyme results in increased entry and increased infection by Varicella-zoster virus 3.4.24.56 insulysin medicine enzyme is capable of cleavage of the 34 amino acid peptides resulting from internal proteolysis of genetically defect type 2 transmembrane protein BRI2 in patients with familial British dementia or familial Danish dementia. Enzymic degradation of peptide is more efficient with monomeric peptide than with aggregated peptide. Proteolysis of monomeric soluble peptide precursors by enzyme may delay peptide ABri and ADan aggregation in vivo 3.4.24.56 insulysin medicine in isolated brain microvessels from patients with Alzheimer’s disease with cerebral amyloid angiopathy enzyme protein level is up to 44% increased, but enzyme activity is significantly reduced 3.4.24.56 insulysin medicine in patients with diabetes, the degradation of insulin by wound fluid correlates with glucose control, patients with worse outcomes have higher wound fluid insulin degradation. Reduction of enzyme activity in the wound fluid as potential therapeutic target 3.4.24.56 insulysin medicine after the development of first amyloid beta plaques in brain of transgenic mice with alzheimer's disease-like neuropathology, cortical mRNAand protein levels of IDE are significantly up-regulated in the transgenic mice compared to their non-transgenic littermates. Up-regulation of IDE mRNA-levels occurrs in parallel with increased amyloid beta40 and amyloid beta42 production. A significant positive correlation is observed between protein levels of IDE and full-length amyloid precursor protein in the cerebral cortex 3.4.24.56 insulysin medicine in patients with V97L mutation of presenilin 1, insulysin activity on the plasma membranes is reduction concomitantly with increased levels of extracellular and intracellular amyloid beta42. In the presenilin 1 V97L mutant-transfected SH-SY5Y cell line, increase of intracellular amyloid beta42 is associated with decreased expression and activity of insulysin in the cytosol and endoplasmic reticulum 3.4.24.56 insulysin medicine study on cortical expression of insulysin and neprilysin in sporadic and familial Alzheimer's disease samples carrying the E280A presenilin-1 missense mutation. Insulysin is linked with aggregated amyloid beta40 isoform while neprilysin negatively correlates with amyloid angiopathy. Neprilysin, but not insulysin, is over-expressed in dystrophic neurites, both proteases are immunoreactive in activated astrocytes but not in microglia and insulysin is the only one detected in astrocytes of white matter from familial alzheimer's disease cases 3.4.24.56 insulysin medicine beta-site amyloid precursor protein-cleaving enzyme BACE2 overexpression in cultured cells lowers net amyloid beta levels to a greater extent than multiple, well-established amyloid beta-degrading proteases, including neprilysin and endothelinconverting enzyme-1, while showing comparable effectiveness to insulin degrading enzyme 3.4.24.56 insulysin medicine peptide inhibitors cand function as potentially meaningful candidates for the development of type-2 diabetes therapeutics 3.4.24.56 insulysin medicine the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin. Insulin-degrading enzyme inhibitors to treat diabetes, therefore, should prevent insulin-degrading enzyme-mediated insulin degradation, but not glucagon degradation. Using a high-throughput screen for non-active-site ligands, potent and highly specific small-molecule inhibitors are discovered that alter substrate selectivity of insulin-degrading enzyme. X-ray co-crystal structures, including an insulin-degrading enzyme-ligand-glucagon ternary complex, reveal substrate-dependent interactions that enable these inhibitors to potently block insulin binding while allowing glucagon cleavage, even at saturating inhibitor concentrations 3.4.24.56 insulysin medicine therapeutic and/or preventative approaches combining resveratrol and insulin-degrading enzyme may hold promise for sporadic Alzheimer's disease 3.4.24.57 O-sialoglycoprotein endopeptidase medicine glycoprotease is a potential target for the development of antimicrobials against Staphylococcus aureus infection 3.4.24.58 russellysin medicine russellysin is able to inhibit platelet aggregation but the RGD sequence is replaced by Arg-Asp-Glu in the corresponding region 3.4.24.58 russellysin medicine thrombin is a common hemostatic drug used in surgical practice. Investigation of a method with the optimum conditions for rapid preparation of thrombin from cryoprecipitate-depleted plasma using RVV-X 3.4.24.61 nardilysin medicine the enzyme plays a role in the pathophysiology of schizophrenia 3.4.24.61 nardilysin medicine rising serum nardilysin concentrations following malignant cerebral infarction are strongly related to stroke severity, inflammatory extent and a higher risk of mortality, substantializing serum nardilysin is a potential prognostic biomarker for malignant cerebral infarction 3.4.24.61 nardilysin medicine serum nardilysin has potential as a novel prognostic biomarker for intrahepatic cholangiocarcinoma, which may reflect epithelial-mesenchymal transition features in primary tumor regions. It is proposed that the preoperative evaluation of serum nardilysin is a potential clinical tool for predicting tumor recurrence in and the overall prognosis of patients after curative-intent surgery 3.4.24.63 meprin B medicine results suggest that meprinbeta may play a protective role against the progression of renal injury through the degradation of extracellular matrix and bioactive peptides 3.4.24.65 macrophage elastase medicine abnormal expression of HME may contribute to destructive processes such as pulmonary empysema and vascular aneurysm formation 3.4.24.65 macrophage elastase medicine inhibition of MMP-12 may be a potential modality for the treatment of rheumatoid arthritis 3.4.24.65 macrophage elastase medicine role in idiophathic diseases, may be even more important in the causation of inflammatory bowel disease than MMP-3, markedly upregulated in a T-cell-mediated model in inflammatory bowel disease, local immune response can increase MMP-12 expression in resident lamina propria macrophages 3.4.24.65 macrophage elastase medicine chronic cigarette smoke exposure leads to macrophage accumulation and restores adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity 3.4.24.65 macrophage elastase medicine expression of macrophage metalloelastase improves the overall antitumor efficacy of oncolytic adenovirus in subcutaneous HCT116 xenografts. In a liver metastatic colorectal cancer model, intra-tumoral treatment of primary tumors from HT29 cells with macrophage metalloelastase monotherapy or with oncolytic adenovirus inhibits tumor growth. Combination therapy shows no increased mortality in comparison with either monotherapy alone. In a metastatic animal model, macrophage metalloelastase, as a monotherapy or in combination with oncolytic virus, does not increase tumor invasiveness 3.4.24.65 macrophage elastase medicine expression of MME12 inversely correlates with the expression of basic fibroblast growth factor and tumor angiogenesis in a model of murine colon cancer 3.4.24.65 macrophage elastase medicine in human ejaculate, MMP-12 concentrations are significantly higher in leucocytospermic samples than in nonleucocytospermic ones. The MMP-12 levels between the normozoospermic samples, oligoasthenoteratozoospermic samples and azoospermic samples do not differ. MMP-12 levels correlate with the presence of peroxidase-positive leucocytes. No correlation with CD 14 positive monocytes/macrophages is detected 3.4.24.65 macrophage elastase medicine in MMP-12 deficient mice, deficiency has no significant effect on total body weight or on subcutaneous or gonadal adipose tissue mass. Adipocyte and blood vessel size and density in subcutaneous and gonadal adipose tissues of obese mice are also comparable in MMP-12 deficient and control mice. Macrophage infiltration in subcutaneous and gonadal adipose tissues is not affected by MMP-12 deficiency, but the amount of crown-like structures is significantly lower. MMP-12 deficiency does not affect elastin content in the extracellular matrix of subcutaneous or gonadal adipose tissue 3.4.24.65 macrophage elastase medicine the enzyme is a potential target in treatment of cystic fibrosis 3.4.24.68 tentoxilysin medicine causative agent of the disease tetanus 3.4.24.68 tentoxilysin medicine sole causal agent of the pathological condition known as tetanus 3.4.24.68 tentoxilysin medicine sole cause of the devastating disease tetanus 3.4.24.68 tentoxilysin medicine very powerful neurotoxin, agent responsible for all clinical symptoms of tetanus 3.4.24.68 tentoxilysin medicine HuscFv antibodies specific for heavy chain can protect against tetanus neurotoxin by inhibiting binding of the enzyme to ganglioside GT1b 3.4.24.68 tentoxilysin medicine monoclonal antibody MAb 5C4 is the only anti-fragment C (heavy chain) antibody which is capable of blocking the binding of recombinant fragment C to GT1b gangliosides 3.4.24.68 tentoxilysin medicine the antibodies 2-7G, 2-2D, and S-4-7H can effectively inhibit the binding between the heavy chain fragment of the enzyme (TeNT-Hc) and differentiated PC-12 cells in vitro. Moreover, 2-7G inhibits TeNT-Hc binding to the receptor via carbohydrate-binding sites of the W pocket while 2-2D and S-4-7H inhibit binding of the R pocket. Although no single antibody completely protect mice from the toxin, they can prolong survival 3.4.24.68 tentoxilysin medicine treatment of T cells with recombinant carboxy-subdomain of the heavy chain results in development of Th1 lineage phenotype, which might lead to a specific and protective antibody mediated response against the enzyme 3.4.24.69 bontoxilysin medicine BoNT/A is the best available therapeutic agent of a variety of human diseases that benefit from a finctional inhibition of cholinergic terminals 3.4.24.69 bontoxilysin medicine design of inhibitors to treat food-borne, wound and infant botulism, rare but severe diseases, moreover, the enzyme can be used as biological warfare, because of its easiness of production and very high toxicity 3.4.24.69 bontoxilysin medicine designing of novel drugs 3.4.24.69 bontoxilysin medicine drug to treat certain muscle dysfunctions 3.4.24.69 bontoxilysin medicine most lethal biological substance have been weaponized in highly toxic aerosol form to pose a significant dual threat to both civilian and military populations, there is an urgent need for therapeutic countermeasures against BoNTs 3.4.24.69 bontoxilysin medicine remarkably effective drug for treating a wide variety of muscle dysfunctions in humans 3.4.24.69 bontoxilysin medicine retargeting of BoNT endopeptidase into specific cells has an enormous potential of therapeutic use, not only for moderating release of hormones, peptides, and metabolites, but also disrupting cancer cell growth and functioning 3.4.24.69 bontoxilysin medicine the enzyme is a useful therapeutic agent for many human syndroms caused by hyperactivity of cholinergic nerve terminals. Human diseases treated with BoNT/A: blepharospasm, hemifacial spasm, laryngeal dysphonia, head and neck dystonias, strabismus, limb dystonias, occupational cramps, anal fissure and rectal spasms, palmar and ascellar hyperhydrosis, hypersalivation and hypersweating, migraine headache, pain, bruxism, spasticity, urinary retention and pain, essential tremors, dysphagia and achalasia esophagea. BoNT/A is extensively used as a pharmaco-cosmetic 3.4.24.69 bontoxilysin medicine botulinum neurotoxins BoNT/A-G are used as therapeutics in a variety of neuromuscular disorders of the skeletal, glandular, and smooth muscles and pain disorders 3.4.24.69 bontoxilysin medicine process development for production of a candidate vaccine antigen by recombinant expression of the C-terminal heavy chain fragment of botulinum neurotoxin serotype E Pichia pastoris strain GS115 3.4.24.69 bontoxilysin medicine BoNT/E can reduce seizure incidence in Mus musculus strain C57BL/6N, a mouse model of mesial temporal lobe epilepsy (electroencephalography analysis) 3.4.24.69 bontoxilysin medicine candidate for treatment of lower urinary tract symptoms due to benign prostatic enlargment 3.4.24.69 bontoxilysin medicine analgesic effect of BoNT/A on neuropathic pain, e.g. chronic refractory neck pain, application on human neck and shoulder muslces 3.4.24.69 bontoxilysin medicine BoNT-A can be administered subcutaneously or topically, in addition to the common application by intradermal and intramuscular injection, with a transdermal delivery peptide to reduce inflammation produced by activating nociceptors in the skin. Peptide-mediated delivery of BoNT-A is an easy and non-invasive way of administering the toxin that may prove to be useful in clinical practice, overview 3.4.24.69 bontoxilysin medicine BoNT-A treatment of bladder of human hosts, patients with neurogenic bladder dysfunction, improves bladder capacity, reflex volume, continence status, and detrusor compliance, maximum detrusor pressure iss significantly reduced, long-term effects of repeated intradetrusor BoNT-A injections on detrusor function in human hosts result in a succes rate of 74%, overview 3.4.24.69 bontoxilysin medicine BoNT/A is largely employed in human therapy because of its specific inhibition of peripheral cholinergic nerve terminals 3.4.24.69 bontoxilysin medicine BoNT/A is very effective in the therapy of a wide range of human syndromes characterized by hyperactivity of peripheral cholinergic nerve terminals 3.4.24.69 bontoxilysin medicine BoNT/A is widely used as a therapeutic agent and to reduce wrinkles. The toxin is used at very low doses, which have to be accurately quantified 3.4.24.69 bontoxilysin medicine BoNTs are among the most useful reagents to treat neuromuscular afflictions 3.4.24.69 bontoxilysin medicine clinical evidence on the effectiveness and reliability of minimally invasive and reversible sacral neuromodulation and botulinum tox­in A treatment as well as the current significance of sacral neuromodulation and botulinum toxin A for the second-line treat­ment of adult syndrome of idiopathic overactive blad­der, overview 3.4.24.69 bontoxilysin medicine evaluation of catalytically inactive BoNT/A1 mutant H223A/E224A/H227A holoprotein as a vaccine candidate by comparison against recombinant BoNT/A1 LC, LC-belt, LC-Hn, and Hc antigens and a LC-Hn +Hc combination in mouse potency and efficacy bioassays when challenged with BoNT/A subtypes /A1, /A2, and /A3, overview 3.4.24.69 bontoxilysin medicine Hn-33 and other neurotoxin associated proteins can potentially be employed as adjuvants for development of vaccines against botulism and can be a good surrogate for botulinum diagnostics. Medical implications of immunogenicity of different components of BoNT/A complex 3.4.24.69 bontoxilysin medicine LHN/A vaccine protects mice against challenge with BoNT/A subtypes A1, A2, and A3 3.4.24.69 bontoxilysin medicine LHN/A vaccine protects mice against challenge with BoNT/A subtypes A1, A2, and A3,the LHN/B vaccine is also highly efficacious 3.4.24.69 bontoxilysin medicine LHN/B vaccine protects mice against challenge with BoNT/A subtypes A1, A2, and A3 3.4.24.69 bontoxilysin medicine localized injections of BoNT/A are widely employed in clinical neurology to treat several human diseases characterized by muscle hyperactivity 3.4.24.69 bontoxilysin medicine RNA aptamers are a unique group of molecules acting as therapeutics and as an antidote against botulism 3.4.24.69 bontoxilysin medicine a number of peptides are selected on the basis of their involvement in BoNT/A binding in vitro to snps and/or to blocking Abs, for their ability to exert an inhibitory effect on the action of the toxin in vivo 3.4.24.69 bontoxilysin medicine subtype BoNT/A2 has greater clinical therapeutic value for treating subjects with Parkinson's disease compared to that ofsubtype BoNT/A1 3.4.24.71 endothelin-converting enzyme 1 medicine design of new potent and selective inhibitors might eventually lead to drugs against hypertension 3.4.24.71 endothelin-converting enzyme 1 medicine elevated plasma levels of endothelin-1 found in several diseases like asthma, hypertension, cerebral vacospasm, congestive heart failure and chronic and acute renal failure, blockade of the ET-1 system could have therapeutic utility 3.4.24.71 endothelin-converting enzyme 1 medicine analysis of effect of various ECE inhibitors in myocardial infarction, pulmonary hypertension, arterial hypertension. Overview is given on human studies 3.4.24.71 endothelin-converting enzyme 1 medicine ECE-1 is a potential target for RNAi in order to prevent premature delivery 3.4.24.71 endothelin-converting enzyme 1 medicine the enzyme is a therapy target for Alzheimer's disease 3.4.24.71 endothelin-converting enzyme 1 medicine high enzyme expression independently predicts poor survival of patients with esophageal squamous cell carcinoma 3.4.24.72 fibrolase medicine development of more effective therapeutic approaches for treating occlusive thrombotic diseases, potential clinical interest in fibrolase for pharmacologic dissolution of an established thrombus 3.4.24.72 fibrolase medicine treatment of occlusive thrombi 3.4.24.72 fibrolase medicine the enzyme effectively protects against acute pulmonary thromboembolism via degradation of thrombi with less activation of plasminogen 3.4.24.72 fibrolase medicine the use of the recombinant fibrolase alfimeprase results in rapid restoration of arterial patency in less than 4 h in most peripheral arterial occlusion patients 3.4.24.72 fibrolase medicine starase has the potential to be a potent thrombolytic agent due to its bi-functional properties (containing both direct-acting and plasminogen-activating activities) and lack of hemorrhagic activity 3.4.24.72 fibrolase medicine the enzyme has therapeutic potential in peptide-based cardiovascular drug development 3.4.24.72 fibrolase medicine the enzyme is a candidate for antithrombotic drug development 3.4.24.72 fibrolase medicine the enzyme is used as thrombolytic drug 3.4.24.72 fibrolase medicine the enzyme is useful for reducing or preventing thrombotic challenge 3.4.24.73 jararhagin medicine useful tool for studying the molecular basis of collagen-induced cellular activities in human skin fibroblasts for comparison and contrast with other cell types 3.4.24.73 jararhagin medicine appropriate jararhagin concentration can have apoptotic and suppressant effects on SK-Mel-28 cells and can be used to develop potential anti-cancer drugs 3.4.24.74 fragilysin medicine among stool strains from colon cancer patients, bft-1 is found to be more common than bft-2, isoform bft-1 is also found in almost all isolates from extraintestinal sites, strain NCTC 11295 harbours the isoform bft-2 3.4.24.74 fragilysin medicine stimulates interleukin-8 secretion by human intestinal epithelial HT29/C1 cells, biological active BFT, but not serum, is required for interleukin-8 production, NF-kB, tyrosine kinase and mitogen activated protein kinase signaling pathways are involved in BFT-induced interleukin-8 stimulation 3.4.24.74 fragilysin medicine oral administration with lower-dose biologically active recombinant isoform BFT-2 inhibits colorectal tumorigenesis in mice 3.4.24.75 lysostaphin medicine application as effective antibiotic drug against infections with Staphylococcus aureus 3.4.24.75 lysostaphin medicine staphylococcal disease pathogenesis 3.4.24.75 lysostaphin medicine therapeutic agent for the treatment of Staphylococcus aureus infections 3.4.24.75 lysostaphin medicine treatment of staphylococcal infections 3.4.24.75 lysostaphin medicine lysostaphin is useful in treatment of neonatal Staphylococcus aureus infection, overview 3.4.24.75 lysostaphin medicine potential therapeutic agent against antibiotic-resistant Staphylococcus aureus infections 3.4.24.75 lysostaphin medicine lysostaphin can be used potentially as a topical disinfectant or decolonizing agent against methicillin-resistant Staphylococcus aureus infection on on human skin prior to operations. The combination is significantly more effective than treatment with ranalexin or lysostaphin alone, overview 3.4.24.75 lysostaphin medicine lysostaphin is an effective treatment as well as prophylaxis for Staphylococcus aureus biofilms on indwelling catheters 3.4.24.75 lysostaphin medicine lysostaphin, in combinantion with the antibiotic ranalexin, is effective against wound or systemic infections caused by meticillin-resistant Staphylococcus aureus. The combination is significantly more effective than treatment with ranalexin or lysostaphin alone. Ranalexin and lysostaphin can be incorporated in wound dressings for the prevention and treatment of topical Staphylococcus aureus infections 3.4.24.75 lysostaphin medicine lysostaphin can be used in combination with clarithromycin for the eradication of Staphylococcus aureus biofilms with a minimal biofilm eradication concentration reduction of 9 and 6fold dilutions on meticillin-resistant S. aureus and meticillin-susceptible S. aureus, respectively 3.4.24.75 lysostaphin medicine lysostaphin has potential for use as an antistaphylococcal agent for treatment of infections caused by antibiotic-resistant strains of Staphylococcus aureus 3.4.24.75 lysostaphin medicine lysostaphin is an antistaphylococcal agent. The enzyme is efficacious in the treatment of bovine mastitis caused by staphylococci 3.4.24.75 lysostaphin medicine lysostaphin-functionalized cellulose fibers show activity against Staphylococcus aureus in an in vitro skin model (HaCaT keratinocyte) with low toxicity toward keratinocytes, suggesting good biocompatibility for these materials as antimicrobial matrices in wound healing applications 3.4.24.75 lysostaphin medicine lysostaphin exerts high levels of activity against antibiotic-resistant strains of Staphylococcus aureus 3.4.24.75 lysostaphin medicine lysostaphin is a therapeutic agent for methicillin-resistant Staphylococcus aureus pneumonia 3.4.24.75 lysostaphin medicine a bone morphogenetic protein 2-loaded lysostaphin-delivering hydrogel simultaneously prevents Staphylococcus aureus infection and repairs nonhealing segmental bone defects in the murine radius 3.4.24.75 lysostaphin medicine enzyme-functionalized gold and silver nanoparticles are an antibacterial platform for combating methicillin-resistant Staphylococcus aureus bacterial infections 3.4.24.75 lysostaphin medicine the enzyme can be used in life-threatening infections, such as endocarditis to increase the early in vivo activity of the antibiotics, and to prevent the emergence of linezolid resistant mutants 3.4.24.75 lysostaphin medicine the enzyme is a potential antimicrobial agent for Staphylococcus aureus infections 3.4.24.75 lysostaphin medicine the enzyme is used against established staphylococcal biofilms as an alternative to bovine mastitis control 3.4.24.79 pappalysin-1 medicine administation of insulin-like growth factor binding protein (IGFBP)-4 causes significant increase in bone formation parameters, possibly through increased IGF bioavailability via proteolysis of insulin-like growth factor binding protein (IGFBP)-4 3.4.24.79 pappalysin-1 medicine enhancing IGF bioavailability by PAPP-A can be a powerful strategy in the treatment of certain metabolic diseases such as osteoporosis 3.4.24.79 pappalysin-1 medicine a detailed analysis is performed of first trimester screening results in singleton pregnancies conceived using assisted reproductive technologies and non-assisted reproductive technologies pregnancies. A record linkage study compared outcomes in 1739 assisted reproductive technologies-conceived and 50.253 naturally conceived pregnancies. Assisted reproductive technologies pregnancies have reduced first trimester screening PAPP-A levels leading to an increased likelihood of receiving a false-positive result and having a CVS/amniocentesis. Lower PAPP-A may reflect impairment of early implantation with some forms of assisted reproductive technologies 3.4.24.79 pappalysin-1 medicine a prospective screening study for trisomy 21 in singleton pregnancies is carried out by a combination of maternal age, fetal nuchal translucency, free beta-hCG and PAPP-A in a one-stop-clinic for first-trimester assessment of risk at 11-13 weeks of gestation. All three trisomies (13,18 and 21) are associated with increased maternal age, increased fetal nuchal translucency and decreased maternal serum PAPP-A 3.4.24.79 pappalysin-1 medicine contribution of maternal variables that influence the measured concentration of free beta-human chorionic gonadotropin and PAPP-A, and the interaction between these covariates, in first-trimester biochemical screening for trisomy 21 are analysed. In a multicenter study of prospective first-trimester biochemical screening for trisomy 21 it is shown that it is essential to adjust the measured values of free beta-human chorionic gonadotropin and PAPP-A for maternal and pregnancy characteristics 3.4.24.79 pappalysin-1 medicine it is examined whether maternal Rhesus status has any effect on the levels of first-trimester markers free beta-human chorionic gonadotropin, PAPP-A and nuchal translucency. First-trimester markers from pregnant women are converted into multiples of medians and corrected for maternal weight, ethnicity, and smoking status. Totally, 15045 normal, singleton pregnancies are retrieved with full records. Maternal Rhesus status does not influence the levels of free beta-human chorionic gonadotropin and PAPP-A in the first trimester of pregnancy in this almost exclusively Caucasian population studied. Therefore, correction for maternal Rhesus status is not suggested 3.4.24.79 pappalysin-1 medicine levels of PAPP-A and C-reactive protein in pre-eclampsia and their association with the mean arterial blood pressure are determined. 67 women with pre-eclampsia symptoms are matched with 56 normal pregnant controls for gestational age, maternal age and parity. Both of the groups are third trimester. PAPP-A and C-reactive protein are measured in serum. Maternal serum levels of PAPP-A and C-reactive protein are increased in women with pre-eclampsia compared to controls 3.4.24.79 pappalysin-1 medicine PAPP-A levels in adults with growth hormone deficiency at baseline and after growth hormone replacement is evaluated: 14 growth hormone deficiency adults are evaluated at baseline and after 1 year of growth hormone therapy. All patients are compared at baseline with 28 age-, sex- and body mass index (BMI)-matched control subjects. At baseline, growth hormone deficiency adults show higher PAPP-A levels and higher leptin, fibrinogen and highly sensitive C-reactive protein values than controls. Therapy with growth hormone reduces PAPP-A and fibrinogen levels while increased BMI and reduced waist-hip ratio are observed 3.4.24.79 pappalysin-1 medicine PAPP-A, IGF1, inflammatory markers and adiponectin concentrations in type 2 diabetic patients with and without carotid plaques are compared and the relationship between these serum parameters and ultrasound carotid markers of atherosclerosis is evaluated. 125 consecutive type 2 diabetic patients are examined. Serum PAPP-A and IGF1 do not appear to be useful serum biomarkers for carotid atherosclerosis in type 2 diabetic patients with stable glycemic control, despite scientific evidence of their local role in atherosclerosis 3.4.24.79 pappalysin-1 medicine the effect of smoking on three first trimester screening markers for Down’s syndrome that constitute the Combined test, namely nuchal translucency (NT), PAPP-A and free beta human chorionic gonadotophin is examined. In addition it is determined which of these markers need to be adjusted for smoking and by how much. The effect of adjusting for smoking on the Combined test is small, with an estimated less than 0.5% increase in the detection rate for a 3% false-positive rate and less than 0.2% decrease in the false-positive rate for an 85% detection rate 3.4.24.79 pappalysin-1 medicine the performance of first-trimester combined screening by maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin and PAPP-A is examined 3.4.24.79 pappalysin-1 medicine pregnancy-associated plasma protein A is a cardiac risk marker 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine the understanding of the regulatory mechanisms that control the activity of the key proteinase in tumor cell invasion, is essential for the design of potent and safe anti-cancer therapies 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine complex reciprocal effects of ERK1/2 and p38 MAPK in the regulation of MT1-MMP activity, which may complicate the use of MAPK-specific inhibitors as therapeutic agents to down-regulate the biologic effects of TGF-beta1 on pericellular collagen degradation and tumor invasion 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine endothelial cell invasion of collagen I gels is MT1-MMP dependent 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine full enzymatic activity of MT1-MMP is required for a specific up-regulation of VEGF-A through an activation of Src tyrosine kinase pathways 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine mechanistic association between MT1-MMP levels and post-I/R remodeling, multiple targets for the interruption of augmented MT1-MMP activity and abundance with I/R 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine MT1-MMP and MMP gelatinase A function together in the extracellular matrix degradation or remodeling associated with metamorphosis, MT1-MMP has additional MMP gelatinase A independent roles in the development of adult longitudinal muscle in the intestine 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine MT1-MMP initiates substrate degradation and enhances cell migration, hemopexin-like domain and a nonenzymatic component of the catalytic domain of MT1-MMP are essential for MT1-MMP-mediated cell migration, Rac1 participates in the MT1-MMP signal transduction pathway 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine MT1-MMP is involved in cell migration and collagen-induced mitogen-activated protein kinase-extracellular signal-related kinase activation, collagen-induced mitogen-activated protein kinase-extracellular signal-related kinase activation inhances MT1-MMP activity, hemopexin-like domain of MT1-MMP inhibits collagen-induced mitogen-activated protein kinase-extracellular signal-related kinase activation and migration 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine MT1-MMP proteolysis of protective antigen markers makes the MT1-MMP-expressing aggressive invasive cells resistant to the cytotoxic effect of bipartite PA/FP59 toxin, synthetic inhibitors of MMPs are likely to increase the therapeutic anti-cancer effect of anthrax toxin, unique role of furin in the activation of protective antigen markers 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine MT1-MMP proteolysis of T cell CD44 regulates adhesion and subsequent transmigration and homing of T cells into the pancreas, inhibition of T cell MT1-MMP is key to delaying the onset of diabetes 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine some mercaptosulfide inhibitors effectively inhibit activation of proMMP-2 by endogenous MT1-MMP produced by HT1080 human fibrosarcoma cells, block fibronectin degradation by prostate cancer LNCaP cells stably transfected with MT1-MPP 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine MT1-MMP is involved in keratinocyte growth factor receptor expression and epithelial cell proliferation after acute airway injury 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine therapeutic target in angiogenesis-related disease 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine considering the important role of apolipoproteinE for lipid metabolism and atherosclerosis protection, MMP-14 might play an essential role for the development of hyperlipidemia and atherosclerosis as a result of degradation of apolipoprotein E 3.4.24.80 membrane-type matrix metalloproteinase-1 medicine the relationship between serum MT1-MMP and bone mineral density as well as bone metabolic markers in 206 Chinese postmenopausal women aged 43-80 years is investigated by Western analysis and ELISA. Multiple linear stepwise regression analysis shows that MT1-MMP is not a determinant factor for bone mineral density. Significant positive correlations between MT1-MMP and serum alkaline phosphatase, N-telopeptides of type I collagen are found, and remain significant after adjustment for age and body-mass index. Moreover, serum MT1-MMP, BAP, and NTX decreased in response to alendronate therapy MT1-MMP and bone turnover markers are correlated, and serum MT1-MMP levels may rise with increase in bone turnover 3.4.24.81 ADAM10 endopeptidase medicine cleavage by ADAM10 of beta-amyloid precursor protein could abolish production of longer peptides and slow down or arrest Alzheimer disease 3.4.24.81 ADAM10 endopeptidase medicine ADAM10 participates in the response to infection by Staphylococcus aureus 3.4.24.81 ADAM10 endopeptidase medicine cleavage by metalloproteinase ADAM10 of PrP cellular protein is constitutive and could inhibit the maintenance of the toxic core of the protein PrP scrapie in spongiform encephalopathies 3.4.24.81 ADAM10 endopeptidase medicine reduction of ADAM10 in Alzheimer disease could allow beta-secretase cleavage of amyloid precursor protein 3.4.24.81 ADAM10 endopeptidase medicine pharmacotherapeutic target for the treatment of cerebral amyloidosis in Alzheimer disease 3.4.24.81 ADAM10 endopeptidase medicine Kuzbanian is required for pericardial cell and lymph gland development 3.4.24.81 ADAM10 endopeptidase medicine potential therapeutic target for the treatment of allergic diseases 3.4.24.81 ADAM10 endopeptidase medicine ADAM 10, 12 and 17 show different expression pattern in basal cell carcinomas histologic subtypes, indicating their different role in the basal cell carcinoma pathogenesis. Overexpression of ADAM 10, 12 and 17 immunoreactivity in deep invasion area of BCC indicates that these three proteases may play an important role in the locally invasive and highly destructive growth behavior of basal cell carcinomas 3.4.24.81 ADAM10 endopeptidase medicine since C4.4A is likely involved in tumor invasion, these results indicate that the cleavage of C4.4A by ADAM10 and ADAM17 contributes to tumor progression 3.4.24.81 ADAM10 endopeptidase medicine ADAM10 as target for Alzheimer’s disease therapy 3.4.24.81 ADAM10 endopeptidase medicine ADAM10 plays a critical role in Alzheimer’s disease. Tetraspanin12 serves as a robust partner for ADAM10 and promotes ADAM10 maturation, thereby facilitating ADAM10-dependent proteolysis of amyloid precursor protein. This mode of regulating amyloid precursor protein cleavage is of relevance to Alzheimer’s disease therapy. Promotion of TSPAN12-ADAM10-dependent functions should be therapeutically beneficial in Alzheimer’s disease, whereas inhibition of TSPAN12-ADAM functions may be beneficial in cancer 3.4.24.81 ADAM10 endopeptidase medicine upregulation of ADAM10 is a therapeutic target in Alzheimer’s disease 3.4.24.81 ADAM10 endopeptidase medicine Staphylococcus aureus alpha-hemolysin, a pore-forming cytotoxin, is required for full virulence in a murine sepsis model. The alpha-hemolysin binding to its receptor A-disintegrin and metalloprotease ADAM10 upregulates the receptor’s metalloprotease activity on endothelial cells, causing vascular endothelial-cadherin cleavage and concomitant loss of endothelial barrier function 3.4.24.81 ADAM10 endopeptidase medicine patients with nasopharyngeal carcinoma with high expression of the enzyme have shorter overall survival rates 3.4.24.82 ADAMTS-4 endopeptidase medicine therapeutic target in osteoarthritis 3.4.24.82 ADAMTS-4 endopeptidase medicine stop progression of cartilage degradation in osteoarthritis by prevention of aggrecan cleavage via inhibition of aggrecanase-1 3.4.24.82 ADAMTS-4 endopeptidase medicine design and development for potent and selective inhibitors of ADAMTS-4 and ADAMTS-5, which will be required for chronic osteoarthritis therapy 3.4.24.82 ADAMTS-4 endopeptidase medicine the pattern of ADAMTS4 release observed is clearly different in various forms of ACS. ADAMTS4 shows a weak correlation with high-sensitivity C-reactive protein. However, no significant correlation is found between ADAMTS4 and troponin T in acute coronary syndromes patients 3.4.24.82 ADAMTS-4 endopeptidase medicine ADAMTS-4 is a key enzyme in osteoarthritis 3.4.24.82 ADAMTS-4 endopeptidase medicine full-length ADAMTS4 and its catalytically more active N-terminal 53 kDa autocatalytic fragment both promote B16 melanoma growth and angiogenesis in mice. Overexpression of its catalytically inactive E362A mutant or truncated fragments containing only the C-terminal ancillary domains suppresses melanoma growth and angiogenesis under similar conditions. The single thrombospondin-type 1 repeat domain is essential and sufficient for the antitumorigenic activity of the catalytically inactive ADAMTS4 isoforms. Suppression of tumor growth and angiogenesis in mice is accompanied by a significant increase in tumor cell apoptosis, whereas tumor cell proliferation is not affected 3.4.24.82 ADAMTS-4 endopeptidase medicine in synovial fluid of most orthopaedic patients ADAMTS-4 activity is undetectable. ADAMTS-4 ranges from 0 to 2.8 ng/mL in synovial fluid from patients with an injury, 0-4.1 ng/mL in osteoarthritic patients and 4.0-12.3 ng/mL in patients with large effusions 3.4.24.83 anthrax lethal factor endopeptidase medicine human medical countermeasures for anthrax 3.4.24.83 anthrax lethal factor endopeptidase medicine inducing strong mucosal and systemic immune responses against both anthrax toxins and bacilli after nasal immunization using a synthetic double-stranded RNA (dsRNA), polyriboinosinic-polyribocytidylic acid as adjuvant. The capsular poly-gamma-D-glutamic acid (PGA) from bacillus is immunogenic when conjugated to a carrier protein and dosed intranasally to mice. The nasal immunization with the poly-gamma-D-glutamic acid-carrier protein conjugate in combination with the anthrax protective antigen (PA) protein induces both anti-PGA and anti-PA immune responses in mouse sera and lung mucosal secretions. The anti-PA antibody response is shown to have anthrax lethal toxin neutralization activity. The anti-PGA Abs induced are able to activate complement and kill PGA-producing bacteria. It is feasible to develop a novel dual-action nasal anthrax vaccine 3.4.24.83 anthrax lethal factor endopeptidase medicine mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge 3.4.24.83 anthrax lethal factor endopeptidase medicine sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival 3.4.24.83 anthrax lethal factor endopeptidase medicine the antitumor toxin has potential for use in cancer therapy 3.4.24.83 anthrax lethal factor endopeptidase medicine engineered lethal anthrax toxin prevents tumor growth by inhibiting angiogenesis (10 nmol/l engineered protective antigen + 5.5 nmol/l lethal factor) 3.4.24.83 anthrax lethal factor endopeptidase medicine the use of drugs capable of inhibiting Rho GTPase activity, such as statins, may provide a means to attenuate intoxication during Bacillus anthracis infection 3.4.24.83 anthrax lethal factor endopeptidase medicine anthrax toxin entry and activity differs among immune cells. Macrophages, dendritic cells, and B cells display higher activity of a of fusion protein of the anthrax toxin lethal factor N-terminal domain LFn, residues 1-254, with beta-lactamase, i.e. LFnBLA, than CD4+ and CD8+ T cells in both spleen cell suspension and the purified samples of individual cell types. Expression of anthrax toxin receptor CMG2 is higher in CD4+ and CD8+ T cells, which is not correlated to the intracellular LFnBLA activity 3.4.24.83 anthrax lethal factor endopeptidase medicine neuronal nitric oxide synthase deficiency in mice causes strikingly increased sensitivity to anthrax lethal toxin, while deficiencies in NOS enzymes iNOS and eNOS have no effect on anthrax lethal toxin-mediated mortality. The increased sensitivity of nNOS2/2 mice is independent of macrophage sensitivity to toxin, or cytokine responses, and can be replicated in nNOS-sufficient wild-type mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Anthrax lethal toxin induces architectural changes in heart morphology of nNOS2/2 mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. Anthrax lethal toxin-treated wild-type mice have no histopathology observed at the light microscopy level. Electron microscopic analyses reveal striking pathological changes in the hearts of both nNOS2/2 and wild-type mice, varying only in severity and timing. Endothelial andcapillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae are observed in both anthrax lethal toxin-treated wild-type and nNOS2/2 mice. Biomarkers of cardiac injury, myoglobin, cardiac troponin-I, and heart fatty acid binding protein, are elevated in anthrax lethal toxin-treated mice very rapidly and reach concentrations rarely reported in mice. The potent nitric oxide scavenger, 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide, i.e. carboxy-PTIO, shows some protective effect against anthrax lethal toxin 3.4.24.83 anthrax lethal factor endopeptidase medicine anthrax lethal factor is a specific biomarker of active infection by Bacillus anthracis 3.4.24.83 anthrax lethal factor endopeptidase medicine blood borne lethal toxin is a novel therapeutic target for combating anthrax 3.4.24.83 anthrax lethal factor endopeptidase medicine administration of lethal factor proteases early in the infection inhibits dissemination of vegetative bacteria to the organs in the first 32 h following infection. Neutralizing antibodies against edema factor also inhibit bacterial dissemination with similar efficacy 3.4.24.83 anthrax lethal factor endopeptidase medicine in a murine model of intoxication, lethal factor causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. The pathology correlates with a blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. Treated mice nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. Intestinal pathology depends upon lethal factor proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics 3.4.24.83 anthrax lethal factor endopeptidase medicine seven of eleven acute myeloid leukemia cell lines show cytotoxic responses to anthrax lethal toxin LeTx. Cytotoxicity is mimicked by the specific mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor U0126, indicating involvement of the ERK1/2 branch of the MAPK pathway. The four LeTx-resistant cell lines are sensitive to the phosphatidylinositol 3-kinase inhibitor LY294002. with a lack of additive/synergistic effects when both pathways are inhibited. Phospho-ERK1/2 is only present in LeTx-sensitive cells. LeTx-induced cell death is caspase-independent and nonapoptotic 3.4.24.84 Ste24 endopeptidase medicine existence of a checkpoint response activated by the nuclear abnormalities caused by prelamin A accumulation, hyperactivation of the tumour suppressor p53 may cause accelerated ageing 3.4.24.84 Ste24 endopeptidase medicine restrictive dermopathy is an autosomal recessive laminopathy caused by inactivating Zmpste24 mutations that result in defective processing and nuclear accumulation of prelamin A 3.4.24.84 Ste24 endopeptidase medicine identification of compound heterozygous frameshifting mutations in exon 1, c.50delA, and exon 5, c.584_585delAT of the ZMPSTE24 gene in two brothers affected with restrictive dermopathy, who died in the neonatal period. Both deletions are frameshifting and are predicted to cause the appearance of premature termination codons 3.4.24.84 Ste24 endopeptidase medicine mutations in the ZMPSTE24 gene lead to incomplete maturation of prelamin A and as a consequence to the premature aging disease Hutchinson-Gilford Progeria Syndrome. In general, the residual activity of ZMPSTE24 patient alleles correlates with disease severity. Complete loss-of-function alleles are associated with restrictive dermopathy, whereas retention of partial, measureable activity results in mandibuloacral dysplasia type B or severe progeria 3.4.24.85 S2P endopeptidase medicine nelfinavir and its analogs inhibit castration-resistant prostate cancer proliferation by blocking regulated intramembrane proteolysis through suppression of site-2 protease cleavage activity. This leads to accumulation of precursors of sterol regulatory element-binding protein SREBP-1 and activating transcription factor ATF6, and development of insufficient reserves of their transcriptionally-active forms 3.4.24.86 ADAM 17 endopeptidase medicine over-expression of TNF-alpha has been implicated in diseases such as rheumatoid arthritis, Crohn's disease, septic shock, AIDS, insulin resistance, cachexia and cancer 3.4.24.86 ADAM 17 endopeptidase medicine TACE inhibitors prevent TNFalpha release and protect against TNFalpha-mediated disease 3.4.24.86 ADAM 17 endopeptidase medicine tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor, activating TACE by pharmacological manipulation might prove beneficial in Alzheimer's disease 3.4.24.86 ADAM 17 endopeptidase medicine targeting this key enzyme for therapeutic intervention in inflammatory diseases, cancer and AIDS 3.4.24.86 ADAM 17 endopeptidase medicine TACE plays a role in the pathogenesis of endometriosis, a benign gynecologic disorder 3.4.24.86 ADAM 17 endopeptidase medicine TACE as target for drug discovery, potential therapeutic target in the areas of arthritis, cancer, diabetes and HIV cachexia 3.4.24.86 ADAM 17 endopeptidase medicine pharmaceutical industry is attempting to design specific TACE inhibitors to treat inflammatory diseases, may also be beneficial in treating certain cancers 3.4.24.86 ADAM 17 endopeptidase medicine isolation of TACE facilitates the development of therapeutically useful inhibitors of TNF-alpha release 3.4.24.86 ADAM 17 endopeptidase medicine putative cellular targets of a therapeutic strategy in neurodegenerative prion diseases 3.4.24.86 ADAM 17 endopeptidase medicine TNF-alpha thought to be a selective anti-tumor agent and a contributor to cachexia in cancer patients, clinical trials for cancer 3.4.24.86 ADAM 17 endopeptidase medicine therapeutic potential of TACE inhibitors benefit in treating autoimmune diseases like Crohn's disease or rheumatoid arthritis 3.4.24.86 ADAM 17 endopeptidase medicine implicated in the pathogenesis of dilated cardiomyopathy 3.4.24.86 ADAM 17 endopeptidase medicine TACE has implications in the pathogenesis of myocarditis and may have influence on advanced cardiac dysfunction in myocarditis 3.4.24.86 ADAM 17 endopeptidase medicine ADAM-17 is a putative target for treatment of neuroinflammatory diseases 3.4.24.86 ADAM 17 endopeptidase medicine ADAM17/TACE might be an important therapeutic target. The blocking of ADAM17/TACE expression and/or the evaluation and development of specific TACE inhibitors might have therapeutic potential even in later stages of cancer. Furthermore, ADAM17/TACE might be useful as a diagnostic marker of pancreatic cancer to distinguish between PDAC and chronic pancreatitis. Aberrant ADAM17/TACE expression might be a diagnostic and therapeutic target in human pancreatic ductal adenocarcinoma 3.4.24.86 ADAM 17 endopeptidase medicine inhibition of TACE might be a potential therapeutic strategy for neuroprotection after focal ischemic stroke 3.4.24.86 ADAM 17 endopeptidase medicine TACE proteolysis is a promoter of stroke-induced SVZ progenitor cell neurogenesis, and suggest this protease activity may represent an attractive therapeutic target for stroke recovery 3.4.24.86 ADAM 17 endopeptidase medicine in order to explore the role of TACE and NF-kappa B in hyperoxia-induced brain-ischemic tolerance, rodents are exposed to 95% inspired hyperoxia 4 h/day for six consecutive days or for 24 continous hours (prolonged hyperoxia). 24 h after the treatment. TACE, serum TNF-alpha and phosphor-kappaBalpha expression is up-regulated. Brain ischemic tolerance, inspired hyperoxia and prolonged hyperoxia may partly exert their effects via triggering TACE/TNF-alpha /NF-kappaB 3.4.24.86 ADAM 17 endopeptidase medicine in this study the relationship between long-term alcohol consumption and the concentration of TACE in peripheral blood mononuclear cells and its substrate- soluble TNF-alpha receptor type 1 in plasma in psoriasis patients is analysed. The study is conducted among 44 patients (aged 30-59 years) with early-onset, plaque-type psoriasis. 38 patients (aged 29-61 years) with other than psoriasis chronic dermatologic disorders are controls. The data on alcohol consumption during previous 10 years are obtained with a structured questionnaire. The severity of the disease is assessed using Psoriasis Area and Severity Index (PASI), and concentrations of TACE in peripheral blood mononuclear cells lysate and soluble TNF-alpha receptor type 1 in plasma is assessed with a quantitative sandwich enzyme immunoassay technique. The alcohol abuse contributes to the increase of TACE expression in blood mononuclear cells and also to the elevated plasma soluble TNF-alpha receptor type 1 concentration in psoriasis patients 3.4.24.86 ADAM 17 endopeptidase medicine the data presented herein show TACE expression in endocrine cancers and further support a role for TACE in breast cancer apoptosis 3.4.24.86 ADAM 17 endopeptidase medicine the increased gingival crevicular fluid TACE levels in persons with periodontitis and their positive correlation with receptor activator of NF-kappaB ligand indicate an association of this enzyme with alveolar bone loss 3.4.24.86 ADAM 17 endopeptidase medicine the relationship between ADAM17 and TNF polymorphisms, circulating levels of shed ADAM17 substrates, and cardiovascular risk in a prospective cohort of coronary artery disease patients is investigated. Five tag single-nucleotide polymorphisms (SNPs) of the ADAM17 gene as well as four previously described TNF SNPs are genotyped in the Atherogene Study composed of 1400 coronary artery disease patients among which 136 died from a cardiovascular cause. Soluble TNF, soluble TNF receptor 1, and soluble TNF receptor 2 concentrations are all significantly elevated in patients with future cardiovascular death, independently of other clinical/biological variables. The ADAM17-154A allele is found associated with a 14% increase of soluble TNF levels as compared to the -154C allele. Individuals carrying the 747Leu allele display a borderline increased risk of future cardiovascular death 3.4.24.86 ADAM 17 endopeptidase medicine 1,25-dihydroxyvitamin D inhibition of TACE is a potential common mechanism underlying the efficacy of therapy with 1,25-dihydroxyvitamin D or its analogs to improve outcomes in chronic kidney disease. 1,25-dihydroxyvitamin D prevents/moderates not only the onset and progression of parathyroid TACE/TGFalpha-driven secondary hyperparathyroidism, but renal TACE/TGFalpha-driven fibrotic and inflammatory lesions to the renal parenchyma, and TACE/TNFalpha-driven systemic inflammation 3.4.24.86 ADAM 17 endopeptidase medicine anti-Ro/SSA autoantibodies determine TACE pro-domain shedding suggesting that TACE activity is necessary for the release of TNF-alpha observed in anti-Ro/SSA autoantibody-stimulated cells. Adalimumab appears to be significantly more efficacious than Etanercept in preventing TACE activation caused by anti-Ro/SSA autoantibodies. Regulation of TACE may participate in the pathogenic role of autoantibodies and the modulation of TACE expression by TNF-alpha antagonists might contribute to the beneficial effect of these drugs in inflammatory and autoimmune diseases 3.4.24.86 ADAM 17 endopeptidase medicine during acute H pylori infection, CagL dissociates ADAM17 from the integrin alpha(5)beta1 and activates ADAM17-dependent, nuclear factor-kappaB-mediated repression of HKalpha, i.e. gastric H, K-adenosine triphosphatase alpha-subunit. This might contribute to transient hypochlorhydria in patients with H pylori infection 3.4.24.86 ADAM 17 endopeptidase medicine expression of ADAM-17 is significantly increased in gallbladder carcinoma with high histological grade and pT stage compared with low histological grade and pT stage tumors and is not associated with patients’ gender, age, histological type, and resection margin involvement. Patients with high expression of ADAM-17 have a significantly shorter overall survival compared with those with low expression. The prognostic impact of ADAM-17 is independent of conventional prognostic factors for gallbladder carcinoma 3.4.24.86 ADAM 17 endopeptidase medicine increased expression and shedding of fractalkine by endothelial cells under pro-inflammatory conditions is not regulated by an increased activity of ADAM-17 3.4.24.86 ADAM 17 endopeptidase medicine increased TACE activity is necessary for the release of TNF-alpha observed in anti-Ro/SSA antibodies-stimulated salivary gland epithelial cells 3.4.24.86 ADAM 17 endopeptidase medicine inhibition of ADAM17 increases the cytotoxicity of bortezomib and MDX-060 against L-540 cells 3.4.24.86 ADAM 17 endopeptidase medicine metalloproteases ADAM-9, ADAM-15, and ADAM-17 are upregulated in advanced human atherosclerotic lesions in samples from carotid, aortic, and femoral territories compared to samples from internal thoracic artery free of atherosclerotic plaques. The enzymes are in the catalytically active form. ADAM-9, ADAM-15, and ADAM-17-expressing cells colocalize with CD68-positive cells of monocytic origin in the atherosclerotic plaques. Colocalization is demonstrated in all vascular territories 3.4.24.86 ADAM 17 endopeptidase medicine study on the association of ADAM-17 single nucleotide polymorphisms with insulin-resistance phenotypes and obesity risk. G allele carriers at the ADAM17_m1254A > G polymorphism exhibit significantly higher risk of obesity, are shorter, have higher insulin, and lower HDL-C concentrations than AA subjects. For the ADAM17_i33708A > G single nucleotide polymorphism, homozygotes for the A allele display higher risk of obesity, are heavier, have higher body-mass-index and higher waist measurements than GG subjects. There is a significant gene-diet interaction, in which the deleterious association of the i33708A allele with obesity is observed in subjects with low intakes from n-6 polyunsaturated fatty acids, whereas no differences in obesity risk are seen among subjects with high n-6 polyunsaturated fatty acid intake 3.4.24.86 ADAM 17 endopeptidase medicine transcription factor Sp1 binds to the ADAM17 promoter, and Sp1 regulates ADAM17 expression under hypoxia. Suppression of Sp1 decreases invasiveness and migration in U87 tumor cells 3.4.24.86 ADAM 17 endopeptidase medicine treatment of mice in a lipopolysaccharide-induced endotoxemia model group with recombinant TACE prodomain protein prior to the injection of lipopolysaccharide. The recombinant prodomain protein decreases the release of the secreted TNF-alpha, which mediates the accumulation of TNF-alpha on the surface of macrophage cells. The recombinant protein can decrease the inflammatory response in internal organs of endotoxaemia mice 3.4.24.86 ADAM 17 endopeptidase medicine ADAM17 is a potential drug target in tumor necrosis factor and/or epidermal growth factor receptor–dependent pathologies in inflammation and cancer 3.4.24.86 ADAM 17 endopeptidase medicine the enzyme serves as a potential biomarker of periodontitis 3.4.24.86 ADAM 17 endopeptidase medicine ADAM17 expression levels are correlated with the invasive ability of androgen-independent prostate cancer cell lines. ADAM17 is overexpressed in cells showing high invasion characteristics, activation of the EGFR-MEK-ERK pathway, up-regulation of MMP-2, MMP-9, and an increased TGF-alpha release into the supernatant. AG1478, PD98059 and antibody against TGF-alpha deactivating the EGFR-MEK-ERK signaling pathway, abolish up-regulation of MMP-2, MMP-9 and prevent cell invasion. Cells with knock-down of ADAM17 by siRNA exhibit low invasive ability, deacti­vated EGFR-MEK-ERK signaling pathway, reduced TGF-alpha release and down-regulation of MMP-2, MMP-9 3.4.24.86 ADAM 17 endopeptidase medicine ectopic over-expression of ADAM17 results in increased cell proliferation. ADAM17 promotes G1 to S phase transition concomitantly with upregulation of cyclin E, CDK2 and downregulation of p21 and p27 proteins. ADAM17 over-expression cells show more TGF-alpha released to the supernatant and activate the EGFR/PI3K/AKT pathway. Silencing ADAM17 leads to the opposite effect. Both siRNAs knockdown of ADAM17 and blocking the EGFR/PI3K/AKT pathway cause downregulation of cyclin E,CDK2,and upregulation of p21 and p27 in prostate cancer cells 3.4.24.86 ADAM 17 endopeptidase medicine human IgG Fc receptor CD16, i.e. FcgammaRIII plasma levels are significantly decreased in patients administered a selective inhibitor targeting the metalloproteases ADAM10 and ADAM17. Inhibition of ADAM17 significantly blocks the cleavage of CD16b following neutrophil activation and apoptosis 3.4.24.86 ADAM 17 endopeptidase medicine inhibition of ADAM17-mediated processing of TNF-alpha by CD8+ T cells significantly attenuates the diffuse alveolar damage that occurs after T-cell transfer, resulting in enhanced survival. TNF-alpha processing is required for lung epithelial cell expression of CXCL2 and the subsequent inflammatory infiltration. CXCL2 expression is important in acute lung injury 3.4.24.86 ADAM 17 endopeptidase medicine the enzyme activity plays a positive role to predict cardiovascular events 3.4.24.86 ADAM 17 endopeptidase medicine the enzyme is upregulated in gastric cancer cells with high metastatic potential 3.4.24.87 ADAMTS13 endopeptidase medicine analysis of vWF protease and vWF multimeric distribution are valuable tools in making the distinction between bone marrow transplant-associated thrombotid microangiopathy and thrombotic thrombocytopenic pupura 3.4.24.87 ADAMTS13 endopeptidase medicine ADAMTS-13 is deficient in congenital thrombotic thrombocytopenic purpura and inhibited in aquired thrombotic thrombocytopenic purpura. The availability of recombinant ADAMTS-13 raises the prospect of developing a recombinant substitution therapy to improve thrombotic thrombocytopenic purpura treatment and allows present diagnostic assays to be simplified 3.4.24.87 ADAMTS13 endopeptidase medicine assay using recombinant or synthetic substrates (high-throughput methods) will contribute significantly to the accurate diagnosis of microangiopathies, ultimately leading to improved treatment of these diseases. These assays may also help clarify the role of ADAMTS13 in thrombotic disorders including disseminated intravascular coagulation, stroke, and myocardial infarction 3.4.24.87 ADAMTS13 endopeptidase medicine description of a simple procedure to analyse the kinetics of von Willebrand factor proteolysis that is suitable for routine diagnostic use 3.4.24.87 ADAMTS13 endopeptidase medicine in order to develop new strategies for improving the diagnosis and treatment of thrombotic thrombocytopenic purpura, this study systemically analyzed a series of ADAMTS13 mutant proteins to identify variant forms that are proteolytically active and yet resistant to suppression by inhibitory antibodies. A deficiency ofADAMTS13, due to mutations in the ADAMTS13 gene or the presence of antibodies that inhibit the activity of the protease,causes thrombotic thrombocytopenic purpura. Plasma therapy, the conventional therapy for TTP, may cause serious adverse reactions and is ineffective in some patients 3.4.24.87 ADAMTS13 endopeptidase medicine VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13. VWF73 could be a powerful tool to establish clinical enzymatic assays. It may contribute to improve the prognosis and prevention of thrombotic thrombocytopenic purpurea 3.4.24.87 ADAMTS13 endopeptidase medicine ADAMTS13 deficiency and the resultant increase in von Willebrand factor adhesion activity may be clinically significant for association with the severity of thrombocytopenia and clinical prognosis in sepsis, sickle cell disease, and and increased risk for stroke 3.4.24.87 ADAMTS13 endopeptidase medicine ADAMTS13 deficiency is linked to thrombotic thrombocytopenic purpura 3.4.24.87 ADAMTS13 endopeptidase medicine levels of ADAMTS13 are lower and levels of Von Willebrand Factor are higher in young patients with cardiovascular disease compared to healthy individuals. Individuals with low levels of ADAMTS13 had five times more risk on cardiovascular disease than subjects with normal levels of ADAMTS13. The relationship is strongest in the subgroup of patients with coronary heart disease. This may be of importance for identifying individuals who are prone to have a cardiovascular event 3.4.24.87 ADAMTS13 endopeptidase medicine ADAMTS13 may be a useful therapeutic agent for stroke in humans 3.4.24.87 ADAMTS13 endopeptidase medicine correction of ADAMTS13 deficiency by in utero gene transfer of lentiviral vector encoding ADAMTS13 genes 3.4.24.87 ADAMTS13 endopeptidase medicine infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Thus, recombinant ADAMTS13 can be considered as a therapeutic agent for prevention and/or treatment of stroke. Recombinant ADAMTS13 does not enhance bleeding in a hemorrhagic stroke model 3.4.24.87 ADAMTS13 endopeptidase medicine ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura. Cyclosporin A, an inhibitor of cyclophilin B, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. Cyclophilin B and ADAMTS13 show a direct, functional interaction 3.4.24.87 ADAMTS13 endopeptidase medicine exposure of ADAMTS13 to activated human neutrophils results in oxidation of residues Met249, Met331, and Met496 in important functional domains ofADAMTS13. ADAMTS13 treated with either neutrophil elastase or plasmin is inhibited to a lesser extent, especially in the presence of plasma. 3.4.24.87 ADAMTS13 endopeptidase medicine increased plasma enzyme activity after 1 year entecavir treatment is associated with a higher seroconversion, and can be used surrogate of hepatitis B virus e antigen seroconversion in chronic hepatitis B patients during 5-year entecavir treatment 3.4.25.1 proteasome endopeptidase complex medicine nuclear localization of 20S proteasome seems to be associated with the pathogeneses of Parkinson's disease 3.4.25.1 proteasome endopeptidase complex medicine inhibitor development and optimization of the molecules can lead to better anticancer therapy, overview 3.4.25.1 proteasome endopeptidase complex medicine Nrf1-mediated proteasome homeostasis can be an attractive target for therapeutic intervention in cancer 3.4.25.1 proteasome endopeptidase complex medicine possible use of proteasome inhibitors for immunosuppression 3.4.25.1 proteasome endopeptidase complex medicine proteasome inhibitors and other Hsp70 inducing agents may be useful in the treatment of a variety of genetic diseases caused by missense mutations 3.4.25.1 proteasome endopeptidase complex medicine proteasome inhibitors are used for the treatment of multiple myeloma and recurring mantle cell lymphoma, e.g. inhibitors MLN9708 and bortezomib, overview 3.4.25.1 proteasome endopeptidase complex medicine curcumin diminishes DYRK2-mediated 26S proteasome phosphorylation in cells, leading to reduced proteasome activity and impaired cell proliferation. Curcumin synergizes with the therapeutic proteasome inhibitor carfilzomib to induce apoptosis in a variety of proteasome-addicted cancer cells, the drug combination exhibits modest to no cytotoxicity to noncancerous cells. In a breast cancer xenograft model, curcumin treatment significantly reduces tumor burden in immunocompromised mice, showing a similar antitumor effect as CRISPR/Cas9-mediated DYRK2 depletion 3.4.99.B1 RCE1 medicine excision of RCE1 from skin carcinoma cell line retards the growth of cells significantly, and this effect was exaggerated by co-treatment with farnesyl-transferase inhibitor 3.4.99.B1 RCE1 medicine Rce1 knockout mice have a dilated cardiomyopathy, by contrast, liver-specific Rce1 knockout mice appear healthy, endoproteolytic processing of CAAX proteins is essential for cardiac function but less important for the liver 3.4.99.B1 RCE1 medicine expression of Rce1 is significantly decreased in hepatocellular carcinoma compared with noncancerous tissues, while H-Ras expression is increased in the tumor. The expression of both is a close association with the differentiation and tumor-node-metastasis stage of the tumor. Rce1 is an independent prognostic indicator. Lower expression of Rce1 facilitates epithelial-mesenchymalctransition and promotes the invasion and metastasis of hepatocellular carcinoma 3.5.1.1 asparaginase medicine enzyme has antitumor activity 3.5.1.1 asparaginase medicine enzyme is used in the treatment of acute lymphomic leukemia 3.5.1.1 asparaginase medicine a prospective therapeutic enzyme for leukemia treatment 3.5.1.1 asparaginase medicine the use of asparaginase II as a drug for the treatment of acute lymphoblastic leukemia is complicated by the significant glutaminase side activity of the enzyme. Selective reduction in glutaminase activity in variant B248A and other N248 variants 3.5.1.1 asparaginase medicine potent antineoplastic agent in animals which has given complete remission in some human leukemias 3.5.1.1 asparaginase medicine used for treatment of acute lymphoblastic leukemia, pancreatic carcinoma, and bovine lymphosarcoma 3.5.1.1 asparaginase medicine L-asparaginase is an anti-leukemic enzyme 3.5.1.1 asparaginase medicine L-asparaginase is important in the induction regimen for treating human acute lymphoblastic leukemia, cytotoxic complications are clinically significant problems lacking mechanistic insight, the enzyme is used in the treatment of both pediatric and adult forms of acute lymphoblastic leukemia, ALL 3.5.1.1 asparaginase medicine L-asparaginase is important in the induction regimen for treating human acute lymphoblastic leukemia, cytotoxic complications are clinically significant problems lacking mechanistic insight, the enzyme is used in the treatment of both pediatric andadult forms of acute lymphoblastic leukemia, ALL 3.5.1.1 asparaginase medicine the enzyme is a potential therapeutic agent in acute lymphocytic leukemia, acute lymphoblastic leukemia, and chromic myelogenyous leukemia, but causes high allergic reactions 3.5.1.1 asparaginase medicine the enzyme is used as therapeutic agent in the treatment of acute childhood lymphoblastic leukemia 3.5.1.1 asparaginase medicine the enzyme is used for acute lymphoblastic leukemia treatment, the enzyme does not reduces alpha-antiplasmin and plasminogen levels in human patients, overview 3.5.1.1 asparaginase medicine the enzyme is used for acute lymphoblastic leukemia treatment, the enzyme reduces alpha-antiplasmin and plasminogen levels in human patients, this together with the elevated level of thrombin activity in the patients lead to an enhanced risk for thrombosis due to delay in fibrin elimination in Escherichia coli L-asparaginase-treated patients, overview 3.5.1.1 asparaginase medicine the enzyme is widely used in chemotherapy for treatment of children with acute lymphoblastic leukemia, in vivo and in vitro resistance of the cells to the enzyme can occur 3.5.1.1 asparaginase medicine asparaginase is used in the treatment of acute lymphoblastic leukemia. It depletes plasma asparagine and glutamine, killing leukemic lymphoblasts but also causing immunosuppression. Asparaginase reduces maturing populations of normal B and T cells in thymus, bone marrow, and spleen of mice. Oral consumption of alanyl-glutamine mitigates metabolic stress in spleen, supporting the peripheral immune system and cell-mediated immunity during asparaginase chemotherapy 3.5.1.1 asparaginase medicine L-asparaginase is an anticancer agent. Developing an asparaginase production process based on bran of Glycine max as a substrate in solid state fermentation is economically attractive as it is a cheap and readily available raw material in agriculture-based countries 3.5.1.1 asparaginase medicine the enzyme can be efficiently immobilized on epoxy-activated Sepharose CL-6B. The immobilized enzyme retains most of its activity (60%) and shows high stability at 4°C. The approach offers the possibility of designing an L-asparaginase from Erwinia chrysanthemi bioreactor that can be operated over a long period of time with high efficiency, which can be used in leukaemia therapy 3.5.1.1 asparaginase medicine the enzyme is important to the treatment of acute lymphoblastic leukemia. Intravenous PEG-asparaginase (L-asparaginase covalently linked to polyethylene glycol) will eliminate painful injection, and achieve rapid peak levels and asparagine depletion 3.5.1.1 asparaginase medicine chemotherapeutic agent 3.5.1.1 asparaginase medicine treatment of lymphoma 3.5.1.1 asparaginase medicine asparaginase is one of the important bioactive compounds, which have curative effects in cancer treatment 3.5.1.1 asparaginase medicine L-asparaginase II from Erwinia carotovora may represent an important alternative therapy in the treatment of acute childhood lymphoblastic leukaemia, despite its promising lower glutaminase activity than Escherichia coli and Erwinia chrysanthemi L-asparaginases II 3.5.1.1 asparaginase medicine the enzyme is an important biopharmaceutical product used in the treatment of acute lymphoblastic leukaemia 3.5.1.1 asparaginase medicine anticancer drug 3.5.1.1 asparaginase medicine the enzyme is an important drug in the treatment of childhood acute lymphoblastic leukemia 3.5.1.1 asparaginase medicine the recombinant enzyme potentiate a lectin's induction of leukemic K562 cell apoptosis 3.5.1.1 asparaginase medicine enzyme potentiates a lectin's induction of leukemic K562 cell apoptosis, allowing lowering of the drug dosage and shortening of the incubation time 3.5.1.1 asparaginase medicine covalent immobilization of enzyme on functionalized aluminium oxide nanoparticles (AONP) and titanium oxide nanoparticles (TONP) for anticancer therapy. The nano-bioconjugates are optimally active at pH 7.0 and 40°C. TONP-asparaginase activity is enhanced in the presence of NH4+ (160%) and Mn2+ (165%) while AONP-asparaginase bioconjugates show increased relative activity with ethyl acetate (142%) and toluene (160%). The nano-bioconjugates display good reusability and maintain over 90% average activity after nine successive cycles. Maximum cytotoxicity (61%) is noticed with AONP-asparaginase against human leukemia MOLT-4 cells. AONP-asparaginase shows better affinity to L-asparagine as compared to free enzyme 3.5.1.1 asparaginase medicine enzyme shows antitumor proterties with IC50 values 0.036 mg/ml for MCF-7 cells, 0.037 mM/ml for HCT-116 cells, 0.046 mg/ml for Hep-G2 cells, respectively 3.5.1.1 asparaginase medicine L-asparaginase may significantly alter the interactions between microvascular endothelial cells, colon cancer cells, and components, resulting in colon cancer cell injury 3.5.1.1 asparaginase medicine purified L-asparaginase does not show hemolysis effect on blood erythrocytes. Recombinant L-asparaginase retains 50% of its initial activity after 90 and 60 min incubation in serum and trypsin separately 3.5.1.1 asparaginase medicine recombinant enzyme is able to inhibit the proliferation of K-562 and Jurkat cell lines 3.5.1.1 asparaginase medicine the anticancer activity of purified asparaginase is comparable or higher than that of commercial Escherichia coli asparaginase. The purified enzyme induces apoptotic cell death in dose-dependent manner, probybly via activation of anintrinsic apoptotic pathway. The purified enzyme is nontoxic for human noncancerous FR-2 cells and human blood lymphocytes 3.5.1.1 asparaginase medicine the purified enzyme inhibits the growth of human cell lines Hep-G2, MCF-7 and PC-3 with IC50 values of 14 microg/ml, 12.5 microg/ml and 37 microg/ml, respectively 3.5.1.1 asparaginase medicine the purified enzyme shows cytotoxicity for the MOLT-4 leukemic cell lineage 3.5.1.2 glutaminase medicine enzyme therapy at the dose of 10 unit/mouse in ascites tumor bearing mice, elicits a reduction in tumor growth. At day 5, 10 and 15 it is reduced by 60%, 95% and 89% respectively. The life span of the enzyme treated mice increases significantly with respect to control mice 3.5.1.2 glutaminase medicine depresses some pro-inflammatory factors that occur during prolonged, exhaustive exercise 3.5.1.2 glutaminase medicine acivicin along with Escherichia coli glutaminase synergistically reduces in vitro proliferation and matrigel invasion of human MCF-7 and OAW-42 cells. Combination of acivicin with glutaminase may provide a better therapeutic option than either of them separately for treating human breast and ovarian cancer 3.5.1.2 glutaminase medicine purified L-glutaminase has a high toxic effect on Hela and Hep G2 cell lines with an IC50 value 18 and 12 microg/ml, respectively, and a moderate cytotoxic effect on HCT-116 and MCF7 cells, with an IC50 value 44 and 58 microg/ml, respectively 3.5.1.2 glutaminase medicine strategy to overcome acquired erlotinib resistance in NSCLC by inhibiting glutaminase activity. Compound 968, an inhibitor of the glutaminase C, when combined with erlotinib potently inhibits the cell proliferation of erlotinib-resistant NSCLC cells HCC827ER and NCI-H1975. The combination of compound 968 and erlotinib decreases glutaminase C and EGFR protein expression and inhibits glutaminase C activity in HCC827ER cells. Compound 968 combined with erlotinib down-regulates the glutamine and glycolysis metabolism in erlotinib-resistant cells 3.5.1.3 omega-amidase medicine in patients with liver disease and encephalopathy there is a good correlation between degree of neurological dysfunction and increase in alpha-ketoglutaramate in cerebrospinal fluid, omega-amidase is suitable for determination of alpha-ketoglutaramate 3.5.1.4 amidase medicine therapy 3.5.1.4 amidase medicine down-regulated state of FAAH - through its effects on CB1 and opioid receptor in the brain reward circuitry - promotes ethanol drinking behavior. Manipulation of the FAAH activity might represent a novel therapeutic target for the treatment of ethanol dependence 3.5.1.4 amidase medicine FAAH inhibition shows potential utility for the clinical treatment of persistent and neuropathic pain 3.5.1.5 urease medicine enhancement of intragastric enzyme activity is not strictly a function of pH-value, but is related to differential effects of the availability of nickel, which is required for enzyme activity 3.5.1.5 urease medicine lack of enzyme activity in most enterohaemorrhagic strains is due to a premature stop codon in ureD encoding a chaperone protein of the urease gene cluster 3.5.1.5 urease medicine use of jack bean urease as a model enzyme for Helicobacter pylori urease. Development of organobismuth components without antifungal activity against Saccharomyces cerevisiae but with antibacterial activity 3.5.1.5 urease medicine the action of urease in the upper intestinal tract is exploited in a non-invasive urease breath test for the diagnosis of bacterial infections of Helicobacter pylori: 13C- or 14C-labelled urea is ingested, and if the bacterium is present in the stomach, the urea is converted into isotope-labelled carbon dioxide. This is absorbed into the blood and exhaled in the breath, where it is detected by mass spectrometer or scintillation counter 3.5.1.5 urease medicine a novel immunoconjugate (L-DOS47) is developed and characterized as a therapeutic agent for tumors expressing CEACAM6. The single domain antibody AFAIKL2, which targets CEACAM6, is expressed in the Escherichia coli BL21 (DE3) pT7-7 system. High purity urease is extracted and purified from Jack bean meal. AFAIKL2 is activated using N-succinimidyl [4-iodoacetyl]aminobenzoate (SIAB) as the cross-linker and then conjugated to urease. The specificity and cytotoxicity of L-DOS47 is confirmed by screening in four cell lines (BxPC-3, A549, MCF7, and CEACAM6-transfected H23). BxPC-3, a CEACAM6-expressing cell line is most susceptible to L-DOS47. L-DOS47 is a potential therapeutic agent in human phase I clinical studies for nonsmall cell lung cancer 3.5.1.5 urease medicine importance of overall cryptococcal urease inhibition, rather than of its enzymatic activity alone, for the future development of therapeutic tools targeting cryptococcosis 3.5.1.5 urease medicine site targeted delivery of urease along with chemotherapeutic drugs can be a promising tool for anti-cancer applications. Urease shows its inhibitory effects on cancer cell lines through the generation of toxic ammonia, which in turn increases the pH of the surrounding medium. This increase in extracellular pH, enhances the cytotoxic effect of weak base chemotherapeutic drugs, doxorubicin (0.05 mM) and vinblastine (0.100 mM) in the presence of urease (5 U/ml) and urea (0-4 mM) significantly 3.5.1.6 beta-ureidopropionase medicine mutation analysis in patients with cloned genes 3.5.1.6 beta-ureidopropionase medicine analysis of putative enzyme defects in patients with neurological disfunctions 3.5.1.6 beta-ureidopropionase medicine pharmacogenetic studies in patients receiving fluoropyrimidine-based chemotherapy should include genetic variants in dihydropyrimidinase (DPYS) and beta-ureidopropionase (UPB1), in addition to DPYD, to improve the understanding of their contribution to severe toxicity from fluoropyrimidine-based chemotherapy. Potential unknown underlying causal variants linked to the associated dihydropyrimidinase and beta-ureidopropionase variants may have a clinically relevant effect on fluoropyrimidine toxicity and should be investigated 3.5.1.12 biotinidase medicine plasma biotinidase activity assay for diagnosis and screen newborn infants for biotinidase deficiency, treatment of inborn metabolism errors with large doses of biotin 3.5.1.12 biotinidase medicine naturally occuring missense mutations result in biotinidase deficiency, an autosomal recessively inherited disorder in which affected individuals have multiple carboxylase deficiency due to secondary deficiency of free biotin 3.5.1.12 biotinidase medicine thirteen novel mutations in children with biotinidase deficiency. Biotinidase deficiency is a defect in the recycling of the vitamin biotin. Biotin supplementation can markedly improve the neurological and cutaneous symptoms of affected children and prevents symptoms in children identified by newborn screening or treated since birth 3.5.1.12 biotinidase medicine serum biotinidase is a sensitive and specific biochemical marker of hepatic dysfunction 3.5.1.14 N-acyl-aliphatic-L-amino acid amidohydrolase medicine N-acetyl-L-cysteine used for drugs against lung disorders and HIV infections, test of potential antitumor agents 3.5.1.14 N-acyl-aliphatic-L-amino acid amidohydrolase medicine preparation of commercially important amino acids as components for semisynthetic penicillins and cephalosporins 3.5.1.14 N-acyl-aliphatic-L-amino acid amidohydrolase medicine the enzyme is an important biomarker with potential prognostic utility in patients with delayed graft function following renal transplantation 3.5.1.15 aspartoacylase medicine diagnosis of Canavan disease, an autosomal recessive neurodegenerative disorder characterized by aspartoacylase deficiency, technique for prenatal diagnosis 3.5.1.15 aspartoacylase medicine mutations in the aspartoacylase aspA gene are implicated as the cause of Canavan Disease 3.5.1.16 acetylornithine deacetylase medicine enzymatic target for a novel set of antibiotics 3.5.1.18 succinyl-diaminopimelate desuccinylase medicine inhibition of the catalytic action of the microbial enzyme DapE is fatal to the growth of bacteria and critical to the use of this enzyme as a potential antibiotic target 3.5.1.19 nicotinamidase medicine Riemerella anatipestifer AS87_01735 gene encodes PncA, which is an important virulence factor. The Yb2DELTApncA mutant can be used as a novel live vaccine candidate 3.5.1.19 nicotinamidase medicine the absence of nicotinamidase in humans makes it a promising drug target 3.5.1.20 citrullinase medicine clinical biochemistry, therapeutic measurement of citrulline 3.5.1.23 ceramidase medicine CDase from Pseudomonas aeruginosa may be a virulence factor in infections, may be involved in the ceramide deficiency in the horny layer of the epidermis of patients with atopic dermatitis suffering from bacterial infections 3.5.1.23 ceramidase medicine patients with the lipid storage disorder, the Farber disease, have a marked AC deficiency 3.5.1.23 ceramidase medicine Farber disease is diagnosed by the demonstration of reduced acid ceramidase activity, abnormally high ceramide levels in cultured cells, biopsy samples or urine, and the presence of Farber bodies, comma-shaped curvilinear tubular structures. The enzyme is likely to continue to be a target for new drug development in cancer and other disorders 3.5.1.23 ceramidase medicine downregulation of acid ceramidase increases sensitivity to radiation 3.5.1.23 ceramidase medicine in human prostate tissues, acid ceramidase and cathepsin B overexpression are strongly associated and may relate to poor outcome 3.5.1.23 ceramidase medicine inhibition of acid ceramidase is useful in cancer treatment 3.5.1.23 ceramidase medicine because of its central role in the ceramide metabolism, the enzyme may offer a novel molecular target in disorders with dysfunctional ceramide-mediated signaling 3.5.1.24 choloylglycine hydrolase medicine cholesterol lowering in pigs through enhanced bacterial bile salt hydrolase activity 3.5.1.24 choloylglycine hydrolase medicine protein encapsulation is an excellent tool to protect enzymes during transit through gastric conditions and release enzyme activity in the proximal small intestine 3.5.1.24 choloylglycine hydrolase medicine using bile salt deconjugation to lower serum cholesterol levels in hypercholesteremic patients and prevent hypercholesteremia in normal people is of great interest 3.5.1.24 choloylglycine hydrolase medicine effect of oral administration to Wistar rats of the immobilized bile salt hydrolase enzyme on serum cholesterol, triglyceride, high density lipoprotein levels and its application in the therapeutic treatment of hypercholesteremia, overview 3.5.1.24 choloylglycine hydrolase medicine active BSH derived from the probiotic Lactobacillus johnsonii strain La1 may yield anti-giardial effects in vitro and in vivo. The enzyme may be useful in approaches for the treatment of widely spread but neglected infectious disease, such as giardiasis, both in human and in veterinary medicine 3.5.1.24 choloylglycine hydrolase medicine bile salt hydrolase (BSH) active probiotic strains are being used in the treatment of hypercholesterolemia related diseases 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine fluorometric assay in blood samples allows specific detection of the enzyme defect in aspartylglycosaminuria patients 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine diagnosis of aspartylglycosaminuria in urine samples 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine deficient AGA activity results in a lysosomal storage disease, aspartylglucosaminuria, resulting in progressive neurodegeneration, most of disease-causing mutations lead to defective molecular maturation of AGA 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine enzyme deficiency or its absence gives rise to aspartylglycosaminuria, an autosomal recessive inherited disorder that results in the accumulation of glycoasparagines in lysosomes, most common disorder of glycoprotein metabolism 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine enzyme deficiency or its absence gives rise to aspartylglycosaminuria, the most common disorder of glycoprotein metabolism 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine a high dose enzyme replacement therapy with glycosylasparaginase in newborn aspartylglycosaminuria mice is up to 2fold more effective in reducing the amount of the accumulated storage material from the brain tissue than enzyme replacement therapy in adult aspartylglycosaminuria animals 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine human glycosylasparaginase is a potential anticancer agent to induce apoptosis in L-asparagine-dependent cancer cells 3.5.1.26 N4-(beta-N-acetylglucosaminyl)-L-asparaginase medicine use of codon-optimized AGA may be beneficial for the therapy options in treatment of the lysosomal storage disorder aspartylglucosaminuria (AGU) 3.5.1.33 N-acetylglucosamine deacetylase medicine nonfunctional enzyme mutant, reduced virulence in intraperitoneal mouse model 3.5.1.38 glutamin-(asparagin-)ase medicine L-glutaminase has a significant efficiency against Hep-G2 cell (IC50 6.8x02g/ml) and HeLa cells (IC50 8.3 g/ml), while the growth of MCF-7 cells is not affected. L-glutaminase has a moderate cytotoxic effect against HCT-116 cells (IC50 64.7 g/ml) and RAW 264.7 cells (IC50 59.3 g/ml). In vivo, L-glutaminase shows no observed changes in liver, kidney functions, hematological parameters and slight effect on red blood cells and level of platelets after 10 days of rabbit's injection 3.5.1.41 chitin deacetylase medicine chitosan is necessary for cell wall integrity in Cryptococcus neoformans. Chitin deacetylases and the chitosan made by them may prove to be excellent antifungal targets 3.5.1.60 N-(long-chain-acyl)ethanolamine deacylase medicine modulation of the tissue levels of palmitoylethanolamide by inhibition of enzymes responsible for the breakdown of this lipid mediator, including the N-acylethanolamine acid amidase, may represent therefore a therapeutic strategy for the treatment of pain and inflammation 3.5.1.88 peptide deformylase medicine attractive target for antibacterial drug discovery 3.5.1.88 peptide deformylase medicine the enzyme is a potential antibacterial and antimalarial drug target 3.5.1.88 peptide deformylase medicine possible target for new broad spectrum antimicrobial agents 3.5.1.88 peptide deformylase medicine antibacterial activity against clinically significant Gram-positive and Gram-negative pathogens 3.5.1.88 peptide deformylase medicine peptide deformylase has been considered an attractive target for antibacterial chemotherapy 3.5.1.88 peptide deformylase medicine peptide deformylase has been considered as a potential target in antimicrobial chemotherapy 3.5.1.88 peptide deformylase medicine peptide deformylase inhibitors have a strong potential to be used as antibiotics 3.5.1.88 peptide deformylase medicine peptide deformylase is a promising antibacterial and herbicide target 3.5.1.88 peptide deformylase medicine peptide deformylase is a target for novel antibiotics 3.5.1.88 peptide deformylase medicine peptide deformylase may be a potential target for designing new antibiotics 3.5.1.88 peptide deformylase medicine peptide deformylase represents a target for the discovery of broad spectrum antibacterial drugs 3.5.1.88 peptide deformylase medicine potential drug target, antimalarial drugs 3.5.1.88 peptide deformylase medicine target for anti-Helicobacter pylori drugs 3.5.1.88 peptide deformylase medicine target for antibacterial agents 3.5.1.88 peptide deformylase medicine target for antibacterial agents against Staphylococcus aureus 3.5.1.88 peptide deformylase medicine target for the development of new antibacterial drugs 3.5.1.88 peptide deformylase medicine target of antibiotic drugs 3.5.1.88 peptide deformylase medicine peptide deformylase becomes a target for the design of new antibiotics 3.5.1.88 peptide deformylase medicine peptide deformylase is a target for the design of novel antibiotics 3.5.1.88 peptide deformylase medicine peptide deformylase is a target protein for the development of anti-bacterial drugs 3.5.1.88 peptide deformylase medicine possibility of future design of novel mycobacteria-specific peptide deformylase inhibitors 3.5.1.88 peptide deformylase medicine the gene encoding peptide deformylase is present in all sequenced pathogenic bacterial genomes, therefore peptide deformylase is an attractive target for antibacterial chemotherapy 3.5.1.88 peptide deformylase medicine the specific bacterial requirement for peptide deformylase in protein synthesis provides a rational basis for selectivity, making it an attractive potential drug discovery target 3.5.1.88 peptide deformylase medicine peptide deformylase is a therapeutic target for antibacterial drug discovery 3.5.1.88 peptide deformylase medicine peptide deformylase is a therapeutic target for tuberculosis 3.5.1.89 N-acetylglucosaminylphosphatidylinositol deacetylase medicine comparison of substrate specificity of human and parasite enzyme 3.5.1.92 pantetheine hydrolase medicine the pantetheinase activity of vanin-1 molecule could be a target for a new anti-inflammatory strategy 3.5.1.92 pantetheine hydrolase medicine manipulation the Vanin-1/pantetheinase activity represents an attractive therapeutic strategy for the treatment of inflammatory bowel disease 3.5.1.92 pantetheine hydrolase medicine vanin-1 is a potential biomarker for nephrotoxicant-induced renal injury 3.5.1.97 acyl-homoserine-lactone acylase medicine therapeutic efficacy of PvdQ acylase as a quorum quenching agent during Pseudomonas aeruginosa infection (mouse model of pulmonary Pseudomonas aeruginosa infection) 3.5.1.98 histone deacetylase medicine general inhibition of histone deacetylases alters the balance of T helper 1 and T helper 2 effector cell activation and migration 3.5.1.98 histone deacetylase medicine inhibitors of histone deacetylase activity sensitize colon cancer cells to interferon gamma-induced apoptosis through cooperative negative regulation of the Bcl-x expression 3.5.1.98 histone deacetylase medicine knock-down of isoform HDAC8 expression by RNAi inhibits growth of human lung, colon, and cervical cancer cell lines 3.5.1.98 histone deacetylase medicine a representative compound, (2E)-N-hydroxy-3-[2-(2-phenylethyl)-1-(2-pyrrolidin-1-ylethyl)-1H-benzimidazol-5-yl]prop-2-enamide, SB639, has demonstrated antitumor activity in a colon cancer xenograft model 3.5.1.98 histone deacetylase medicine application of HDAC inhibitors in cancer cell lines and mouse model systems leads to interruption of the cell cycle, differentiation and apoptosis, clinical studies have shown tumor repression and improvement of patient symptoms without significant side effects 3.5.1.98 histone deacetylase medicine because of their fundamental role in gene expression, histone deacetylase proteins are promising targets for cancer treatment 3.5.1.98 histone deacetylase medicine class I and II HDACs are generally considered valuable therapeutic targets for the treatment of leukemia and solid tumors 3.5.1.98 histone deacetylase medicine HDAC inhibition is a clinically validated therapeutic strategy for cancer treatment 3.5.1.98 histone deacetylase medicine HDAC inhibitors are a promising class of anticancer agents 3.5.1.98 histone deacetylase medicine HDAC inhibitors have attracted a great deal of interest as drug targets 3.5.1.98 histone deacetylase medicine HDAC inhibitors have attracted a great deal of interest as drug targets in recent years 3.5.1.98 histone deacetylase medicine HDAC inhibitors in food may help reverse aberrant patterns of histone changes in cancer cells 3.5.1.98 histone deacetylase medicine HDAC inhibitors offer a promising strategy for cancer therapy 3.5.1.98 histone deacetylase medicine HDACs are the most relevant, tractible cancer targets 3.5.1.98 histone deacetylase medicine histone deacetylase activities are elevated in patients with primary myelofibrosis 3.5.1.98 histone deacetylase medicine inhibition of HDAC activity has emerged as a promising approach for reversing the anomalous epigenetic states associated with cancer and other chronic diseases 3.5.1.98 histone deacetylase medicine it is proposed that induction of Hsp70 and subsequent activation of HDAC2 are important triggering signals of cardiac hypertrophy 3.5.1.98 histone deacetylase medicine type I ribosome-inactivating proteins derived from plants are HDAC inhibitors that can be utilized in the prevention and treatment of prostate cancer 3.5.1.98 histone deacetylase medicine histone deacetylase 1 is a gene therapy target in pancreatic ductal adenocarcinoma 3.5.1.98 histone deacetylase medicine compared with healthy non-smokers, HDAC activity in the peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease is decreased by 40%. In patients with chronic obstructive pulmonary disease, HDAC activity is negatively correlated to smoke intensity. In chronic obstructive pulmonary disease patients who have smoked for more than 40 pack-years, HDAC activity in peripheral blood mononuclear cells is 40% lower than that in chronic obstructive pulmonary disease patients who have smoked fewer than 40 pack-years. Serum CXCL8 levels in patients with chronic obstructive pulmonary disease are significantly higher than that in controls and are negatively correlated to HDAC activities 3.5.1.98 histone deacetylase medicine HDAC2 is nitrated under nitrative/oxidative stress and in the peripheral lung tissues of smokers and patients with chronic obstructive pulmonary disease 3.5.1.98 histone deacetylase medicine loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage. Suppression of class IIa HDACs in mouse models of type 2 diabetes ameliorates hyperglycemia, suggesting that inhibitors of class I/II HDACs may be potential therapeutics for metabolic syndrome 3.5.1.98 histone deacetylase medicine 1,2,4-oxadiazole-containing hydroxamic acid derivatives are discovered as histone deacetylase inhibitors for potential application in cancer therapy 3.5.1.99 fatty acid amide hydrolase medicine FAAH is a promising target for the treatment of several central and peripheral nervous system disorders, such as anxiety, pain and hypertension 3.5.1.99 fatty acid amide hydrolase medicine there is significant therapeutic potential for FAAH inhibitors as analgesic, neuroprotective, anti-inflammatory and anti-anxiety drugs, and as agents for the treatment of metabolic and sleep disorders 3.5.1.99 fatty acid amide hydrolase medicine fatty acid amide hydrolase is a promising target for the development of drugs to treat neurological diseases 3.5.1.99 fatty acid amide hydrolase medicine fatty acid amide hydrolase is involved in many human diseases, particularly cancer, pain and inflammation as well as neurological, metabolic and cardiovascular disorders. Therefore, FAAH is an attractive target for the development of low-molecular-weight inhibitors as therapeutics, which requires robust assays that can be used for high-throughput screening of compound libraries. A highly sensitive fluorescence-based assay with the substrate N-(6-methoxypyridin-3-yl)decanamide is described 3.5.1.99 fatty acid amide hydrolase medicine inhibition of fatty acid amide hydrolasis is considered a powerful approach to enhance the endocannabinoid signalling and is a potential target for the treatment of neurological disorders such as anxiety or depression, or of inflammatory process 3.5.1.99 fatty acid amide hydrolase medicine inhibitors of fatty acid amide hydrolase may represent new drug candidates for the treatment of inflammation 3.5.1.99 fatty acid amide hydrolase medicine there is evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of endocannabinoid degradation by fatty acid amide hydrolase blockade, is the best-known option to increase N-acyl-ethanolamines-mediated signaling. By showing the efficacy of intranasal FAAH inhibition, evidence is provided that nose-to-brain delivery is a suitable alternative to enhance brain endocannabinoid tone for the treatment of neurodegenerative disorders and improve patients' compliance 3.5.1.103 N-acetyl-1-D-myo-inositol-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase medicine antisense oligonucleotides to GlcNAc-Ins deacetylase (Rv1170) mRNA affect mycobacterial growth. The enzyme is sensitive to free radical generating antituberculosis drugs and may be a useful targets for new drug development 3.5.1.104 peptidoglycan-N-acetylglucosamine deacetylase medicine construction of a mutant pgdA strain and a pgdA-overexpressing strain and comparison of the pharmacokinetics properties of these recombinant strains with that of a wild-type strain, all producing the same model antigen, the human papillomavirus type-16 E7 protein, in the gastrointestinal tract of mice. There is no correlation between survival, at the ileum level, of bacteria intragastrically administered in mice and bacteria sensitivity or resistance to lysozyme. Neither lysozyme-sensitive nor lysozyme-resistant phenotype in Lactococcus lactis enhances significantly the potential of this bacterium as mucosal delivery live vector 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase medicine LpxC is one of the key enzymes of bacterial lipid A biosynthesis, catalyzing the removal of the N-acetyl group of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine. The lpxC gene is essential in Gram-negative bacteria but absent from mammalian genomes, making it an attractive target for antibacterial drug discovery 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase medicine this enzyme catalyzes a committed step in the biosynthesis of lipid A, and for this reason, LpxC is a target for the development of antibiotics in the treatment of Gram-negative bacterial infections 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase medicine as it is essential for the survival of many pathogens, the enzyme is an attractive target for antibacterial therapeutics 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase medicine promising target in the development of novel antibiotics against Gram-negative bacteria 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase medicine the enzyme is an antibacterial drug target 3.5.1.109 sphingomyelin deacylase medicine glucosylceramide sphingomyelin deacylase, is expressed in the skin of patients with atopic dermatitis, which plays an important role in ceramide deficiency (including acylceramides) in the stratum corneum 3.5.1.114 N-acyl-aromatic-L-amino acid amidohydrolase medicine expression is significantly elevated in the livers of hepatocellular carcinoma patients and hepatocellular carcinoma cell lines. Treatment of HepG2 cells with AA3 inhibitors, and HepG2 and HuH7 with AA3 siRNA significantly decreases Ras membrane association and is toxic to these HCC cell lines. AA3 inhibition may be an effective approach in the therapy of hepatocellular carcinoma and elevated AA3 expression in hepatocellular carcinoma is potentially an important diagnostic marker 3.5.1.115 mycothiol S-conjugate amidase medicine homology model built for Mca protein of Mycobacterium tuberculosis have high reliability and docking analysis show that Arenosclerin E is a potent drug candidate for tuberculosis 3.5.1.119 Pup amidohydrolase medicine since Dop is necessary for persistent infection by Mycobacterium tuberculosis, its selective inhibition holds potential for tuberculosis therapy 3.5.2.2 dihydropyrimidinase medicine - 3.5.2.2 dihydropyrimidinase medicine D-amino acids for preparation of beta-lactam antibiotics like semisynthetic penicillins and cephalosporins such as ampicillin, amoxicillin and cefadroxyl, peptide hormones and pesticides 3.5.2.2 dihydropyrimidinase medicine industrial production of L-amino acids 3.5.2.2 dihydropyrimidinase medicine development of the enzymatic process for production of D-p-hydroxyphenylglycine from DL-5-hydroxyphenylhydantoin, new drugs based on p-hydroxyphenylglycine like aspoxicillin, cefbuperazine and cepyramide expected to be marketed in near future 3.5.2.3 dihydroorotase medicine activation of the cardioprotective agent dexrazoxane by the enzyme in heart, mechanism 3.5.2.3 dihydroorotase medicine involved in metabolism of the cardioprotective druc dexrazoxane 3.5.2.6 beta-lactamase medicine putative development of a screening of MBL producing strains by routine clinical microbiology laboratories. The detection of the MBL phenotype of resistance is of crucial importance for selecting the most appropriate therapy and applying infection control measures 3.5.2.6 beta-lactamase medicine putative development of a screening of MBL producing strains by routine clinical microbiology laboratories. The detection of the MBL phenotype of resistance is of crucial importance for selecting the most appropriate therapy and applying infection control measures. 3.5.2.6 beta-lactamase medicine putative development of a screening of MBL producing strains by routine clinical microbiology laborities. The detection of the MBL phenotype of resistance is of crucial importance for selecting the most appropriate therapy and applying infection control measures 3.5.2.6 beta-lactamase medicine beta-lactamases, which catalyze the inactivation of beta-lactam antibiotics such as penicillins and cephalosporins are of great interest because of their high incidence in pathogenic bacteria 3.5.2.9 5-oxoprolinase (ATP-hydrolysing) medicine - 3.5.2.9 5-oxoprolinase (ATP-hydrolysing) medicine clinical applications, substrate 5-oxo-L-proline sensitizes tumors to the alkylating agent melphalan 3.5.2.9 5-oxoprolinase (ATP-hydrolysing) medicine potenial implications for carcinogenesis and cancer chemotherapy 3.5.2.9 5-oxoprolinase (ATP-hydrolysing) medicine animal model for the human condition 5-oxoprolinuria, an inborn deficiency of renal 5-oxoprolinase activity 3.5.2.9 5-oxoprolinase (ATP-hydrolysing) medicine reduces normal tissue toxicity of anticancer agents 3.5.2.9 5-oxoprolinase (ATP-hydrolysing) medicine 5-oxoprolinuria is primarily associated with inborn errors of the gamma-glutamyl cycle 3.5.2.9 5-oxoprolinase (ATP-hydrolysing) medicine occurrence of a futile cycle in patients with cystinosis. The enzyme gamma-glutamyl cysteine synthetase, in the absence of cysteine, forms 5-oxoproline instead of the normal substrate, gamma-glutamyl cysteine, and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. In cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells 3.5.2.10 creatininase medicine to assess renal function 3.5.2.10 creatininase medicine diagnosis of renal, muscular and thyroid functions 3.5.2.17 hydroxyisourate hydrolase medicine point mutation Y98Cin the gene encoding mouse HIU hydrolase, Urah, results in undetectable protein expression. Mice homozygous for this mutation develop elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also develop hepatocellular carcinoma, and tumor development is accelerated by exposure to radiation 3.5.3.1 arginase medicine enzyme is a target for inhibitors used in therapeutic treatment of smooth muscle disorders, such as erectile dysfunction 3.5.3.1 arginase medicine agents that elevate cAMP level significantly enhance induction of enzyme by cytokines. Consequences of increased enzyme expression should be evaluated when phosphodiesterase inhibitors are used for treatment of inflammatory disorders in which IL-4 and/or TGF-beta predominate 3.5.3.1 arginase medicine enzyme is involved in T-cell function during infection. Helicobacter pylori extracts and intact Helicobacter pylori of wild-type, but not of enzyme deficient mutant, induce a decreased expression of CD3zeta-chain of the TCR in Jurkat cells and reduce proliferation of freshly isolated human normal T-lymphocytes 3.5.3.1 arginase medicine H2O2 specifically impairs endothelium-dependent NO-mediated dilation of coronary microvessels by reducing L-arginine availability through upregulation of enzyme 3.5.3.1 arginase medicine in coronary arteriole, enzyme activity increases twofold with hypertension. Inhibition of enzyme activity by Nomega-hydroxy-nor-L-arginine or incubation with L-arginine partially restores NO release and dilation to adenosine in hypertrophic vessels 3.5.3.1 arginase medicine oopherectomized animals treated with 0.5% cholesterol-enriched diet. Diet results in increase in plasma lipids, atheromatous lesions as well as expression of enzyme isoforms arginase I and II and an increase in cellular proliferation. Diet plus supplementation of 17beta-estradiol results in a decrease of atheromatous lesions and reduced expression of both enzyme isoforms and inducible NO synthase. Inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis 3.5.3.1 arginase medicine patients with cystic fibrosis, before and after 14 days of antibiotic treatment for pulmonary exacerbation. Systemic enzyme levles are significantly increased in cystic fibrosis with exacerbation. Enzyme levels normalize with antibiotic treatment. Plasma L-arginine is reduced before, but not after treatment, L-ornithine, L-proline, and L-glutamic acid are normal before and increased after treatment 3.5.3.1 arginase medicine plasma arginase activity is significantly elevated in patients with sickle cell disease, with highest activity found in patients with secondary pulmonary hypertension. Arginase activity correlates with the arginine-ornithine ratio, and lower ratios are associated with greater severity of pulmonary hypertension and with mortality. Increased plasma enzyme activity is correlated with increased intravascular hemolytic rate and, to a lesser extent, with markers of inflammation and soluble adhesion molecule levels 3.5.3.1 arginase medicine rejection of skin xenografts, but not allografts, is associated with a local high production of Th2 cytokines IL-4 and IL-10, overexpression of enzyme, strongly enhanced enzyme activity and attenuated NO generation in the graft. Upregulation of enzyme activity limits the bioavailability of L-arginine for the inducible NO synthase and thus attenuates generation of NO by the graft-infiltrating macrophages 3.5.3.1 arginase medicine significant decrease of enzyme activity during 7th-21st day of gestation, significant increase in enzyme activity at term gestation, day 22. Gestational changes in enzyme activity negatively correlate with those in cyclic GMP production and positively correlate with those in endogenous NO synthase inhibitors and endothelin-1 contents. Enhanced enzyme activity at term gestation may be implicated in increasing myometrial contractions mediated by increase in endothelin-1 3.5.3.1 arginase medicine targeting vascular arginase as a therapeutic possibility for atherosclerosis. Thrombin enhances enzyme activity via small G-protein RhoA/ROCK in endothelial cells 3.5.3.1 arginase medicine overexpression of arginase in the penis contributes to erectile dysfunction 3.5.3.1 arginase medicine arginase gene expression in the lung is linked to asthma both in clinical studies of human patients and in the well-studied mouse model of ovalbumin-induced airway inflammation 3.5.3.1 arginase medicine enzyme serves as a therapeutic target for the treatment of asthma, erectile dysfunction, and atherosclerosis 3.5.3.1 arginase medicine new forms of efficient arginase inhibitors, could be useful as therapeutic regimen in hemoglobinopathies and other related inflammation-mediated diseases 3.5.3.1 arginase medicine a significant decrease in arginase activity, dependent of the liver clinical stage, is observed in cirrhotic tissue. Arginase AI activity and its mRNA level are significantly decreased in cirrhotic liver, whereas the activity and expression of arginase AII are concurrently raised, as compared to normal liver 3.5.3.1 arginase medicine bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition 3.5.3.1 arginase medicine both ARG1 and ARG2 are expressed by hormone-sensitive and hormone-refractory prostate cancer cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 is more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 are overexpressed. The regulation of arginase expression following androgen stimulation is dependent on the androgen receptor. This observation is correlated in vivo in patients by immunohistochemistry. Patients treated by androgen-deprivation therapy prior to surgery have lower ARG2 expression in both nonmalignant and malignant tissues. ARG1 and ARG2 are enzymatically active and their decreased expression by siRNA results in reduced overall arginase activity and L-arginine metabolism. The decreased ARG1 and ARG2 expression also translates with diminished LNCaP cells cell growth and increased peripheral blood mononuclear cell activation following exposure to LNCaP cells conditioned media. Interleukin-8 is also upregulated following androgen stimulation and it directly increases the expression of ARG1 and ARG2 in the absence of androgens 3.5.3.1 arginase medicine coinhibitory and costimulatory molecules PD-1 and CTLA-4 on the Gr-1+CD11b+ myeloid-derived suppression cells regulate the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules can significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results are also observed while their ligands B7-H1 and/or CD80 are blocked or silenced. CD80 deficiency also decreases the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduces the suppressive potential of PD-1+CTLA-4+ myeloid-derived suppression cells. Blockade of PD-1, CTLA-4 or both also slows tumor growth and improves the survival rate of tumor-bearing mice 3.5.3.1 arginase medicine comparison of the infectivity of arg- and wild-type Plasmodium berghei by inoculation of mice using sporozoites dissected from mosquito salivary glands shows a significant reduction in infectivity in the arg- strain 40 h postinfection 3.5.3.1 arginase medicine Co2+ substitution of the Mn2+ metal cofactor confers more than 10fold higher catalytic activity and 5fold greater stability. Based on the hypothesis that the Co-ArgI enzyme would decrease tumor burden by systemic elimination of L-arg in a murine model, Co-hArgI was conjugated to 5-kDa PEG to enhance circulation persistence and applied as monotherapy for hepatocellular carcinoma and pancreatic carcinoma in vitro and in vivo murine xenografts. Weekly treatment of 8 mg/kg Co-hArgI-PEG effectively controls human HepG2 and Panc-1 tumor xenografts. Both cell lines underwent apoptosis in vitro with significant increased expression of activated caspase-3 and showed evidence of autophagy in vitro and in vivo 3.5.3.1 arginase medicine exposure to ONOO- generator SIN-1 or to H2O2 increases arginase I expression and arginase activity by 35% and 50%, respectively, which is prevented by ROCK inhibitor, Y-27632, PKC inhibitor, Gö6976 or siRNA to p115-Rho GEF. The oxidative species ONOO- and H2O2 increase arginase activity/expression through PKC-mediated activation of RhoA/Rho kinase pathway 3.5.3.1 arginase medicine inhibition of Leishmania arginase leads to a decrease in parasite growth and infectivity and thus represents an attractive therapeutic strategy 3.5.3.1 arginase medicine Leishmania arginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiates de novo polyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections 3.5.3.2 guanidinoacetase medicine enzymic determination of guanidinoacetic acid in urine, guanidinoacetic acid decreases in patients with kidney disease or patients who have undergone kidney transplantation, low amount of guanidinoacetic acid in urine is an indicator of renal dysfunction 3.5.3.3 creatinase medicine creatinase may play a role in the disease process caused by Actinobacillus 3.5.3.3 creatinase medicine creatinine determination in biological fluids 3.5.3.6 arginine deiminase medicine possibility of a future use of arginine deiminase for the therapy of leukemia. The enzyme is 100fold more potent in inhibiting the proliferation of cultured human lymphatic leukemia cell lines while it appears to be less effective in leukemia cells of myeloid origin 3.5.3.6 arginine deiminase medicine arginine deiminase is a chemotherapeutic agent against arginine-requiring tumours and has potential application in antiviral therapy (suppressive factor of HIV-1 replication) 3.5.3.6 arginine deiminase medicine arginine deiminase conjugated to PEG 20 000 reduces extracellular arginine, has minimal toxicity, decreases tumor burden and improves liver function in patients with chronic hepatitis C virus infection and inoperable hepatocellular carcinoma, overview 3.5.3.6 arginine deiminase medicine arginine deprivation by arginine deiminase I can provide a beneficial strategy for the treatment of pancreatic cancer 3.5.3.6 arginine deiminase medicine the recombinant enzyme can effectively inhibit H22 tumor growth at a total dose of 5 U/mouse over a 2-week dosing period 3.5.3.6 arginine deiminase medicine the recombinant enzyme has a potentially therapeutic role in inducible nitric oxide synthase-related neuronal diseases 3.5.3.6 arginine deiminase medicine pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in human hepatocellular carcinoma 3.5.3.6 arginine deiminase medicine the enzyme has potential for the suppression of excessive cell proliferation 3.5.3.12 agmatine deiminase medicine developing of an analytic method for agmatine, being an important reagent for medical research 3.5.3.12 agmatine deiminase medicine remove of dental plaque biofilms 3.5.3.14 amidinoaspartase medicine test for N-amidino-L-aspartate in the urine of uremic patients 3.5.3.15 protein-arginine deiminase medicine PAD4 is a potential therapeutic target for the treatment of rheumatoid arthritis. PAD4 mutations are associated with anti-CCP antibody production and the increased expression of PAD4 in the rheumatoid arthritis synovium 3.5.3.15 protein-arginine deiminase medicine peptidyl arginine deiminase is an immunohistochemical marker for liver fibrosis in patients with chronic hepatitis 3.5.3.15 protein-arginine deiminase medicine in a a triple-culture system of neutrophils and human dental follicle stem cells primed with Porphyromonas gingivalis, infection of dental follicle stem cells with Porphoyromonas gingivalis prolongs the survival of neutrophils and increases their migration. The phenotypic changes depend on direct cellular contacts and PPAD expression by Porphyromonas gingivalis 3.5.3.16 methylguanidinase medicine useful as a means of detoxication and/or assay of methylguanidine in body fluids 3.5.3.18 dimethylargininase medicine 2-chloroacetamidine may potentially find wide applicability as a general pharmacophore, useful in delineating characteristics of the amidinotransferase superfamily 3.5.3.18 dimethylargininase medicine DDAH activity and elevated endogenous asymmetric dimethylarginine is implicated in endothelial dysfunction exposed to glycosylated bovine serum albumin, aminoguanidine can protect endothelium against injury induced by glycosylated bovine serum albumin both in vitro and in vivo 3.5.3.18 dimethylargininase medicine decreased DDAH-1 expression may cause accumulation of endogenous inhibitors of enothelial NO synthase, thereby contributing to endothelial dysfunction in the failing heart 3.5.3.18 dimethylargininase medicine endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (hydrolyzed by DDAH) is elevated in many patients and may contribute to the initiation and progression of their disease 3.5.3.18 dimethylargininase medicine epoetin beta and darbepoetin alpha posttranslationally impair DDAH activity via increased oxidative stress, causing NG,NG-dimethyl-L-arginine as an important cardiovascular risk factor to accumulate and inhibit NO-synthesis 3.5.3.18 dimethylargininase medicine expression and secretion of the vascular endothelial growth factor is not increased in DDAH1-transfected cells 3.5.3.18 dimethylargininase medicine in vivo administration of DDAH inhibitors (2-amino-4-(NG-methyl-guanidino)butanoic acid and its analogues) increases plasma NG,NG-dimethyl-L-arginine levels, giving proof of concept that these can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated 3.5.3.18 dimethylargininase medicine protective effect of probucol on endothelium related to enhancement of DDAH activity 3.5.3.18 dimethylargininase medicine structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases 3.5.3.18 dimethylargininase medicine placental dysfunction of dimethylarginine dimethylaminohydrolase has been suggested as one of the initiating events in the development of preeclampsia 3.5.3.18 dimethylargininase medicine DDAH influences insulin sensitivity by regulating the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine 3.5.3.18 dimethylargininase medicine influence on atherosclerosis in experimental models by increased ADMA concentrations and reduced NO synthesis 3.5.3.18 dimethylargininase medicine novel therapeutic strategy for the treatment of chronic kidney disease 3.5.3.18 dimethylargininase medicine hyperhomocysteinemia is induced in human DDAH1 transgenic mice and wild-type littermates using a high methionine/low folate diet. Plasma total homocysteine is elevated approximately 3fold in both wild-type and DDAH1 transgenic mice fed the high methionine/low folate diet compared with the control diet. Plasma asymmetrical dimethylarginine is approximately 40% lower in DDAH1 transgenic mice compared with wild-type mice irrespective of diet. Responses to 10 microM papaverine, a direct smooth muscle dilator, are impaired with the high methionine/low folate diet in wild-type mice but not DDAH1 transgenic mice. DDAH1 transgenic mice also are protected from hypertrophy of cerebral arterioles but not from accelerated carotid artery thrombosis induced by the high methionine/low folate diet 3.5.3.18 dimethylargininase medicine seven days after coronary artery ligation, L-Arg and methylated arginine content, as well as DDAH activity are determined in homogenates of left ventricular infarct and border. In healthy hearts, DDAHI is absent, and DDAHII is localized to endothelium and endocardium with a similar distribution to that of eNOS. Following myocardial infarction, left ventricular DDAH activity is increased to 210% of control. Both DDAHI and DDAHII proteins are detected in peri-infarct cardiomyocytes, while DDAHII immunoreactivity is additionally localized to infiltrating inflammatory cells and blood vessels in the healing infarct. Both plasma and left ventricular concentrations of the DDAH substrate, ADMA, are increased post-myocardial infarction, although the ratio of Arg:ADMA is retained in the left ventricular post-myocardial infarction relative to sham operated controls 3.5.3.18 dimethylargininase medicine global knockout of Ddah2 results in elevated blood pressure during periods of activity and changes in vascular responsiveness mediated by changes in methylarginine concentration, and systemic nitric oxide concentrations. In a model of severe polymicrobial sepsis, Ddah2 knockout affects outcome. Monocyte-specific deletion of Ddah2 results in a similar pattern of increased severity to that seen in globally deficient animals 3.5.3.18 dimethylargininase medicine in a mouse model of severe malaria, Plasmodium berghei ANKA infection inactivates hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue asymmetric dimethylarginine, elevated asymmetric dimethylarginine/arginine ratio in plasma, and decreased whole blood nitrite concentration 3.5.3.18 dimethylargininase medicine in lung adenocarcinoma, isoform DDAH2 is expressed in fibroblasts of stroma of malignancies, with higher expression in minimally invasive adenocarcinoma and invasive adenocarcinoma than in adenocarcinoma in situ. Tumors with high stromal expression of DDAH2 have a poorer prognosis than those without 3.5.3.18 dimethylargininase medicine in patients with type 2 diabetes mellitus, the percentage of senescent endothelial progenitor cells increases while the expression of DDAH2 decreases concomitantly with an increase in the plasma levels of asymmetric dimethylarginine. Exogenous application of asymmetric dimethylarginine accelerates the senescence of cultured endothelial progenitor cells in a dose-dependent manner, and overexpression of DDAH2 inhibits high glucose-induced endothelial progenitor cells senescence. Resveratrol (activating silent information regulator SIRT1) inhibits high glucose-induced endothelial progenitor cells senescence by upregulating the expression of DDAH2 and decreasing the levels of asymmetric dimethylarginine 3.5.3.18 dimethylargininase medicine plasma asymmetric dimethylarginine/arginine ratios are elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children 3.5.3.23 N-succinylarginine dihydrolase medicine immunization of mice with recombinant succinylarginine dihydrolase with a peptide sequence similar to an anti-prion epitope, induces anti-PrP auto-Abs with anti-prion activity and significantly retards survival times of the mice subsequently infected with Fukuoka-1 prions 3.5.4.1 cytosine deaminase medicine - 3.5.4.1 cytosine deaminase medicine oral 5-fluorocytosine in combination with selective delivery of CDase to cancerous cells by selectively introducing the bacterial CDase gene into the genome 3.5.4.1 cytosine deaminase medicine treatment of cancer by infecting or implanting cytosine deaminase capsules near the tumor of a cancer patient 3.5.4.1 cytosine deaminase medicine gene therapy for treatment of primary and metastatic tumors in the liver, development of gene therapy treatment for metastatic colorectal carcinoma 3.5.4.1 cytosine deaminase medicine new approach to chemotherapy of cancer, using substrate 5-fluorocytosine orally and enzyme capsules implanted locally, using conversion of product 5-fluorouracil, a potent antineoplastic substance, which is strongly toxic for mammalian cells as chemotherapeutic tool against tumors, enzyme/prodrug gene therapy, artificial gene composed for metastatic colorectal carcinoma 3.5.4.1 cytosine deaminase medicine facilitate pharmacological advance, possible application is transfer of FCY1 and FCA1 to mammalian cells naturally lacking enzyme activity, these genes should confer lethal sensitivity to 5-fluorocytosine 3.5.4.1 cytosine deaminase medicine enzyme is interesting for anticancer gene therapy since it deaminates the prodrug 5-fluorocytosine to the active drug 5-fluorouracil 3.5.4.1 cytosine deaminase medicine enzyme is of interest both for antimicrobial drug design and for gene therapy applications against tumors 3.5.4.1 cytosine deaminase medicine construction of secreted form of enzyme by fusion with pre-prosegment of human tissue plasminogen activator. Secreted enzyme temporarily spares transduced cells and enhanced accumulation of extracellular 5-fluorouracil. Tumors expressing the secreted enzyme have an improved response to 5-fluorocytosine treatment compared to tumors expressing intracellular enzyme 3.5.4.1 cytosine deaminase medicine efficiency of liposome-mediated cytosine deaminase suicide gene therapy can be improved by radiation. With HR-8348 tumor xenograft model, tumor volume is inhibited by 81.5%, 48.5%, and 37.5%, in the combined enzyme/5-fluorocytosine with radiation group, enzyme/5-fluorocytosine group and radiation group, and the wet weight of tumor is decreased by 80%, 41.7%, and 37.7%, resp. 3.5.4.1 cytosine deaminase medicine inhibition of tumor growth in mice treated with gene transfer of interleukin IL-12 plus enzyme/5-fluorcytosine is significantly greater than in mice treated with enzyme or IL-12 alone. Combined gene transfer increases splenic natural killer cell activity and interferon-gamma production by slenocytes and increases tumor growth inhibition and mean animal survival time 3.5.4.1 cytosine deaminase medicine mutant enzyme with improved activity towards cancer prodrug 5-fluorouracil for suicide gene therapy 3.5.4.1 cytosine deaminase medicine cytosine deaminase gene therapy combined with radiation treatment in breast carcinoma bone tumor, which is painful and causes osteolysis, is evaluated in a 4T1murine breast carcinoma model, overview 3.5.4.1 cytosine deaminase medicine establishment of a hypoxia-dependent prodrug-activating system using the enzyme cloned into a hypoxia-targeted adenoviral vector, overview 3.5.4.1 cytosine deaminase medicine hypoxia-inducible cytosine deaminase/5-fluorocytosine therapy in combination with radiation therapy shows both a pronounced bystander effect and a radiosensitizing effect under hypoxic conditions 3.5.4.1 cytosine deaminase medicine the enzyme is useful in gene therapy for treatment of cancer, bladder tumor model, overview 3.5.4.1 cytosine deaminase medicine the enzyme is useful in gene therapy of cancers, conjugation of poly-L-lysine to cytosine deaminase improves the efficacy of enzyme/prodrug cancer therapy, overview 3.5.4.1 cytosine deaminase medicine the enzyme is useful in treatment of human ovarian cancer by genetic prodrug activation therapy, overview 3.5.4.1 cytosine deaminase medicine cytosine deaminase is used in combination with 5-fluorocytosine as an enzyme-prodrug combination for targeted genetic cancer treatment 3.5.4.1 cytosine deaminase medicine the cytosine deaminase-human mesenchymal stem cell/5-fluorocytosine system is a potential molecular chemotherapeutic tool for cancer treatment 3.5.4.1 cytosine deaminase medicine the hyaluronan binding domain of tumor necrosis factor alpha-stimulated gene-6-cytosine deaminase fusion protein is an alternative to antibody-directed prodrug enzyme therapy approaches for cancer treatment 3.5.4.1 cytosine deaminase medicine efficiency of gene-directed enzyme/prodrug therapy (GDEPT) based on combination of fusion yeast cytosine deaminase (yCD) and 5-fluorocytosine (5FC) on model human medullary thyroid carcinoma (MTC) cell line TT is determined. Significant bystander effect is shown in vitro and 5-fluorocytosine administration results in potent antitumor effect in vivo. In addition high efficiency of cell-mediated GDEPT is shown, when human mesenchymal stromal cells are used as delivery vehicles in direct cocultures in vitro 3.5.4.1 cytosine deaminase medicine a Salmonella typhimurium strain overexpressing CodA and resistant to 5-fluorouracyl due to deletion of the Upp gene sequence, after infecting tumour cell cultures, shows increased cytotoxic and bystander effects under standard induction conditions. A PurD mutation in the producer strain controls its intracellular proliferation by the presence of adenine and avoids the intrinsic Salmonella cell death induction 3.5.4.3 guanine deaminase medicine enzyme has been implicated in cancer, liver disease, saturine gout, psoriasis and autoimmune disease, histochemical method for demonstration of guanase should be useful clinically, guanase activity increases significantly in lung and gastric cancer tissues or in patients with liver diseases like hepatitis, guanase is a biochemical indicator of rejection in liver transplant recipients, serum enzyme activity is the most sensitive indicator of liver disease, inhibition of guanase has beneficial implications in cancer chemotherapy, an inhibitor as chemotherapeutic agent selectively inhibit the growth of rapidly proliferating cancerous cells via depletion of the purine nucleotide pool 3.5.4.3 guanine deaminase medicine test for cancerous tissues, lower guanase activities compared with non-cancerous ones 3.5.4.3 guanine deaminase medicine colorimetric and HPLC assay method using guanosine as a prosubstrate. Method is suitable for routine assays for measuring plasma enzyme over a wide range of activites 3.5.4.3 guanine deaminase medicine GDA is an attractive and potential drug target for treatment of both liver diseases and cognitive disorders 3.5.4.4 adenosine deaminase medicine therapy for adenosine-deficient patients with combined immunodeficiency 3.5.4.4 adenosine deaminase medicine genetic polymorphisms of adenosine receptors A1 and A2A are associated with aspirin-intolerant asthma, suggesting that adenosine might play a crucial role in the development of aspirin-intolerant asthma through interactions with the A1 and A2A receptors. In this study no association between ADA and aspirin-intolerant asthma development is found 3.5.4.4 adenosine deaminase medicine the adenosine deaminase-adenosine pathway plays a significant role in hemolytic-anemia-associated pulmonary hypertension, and modulation of this pathway may offer protective/therapeutic effects in hemolysis-associated pulmonary hypertension, in particular, under conditions of severe NO deficiency/NO resistance 3.5.4.4 adenosine deaminase medicine ADA is an adjuvant for a dendritic cell-based vaccine against HIV. ADA potentiates human T-lymphocyte proliferation 4.5fold in co-cultures of HIV-inactivated-pulsed dendritic cells and autologous T cells of HIV-1-infected individuals. ADA enhances cytokine secretion in co-cultures of HIV-pulsed dendritic cells with T cells 3.5.4.4 adenosine deaminase medicine ADA2 is a drug candidate to modulate the immune responses during inflammation and cancer. ADA2 and its inhibitors are drug candidates to activate the immune systems of immunocompromised patients and to treat various types of blood cancers 3.5.4.4 adenosine deaminase medicine the mean values for total ADA and ADA2 activities in the serum and tumor of benign breast disease and breast cancer are significantly higher than those of healthy controls 3.5.4.4 adenosine deaminase medicine the adenosine deaminase activity in the cerebrospinal fluid is a good tool for early initiation of anti-tuberculous therapy while waiting for definite confirmation. A simple algorithm is identified that combines adenosine deaminase activity and some readily available biochemical parameters in cerebrospinal fluid, adenosine deaminase above 11.5 U/l + glucose above 65 mg/dl + leukocytes aboved 13.5 cell/mm3, as the better predictor to guide prompt initiation of anti-tuberculous therapy and should be considered in patients with low prevalence of tuberculosis 3.5.4.5 cytidine deaminase medicine - 3.5.4.5 cytidine deaminase medicine activation and inactivation of several deoxycytidine antimetabolites 3.5.4.5 cytidine deaminase medicine enzyme limits the effectiveness of the antineoplastic agent cytosine arabinoside or aracytidine in the treatment of acute myeloblastic leukemias, chemotherapeutic use of the inhibitor THU to protect antileukemic agents from deaminase attack, inhibitors of cytidine deaminase prolongs the plasma halflife of antitumor or antiviral drugs 3.5.4.5 cytidine deaminase medicine different effect of cytidine in blood cells from healthy donors and chronic lymphocytic and acute myeloblastic leukemia patients 3.5.4.5 cytidine deaminase medicine studies on radiosensitization of glioblastoma multiforme (GBM), deoxynucleoside analogue gemcitabine (dFdC) considered for combination therapy with radiation in glioblastomas 3.5.4.5 cytidine deaminase medicine cytidine deaminase as prognostic marker in non-small-cell lung cancer. In the patients with high versus low CDA activity the response rate is 25.0% and 54.1%, the 6-month progression rate is 34.5% and 54.1%, the 1-year survival rate is 23.3% and 57.3%, respectively 3.5.4.6 AMP deaminase medicine AMPD3 is a potential candidate for a pharmacological therapeutic strategy for remote reperfusion lung injury 3.5.4.6 AMP deaminase medicine the C34T T allele of the adenosine monophosphate deaminase-1 gene is associated with improved outcome in patients with cardiac dysfunction. Possession of the adenosine monophosphate deaminase-1 T allele is associated with decreased inotropic requirements before heart donation 3.5.4.9 methenyltetrahydrofolate cyclohydrolase medicine enzyme represents a potential pharmaceutical target for manipulation of cell growth and development and hence cancer prevention or treatment 3.5.4.9 methenyltetrahydrofolate cyclohydrolase medicine the enzyme (MTHFD2) is highly relevant as an anticancer target 3.5.4.B9 cytosine deaminase APOBEC3G medicine APOBEC3G mediated checkpoint activation through checkpoint kinase 2 (Chk2) is one of the critical regulatory mechanisms that underlies the preferential DNA damage checkpoint response and radioresistance of Glioma Initiating Cells. Thus, anti-APOBEC3G therapy may synergize with radiotherapy and other current treatments to overcome the therapeutic resistance of gliomas. APOBEC3G represents a potential molecular target for novel therapeutics that will improve the treatment outcome of glioma patients 3.5.4.10 IMP cyclohydrolase medicine determination of differentially expressed genes in HT-29 cells, both after short treatment with methotrexate and after the resistance to methotrexate has been established. Enzyme as well as survivin and inosine monophosphate dehydrogenase type II are upregulated 3.5.4.12 dCMP deaminase medicine associated mainly with dividing tissues, potential diagnostic tool for various disease states in which enzyme is elevated 3.5.4.12 dCMP deaminase medicine the enzyme is a major target for cancer chemotherapy 3.5.4.15 guanosine deaminase medicine caffeine biosynthesis and purine metabolism 3.5.4.16 GTP cyclohydrolase I medicine endothelium-specific GTPCH I overexpression retards the progression of hypertension through preservation of the structure and function of resistance mesenteric arteries, endothelium-specific GTPCH I overexpression abrogates superoxide anion production and preserves endothelial nitric oxide synthase phosphorylation, which results in preserved structural and functional integrity of resistance mesenteric arteries and lowered blood pressure in low-renin hypertension 3.5.4.16 GTP cyclohydrolase I medicine mutations in GCH are associated with dopa-responsive dystonia and hyperphenylalaninemia 3.5.4.16 GTP cyclohydrolase I medicine the mutation in the intron 5 splicing site of the GCH1 gene, IVS5+3insT, causes Dopa-responsive dystonia (also known as Segawa syndrome or hereditary progressive dystonia with diurnal fluctuation) 3.5.4.16 GTP cyclohydrolase I medicine cardiomyocyte GTP cyclohydrolase 1 is a therapeutic target for cardiac remodeling and dysfunction after myocardial infarction 3.5.4.37 double-stranded RNA adenine deaminase medicine ADAR2 is a promising target for an anti-tumoral strategy, since ADAR2 alone can simultaneously modulate more than one miRNA and cellular pathway altered in cancer cells 3.5.4.37 double-stranded RNA adenine deaminase medicine enzyme (ADAR1) expression is an independent predictor of tumor recurrence. Small molecule inhibition of focal adhesion kinase activity may be a potential therapeutic strategy for the treatment of lung adenocarcinoma with high ADAR1 expression 3.5.4.37 double-stranded RNA adenine deaminase medicine the levels of RNA editing by ADAR1 can serve as new tools for diagnosis in cancer stem cell-related illnesses. In situations where ADAR1 overexpression contributes to disease progression, as in several cancers, or where ADAR1 interacts with other proteins in editing-independent manners, inhibition of ADAR1 could potentially be another strategy in treatment 3.5.4.38 single-stranded DNA cytosine deaminase medicine APOBEC3G mediated checkpoint activation through checkpoint kinase 2 (Chk2) is one of the critical regulatory mechanisms that underlies the preferential DNA damage checkpoint response and radioresistance of Glioma Initiating Cells. Thus, anti-APOBEC3G therapy may synergize with radiotherapy and other current treatments to overcome the therapeutic resistance of gliomas. APOBEC3G represents a potential molecular target for novel therapeutics that will improve the treatment outcome of glioma patients 3.6.1.5 apyrase medicine enzyme in lipid vesicles effectively inhibits platelet aggregation when activated by ADP, collagen, or thrombin, and also promotes platelet disaggregation. Treatment with enzyme lipid vesicles preserves platelet counts after thromboplastin injection 3.6.1.5 apyrase medicine enzyme inhibits ADP- collagen- and thrombin-induced human platelet aggregation in dose-dependent manner, use as a therapeutic agent for inhibition of platelet-mediated thrombosis 3.6.1.5 apyrase medicine significant IgG antibody reactivity was observed in sera from patients with American cutaneous leishmaniasis and schistosomiasis using potato apyrase as antigen, development of drug targets or molecular markers 3.6.1.5 apyrase medicine significant IgG antibody reactivity was observed in sera from patients with American cutaneous leishmaniasis and schistosomiasis using Schistoma mansoni adult worm or egg as antigen, development of drug targets or molecular markers 3.6.1.5 apyrase medicine its unique enzymatic activity makes the salivary apyrase an attractive candidate as a therapeutic agent for the treatment of thrombotic pathologies 3.6.1.5 apyrase medicine activation of CD39 has potential for treating inflammatory diseases, while inhibition is suggested as a strategy for the immunotherapy of cancer 3.6.1.5 apyrase medicine augmenting CD39 activity is a potential therapy to improve both short- and long-term outcomes of ischemia-reperfusion injury (IRI) by reducing the extracellular concentration of proinflammatory ATP and promoting adenosine generation. In mouse models of IRI, treatment with soluble CD39 (apyrase) or expression of a human CD39 (hCD39) transgene in mice (CD39Tg mice) reduce the severity of acute kidney injury (AKI) as evidenced by decreased serum creatinine and reduced tubular injury score at 24 hours 3.6.1.7 acylphosphatase medicine protein aggregation is associated with a number of human pathologies including Alzheimer’s and Creutzfeldt-Jakob diseases and the systemic amyloidoses. In presence of 15–25% (v/v) trifluoroethanol, enzyme forms aggregates able to bind specific dyes such as thioflavine T, Congo red, and 1-anilino-8-naphthalenesulfonic acid. The monomeric form adopted by the enzyme prior to aggregation under these conditions retains enzymatic activity, in addition, folding was remarkably faster than unfolding. Electron microscopy reveals the presence of small aggregates generally referred to as amyloid protofibrils 3.6.1.9 nucleotide diphosphatase medicine E-NPP3 might be a tumor marker of colon carcinoma 3.6.1.9 nucleotide diphosphatase medicine variants in the distal region of the ENPP1 gene may contribute to diabetes or diabetic nephropathy susceptibility in African Americans 3.6.1.12 dCTP diphosphatase medicine enzyme accumulates in the nucleus of cancer cells compared to the paired adjacent tissue cells in multiple carcinomas including lung, breast, liver, cervical, gastric and esophagus cancer. The higher expression in the nucleus of lung, gastric and esophagus cancer cells is associated with histological subtypes. The nucleic accumulation is apparently observed as well when tumor cell line MCF-7 is treated with H2O2 in vitro 3.6.1.15 nucleoside-triphosphate phosphatase medicine considered attractive target for anti-hepatitis C virus chemoterapy 3.6.1.22 NAD+ diphosphatase medicine enzyme may serve a regulatory role in modifying the inhibitory effect of ecto-NAD on T-cell activation 3.6.1.23 dUTP diphosphatase medicine potential drug target 3.6.1.23 dUTP diphosphatase medicine potential target for anti-tuberculosis therapy 3.6.1.23 dUTP diphosphatase medicine potential target for treatment of Chagas' disease 3.6.1.23 dUTP diphosphatase medicine dUTPase is a target for antitubercular drugs 3.6.1.39 thymidine-triphosphatase medicine potential prognostic marker for different diseases e.g. leukemia 3.6.1.56 2-hydroxy-dATP diphosphatase medicine increased amounts of 8-oxoguanine in the RNA, and decreased expression of MTH1 are observed in the hippocampi of patients suffering from Alzheimer's disease 3.6.1.56 2-hydroxy-dATP diphosphatase medicine measurements of 8-oxo-dGTPase activity in brains, testes and kidneys may serve as a rough indicator rather than a quantifiable marker of radiation-induced oxidative stress 3.6.1.59 5'-(N7-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase medicine identification of DcpS as a candidate molecular target of the C5-substituted quinazolines for the potential treatment of spinal muscular atrophy 3.6.1.60 diadenosine hexaphosphate hydrolase (AMP-forming) medicine suppressing the expression of NUDT11, SLC22A3, and HNF1B influences cellular phenotypes associated with tumor-related properties in prostate cancer cells. 4 of the 12 known risk polymorphisms are strongly associated with transcripts NUDT11, MSMB, NCOA4, SLC22A3, and HNF1B in histologically normal tissue. Although associations are also observed in tumor tissue, they tend to be more attenuated 3.6.1.70 guanosine-5'-diphospho-5'-[DNA] diphosphatase medicine ataxia-oculomotor apraxia, AOA1, is a neurological disorder with symptoms that overlap those of ataxiatelangiectasia, characterized by abnormal responses to double-strand DNA breaks and genome instability. The gene mutated in AOA1, APTX, codes for aprataxin which contains domains of homology with proteins involved in DNA damage signalling and repair. Cells from AOA1 show enhanced sensitivity to agents that cause single-strand breaks in DNA but there is no evidence for a gross defect in single-strand break repair 3.6.1.70 guanosine-5'-diphospho-5'-[DNA] diphosphatase medicine cells from patients with ataxia oculomotor apraxia AOA1 show reduced expression of poly-ADP ribose polymerase PARP-1, apurinic endonuclease APE1 and N-glycosylase/DNA lyase OGG1. AOA1 cells exhibit elevated levels of oxidative DNA damage coupled with reduced base excision and gap filling repair efficiencies 3.6.1.70 guanosine-5'-diphospho-5'-[DNA] diphosphatase medicine cells of an ataxia-oculomotor apraxia type 1 patient, homozygous for aprataxin mutation T739C, treated with camptothecin, inhibitor of DNA topoisomerase I which induces DNA single-strand breaks, show marked and dose-related increases in induced chromosomal aberrations compared to the intrafamilial wild-type control 3.6.1.70 guanosine-5'-diphospho-5'-[DNA] diphosphatase medicine in cells from patients with ataxia with oculomotor apraxia type 1, AOA1, lacking aprataxin, the stability of nucleolin is significantly reduced 3.6.1.70 guanosine-5'-diphospho-5'-[DNA] diphosphatase medicine mutations in aprataxin cause ataxia–ocular apraxia 1, leading to early onset ataxia, oculomotor apraxia and cerebellar atrophy as well as axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol 3.6.1.70 guanosine-5'-diphospho-5'-[DNA] diphosphatase medicine in bone marrow of patients from a phase 2 study of the farnesyltransferase inhibitor tipifarnib in older adults with previously untreated acute myeloid leukemia, te RASGRP1/APTX gene expression ratio predicts response to tipifarnib with the greatest accuracy. RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair 3.6.1.71 adenosine-5'-diphospho-5'-[DNA] diphosphatase medicine ataxia-oculomotor apraxia, AOA1, is a neurological disorder with symptoms that overlap those of ataxiatelangiectasia, characterized by abnormal responses to double-strand DNA breaks and genome instability. The gene mutated in AOA1, APTX, codes for aprataxin which contains domains of homology with proteins involved in DNA damage signalling and repair. Cells from AOA1 show enhanced sensitivity to agents that cause single-strand breaks in DNA but there is no evidence for a gross defect in single-strand break repair 3.6.1.71 adenosine-5'-diphospho-5'-[DNA] diphosphatase medicine cells from patients with ataxia oculomotor apraxia AOA1 show reduced expression of poly-ADP ribose polymerase PARP-1, apurinic endonuclease APE1 and N-glycosylase/DNA lyase OGG1. AOA1 cells exhibit elevated levels of oxidative DNA damage coupled with reduced base excision and gap filling repair efficiencies 3.6.1.71 adenosine-5'-diphospho-5'-[DNA] diphosphatase medicine cells of an ataxia-oculomotor apraxia type 1 patient, homozygous for aprataxin mutation T739C, treated with camptothecin, inhibitor of DNA topoisomerase I which induces DNA single-strand breaks, show marked and dose-related increases in induced chromosomal aberrations compared to the intrafamilial wild-type control 3.6.1.71 adenosine-5'-diphospho-5'-[DNA] diphosphatase medicine in cells from patients with ataxia with oculomotor apraxia type 1, AOA1, lacking aprataxin, the stability of nucleolin is significantly reduced 3.6.1.71 adenosine-5'-diphospho-5'-[DNA] diphosphatase medicine mutations in aprataxin cause ataxia-ocular apraxia 1, leading to early onset ataxia, oculomotor apraxia and cerebellar atrophy as well as axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol 3.6.1.71 adenosine-5'-diphospho-5'-[DNA] diphosphatase medicine in bone marrow of patients from a phase 2 study of the farnesyltransferase inhibitor tipifarnib in older adults with previously untreated acute myeloid leukemia, the RASGRP1/APTX gene expression ratio predicts response to tipifarnib with the greatest accuracy. RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair 3.6.1.72 DNA-3'-diphospho-5'-guanosine diphosphatase medicine in bone marrow of patients from a phase 2 study of the farnesyltransferase inhibitor tipifarnib in older adults with previously untreated acute myeloid leukemia, te RASGRP1/APTX gene expression ratio predicts response to tipifarnib with the greatest accuracy. RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair 3.6.4.B1 kinesin K16 medicine in muscles of patients with idiopathic inflammatory myopathies, KIF4-positive inflammatory cells are found. In polymyositis and inclusion body myositis, KIF4-positive cells are mainly located around individual muscle fibers, whereas in dermamyositis, KIF4-positive cells are also near blood vessels. KIF4-positive cells are not specific to any immune lineage. In peripheral blood lymphocytes stimulated with mitogens, KIF4 expression is upregulated, and the protein is localized in the cytoplasm associated with lysosome-associated protein 1+ and perforin+ lysosomal vesicles 3.6.4.6 vesicle-fusing ATPase medicine HsPEX1 is the causative gene for peroxisome-deficiency autosomal recessive disorders like cerebro-hepato-renal Zellweger syndrome, neonatal adrenoleukodystrophy and infantile refsum disease 3.6.4.6 vesicle-fusing ATPase medicine diagnosis, HsPex6p mutations are one of the causes of Zellweger syndrome 3.6.4.6 vesicle-fusing ATPase medicine dysfunction of p97 has serious pathological consequences and has been implicated in a variety of cancers and neurodegenerative deseases 3.6.4.7 peroxisome-assembly ATPase medicine - 3.6.4.7 peroxisome-assembly ATPase medicine development of gene therapy, restoring of peroxisome assemblyby gene transfer to fibroblasts of Zellweger syndrome group C patients 3.6.4.7 peroxisome-assembly ATPase medicine diagnosis of inherited peroxisome-deficient diseases such as Zellweger syndrome by functional complementation 3.6.4.7 peroxisome-assembly ATPase medicine phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 3.6.4.7 peroxisome-assembly ATPase medicine autosomal recessive mutations in the PEX genes cause peroxisome biogenesis disorders, such as Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease 3.6.4.7 peroxisome-assembly ATPase medicine more than 80% of all patients with Zellweger syndrome, the most severe peroxisome biogenesis disorder, carry mutations in Pex1p or Pex6p 3.6.4.7 peroxisome-assembly ATPase medicine patients with Zellweger syndrome carry mutations in Pex1p or Pex6p 3.6.4.10 non-chaperonin molecular chaperone ATPase medicine development of a potent cytostatic anti-tumor and immunosuppressive agent, 15-deoxyspergualin, a synthetic analogue of the antibiotic spergualin, to prevent rejection in kidney transplant recipients 3.6.4.10 non-chaperonin molecular chaperone ATPase medicine Hsp90 is a molecular target for cancer therapy 3.6.4.10 non-chaperonin molecular chaperone ATPase medicine Hsp90 is a target for cancer therapy 3.6.4.B10 chaperonin ATPase (protein-folding, protecting from aggregation, protein stabilizing) medicine subunit CCT2 is a chemotherapeutic target in uterine cancer 3.6.4.B10 chaperonin ATPase (protein-folding, protecting from aggregation, protein stabilizing) medicine TRiC is a therapeutic target in breast cancer 3.6.4.13 RNA helicase medicine DDX4 can serve as a useful and highly specific biomarker for the diagnosis of germ cell tumors 3.6.4.13 RNA helicase medicine mutation within hBrr2p can be linked to autosomal dominant retinitis pigmentosa 3.6.4.13 RNA helicase medicine analysis of tumorigenic function of p68 in association with its targeting potential for the treatment of breast cancer 3.6.5.1 heterotrimeric G-protein GTPase medicine mutations in the gene for the alpha-subunit of cone transducin, GNAT2, cause cone-rod degeneration, CRD 3.6.5.1 heterotrimeric G-protein GTPase medicine the enzyme is important as a potential therapeutic target for the treatment of non small cell lung cancer 3.6.5.2 small monomeric GTPase medicine potential target for cancer therapeutics 3.6.5.2 small monomeric GTPase medicine Rab27a is associated with the Griscelli syndrome type 2, mutations in the Rab27a gene cause pigment as well as cytotoxic granule transport defects, accounting for the partial albinism and severe immune disorder characteristics of this syndrome 3.6.5.2 small monomeric GTPase medicine regulation of small Rho GTPases might serve as a new pharmacological tool for protection of dendridic cell vaccines from tumor-induced inhibition and functional failure 3.6.5.2 small monomeric GTPase medicine small Rho GTPases might serve as new targets for modulating functional activity of dendritic cell vaccines or endogenous dendritic cells in various immunotherapeutic or chemoimmunotherapeutic strategies 3.6.5.2 small monomeric GTPase medicine neither the overall survival nor the disease-free survival rate in diffuse large B-cell lymphoma can be linked to hypermutation of the RHOH gene 3.6.5.3 protein-synthesizing GTPase medicine - 3.6.5.3 protein-synthesizing GTPase medicine termination of ribosome-dependent protein synthesis 3.6.5.3 protein-synthesizing GTPase medicine polypeptide chain synthesis 3.6.5.3 protein-synthesizing GTPase medicine polyphenylalanine synthesis 3.6.5.3 protein-synthesizing GTPase medicine chaperon-activity 3.6.5.3 protein-synthesizing GTPase medicine protein biosynthesis 3.6.5.3 protein-synthesizing GTPase medicine elongation factor Tu may have in vivo role in tetracycline inhibition of protein synthesis 3.6.5.4 signal-recognition-particle GTPase medicine protein translocation across the endoplasmic reticulum 3.6.5.5 dynamin GTPase medicine dynamin-1 interacts with TULP1, TULP1 is a photoreceptor-specific protein that is mutated in retinitis pigmentosa 3.6.5.5 dynamin GTPase medicine it is shown that mitochondrial fission plays a causal role in neuronal demise, blocking fission by dominant-negative mutant Drp1K38A prevents mitochondrial fragmentation and rescues neurons from degeneration and cell death evoked by NO or rotenone 3.6.5.5 dynamin GTPase medicine mitochondrial fission plays a causal role in neuronal demise, blocking fission by wild-type Mfn1 prevents mitochondrial fragmentation and rescues neurons from degeneration and cell death evoked by NO or rotenone 3.6.5.5 dynamin GTPase medicine mutations in the dynamin family GTPase OPA1 are reportedly the cause of autosomal dominant optic atrophy 3.6.5.5 dynamin GTPase medicine three autosomal dominant neuropathies in humans are caused by defects in mitochondrial fusion, and a defect in mitochondrial fission is reported as being lethal, mitochondrial morphology is proposed to be maintained by a balance of mitochondrial fusion and fission involving at least four dynamin-like GTPases 3.7.1.2 fumarylacetoacetase medicine plays a role in hereditary tyrosinemia 3.7.1.2 fumarylacetoacetase medicine plays a role in degradation pathway of phenylalanine and tyrosine 3.7.1.2 fumarylacetoacetase medicine hereditary tyrosinaemia type 1 results from deficiency of fumarylacetoacetase 3.7.1.2 fumarylacetoacetase medicine in humans, deficiency of this activity is associated with the metabolic disease hereditary tyrosinaemia type 1, which is also known as hepatorenal tyrosinaemia 3.7.1.2 fumarylacetoacetase medicine type I tyrosinemia is caused by mutations in the fumarylacetoacetate hydrolase gene, the results establish worms as a model for the study of type I tyrosinemia 3.7.1.3 kynureninase medicine - 3.7.1.3 kynureninase medicine NAD+ biosynthesis 3.7.1.3 kynureninase medicine tryptophan metabolism 3.7.1.3 kynureninase medicine progressive decline in the enzyme activity involved in tryptophan metabolism along the kynurenine pathway in rat tissue with age 3.7.1.3 kynureninase medicine xanthurenic aciduria is linked to a mutation in the gene encoding kynureninase 3.7.1.4 phloretin hydrolase medicine rapid genotyping assay for LPH-13910 polymorphism based on real-time PCR, which may assist in differentiating patients with primary hypolactasia from those with secondary hypolactasia and lactose intolerance 3.7.1.4 phloretin hydrolase medicine adult-type hypolactasia is characterized by a fall of lactase activity levels to 5 - 10% of birth levels occuring during childhood and adolescence 3.7.1.4 phloretin hydrolase medicine adult-type hypolactasia results from the progressive decline of lactase-phlorizin hydrolase activity in enterocytes after weaning, lactase nonpersistence may determine a primary lactose intolerance with reduced diary product consumption, which is possibly related to an increased risk of colon cancer 3.7.1.4 phloretin hydrolase medicine hypolactasia seems to be strongly corretated with genotype C/C of the genetic variant C->T-13910 upstream of the lactase-phlorizin hydrolase gene 3.9.1.3 phosphohistidine phosphatase medicine high PHPT1 expression levels are associated with larger tumour size, higher Fuhrman nuclear grade and advanced pathological tumor-node-metastasis stage in clear-cell renal cell carcinoma 3.9.1.3 phosphohistidine phosphatase medicine the knockdown of enzyme expression by lentivirusdelivered siRNA is a therapeutic approach for the treatment of hepatocellular carcinoma 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine enzyme-replacement or gene-replacement therapy 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine enzyme-replacement therapy from birth delays the development of behavior and learning problems in mucopolysaccharidosis type IIIA mice. Recombinant human sulfamidase administered to mucopolysaccharidosis type IIIA mice 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine intracerebral injection of recombinant human sulfamidase delays neuropathology in murine MPS-IIIA. Treatment reduces vacuolation and gliosis and delays the onset of ubiquitin-positive neurodegenerative changes in widespread areas of mucopolysaccharidosis type IIA brain, assessed at 24 weeks of age 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine recombinant murine sulfamidase is able to correct the storage phenotype of mucopolysaccharidosis type IIIA fibroblasts after endocytosis via the mannose-6-phosphate receptor 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine the relative quantification of hexosamine-N-sulfate[alpha-1,4]hexuronic acid should prove to be a useful indicator of the effectiveness of enzyme replacement therapy within the mucopolysaccharidosis type IIIA mouse central nervous system 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine the enzyme might be an immediately applicable method for in vivo to treatment of lysosomal disorders like mucopolysaccharidosis type IIIA and similar lysosomal diseases in the central nervous system 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine mucopolysaccharidosis type IIIA is caused by a deficiency in sulphamidase 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine administration of recombinant human heparan-N-sulfatase via intrathecal drug delivery device appears generally safe and well tolerated in patients with mucopolysaccharidosis IIIA. Treatment results in consistent declines in heparan sulfate in cerebrospinal fluid, suggesting in vivo activity in the relevant anatomical compartment 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine intrathecal administration of recombinant human heparan-N-sulfatase reduces heparan sulfate and glycosaminoglycan levels in treated patients 3.10.1.1 N-sulfoglucosamine sulfohydrolase medicine mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A) is a neurodegenerative lysosomal storage disorder caused by the deficiency of sulphamidase enzyme (SGSH) leading to accumulation of heparan sulfate. Primary stored heparan sulfate and other glycosaminoglycans possibly accumulated through a secondary storage in brain, liver, kidney and lung of MPS IIIA mouse model is quantitatively and structurally characterized. The analysis is also performed in MPS IIIA mice upon the intravenous treatment with an engineered human sulphamidase (chimeric hSGSH) capable to increase its secretion from the liver and to cross the bloodbrain barrier. MPS IIIA animals show a huge accumulation of heparan sulfate, from about 15 up to about 24times higher than wild type and also of hyaluronic acid (from 2.5 up to about 5.0times more) and chondroitin sulfate/dermatan sulfate (from about 2 up to about 5times more) in all studied organs. A significant increase in the overall heparan sulfate charge density is observed and in particular of 2-O-sulfation in MPS IIIA mice organs. 8 months after a systemic treatment with an engineered SGSH, the enzyme is highly efficient in the reduction of all accumulated glycosaminoglycans in liver, brain and lung up to values of wild type mice. Even if reduced, glycosaminoglycans levels still remain significantly elevated in kidney. The data obtained by analysis of glycosaminoglycans in the different organs of affected and treated animals with chimeric human sulphamidase enzyme may have implications for the evaluation of an effective therapeutic option of MPS IIIA and for the reduction of related neuropathology 3.13.1.1 UDP-sulfoquinovose synthase medicine sulfolipids, in which synthesis the enzyme is involved, promise anti-tumor and anti-HIV therapeutics based on their inhibition of DNA polymerase and reverse transcriptase 3.13.2.1 adenosylhomocysteinase medicine antimalaric drug design 3.13.2.1 adenosylhomocysteinase medicine antiviral drug design 3.13.2.1 adenosylhomocysteinase medicine anti-parasitic drug design 3.13.2.1 adenosylhomocysteinase medicine antineoplastic drug design 3.13.2.1 adenosylhomocysteinase medicine chemotherapeutic drug design 3.13.2.1 adenosylhomocysteinase medicine development of a specific inhibitor for Plasmodium falciparum SAH hydrolase as a chemotherapeutic agent against malaria 3.13.2.1 adenosylhomocysteinase medicine SAH hydrolase is an attractive target for antiparasitic and antiviral drug design 3.13.2.1 adenosylhomocysteinase medicine SAHH inhibitors are expected to provide a new type of chemotherapeutic agent against malaria 3.13.2.1 adenosylhomocysteinase medicine adenosine-induced apoptosis is likely due to intracellular action of enzyme resulting in altered gene expression and is independent of AMP-activated kinase and adenosine receptors 3.13.2.1 adenosylhomocysteinase medicine carbon monoxide lowers renal adenosylhomocysteinase mRNA expression by 64% without change in enzyme activity during 4 h of exposure. Immunodetection of enzyme in nuclei of single interstitial cells of renal cortex and outer medula of the hypoxic rat 3.13.2.1 adenosylhomocysteinase medicine in rats fed by the enzyme inhibitors (2R,3R)-4-(3-deazaadenin-9-yl)-2,3-dihydroxybutanoic acid and (2R,3R)-methyl-4-(3-deazaadenin-9-yl)-2,3-dihydroxybutanoic acid, the total plasma cholesterol and phospholipids decrease by 36-40% and 23%, respectively 3.13.2.1 adenosylhomocysteinase medicine S-adenosylhomocysteine-synthetic activity significantly increases in animals fed a vitamin B6-free diet, while S-adenosylhomocysteine hydrolytic activity shows no significant difference in animals fed a vitamin B6-free diet or control diet. Enzyme mRNA in the liver does not show changes due to diet 3.13.2.1 adenosylhomocysteinase medicine the cofactor NAD+ always dissociates more rapidly from Trypanosoma cruzi enzyme than from human enzyme, and binds more rapidly to human than to trypanosomal enzyme 3.13.2.1 adenosylhomocysteinase medicine AHCY polymorphisms and AHCY inhibitors, which are promising in treating autoimmunity and other disorders, may be a risk factor for steatosis, particularly in patients with diabetes, obesity and liver disorders such as hepatitis C infection 3.13.2.1 adenosylhomocysteinase medicine results indicate that SAHH is a tumor suppressor 3.13.2.1 adenosylhomocysteinase medicine Sah1 activity has a major impact on cellular lipid homeostasis, and its deficiency results in dysregulated lipid metabolism, leading to an imbalance of phospholipid and triacylglycerol synthesis, with implications for mammalian lipid-associated disorders 3.13.2.1 adenosylhomocysteinase medicine identification of 39 polymorphisms by sequencing 240 DNA samples from Caucasian-American, African-American, Han Chinese-American and Mexican-American subjects. Four single nucleotide polymorphisms are associated with decreased expression 3.13.2.1 adenosylhomocysteinase medicine in lymphoblastoid cell lines from patients with Down syndrome, an increase in NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine hydrolase activities is found 3.13.2.1 adenosylhomocysteinase medicine over-expression of Down-syndrome associated kinase Dyrk1a increases the hepatic NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine hydrolase activities, concomitant with decreased level of plasma homocysteine in three mice models overexpressing Dyrk1a. These effects are abolished by treatment with harmine, the most potent and specific inhibitor of Dyrk1a 3.13.2.1 adenosylhomocysteinase medicine identification of 27 immunogenic proteins from the two-dimensional electrophoresis immunoblot profiles by liquid chromatography tandem MS and expression of the gene encoding one immunodominant protein of interest, S-adenosyl-L-homocysteine hydrolase in Escherichia coli. The recombinant protein induces a strong antibody response in BALB/c mice, and the polyclonal antibody recognizes a band of approximately 52 kDa in the immunoblots of soluble protein extracts from five Brucella strains. The recombinant protein significantly stimulates the production of interferon-gamma and interleukin-2, and induces a high level of protection against Brucella melitensis 16M challenge at 4 weeks postchallenge 4.1.1.2 oxalate decarboxylase medicine OxDc-CLEC reduces hyperoxaluria and ameliorates nephrocalcinosis and urolithiasis 4.1.1.2 oxalate decarboxylase medicine treatment of hyperoxaluria, urolithiasis, nephrocalcinosis, and depletion of dietary oxalate with enzyme formulation 4.1.1.2 oxalate decarboxylase medicine the transgenic Lactobacillus plantarum strain WCFS1 expressing the enzyme from Bacillus subtilis may provide possible therapeutic approach by degrading intestinal oxalate in the human host of Lactobacillus plantarum 4.1.1.2 oxalate decarboxylase medicine HEK-293 cells expressing the enzyme capable of degrading oxalate protect cells from oxidative damage and thus serve as a therapeutic option for prevention of calcium oxalate stone disease 4.1.1.8 oxalyl-CoA decarboxylase medicine gene transfer to human cells for urolithiasis therapy, considered 4.1.1.9 malonyl-CoA decarboxylase medicine enzyme deficiency is associated with mild mental retardation, seizures, hypotonia, cardiomyopathie, vomiting, hypoglycemia, metabolic acidosis and malonic aciduria 4.1.1.9 malonyl-CoA decarboxylase medicine enzyme deficiency is characterized by malonic aciduria, developmental delay, seizure disorder, and mental retardation 4.1.1.9 malonyl-CoA decarboxylase medicine MCD is involved in regulating cardiac malonyl-CoA levels, inhibition of MCD can limit rates of fatty acid oxidation, leading to a secondary increase in glucose oxidation associated with an improvement in the functional recovery of the heart during ischaemia/reperfusion injury 4.1.1.9 malonyl-CoA decarboxylase medicine MCD is a potential novel target for cancer treatment 4.1.1.15 glutamate decarboxylase medicine positivity for either GAD65 or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group 4.1.1.15 glutamate decarboxylase medicine the autoantibody profile in a variety of patients with diabetes and thyroid autoimmune diseases is probed by a set of GAD65/67 variants: GAD65, GAD65/67 hybrids spanning residues 1-95, 96-444 and 445-585, deltaGAD65, a truncated GAD65 spanning residues 69-585 and GAD67. DeltaGAD65 and GAD65 detect 137 and 125 positive patients, respectively. The hybrids react with 113 sera and in 3 cases disclosed cryptic epitopes. Eighteen patients react with GAD67, indicating GAD65-GAD67 cross-reactivity 4.1.1.15 glutamate decarboxylase medicine enzyme plus murine IL-4 expressed in tobacco and fed to nonobese diabetic mice protects from diabetes. Feeding enhances levels of IgG1 anti-enzyme antibodies, increases splenocyte IL-4/IFN-gamma cytokine responses and produces protective regulatory T-cells 4.1.1.15 glutamate decarboxylase medicine hamsters treated with low-dose cocaine throughout adolescence show significant differences to control in enzyme immunoreaction in anterior hypothalamus, medial and central amygdaloid nuclei, lateral septum 4.1.1.15 glutamate decarboxylase medicine mutation screen of isoform GAD67 in patients diagnosed with major unipolar depression shows a significant within-gene linkage disequilibrium. A common genetic variation within the GAD67 gene does not play a major role in predisposition to unipolar depression 4.1.1.15 glutamate decarboxylase medicine eight hours following kainate- or pilocarpine-induced seizure of piriform cortex, severe neuronal damage is observed accompanied by significant decreases in enzyme protein. In layer II of the central pirifiorm cortex, significant increase in isoforms GAD65 and GAD67 mRNA is determined 4.1.1.15 glutamate decarboxylase medicine glutamic acid specific T-cells play a key role in type I diabetes. Isolation of several populations of glutamic acid decarboxylase peptide-specific T-cells from diabetes-prone non-obese and diabetes-resistant mice. The repertoire of T cells specific for these peptides is biased toward Tr cells that inhibit diabetes rather than toward pathogenic T cells that induce diabetes 4.1.1.15 glutamate decarboxylase medicine incubation of rat hippocampal slices with the potassium channel antagonis tetraethyl ammonium results in widespread excitotoxic death of pyramidal and granule cell neurons. Treatment with bacterial enzyme significantly reduces excitotoxicity induced by tetraethyl ammonium without showing neurotoxicity. Targeting of enzyme to the interior of synaptic vesicles may enhance its potency as a neuroprotectant 4.1.1.15 glutamate decarboxylase medicine injection of gamma-aminobutanoate agonists baclofen and muscimol increases luteinising hormone in serum after 6 h. Intraperitoneal treatment with gamma-aminobutanaote A agonist muscimol decreases mRNA of isoform GAD65 approximately 10fold, gamma-aminobutanaote transaminase approximately 15fold and tyrosine hydroxylase approximately 3fold in telencephalon. Intraperitoneal treatment with gamma-aminobutanaote B agonist baclofen reduces mRNA levels of isoform GAD67 approximately 2fold and gamma-aminobutanaote transaminase approximately 2fold in hypothalamus 4.1.1.15 glutamate decarboxylase medicine herpes simplex virus -based GAD gene transfer to bladder afferent pathways represents an approach for treatment of neurogenic detrusor overactivity 4.1.1.17 ornithine decarboxylase medicine after induction of regenerative hyperplasia or renal hypertrophy by administration of folates or testosterone resp., enzyme activity increases 80- to 1000fold in enzyme activity 4.1.1.17 ornithine decarboxylase medicine assay to quantify enzyme levels in formalin-fixed tumor tissues, semiquantitation of tumor-specific variations of enzyme levels 4.1.1.17 ornithine decarboxylase medicine enzyme is overexpressed in prostate of patients suffering from benign prostatic hyperplasia and overexpression is also an early event in prostate carcinogenesis. Prostate-specific overexpression of enzyme in transgenic mice is not sufficient to induce carcinogenesis 4.1.1.17 ornithine decarboxylase medicine Helicobacter pylori-infected gastric mucosa, oral administation of Lactobacillus brevis induces a decrease in gastric enzyme activity and polyamine levels 4.1.1.17 ornithine decarboxylase medicine ODC can be useful in gene diagnosis and gene therapy of cancers, since some chemotherapeutic agents aim at reducing ODC expression and show inhibitory effects on cancer cell growth 4.1.1.17 ornithine decarboxylase medicine ODC inhibition enhances the anti-tumor effect of antiangiogenesis therapy 4.1.1.17 ornithine decarboxylase medicine polyamine-depletion as an antimalarial strategy, cytostasis caused by the co-inhibition of S-adenosylmethionine decarboxylase/ornithine decarboxylase in Plasmodium falciparum 4.1.1.17 ornithine decarboxylase medicine high ODC mRNA expression shows significant correlation with poor survival prognosis in Kaplan-Meier analyses, elevated ODC mRNA expression level correlates with several unfavorable genetic and clinical features in neuroblastoma 4.1.1.17 ornithine decarboxylase medicine low levels of timorous ODC expression are associated with a more aggressive tumor biology 4.1.1.17 ornithine decarboxylase medicine ODC1 single nucleotide polymorphism may be protective for colon adenoma recurrence and detrimental for survival after colon cancer diagnosis 4.1.1.17 ornithine decarboxylase medicine the rs2302615 single nucleotide polymorphism in the ODC gene is not a risk factor for breast cancer 4.1.1.17 ornithine decarboxylase medicine ornithine decarboxylase and sepiapterin reductase physically interact. In a cohort of 88 human neuroblastoma tumors, high sepiapterin reductase mRNA expression correlates significantly with poor survival prognosis, suggesting an oncogenic role for sepiapterin reductase in neuroblastoma tumorigenesis 4.1.1.17 ornithine decarboxylase medicine ornithine decarboxylase is a therapeutic target for endometrial cancer. Some endometrial cancers appear particularly sensitive to DL-alpha-difluromethylornithine and the polyamine pathway in endometrial cancers in general and specifically those most likely to suffer adverse clinical outcomes can be targeted for effective treatment, chemoprevention or chemoprevention of recurrence 4.1.1.17 ornithine decarboxylase medicine targeting both polyamine biosynthesis via ODC through 2-difluoromethylornithine and polyamine transport through MQT 1426 from the tumor microenvironment enhances the efficacy of polyamine-based therapy in this mouse model of squamous cell carcinoma, overview 4.1.1.18 lysine decarboxylase medicine lysine appears important for dental biofilm accumulation and the epithelial barrier to bacterial proinflammatory agents. After oral hygiene restriction, lysine decarboxylase activity seems to determine dental biofilm lysine content and biofilm accumulation. When biofilm lysine exceeds minimal blood plasma content after oral hygiene restriction, less gingival crevicular fluid appears despite more biofilm 4.1.1.22 histidine decarboxylase medicine confirmatory test for identification of Enterobacter aerogenes 4.1.1.22 histidine decarboxylase medicine histamine-mediated signaling contributes to malaria pathogenesis, histidine decarboxylase-deficient mice are highly resistant to severe malaria and display resistance to Plasmodium berghei strains ANKA and NK65 4.1.1.22 histidine decarboxylase medicine histidine decarboxylase-deficient mice present a numerical and functional deficit in invariant NK T cells as evidenced by a drastic decrease of IL-4 and IFN-gamma production 4.1.1.22 histidine decarboxylase medicine loss of HDC is a marker of malignant transformation and dedifferentiation of B-cells infiltrating the skin 4.1.1.22 histidine decarboxylase medicine suppression of histamine signaling by inhibition of HDC may be a novel target of probiotics in preventing allergic diseases 4.1.1.23 orotidine-5'-phosphate decarboxylase medicine orotidine 5-monophosphate decarboxylase of Plasmodium falciparum could be a target for the development of antimalarial drugs 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine development of dopamine treatment ainst Parkinson's disease, drug target for treatment of neurodgenerative diseases 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine novel approaches in the fight against the pathological conditions that the enzyme is implicated in such as cancer, schizophrenia, psychosis and Parkinson's disease 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine coexpression of tyrosine hydroxylase, GTP cyclohydrolase I, aromatic amino acid decarboxylase, and vesicular monoamine transporter 2 from a helper virus-free herpes simplex virus type 1 vector supports high-level, long-term biochemical and behavioral correction of a rat model of Parkinson's disease 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine Because epileptic attacks can be treated with appropriate antiepileptic drugs, a confirmation whether patients with AADC deficiency have both non-epileptic and epileptic seizures in varying proportions, is necessary. The differentiation of epileptic seizures from involuntary non-epileptic movements, such as short-lasting dystonic attacks, chorea, or myoclonus, is indispensable for the adequate treatment of patients with AADC deficiency. 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine combination treatment of Adeno-associated virus type-2 containing human AADC gene, with oral levodopa is a novel therapeutic approach in patients with Parkinson disease 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine Development of therapy of patients with aromatic L-amino acid decarboxylase deficiency. Drug therapy in patients with AADC deficiency aims at correcting the central and peripheral deficiency of serotonin and catecholamines. Treatment is very challenging. There are no established treatment schemes or clear dosages for the individual drugs. 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine diagnosis of neuroblastoma, both tyrosine hydroxylase mRNA and DDC mRNA could be useful for stratifying patients into different treatment groups in future clinical trials. 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine the presence of a natural occurring ddc inhibitor in a peripheral tissue, may have interesting implications for future pharmacological treatment of neurodegenerative diseases such as inhibition of peripheral ddc, as well as, therapeutic approaches of neoplasias that are characterized by elevated levels of Ddc expression 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine therapy of Parkinson disease 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine there is no association between single nucleotide polymorphisms in the DDC gene and suicidal behavior 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine DDC mRNA expression is a potential tissue biomarker in colorectal adenocarcinoma 4.1.1.28 aromatic-L-amino-acid decarboxylase medicine enzyme is responsible for thyronamine biosynthesis via decarboxylation of thyroid hormone. In addition, patients with aromatic L-amino acid decarboxylase-deficiency display thyronamines in plasma at levels similar to those of healthy controls 4.1.1.29 sulfinoalanine decarboxylase medicine 3.6% of patients suffering from autoimmune polyendocrine syndrome type 1 are positive for antibodies against the enzyme. Antibodies cross-react with glutamic acid decarboxylase, aromatic L-amino acid decarboxylase and histidine decarboxylase 4.1.1.32 phosphoenolpyruvate carboxykinase (GTP) medicine inhibitors of PEPCK may be useful in the treatment of type II diabetes 4.1.1.32 phosphoenolpyruvate carboxykinase (GTP) medicine plays a role in the development of type 2 diabetes 4.1.1.32 phosphoenolpyruvate carboxykinase (GTP) medicine chronic administration of phenobarbital reduces hepatic PEPCK mRNA in streptozotocin-induced diabetic and nondiabetic rats, and phenobarbital reduces blood glucose level in diabetic rats 4.1.1.33 diphosphomevalonate decarboxylase medicine the upregulation of microRNA-214 and downregulation of mevalonate diphosphate decarboxylase transcription in the liver both play a role in the development of hypocholesterolemia in stroke-prone spontaneously hypertensive rats 4.1.1.37 uroporphyrinogen decarboxylase medicine malfunction of UROD is associated with porphyria cutanea tarda and hepatoerythropoietic porphyria, denaturing gradient gel electrophoresis technique DGGE assay presents genetic diagnosis method for screening patients from previously uncharacterized families, differential diagnosis between familial and sporadic cases of PCT 4.1.1.37 uroporphyrinogen decarboxylase medicine PCT is a human metabolic disorder, due to the acquired or genetic impairment of uroporphyrinogen decarboxylase activity 4.1.1.37 uroporphyrinogen decarboxylase medicine subnormal activity of uroporphyrinogen decarboxylase in hepatocytes is responsible for the most common form of porphyria in humans, porphyria cutanea tarda 4.1.1.37 uroporphyrinogen decarboxylase medicine a low erythrocytic UROD may be a predisposing factor for porphyria cutanea tarda 4.1.1.37 uroporphyrinogen decarboxylase medicine the clinical manifestations of Porphyria cutanea tarda in dialysis patients can be a result of reduced activity of uroporphyrinogen decarboxylase in addition to the accumulation of photosensitive by-products resulting from a lack of an effective means of excretion 4.1.1.37 uroporphyrinogen decarboxylase medicine uroporphyrinogen decarboxylase is a radiosensitizing target for head and neck cancer 4.1.1.45 aminocarboxymuconate-semialdehyde decarboxylase medicine during the metabolism of tryptophan, ACMSD is able to influence directly the production of quinolinate, a potent endogenous excitotoxin, have roles in the pathogenesiof epilepsy, Huntington's disease, Alzheimer's disease and demetia resulting from AIDS, and picolinate which may influence the immune system in macrophages and apoptosis in human leukaemia cell lines 4.1.1.45 aminocarboxymuconate-semialdehyde decarboxylase medicine quinolinate, non-enzymatically derived from 2-amino-3-(3-oxoprop-2-enyl)-but-2-enedioate is a potent endogenous excitotoxin of neuronal cells, whose elevation in brain is implicated in the pathogenesis of various neurodegenerative disorders, ACMSD is the only known enzyme that can process ACMS to a benign catabolite and thus prevent the accumulation of quinolinate 4.1.1.45 aminocarboxymuconate-semialdehyde decarboxylase medicine the enzyme is an therapeutic target for treating disorders associated with increased levels of tryptophan metabolites 4.1.1.45 aminocarboxymuconate-semialdehyde decarboxylase medicine increased quinolic acid levels may result from reduced activity of ACMSD in suicidal subjects. Suicide attempters have reduced picolinic acid levels and a decreased picolinic acid/quinolinic acid ratio in both cerebrospinal fluid and blood. The minor C allele of the ACMSD SNP rs2121337 is more prevalent in suicide attempters and associated with increased cerebrospinal quinolinic acid level 4.1.1.48 indole-3-glycerol-phosphate synthase medicine IGPS may be a potential target for the development of anti-tuberculosis drugs 4.1.1.49 phosphoenolpyruvate carboxykinase (ATP) medicine Trypanosoma cruzi is the causative agent of Chagas' disease, enzyme is a good target for the development of new anti-chagasic drugs 4.1.1.50 adenosylmethionine decarboxylase medicine essential role of enzyme in embryonic development, polyamines are required for cell proliferation after E3.5 4.1.1.50 adenosylmethionine decarboxylase medicine S-adenosyl methionine decarboxylase activity is required for the outcome of herpes simplex virus type 1 infection and represents a new potential therapeutic target, inhibition of the enzyme by methylglyoxal bis(guanylhydrazone) prevents HSV-1 infection 4.1.1.50 adenosylmethionine decarboxylase medicine adenovirus-mediated expression of both antisense ornithine decarboxylase and S-adenosylmethionine decarboxylase in lung cancer cell line A-549. Antisense enzyme expression inhibits tumor cell growth through blocking the polyamine synthesis pathway. Tumor cells are arrested at G1 phase and invasivness is reduced 4.1.1.50 adenosylmethionine decarboxylase medicine enzyme inhibitor (2E)-2-[4-[amino(imino)methyl]-2,3-dihydro-1H-inden-1-ylidene]hydrazinecarboximidamide, i.e. CGP48664A, SAM486A, suppresses HIV-1 replication, including the replication of viruses that are resistant to multiple reverse transcriptase and protease inhibitos. Antiretroviral effect is based on the fact that regulatory protein Rev activity is severely compromised in drug-treated cells. No toxic effects on cellular metabolism are observed 4.1.1.57 methionine decarboxylase medicine recombinant MetDC (0.50 U/ml) severely inhibits growth of human tumour cells A431 and MDA-MB-231, but shows relatively low cytotoxicity for human normal cell NHDF-Neo 4.1.1.65 phosphatidylserine decarboxylase medicine phosphatidylserine decarboxylase PISD is downregulated by 8fold in migratory cells. Breast cancer cells overexpressing PISD exhibit reduced tumor-initiating potential in a high-throughput microfluidic mammosphere device and mouse xenograft model 4.1.1.72 branched-chain-2-oxoacid decarboxylase medicine in patients with maple syrup urine disease, mutations such as R114W-alpha or R220W-alpha cause a strongly reduced binding of thiamin diphosphate, rendering the enzyme inactive 4.1.1.72 branched-chain-2-oxoacid decarboxylase medicine naturally occuring mutations cause an impaired assembly of enzyme in patients with maple syrup urine disease 4.1.1.84 D-dopachrome decarboxylase medicine strong correlation and covariation of enzyme activity with macrophage migration inhibitory factor, MIF, upon UVB-induction 4.1.1.84 D-dopachrome decarboxylase medicine DDT may be candidates for key enzymes to protect the liver from oxidative stress induced by various causes 4.1.1.90 peptidyl-glutamate 4-carboxylase medicine six out of seven patients with Pseudoxanthoma Elasticum habor mutations in the GGCX gene (gamma-glutamyl carboxylase) 4.1.1.90 peptidyl-glutamate 4-carboxylase medicine warfarin therapy 4.1.1.90 peptidyl-glutamate 4-carboxylase medicine multiplexed single nucleotide polymorphism panel (interrogation of the CYP2C9 *2, *3, VKORC1 (-1639G3A), and GGCX (1181T3G) alleles simultaneously) can be successfully used in genotyping of patient blood samples, whereby results can be combined with other clinical parameters in an algorithm for warfarin dosing 4.1.1.90 peptidyl-glutamate 4-carboxylase medicine single nucleotide polymorphism in the GGCX gene may affect the dose of warfarin and other vitamin K antagonists 4.1.1.90 peptidyl-glutamate 4-carboxylase medicine in WKY rats receiving a vitamin K-deficient diet that results in a 40% decrease of prothrombin activity, compound N-ethyl-2-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)tetradecylamide is able to counteract the effects on vitamin K deficiency and results in the complete restoration of prothrombin activity 4.1.1.94 ethylmalonyl-CoA decarboxylase medicine ECHDC1 expression is increased in gemcitabine-resistant bladder cancer cells, and is involved in their cell growth. Silencing of ECHDC1 significantly inhibits the proliferation of a gemcitabine-resistant UMUC-3-derived cell line. Silencing of ECHDC1 induces upregulation of p27, which is critical for cell cycle arrest in the G1 phase, and induces G1 arrest 4.1.2.4 deoxyribose-phosphate aldolase medicine possible selection as a vaccine candidate. The purified recombinant protein is used to immunize rats. The antibodies obtained are used to verify in vitro expression of the enzyme. The vector pVAX1 is utilized to formulate a DNA vaccine designated as pTgDPA, which is used to evaluate the immunological changes and the level of protection against challenge with the virulent RH strain of Toxoplasma gondii. DNA vaccine, TgDPA revealed that it can induce a strong humoral as well as cellular mediated response in mice. These responses are a contribution of TH1, TH2 and TH17 type of responses. Mice immunized with TgDPA show longer survival rates than do mice in control groups 4.1.2.13 fructose-bisphosphate aldolase medicine aldolase B deficiency causes hereditary fructose intolerance 4.1.2.13 fructose-bisphosphate aldolase medicine mutations in aldolase B gene cause hereditary fructose intolerance, most common intolerance allele encodes a A149P substitution 4.1.2.13 fructose-bisphosphate aldolase medicine potential drug target 4.1.2.13 fructose-bisphosphate aldolase medicine inhibitors of class II Fba can be potential drugs against microorganisms 4.1.2.13 fructose-bisphosphate aldolase medicine useful in the immunodiagnosis of malaria 4.1.2.13 fructose-bisphosphate aldolase medicine the enzyme can be utilized as a broad-spectrum vaccine against various pathogenic bacteria of aquaculture 4.1.2.13 fructose-bisphosphate aldolase medicine the enzyme is a hypoxia-inducible prognostic factor for colorectal cancer 4.1.2.13 fructose-bisphosphate aldolase medicine the enzyme is the antigen target of the monoclonal antibody 3F8 useful for the detection of Listeria genus 4.1.2.14 2-dehydro-3-deoxy-phosphogluconate aldolase medicine 2-keto-3-deoxy-6-phosphogluconate aldolase is an attractive target for drug therapy in the case of human Streptococcus suis infections 4.1.2.25 dihydroneopterin aldolase medicine drugs targeting folate metabolism have long been used as highly successful antimicrobial and anticancer agents 4.1.2.27 sphinganine-1-phosphate aldolase medicine some effects of immune modulator FTY720 are due to disruption of sphingosine-1-phosphate metabolism 4.1.2.27 sphinganine-1-phosphate aldolase medicine all S1PL-deficient genetic models used display lymphopenia, with sequestration of mature T-cells in the thymus and lymph nodes. In addition to the lymphoid phenotypes, S1PL KO mice also develop myeloid cell hyperplasia and significant lesions in the lung, heart, urinary tract, and bone, and have a markedly reduced life span. Complete absence of S1PL affects both maturation/development and egress of mature T cells from the thymus, whereas low level S1PL activity affects T-cell egress more than differentiation 4.1.2.27 sphinganine-1-phosphate aldolase medicine complete loss of SPL activity leads to upregulation of the antiapoptotic proteins Bcl-2 and Bcl-xL and consequently protects against apoptosis induced by chemotherapy and nutrient starvation but not against autophagy 4.1.2.27 sphinganine-1-phosphate aldolase medicine following the oral administration of 10 and 100 mg/kg 2-acetyl-4(5)-tetrahydroxybutyl imidazole to male rats, 2-acetyl-4(5)-tetrahydroxybutyl imidazole is rapidly absorbed and reaches a plasma peak level at 1 h post-dosing. Splenic S1P increases and reaches the peak level at 24 h. Blood lymphocyte count decreases as the splenic S1P level increases. 2-Acetyl-4(5)-tetrahydroxybutyl imidazole plasma concentration is linked to splenic S1P concentration using an indirect model incorporated with a four-step signal transduction model. In turn, the S1P level is directly coupled with blood lymphocyte number 4.1.2.27 sphinganine-1-phosphate aldolase medicine humanized knock-in mice harboring one allele such as S1PLH/- or two alleles such as S1PLH/H of human S1PL express less than 10 and 20% of normal S1PL activity, respectively. This partial restoration of S1PL activity is sufficient to fully protect both humanized mouse lines from the lethal non-lymphoid lesions that develop in S1PL-/- mice, but fails to restore normal T-cell development and trafficking. The complete absence of S1PL affects both maturation/development and egress of mature T-cells from the thymus, whereas low level S1PL activity affects T-cell egress more than differentiation 4.1.2.27 sphinganine-1-phosphate aldolase medicine incubation of lyase-deficient neurons with either sphingosine or S1P results in a similar elevation in cellular S1P, but only S1P addition to the culture medium induces apoptosis. This is not due to S1P acting on the S1P receptor but to hydrolysis of S1P to sphingosine that is phosphorylated by the cells. Although the cells produce S1P from both exogenously added sphingosine as well as sphingosine derived from exogenous S1P, the S1P from these two sources are not equivalent, because the former is primarily produced by SK1, whereas the latter is mainly formed by sphingosine kinase-2 4.1.2.27 sphinganine-1-phosphate aldolase medicine mRNA expression for both sphingosine kinase and sphingosine 1-phosphate lyase are up-regulated throughout all four stages in human breast cancer patients 4.1.2.27 sphinganine-1-phosphate aldolase medicine thymocyte development in SGPL1-deficient mice which exhibit postnatal discontinuation of early thymocytopoies is starting at 2 weeks after birth. SGPL-/- thymi show a loss of developing thymocytes in the thymic cortex between 2 and 4 weeks of age, whereas mature thymocytes accumulate in the medulla. Increased ceramide levels in the thymus of SGPL1-/- mice abrogates thymic development postnatally by enhanced thymocyte apoptosis and depletion of thymic ETP. Potentially therapeutic immunosuppression by SGPL1 inhibition should benefit from monitoring ceramides to prevent their increase to apoptosis-inducing levels 4.1.2.27 sphinganine-1-phosphate aldolase medicine S1P lyase is a therapeutic target for ischemia-reperfusion injury of the heart 4.1.2.27 sphinganine-1-phosphate aldolase medicine in fresh human prostatectomy specimens, a remarkable decrease in sphingosine 1-phosphate lyase enzymatic activity is found in tumor samples, as compared with normal adjacent tissues. A significant relationship between loss of sphingosine 1-phosphate lyase expression and higher Gleason score is confirmed. Sphingosine 1-phosphate lyase protein expression and activity are inversely correlated with those of sphingosine kinase-1, the enzyme producing sphingosine 1-phosphate. Sphingosine 1-phosphate lyase and sphingosine kinase expressions are independently predictive of aggressive cancer on tissue microarray 4.1.2.27 sphinganine-1-phosphate aldolase medicine inducible sphingosine-1-phosphate lyase knockout mice featuring partial reduction of sphingosine-1-phosphate lyase activity are viable but feature profound reduction of peripheral T cells, similar to the constitutive knockout mice. While thymic T cell development in these mice appears normal, mature T cells are retained in thymus and lymph nodes, leading to reduced T cell numbers in spleen and blood, with a skewing towards increased proportions of memory T cells and T regulatory cells. The inducible knockout mice are protected in experimental autoimmune encephalomyelitis. T cell immigration into the CNS is profoundly reduced 4.1.2.27 sphinganine-1-phosphate aldolase medicine inhibition of sphingosine-1-phosphate lyase activity rendes sphingosine 1-phosphate an efficient S1P1 receptor internalizing compound and abrogated sphingosine-1-phosphate-mediated sustained signaling, suggesting that sphingosine-1-phosphate lyase by facilitating S1P1 receptor recycling is essential for sphingosine-1-phosphate-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not sphingosine-1-phosphate lyase substrates 4.1.2.42 D-threonine aldolase medicine efficient biocatalyst for resolution of L-X-3,4-methylenedioxyphenylserine, an intermediate for production of a therapeutic drug for Parkinson's disease 4.1.2.42 D-threonine aldolase medicine low-specificity threonine aldolase can be used in production of L-threo-3-[4-(methylthio)phenylserine], an intermediate for synthesis of antibiotics florfenicol and thiamphenicol 4.1.3.1 isocitrate lyase medicine enzyme provides a potential target for drug design aimed at the control of parasitic infections 4.1.3.1 isocitrate lyase medicine isocitrate lyase inhibitors as possible antituberculosis drugs 4.1.3.1 isocitrate lyase medicine cytoplasm of macrophages possibly glucose-deficient, thus internalized Penicillium marneffei depends on glyoxylate pathway 4.1.3.1 isocitrate lyase medicine overexpression of ICL from Mycobacterium smegmatis (MS-ICL) in Mycobacterium smegmatis (MS) does not suppress apoptosis induced in mouse macrophages upon infection by these recombinant bacteria (rMS-pMS-icl) compared to infection by control MS or MS overexpressing ICL from Mycobacterium tuberculosis 4.1.3.1 isocitrate lyase medicine overexpression of ICL from Mycobacterium tuberculosis (MTB-ICL) in Mycobacterium smegmatis (MS) suppresses apoptosis induced in mouse macrophages upon infection by these recombinant bacteria (rMS-pMTB-icl) compared to infection by control MS 4.1.3.4 hydroxymethylglutaryl-CoA lyase medicine genetically heterogeneous deficiency, participation of S69 codon 2-base pair deletion in some cases 4.1.3.4 hydroxymethylglutaryl-CoA lyase medicine 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency may cause hypoglycaemia which can lead to death 4.1.3.4 hydroxymethylglutaryl-CoA lyase medicine mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria 4.1.3.4 hydroxymethylglutaryl-CoA lyase medicine 3-hydroxy-3-methylglutaryl CoA lyase deficiency is a rare autosomal recessive mitochondrial disease characterized by a deficiency in the enzyme 3-hydroxy-3-methylglutaryl CoA lyase 4.1.3.4 hydroxymethylglutaryl-CoA lyase medicine 3-hydroxy-3-methylglutaric aciduria is an autosomal recessive branched chain organic aciduria caused by the deficiency of the enzyme 3-hydroxy-3-methylglutaryl-CoA lyase 4.1.3.4 hydroxymethylglutaryl-CoA lyase medicine 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency is a rare inborn error affecting leucine catabolism and ketogenesis, usually presenting in the neonatal period 4.1.3.4 hydroxymethylglutaryl-CoA lyase medicine dilated cardiomyopathy is associated with HMG CoA lyase deficiency 4.1.3.6 citrate (pro-3S)-lyase medicine polymorphisms of the citrate lyase gene, may be involved in appetite regulation and antipsychotic induced metabolic syndrome with olanzapine-induced weight gain, are analysed 4.1.3.16 4-Hydroxy-2-oxoglutarate aldolase medicine mutations in the gene encoding for 4-hydroxy-2-oxoglutarate aldolase are associated with an excessive production of oxalate in Primary Hyperoxaluria type 3, PH3. Analysis of nine PH3 human variants reveals that all nine PH3 variants are quite unstable, have a tendency to aggregate, and retain no measurable activity. A buildup of 4-hydroxy-2-oxoglutarate takes place in the urine, sera and liver samples from PH3 patients. One hypothetical component of the molecular basis for the excessive oxalate production in PH3 appears to be the inhibition of glyoxylate reductase by 4-hydroxy-2-oxoglutarate, resulting in a phenotype similar to Primary Hyperoxaluria type 2 4.1.3.27 anthranilate synthase medicine TrpE is a promising target for the design of novel anti-tuberculosis drugs 4.1.3.36 1,4-dihydroxy-2-naphthoyl-CoA synthase medicine mutations in the menB gene, the gene encoding naphthoate synthase, cause the small-colony variant phenotype, small-colony variants are associated with persistent infections and may be selectively enriched during antibody therapy 4.1.99.1 tryptophanase medicine transposon insertion in gene results in a strain unable to form biofilm on polystyrene and to adhere to human pneumocyte cells 4.1.99.3 deoxyribodipyrimidine photo-lyase medicine exploring therapeutic possibilities of ectopic CPD photolyase expression 4.2.1.1 carbonic anhydrase medicine design of novel antitumor properties, mainly for hypoxic tumors that overexpress CA IX 4.2.1.1 carbonic anhydrase medicine overexpressed on cell surfaces of certain cancers, potential target for chemotherapeutic agents 4.2.1.1 carbonic anhydrase medicine relevance for the drug design of novel CA inhibitors, intersting pharmacological applications 4.2.1.1 carbonic anhydrase medicine there are amino acid differences in the active site of AaCA1 of Aedes aegypti and human carbonic anhydrases. Terefore this enzyme could be a potential drug target of selective carbonic anhydrase inhibitors for the control of mosquito populations and the pathogens they carry 4.2.1.1 carbonic anhydrase medicine CA IX is a marker of tumor hypoxia and a prognostic factor in several human cancers, inhibition of this enzyme shows antitumor activity both in vitro and in vivo 4.2.1.1 carbonic anhydrase medicine isoform CA IX is used as a marker of tumor hypoxia and as a prognostic factor for many human cancers 4.2.1.1 carbonic anhydrase medicine isozyme CAIX is a marker for hypoxic tumors and is correlated with poor prognosis in breast cancer patients 4.2.1.2 fumarate hydratase medicine metabolites of ibuprofen may play a role in its anti-cataract effect by protecting lenticular enzymes 4.2.1.2 fumarate hydratase medicine fumarate hydratase activity can be useful in the diagnosis of hereditary leiomyomatosis and renal cell cancer in cases with atypical presentation and undetectable fumarate hydratase mutations. Furthermore, fumarate hydratase activity testing is of value in laboratory investigations to elucidate the mechanism of hereditary leiomyomatosis and renal cell cancer 4.2.1.2 fumarate hydratase medicine fumarate immunohistochemistry may serve as a useful low-cost screening method to identify hereditary leiomyomatosis and renal cancer 4.2.1.2 fumarate hydratase medicine whole-gene fumarate hydratase deletions are not a frequent cause of hereditary leiomyomatosis and renal cell cancer syndrome 4.2.1.2 fumarate hydratase medicine elevation of total fumarase activity may attenuate the development of hypertension 4.2.1.2 fumarate hydratase medicine the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and hyperpolarized [1,4-13C2]malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity. After verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-13C]fumarate magnetic resonance imaging 4.2.1.3 aconitate hydratase medicine mitochondrial enzyme is present in the glandular epithelium of normal glands, hyperplastic glands, adenocarcinomatous glands, and prostatic intraepithelial neoplastic fold. There is no difference in enzyme levels between malignant and non-malignant tissues 4.2.1.3 aconitate hydratase medicine enzyme inhibition, e.g. by deferiprone, is helpful in Friedreich's ataxia treatment 4.2.1.3 aconitate hydratase medicine it is shown that the cytosolic aconitase defect and consequent IRP1 activation occurring in Friedreich's Ataxia (FRDA) cells are reversed by the action of extramitochondrial frataxin 4.2.1.3 aconitate hydratase medicine a high fat diet (60% kcal from fat) shows significantly increased mitochondrial aconitase activity without changes in protein level and produces increased aconitase acetylation at multiple sites 4.2.1.10 3-dehydroquinate dehydratase medicine dehydroquinase is a target for the development of new antibiotics 4.2.1.10 3-dehydroquinate dehydratase medicine dehydroquinate synthase is a target for microbial agents, anti-parasitic agents and herbicides 4.2.1.11 phosphopyruvate hydratase medicine alpha-enolase is a pancreatic ductal adenocarcinoma-associated antigen 4.2.1.11 phosphopyruvate hydratase medicine changes in tumor ENO-1 levels are related to clinical 4-hydroxytamoxifen therapeutic outcome, downregulation of ENO-1 can be utilized as a pharmacological approach for overcoming 4-hydroxytamoxifen resistance in breast cancer therapy 4.2.1.11 phosphopyruvate hydratase medicine salivary neuron specific enolase is an indicator for neuronal damage in patients with ischemic stroke and stroke-prone patients 4.2.1.11 phosphopyruvate hydratase medicine the up-regulation of alpha-enolase expression can be a protective mechanism to neutralize oxidative and nitrative stress in diabetes 4.2.1.11 phosphopyruvate hydratase medicine the recombinant enzyme protein is a useful antigen in vaccination against adult worms 4.2.1.11 phosphopyruvate hydratase medicine the tegumental membrane protein enolase is a vaccine candidate 4.2.1.11 phosphopyruvate hydratase medicine recombinant alpha-enolase can confer effective protection against Streptococcus iniae infection in mice 4.2.1.11 phosphopyruvate hydratase medicine vaccine with the enzyme can produce a 36.4% protection rate in vaccinated rabbits against experimental challenges from Taenia pisiformis eggs 4.2.1.17 enoyl-CoA hydratase medicine ECHS1 down-regulation contributes to high-fat diet-induced hepatic steatosis 4.2.1.18 methylglutaconyl-CoA hydratase medicine sensitive and specific enzymatic assay for 3-methylglutaconyl-CoA hydratase that enables the rapid enzymatic diagnosis of 3-methylglutaconic aciduria type I in cultured skin fibroblasts without the need for radiochemicals 4.2.1.18 methylglutaconyl-CoA hydratase medicine studies on the metabolic disease 3-methylglutaconic aciduria 4.2.1.18 methylglutaconyl-CoA hydratase medicine studies on the metabolic disease 3-methylglutaconic aciduria type I, characterized by abnormal organic acid profile and excessive urinary excretion of 3-methylglutaconic acid, 3-methylglutaric acid and 3-hydroxyisovaleric acid 4.2.1.22 cystathionine beta-synthase medicine inherited deficiency leads to homocystinura, a disease of sulfur metabolism 4.2.1.22 cystathionine beta-synthase medicine inherited deficiency leads to homocystinura, a disease of sulfur metabolism characterized by increased levels of homocysteine and methionine and decreased levels of cysteine 4.2.1.22 cystathionine beta-synthase medicine inherited deficiency leads to homocystinuria, an autosomal recessivlely inherited disease of sulfur metabolism 4.2.1.22 cystathionine beta-synthase medicine inherited dysfunction of the enzyme leads to homocystinurea, mutations can occur at the dimer interface, the active site, the heme-binding site and the predicted interface region between the catalytic domain and the missing regulatory domain of the truncated enzyme 4.2.1.22 cystathionine beta-synthase medicine a deficiency of cystathionine beta-synthase causes various neurodevelopmental defects which result in complex neuropathological features associated with abnormal homocysteine metabolism, and also suggest that radial glia/astrocyte lineage cells might be a new therapeutic target for preventing and treating them 4.2.1.22 cystathionine beta-synthase medicine CBS-deficient patients have significantly elevated plasma levels of prothrombotic N-homocysteine-fibrinogen 4.2.1.22 cystathionine beta-synthase medicine there is no association between the CBS (844ins68) insertion polymorphism and cancer of the upper gastrointestinal tract 4.2.1.22 cystathionine beta-synthase medicine breast cancer patient-derived tissues and breast cancer cells exhibit significantly increased levels of CBS when compared with their normal counterparts, associated with increased levels of H2S and cystathionine. Silencing of CBS in breast cancer cells causes a significant decrease in the levels of H2S and cystathionine but does not affect the growth of these cells per se, in in vitro cultures. CBS-silenced cells exhibit significantly reduced growth in the presence of activated macrophages and in xenograft models, associated with an increase in the steady state levels of reactive aldehyde-derived protein adducts 4.2.1.22 cystathionine beta-synthase medicine treatment with homocysteine upregulates cystathionine gamma lyase CSE but downregulates CBS whereas Na2S or H2S-donoer GYY4137 downregulates CSE but upregulates CBS in a dose-dependent manner. In the homocysteine-treated cardiomyocytes, CBS and miR-133a are downregulated and hypertrophy is inducedIn vivo studies using CBS+/- mice, a model for hyperhomocysteinemia, and sibling CBS+/+ control mice revealed that deficiency of CBS upregulates cardiac CSE 4.2.1.24 porphobilinogen synthase medicine delta-ALA-D activity is a reliable marker for oxidative stress in bone marrow transplantation patients 4.2.1.24 porphobilinogen synthase medicine in blood samples from patients previously treated for lung cancer with chemotherapy, ALAD activity shows a 37% decrease compared with control. Reactive species and thiobarbituric acid reactive substances are 8% and 99% higher in the patient group, respectively. The activity of superoxide dismutase and catalase as well as the vitamin C content are 41%, 35% and 127% lower in patients when compared with controls, respectively. Total thiols and vitamin E levels are 27% and 44% higher in lung cancer patients, respectively 4.2.1.31 maleate hydratase medicine possibly involved in regulation of renal activity 4.2.1.36 homoaconitate hydratase medicine deletion of enzyme gene, results in almost avirulent mutant cells using a low dose intranasal mouse infection model 4.2.1.49 urocanate hydratase medicine L70P and R450C mutations in the coding region of the UROC1 gene in a girl with urocanic aciduria presenting with mental retardation and intermittent ataxia. Both mutations cannot produce a fully functional enzyme, L70P substitution implies the disruption of an alpha-helix in the N-terminus, which alters its properties and therefore, its function. The R450C change renders impossible any interaction between urocanase and its substrate and loses its enzyme activity 4.2.1.92 hydroperoxide dehydratase medicine enzyme is involved in skin differentiation and etiology of ichthyosiform diseases 4.2.1.175 phenyllactyl-CoA dehydratase medicine in mice colonized by a wild-type Clostridium sporogenes strain, the mean indolepropionic acid concentration is around 80 microM, but in mice colonized with theFfldC mutant, indolepropionic acid is undetectable. Animals colonized by the FldC mutant exhibit significantly elevated frequencies of circulating myeloid cells, including neutrophils and classical (Ly6C+) monocytes, as well as increased antigen-experienced effector/memory T cells. Mice colonized by the FldC mutant strain show a significant increase in circulating Clostridium sporogenes-specific IgG 4.2.2.1 hyaluronate lyase medicine the enzyme can be used as a vaccine 4.2.2.1 hyaluronate lyase medicine as compared to bovine-derived enzyme cumulase is safe and effective in an intracytoplasmic sperm injection treatment program and can provide comparable if not improved parameters, including fertilization and embryo developmental rates 4.2.2.1 hyaluronate lyase medicine safe and effective in an intracytoplasmic sperm injection treatment program 4.2.2.1 hyaluronate lyase medicine transient perfusion induces acute hypoxia and may limit the radiotherapy response and induce drug resistance. Hyaluronidase improves perfusion in human osteosarcoma xenografts grown orthotopically and in dorsal skinfold chambers 4.2.2.1 hyaluronate lyase medicine antitumor activity and overall survival of mice bearing highly aggessive tumors are significantly improved by codelivery of oncolytic adenovirus and hyaluronidase when compared with either of the monotherapy-treated groups, and it may prove to be a potent and novel approach to treating patients with cancer 4.2.2.1 hyaluronate lyase medicine distribution of hyaluronate lyase-producing Streptococcus pneumoniae among invasive, noninvasive and carriage isolates from patients and carriers. A total of 100 isolates from various clinical samples all possessed the Hyl gene. Ninety-six isolates including 34 carriage isolates were positive for production of hyaluronate lyase. Four hyaluronate lyase-negative isolates are from blood (2 isolates) and sputum (2 isolates). No significant association is detected among hyaluronate lyase production and bacterial characteristics except for colonial morphology 4.2.2.1 hyaluronate lyase medicine Streptococcus suis hyaluronate lyase does not represent a critical virulence factor in its active form. Exogenous hyaluronic acid appears to modulate several virulence determinants of the bacterium, in addition to promote inflammation 4.2.2.3 mannuronate-specific alginate lyase medicine enzyme is a target for design of chemotherapeutics in the treatment of cystis fibrosis caused by infection with alginate producing Pseudomonas aeruginosa 4.2.2.3 mannuronate-specific alginate lyase medicine once mucoid strains of Pseudomonas aeruginosa have become established in the respiratory tracts of cystic fibrosis patients they can rarely be eliminated by antibiotic treatment alone. Coadministration of antibiotics with alginate lyase, which degrades the exopolysaccharide produced by mucoid strains of pseudomonas aeruginosa might benefit cystic fibrosis patients by increasing the efficacy of antibioticin the respiratory tract 4.2.2.3 mannuronate-specific alginate lyase medicine alginate hydrogels can be enzymatically degraded in a controlled and tunable fashion by incorporating poly(lactide-co-glycolide) microspheres loaded with alginate lyase into alginate hydrogels. Neural progenitor cells can be cultured and expanded in vitro in this degradable alginate hydrogel system. A significant increase in the expansion rate of neural progenitor cells cultured in degrading alginate hydrogels versus neural progenitor cells cultured in standard, i.e. non-degrading, alginate hydrogels. Degradable alginate hydrogels encapsulating stem cells may be widely applied to develop novel therapies for tissue regeneration 4.2.2.3 mannuronate-specific alginate lyase medicine it might be possible to use alginate lyase AlgL as an adjuvant therapeutic medicine for the treatment of disease associated with Pseudomonas aeruginosa infection 4.2.2.3 mannuronate-specific alginate lyase medicine treatment with AlgL improves killing of the mucoid strain PA-489121 of Pseudomonas aeruginosa, the coadministration of DNase and AlgL is essential for enhanced activity in reducing biofilm growth and sputum bacterial counts 4.2.2.3 mannuronate-specific alginate lyase medicine controlled mono-PEGylation of A1-III alginate lyase mutant A53C produces a conjugate with wild type levels of activity. The PEGylated mutant exhibits enhanced solution phase kinetics with bacterial alginate. In vitro binding studies with both enzyme-specific antibodies, from immunized New Zealand white rabbits, and a single chain antibody library, derived from a human volunteer show that the PEGylated enzyme is substantially less immunoreactive. More than 90% of adherent, mucoid, Pseudomonas aeruginosa biofilms are removed from abiotic surfaces following a one h treatment with the PEGylated mutant, whereas the wild type enzyme removes only 75% of biofilms in parallel studies 4.2.2.3 mannuronate-specific alginate lyase medicine alginate lyases are promising therapeutic candidates for treating mucoid Pseudomonas aeruginosa infections. In particular, the enzymes' ability to degrade alginate, a key component of mucoid biofilm matrix, has been the presumed mechanism by which they disrupt biofilms and enhance antibiotic efficacy, but invitro modeling shows that alginate lyase dispersion of Pseudomonas aeruginosa biofilms and enzyme synergy with tobramycin are completely decoupled from catalytic activity 4.2.2.3 mannuronate-specific alginate lyase medicine site-specific mono-PEGylation of genetically engineered A1-III alginate lyase yields an enzyme with enhanced performance relative to therapeutically relevant metrics. Over 90% of adherent, mucoid, Pseudomonas aeruginosa biofilms are removed from abiotic surfaces following a one h treatment with the PEGylated variant, whereas the wild-type enzyme removes only 75% of biofilms 4.2.2.5 chondroitin AC lyase medicine bone marrow-derived mononuclear cells, transfected with our construct and transplanted into CNS, could be a potential tool for studying an alternative chondroitinase AC delivery method 4.2.2.7 heparin lyase medicine in a murine model of thermal injury, mutation of HepP reduces the rate of mortality from 100% for mice infected with wild-type to 7% for mice infected with the mutant strain. Upon intraperitoneal inoculation of the thermally injured mice, the rate of mortality for mice infected the mutant was 0%, whereas it was 66% for mice infected with wild-type. Only wild-type PA14 is recovered from the livers and spleens of infected mice 4.2.2.16 levan fructotransferase (DFA-IV-forming) medicine the product of the enzymatic reaction di-D-fructose-2,6':2',6 dianhydride stimulates calcium absorption mainly in small intestine of rats and has a practical physiological property in preventing osteoporosis 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine cervical dorsal column injury and treatment with chondroitinase ABC treatment leads to robust sprouting of both injured and intact descending projections as well as uninjured primary afferents. Enzyme treatment of uninjured animals does not induce sprouting in any system, so both denervation and chondroitin sulfate proteoglycan degradation are required to promote sprouting within the spinal cord. No increase in connectivity of nociceptive neurons or development of mechanical allodynia or thermal hyperalgesia 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine incubation of immature articular cartilage in serum-supplemented medium results in expansive growth with a marked increase in tissue volume associated with diminution of tensile integritiy. Treatment with chondroitinase ABC on day 0 leads to a marked reduction of glycosaminoglycan content and enhancement of tensile integrity. Subsequent incubation with enzyme leads to maturational growth with minimal changes in tissue volume and maintenance of tensile intregrity at the enhanced levels 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine masked intravitreal injection of chondroitinase, human or porcine plasmin into eye of pigs. Spontaneous posterior vitreous detachment occurs more frequently in human plasmin-treated and all plasmin treated eyes than in placebo controls. Treatment with chondroitinase fails to produce an effect 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine sciatic nerve transsection and end-to-end repair, with one nerve injected with chondroitinase ABC and the contralateral nerve treated with vehicle alone. Intrafascial retrograde axonal growth is equivalent in both control and chondroitinase treated conditions. Chondroitinase treatment causes a pronounced reduction in extrofacial retrograde axional growth. The decrease in axon egress from the nerve is coincident with an increase in antegrade regeneration and improved recovery of motor function 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine treatment with chondroitinase ABC improves motor function and reduces limiting ability of scar tissue to promote axonal regeneration via changing the structure of chondroitin sulfate proteoglycans 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine adult rats that undergo unilateral cervical spared-root lesion exhibit profound sensory deficits for 4 weeks after injury. Delivery of a focal intraspinal injection of the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC (ChABC) is sufficient to restore sensory function after lesion. In vivo electrophysiological recordings confirm that behavioral recovery observed in ChABC-treated rats is consequent on reorganization of intact C7 primary afferent terminals and not regeneration of rhizotomized afferents back into the spinal cord within adjacent segments. These data confirm that intact spinal circuits have a profound influence on functional restoration after spinal cord injury 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine antisense vimentin cDNA and ChABC are administered to hemisected rat spinal cords. Using RT-PCR, Western blotting and immunohistochemistry, it is shown that the combined treatment reduces the formation of glial scar and cystic cavities through degrading chondroitin sulfate proteoglycans molecules and inhibiting intermediate filament proteins 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine effects of degrading chondroitin sulfate glycosaminoglycan with Ch'ase ABC in the injured spinal cords of adult cats is assessed. Recovery of skilled locomotion (ladder, peg, and beam) is significantly accelerated in Ch'ase ABC-treated cats compared to controls. Ch'ase ABC-treated cats also show greater recovery of specific skilled locomotor features including intralimb movement patterns and significantly greater paw placement onto pegs. These findings show that intraspinal cleavage of CS GAGs can enhance recovery of function following spinal cord injury in large animals with sophisticated motor behaviors and axonal growth requirements similar to those encountered in humans 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine immediate and long-term effects of a single injection of chABC on chondroitin sulphate proteoglycans, chondroitin sulphate glycosaminoglycan and axon regeneration after unilateral nigrostriatal lesions in adult rats are investigated. In chABC-treated animals, the total chondroitin sulphate glycosaminoglycan remain at low level throughout the 28 day experimental period. This suggests the persistence of active chABC for at least 10 days after injection which is able to digest chondroitin sulphate proteoglycans released from cells during this time. Results suggest that a single injection of chABC can produce an environment conducive to CNS repair for over 10 days 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine it is shown that cervical spinal cord injury (SCI) results in the significantly increased expression of the chondroitin sulfate proteoglycans (CSPGs) NG2, neurocan, and brevican in the distant denervated dorsal column nuclei (DCN). The CSPGs present a potent barrier to reinnervation by regenerating axons from microtransplanted adult sensory neurons following SCI that can be overcome by chondroitinase ABC (chABC) application and increased neurotrophin-3 (NT-3) expression within the nucleus 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine rats with a crush in the dorsal funiculi of the C4 segment of the spinal cord are treated with chondroitinase ABC delivered to the lateral ventricle. Treatment is started at the time of injury or after a 2, 4 or 7 days delay. Behavioural testing over 6 weeks shows that acutely treated animals show improve skilled forelimb reaching compared to controls. Chondroitinase-treated animals show greater axon regeneration than controls. The treatment effect on contact placing, stride length and axon regeneration is not dependent on the timing of the start of treatment, but in skilled paw reaching acutely treated animals recover better function 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine topical injection of chondroitinase ABC after 15-mm tibial nerve resection can significantly increase the critical length of nerve gap repair by tubulization or artificial nerve placement 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine development of thermostabilized chondroitinase ABC and a system for its sustained local delivery in vivo, obviating the need for chronically implanted catheters and pumps. Presence of with 1M trehalose significantly enhances chondroitinase ABC thermal stability and prolongs enzyme activity. Thermostabilized chondroitinase ABC remains active at 37°C in vitro for up to 4 weeks. Chondroitin sulfate proteoglycan levels remain low in vivo up to 6 weeks post-spinal cord injury when thermostabilized chondroitin sulfate proteoglycan ABC is delivered by a hydrogel-microtube scaffold system. Axonal growth and functional recovery following the sustained local release of thermostabilized chondroitinase ABC versus a single treatment of unstabilized chondroitinase ABC demonstrate significant differences in chondroitin sulfate proteoglycan digestion. Animals treated with thermostabilized chondroitinase ABC in combination with sustained neurotrophin-3 delivery show significant improvement in locomotor function and enhanced growth of cholera toxin B subunit-positive sensory axons and sprouting of serotonergic fibers 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine intraspinal delivery of chondroitinase ABC, following T10 hemisections in adult cats, enhances adaptive movement features during a skilled locomotor task and/or promotes plasticity of spinal and supraspinal circuitry. Chondroitinase ABC enhances crossing of a peg walkway post-spinal cord injury and significantly improves ipsilateral hindlimb trajectories and integration into a functional forelimb-hindlimb coordination pattern. Recovery of these complex movements is associated with significant increases in neurofilament immunoreactivity immediately below the spinal cord injury in the ipsilateral white and contralateral gray matter. Significantly more retrogradely labeled right axotomized red nucleus neurons are seen in chondroitinase ABC-treated compared with control-treated cats indicating that a larger number of red nucleus neurons in chondroitinase ABC-treated cats had axons below the lesion level 4.2.2.20 chondroitin-sulfate-ABC endolyase medicine role of chondroitinase ABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion, and were subjected to continuous intra-infarct infusion of chondroitinase ABC for 7 days 24 h later. The intra-infarct infusion of chondroitinase ABC, by degrading accumulated chondroitin sulfate proteoglycans, rescues neuronal loss and increases the levels of growth-associated protein GAP-43 and synaptophysin in both the ipsilateral cortex and ventroposterior thalamic nucleus, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function 4.2.2.21 chondroitin-sulfate-ABC exolyase medicine sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Animals treated with thermostabilized chABC in combination with sustained neurotrophin-3 delivery show significant improvement in locomotor function and enhanced growth of cholera toxin B subunit-positive sensory axons and sprouting of serotonergic fibers 4.2.2.21 chondroitin-sulfate-ABC exolyase medicine the combination of cell transplantation with ChABC may be a potent therapeutic strategy for spinal cord injury 4.2.2.21 chondroitin-sulfate-ABC exolyase medicine preservation of ChABC activity during release by immobilizing ChABC in chitosan nerve conduits and encapsulating ChABC in poly(DL-lactic acid) microspheres using an appropriate stabilizer. Immobilizing ChABC in nerve conduitss markedly improves its stability. The activity of ChABC that is immobilized in chitosan nerve conduits by ionic bonding is 0.07 U/mg. 48% of this activity is retained at 48 h after immobilization. Poly(DL-lactic acid) microspheres, fabricated by the double emulsion method, are applied as carriers in the controlled release of ChABC. Stabilizers, including nanogold of 10 nm, polylysine of Mw 500-2000 and polylysine of Mw 20000-30000, are added to microspheres to maintain the activity of ChABC. Polylysine stabilizes ChABC most effectively. The ChABC activity is 0.0162 U/ml after seven days of release 4.2.3.1 threonine synthase medicine possibly involved in formation of bacteriocidal antimetabolites 4.2.3.1 threonine synthase medicine the necessity of homoserine and/or threonine biosynthetic genes encoding aspartate kinase (HOM3), homoserine kinase (THR1) and threonine synthase (THR4) for Cryptococcus neoformans growth, particularly at physiologically relevant temperatures, makes threonine biosynthetic genes ideal anti-cryptococcal drug targets 4.2.3.4 3-dehydroquinate synthase medicine the enzymes of the shikimate pathway are attractive drug targets for the treatment of tuberculosis 4.2.3.12 6-pyruvoyltetrahydropterin synthase medicine the decrease of this enzyme is the most frequent cause of atypical phenylketonuria 4.2.3.12 6-pyruvoyltetrahydropterin synthase medicine lack of tetrahydrobiopterin leads to hyperphenylalaninemia and a deficiency of biogenic amine neurotransmitters such as dopamine and serotonin and severe progressive mental retardation 4.2.3.17 taxadiene synthase medicine chemotherapeutic agent against a range of cancers, including ovarian and breast cancer 4.2.3.17 taxadiene synthase medicine taxanes can be used in cancer treatment 4.2.3.24 amorpha-4,11-diene synthase medicine amorpha-4,11-diene is a presursor of artemisinin, artemisinin and derivates are used for the treatment of malaria 4.2.3.134 5-phosphonooxy-L-lysine phospho-lyase medicine phosphohydroxylysinuria results from mutations in the AGXT2L2 gene, encoding phosphohydroxylysine phospholyase, and the resulting lack of activity o the enzyme. Mutants Gly240Arg and Glu437Val isolated from a patient are largely insoluble. The diversity of the clinical symptoms described in three patients with phosphohydroxylysinuria indicates that this is most likely not a neurometabolic disease 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine a decrease in APE1 levels in silencing RNA-treated osteogenic sarcoma cells leads to enhanced cell sensitization to the DNA damaging agents: methyl methanesulfonate, H2O2, ionizing radiation and chemotherapeutic agents 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine the APE-mediated decrease in expression of MSH6 protein results in a reduced cellular mismatch repair capacity as well as the increased generation of microsatellite instability. The potential role of APE to generate microsatellite instability may have clinically important implications for cancer susceptibility and carcinogenesis 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine after catalytically enzymatic activity or expression of APE is decreased, antiviral activity of APOBEC3G is partially inhibited in virus-producing cells 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine APE-1 exonuclease activity plays an important role in the removal of L-configuration nucleoside analogs from DNA inside the cell and can be a determining factor in the drug resistance of the analogs 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine APE-1/Ref-1 is an important regulator of gastric epithelial responses to Helicobacter pylori infections 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine Apn1 could be used as a possible treatment strategy for attenuating or slowing down the pathogenesis of neurodegenerative diseases 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine downregulation of APE1 is found to sensitize tumor cells to chemotherapy with induction of apoptosis 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine selective targeting of APE1/Ref-1 could enhance conventional cancer treatment such as radiotherapy 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine cancer therapy, inflammatory diseases 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine leading therapeutic target molecule for the oxidative stress condition or pathologic conditions such as cancer. Increased levels of APE1/Ref-1 in tumors have been associated greater resistance to chemotherapy and carry a poorer prognosis 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine levels of APE-1 expression in gastric and other cancer tissues may be used to determine chemosensitivity 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine strong candidate as a potential drug-treatable target for the prevention and treatment of human melanoma 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine APE1 is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine patients with tumors containing elevated cytoplasmic Ape1 have a poor prognosis and a 3.722fold risk of tumor recurrence and/or metastasis 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine pharmacological inhibition of APE1 by E3330 suppresses inflammatory response in activated macrophages 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase medicine comparison of mouse and human enzyme. Overall results suggest that human and mouse APE1s have mostly similar biochemical and biophysical properties. The conclusions of mouse studies to elucidate APE1 biology and its role in carcinogenesis may be extrapolated to apply to human biology 4.3.1.1 aspartate ammonia-lyase medicine involvement of enzyme in blood clotting and activation of plasminogen, overview 4.3.1.4 formimidoyltetrahydrofolate cyclodeaminase medicine assay to determine N-formimino-L-glutamate in urine, blood and other fluids for folic acid deficiency 4.3.1.4 formimidoyltetrahydrofolate cyclodeaminase medicine 23 out of 38 patients with type 2 autoimmune hepatitis are positive for antibodies against enzyme, epitopes are mainly in formiminotransferase region 4.3.1.4 formimidoyltetrahydrofolate cyclodeaminase medicine autoantibodies of type 2 autoimmune hepatitis patients are directed against the mature, high-molecular form of enzyme 4.3.1.15 Diaminopropionate ammonia-lyase medicine nonvirulent Salmonella typhimurium PU011 can be used for the production of the enzyme to detoxify the neurotoxin 3-oxalyl and 2,3-dioxalyl diaminopropionate 4.3.1.17 L-serine ammonia-lyase medicine loss of serine deaminase activity results in a hypercolonization phenotype, hypercolonization plays a role in urinary tract infections 4.3.1.18 D-Serine ammonia-lyase medicine loss of serine deaminase activity results in a hypercolonization phenotype, hypercolonization plays a role in urinary tract infections 4.3.1.18 D-Serine ammonia-lyase medicine the established enzymatic method could be used for the quantitative determination of D-serine in human urine 4.3.1.24 phenylalanine ammonia-lyase medicine use of enzyme for substitution treatment of human phenylketonuria. Identification of B and T cell epitopes on the enzyme protein and covering of the immunogenic regions 4.3.1.24 phenylalanine ammonia-lyase medicine use of enzyme in therapy of human phenylketonuria. Preparation of microcapsules containing emulsified enzyme. Emulsification of enzyme solution with water-saturated ether causes no loss in activity but results in loss of protein content in the aqueous phase due to specific loss of impurities in the protein sample. Emulsification of enzyme solution with ether/ethanol mixture results in a 50% decrase in activity. Hydroxypropyl-gamma-cyclodextrin and hydroxypropyl-beta-cyclodextrin protect against emulsion mediated loss in activity 4.3.1.24 phenylalanine ammonia-lyase medicine PAL activity is able to effect a reduction in phenylalanine levels and hence provide the basis of a unique therapy for human hyperphenylalaninemic patients 4.3.1.24 phenylalanine ammonia-lyase medicine the enzyme can be used as oral therapeutic, in an encapsulated form, in phenylketonuria/hyperphenylalaninemia 4.3.1.24 phenylalanine ammonia-lyase medicine enzyme substitution therapy for the treatment of phenylketonuria 4.3.1.24 phenylalanine ammonia-lyase medicine enzyme substitution therapy with the phenylalanine ammonia lyase is a new approach to the treatment of patients with phenylketonuria 4.3.1.24 phenylalanine ammonia-lyase medicine the enzyme can reduce the level of L-Phe in the blood and is a prospective drug for the treatment of phenylketonuria 4.3.1.24 phenylalanine ammonia-lyase medicine the shift of the pH-optimum from pH 8.5 for the wild-type enzyme to pH 7.5 with 30% higher specific activity than that of the wild-type enzyme, the prolonged half-life of the mutant enzyme at 70°C, the higher resistance to a low pH of 3.5 and protease make the mutant enzyme E75L a candidate for oral medicine of phenylketonuria 4.3.1.25 phenylalanine/tyrosine ammonia-lyase medicine enzyme substitution therapy for the treatment of phenylketonuria 4.3.2.1 argininosuccinate lyase medicine argininosuccinate lyase is present in activated microglia cells in the ischemic rat 4.3.2.1 argininosuccinate lyase medicine transient ischemia induces changes in the number and percentage of the nNOS+ neurons also expressing argininosuccinate lyase 4.3.2.1 argininosuccinate lyase medicine argininosuccinate lyase is a valuable marker for estimating hepatopathy 4.3.2.1 argininosuccinate lyase medicine expression of mutant ASL proteins in Escherichia coli. The known classical p.Q286R, the novel classical p.K315E and the known mutations p.I100T, p.E189G and p.R385C, which all have been linked to a mild phenotype of argininosuccinic aciduria, show no significant residual activity. There is some enzyme activity detected with the p.V178M (5% of wild-type), and p.R379C (10% of wild-type) mutations in which Km values for argininosuccinic acid differs significantly from the wild-type ASL protein 4.3.2.1 argininosuccinate lyase medicine loss of function of fumarate hydratase, the mitochondrial tumor suppressor and tricarboxylic acid cycle enzyme, is associated with a highly malignant form of papillary and collecting duct renal cell cancer The accumulation of fumarate leads to reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells from Fh1-deficient humans, making these cells auxotrophic for arginine, which opens a therapeutic perspective for the cure of hereditary leiomyomatosis and renal cell cancer 4.3.2.1 argininosuccinate lyase medicine manipulating the enzyme expression or activity might be of potential benefit for treatment of necrotizing enterocolitis 4.3.2.1 argininosuccinate lyase medicine the enzyme may serve as a target for manipulating NO production and treatment of NO-related diseases 4.3.2.1 argininosuccinate lyase medicine argininosuccinate lyase (ASL) is overexpressed in breast cancer and downregulation of argininosuccinate lyase decreases tumor growth by inhibiting cyclin A2 and NO. Administration of ASL shRNA may be a treatment to prevent cancer cell proliferation and induce cancer cell death 4.3.2.2 adenylosuccinate lyase medicine adenylosuccinate lyase deficiency causes serious neurological and physiological symptoms 4.3.2.2 adenylosuccinate lyase medicine generation of in vitro hybrids that mimic compound heterozygote ASL for studies on disease-associated mutant enzymes. His-tagged wild-type/non-His-tagged wild-type, His-tagged wild-type/non-His-tagged R396C, His-tagged wild-type/non-His-tagged R396H, His-tagged R194C/non-His-tagged R396C, and His-tagged L311V/non-His-tagged R396H enzyme pairs are used in various hybrids generated by denaturing pairs of enzymes in 1 M guanidinium chloride and renaturing them by removing the denaturant. The hybrids have predominant amounts of heterotetramers. Analysis of the Vmax values of the hybrids indicates that most of the subunits behave independently. However, the hybrid tetramers retain weak positive cooperativity 4.3.2.7 glutathione-specific gamma-glutamylcyclotransferase medicine higher levels of ChaC1 transcripts are present in all the tumorigenic cell lines examined 4.3.2.9 gamma-glutamylcyclotransferase medicine in patients with gastrointestinal fistula, levels of alkaline phosphatase and gamma-glutamylcyclotransferase increase significantly on the third day after beginning of enteral feeding and decrease gradually afterwards. The longer the total parenteral nutrition lasted, the more severe the enteral refeeding syndrome becomes. Early enteral nutrition is useful in preventing it 4.3.2.9 gamma-glutamylcyclotransferase medicine enzyme overexpression defines a subgroup of breast tumors with poor clinical outcome. The enzyme is a cancer biomarker and a serological marker 4.3.2.9 gamma-glutamylcyclotransferase medicine gamma-glutamylcyclotransferase is a target molecule for cancer diagnosis and treatment 4.3.2.9 gamma-glutamylcyclotransferase medicine GGCT silencing significantly suppresses proliferation of colorectal cancer cells and arrests cell cycle at the G0/G1 phase by regulating the expression of p21, p27, and cyclin E. GGCT silencing triggers the apoptosis of colorectal cancer cells by activating caspase-3 and cleaved poly-ADPribose polymerase pathways and downregulating the phosphorylation proline-rich Akt substrate of 40 kDa (PRAS40) expression levels. GGCT silencing combined with 5-fluorouracil treatment further induces the apoptotic rate of colorectal cancer cells 4.3.3.1 3-ketovalidoxylamine C-N-lyase medicine 3-ketovalidoxylamine C-N-lyase is one of three key enzymes in the production of valienamine, which is a potent glucosidase inhibitor from validamycin A. Increasing incidence of diabetes has focused attention on glucosidase inhibitors. 4.3.3.2 strictosidine synthase medicine anti-arrhythmic ajmaline agents 4.3.3.2 strictosidine synthase medicine anti-arrhythmic heart disorders, ajmaline agents 4.3.3.2 strictosidine synthase medicine anti-cancer and anti-hypertensive agents 4.3.3.2 strictosidine synthase medicine anti-cancer, anti-hypertensive, anti-malaria and anti-arrhythmic ajmaline agents 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase medicine development of species-specific inhibitors of DHDPS as potential antibacterials 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase medicine L-lysine, one of the essential amino acids required for nutritionin animals and humans, is widely used in the food industry, medical industry, etc. L-lysine has been mainly produced by microbial fermentation employing mutant strains of bacteria. An L-lysine high-yielding strain is developed by modification of aspartokinase III and dihydrodipicolinate synthetase 4.4.1.1 cystathionine gamma-lyase medicine enzyme participates in hydrogen sulfide production in the oral cavity 4.4.1.1 cystathionine gamma-lyase medicine molecular basis of cystathioninuria, MIM 219500, revealed by mutations of enzyme 4.4.1.1 cystathionine gamma-lyase medicine physiologic importance of increased expression and activity of enzyme during lactation 4.4.1.1 cystathionine gamma-lyase medicine high doses of pyridoxine could be an effective therapy for cystathioninuric patients harboring the T67I mutation and be somewhat less effective in ameliorating the symptoms associated with the Q240E mutation 4.4.1.1 cystathionine gamma-lyase medicine inhibition of CSE expression and reduction in formation of the pro-inflammatory component of H(2)S activity contributes to the anti-inflammatory effect of dexamethasone in endotoxic shock. Whether H(2)S plays a part in the anti-inflammatory effect of this steroid in other forms of inflammation such as arthritis or asthma warrants further study 4.4.1.1 cystathionine gamma-lyase medicine inhibition of hydrogen sulfide synthesis attenuates chemokine production and protects mice against acute pancreatitis and associated lung injury 4.4.1.1 cystathionine gamma-lyase medicine CSE is not associated with dextran sulfate sodium-induced colitis in mice 4.4.1.1 cystathionine gamma-lyase medicine chronical treatment of rats with CGL inhibitor (DL)-propargylglycine or cystathionine beta-synthase inhibitor aminooxyacetic acid or a combination of both. Only the rats with combination therapy show a decrease in urinary sulfate excretion rate, which is associated with an increase in mean arterial pressure. Urine flow and sodium excretion are also increased in combination group as consequent to the increase in mean arterial pressure. Glomerular filtration rate does not alter due to these treatments, renal blood flow is lowered only in the combination group compared to the control group 4.4.1.1 cystathionine gamma-lyase medicine cumulative administration of L-cysteine causes a dose-dependent decrease in the amplitude of spontaneous contractions in nonlabouring and labouring myometrium strips. L-cysteine at high concentration increases the frequency of spontaneous contractions and induces tonic contraction. These effects of L-cysteine are blocked by inhibitors of cystathionen beta-synthase and cystathionine gamma-lyase. Pretreatment of myometrium strips with glibenclamide, an inhibitor of ATP-sensitive potassium channels, abolishes the inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects of L-cysteine on the amplitude of spontaneous contractions and baseline muscle tone are less potent in labouring tissues than that in nonlabouring strips 4.4.1.1 cystathionine gamma-lyase medicine covalent binding of enzyme to polyethylene glycol moieties reduces the specific activity from 59.71 U/mg of free enzyme to 48.71 U/mg, with a PEGylation yield of 81.5 and 70.7% modification of surface epsilon-amino groups. The pH stability does not change upon modification, and at 50 ° C, the thermal stability of PEG-CGL is increased by 40% in comparison to free CGL. By in vitro proteolysis, PEG-CGL retains more than 50% of its initial activity compared to less than 10% of the free-CGL for acid protease for 30 min. The biochemical and hematological responses of rabbits indicate nil toxicity of free and PEG-CGL 4.4.1.1 cystathionine gamma-lyase medicine cystathionine-beta-synthase and cystathionine-gamma-lyase are expressed in the normal human colon. Expression is significantly decreased in the ganglionic and aganglionic bowel of patients with Hirschsprung Disease. Expression in smooth muscles, interstitial cells of Cajal, platelet-derived growth factor-alpha receptor-positive cells, enteric neurons and colonic epithelium is markedly decreased in Hirschsprung Disease specimens compared to controls 4.4.1.B1 holocytochrome-c1 synthase medicine microphthalmia with linear skin defects syndrome are associated with mutations-a missense mutation or a nonsense mutation in the HCCS gene, the inability of HCCS-deficient cells to undergo cytochrome c–mediated apoptosis may push cell death toward necrosis that gives rise to severe deterioration of the affected tissues 4.4.1.2 homocysteine desulfhydrase medicine the enzyme displays a strong affinity to homocysteine, followed by methionine and cysteine when compared with non-S amino acids, confirming its potency against homocysteinuria related diseases, and as an anti-cardiovascular agent and a specific biosensor for homocysteinuria 4.4.1.4 alliin lyase medicine no clinical trial should be conducted with a garlic powder supplement that is not standardized upon dissolution allicin release for an effect of garlic that may be related to allicin, as most are 4.4.1.4 alliin lyase medicine major allergen of garlic 4.4.1.4 alliin lyase medicine a chemical conjugate between daidzein and the enzyme alliinase specifically binds to ovarian cancer cells and upon addition of the prodrug alliin, effectively produces cytotoxic allicin molecules which kill the cancer cells. Tumors show a five fold higher uptake as compared to other tissues. Treatment of tumor bearing mice with daidzein-alliinase and alliin effectively attenuates tumor progression during the first 12 days while a 5-fold increase in bioluminescence is detected in placebo-treated animals. Autopsy revealed only small individual foci of luminescence at the site of tumor cells inoculation. Histological examination of organs and tissues did not reveal any additional foci of carcinoma or signs of toxicity 4.4.1.4 alliin lyase medicine Allium sativum is used as a food, spice, and traditional medicine for many centuries. It has also antibacterial, antioxidant, anticancer and cholesterol-lowering effects, many health benefits associated with garlic can be attributed to thiosulfinates, especially allicin (2-propenyl 2-propenethiosulfinate) generated by the enzyme 4.4.1.5 lactoylglutathione lyase medicine decrease of glyoxalase I expression with increasing Alzheimer’s disease stage might be one reason for methylglyoxal-induced neuronal impairment, apoptosis, and advanced glycation end formation in plaques and tangles 4.4.1.5 lactoylglutathione lyase medicine glyoxalase I is critical for pericyte survival under hyperglycemic conditions, its inactivation and/or down-regulation by NO donor may contribute to pericyte death by apoptosis during early stages of diabetic retinopathy 4.4.1.5 lactoylglutathione lyase medicine high degree of similarity between the trypanosomatid and bacterial GLO1 proteins, contrasting substrate specificities of human and trypanosomatid glyoxalase enzymes suggest that the glyoxalase system may be an attractive target for anti-trypanosomal chemotherapy 4.4.1.5 lactoylglutathione lyase medicine possible role of glyoxalase I in the chemoresistance displayed by kidney tumor, possible use of glyoxalase I inhibitors as anticancer drugs, increase in glyoxalase I lowers level of the potent apoptosis activator methylglyoxal 4.4.1.5 lactoylglutathione lyase medicine role in dental caries, LGL functions in the detoxification of methylglyoxal, resulting in increased aciduricity 4.4.1.5 lactoylglutathione lyase medicine upregulation of glyoxalase I in diabetes, this upregulation is inadequate to normalize methylglyoxal levels, which can lead to methylglyoxal retention and chemical modification of proteins 4.4.1.5 lactoylglutathione lyase medicine Glo-I is a molecular target for treatment of Bcr-Abl+ leukemias and, in particular, Abl TKI-resistant quiescent Bcr-Abl+ leukemic cells that have acquired stem-like characteristics in the process of adapting to a hypoxic environment 4.4.1.5 lactoylglutathione lyase medicine polymorphisms in glyoxalase 1 gene are not associated with the prevalence of hypertension, markers of atherosclerosis and advanced glycation endproducts and are weakly associated with pulse pressure and systolic blood pressure, impaired glucose metabolism and type 2 diabetes mellitus 4.4.1.5 lactoylglutathione lyase medicine flow cytometry method for GLO-1 detection in human leukocytes isolated from peripheral blood samples to investigate GLO-1 expression in leukocyte subsets from type 1 and 2 diabetes mellitus patients. Expression index of GLO-1-positive cells is slightly increased in mononuclear leukocytes from diabetic patients. This result correlates with the increase in GLO-1 activity in the whole blood samples of type 2 diabetes patients 4.4.1.5 lactoylglutathione lyase medicine treatment of HL-60 cells leads to significant accumulation of substrate methylglyoxal and the caspase 3 activity of the cell lysate increases. Compound shows anti-proliferative activity against HL-60 cells 4.4.1.11 methionine gamma-lyase medicine cancer therapy 4.4.1.11 methionine gamma-lyase medicine rMETase is an enzyme active in preclinical mouse models of human cancer 4.4.1.11 methionine gamma-lyase medicine PEG treated METase is a potential anticancer agent that can deplete L-methionine from plasma. DTT-treated PEG-METase can be produced on a large scale in sufficient quality for therapeutic use 4.4.1.11 methionine gamma-lyase medicine recombinant METase targets the elevated methionine dependence of tumor cells and arrests their growth as well as makes tumors more sensitive to standard chemotherapy agents. The combination of methoxypolyethylene glycol succinimidyl glutarate 5000 recombinant METase treatment with pyridoxal-5'-phosphate infusion suggests an effective clinical strategy for long-term methionine depletion to arrest cancer growth 4.4.1.11 methionine gamma-lyase medicine combined treatment of B16-F10 melanoma cells with selenomethionine and L-methionine gamma-lyase added to culture medium decreases expression of integrins alpha4, beta1, alphany and beta3 and inhibits melanoa-extracellular matrix adhesion. Caspase-mediated apoptosis is induced following loss of cell adherence 4.4.1.11 methionine gamma-lyase medicine wild-type p53-expressing LNCaP human prostate cancer cells are more sensitive to cotreatment with selenomethionine and methionine gamma-lyase than p53-null PC3 human prostate cancer cells. Selenomethionine and and methionine gamma-lyase co-treatment significantly increases levels of superoxide and apoptosis in LNCaP cells. Cotreatment selenomethionine and methionine gamma-lyase results in increased levels of phosphorylated p53, total p53, Bax, and p21Waf1 proteins. LNCaP cells treated with selenomethionine and methionine gamma-lyase also show p53 translocation to mitochondria, decreased mitochondrial membrane potential, cytochrome c release into the cytosol, and activation of caspase 9. The effects selenomethionine and methionine gamma-lyase are suppressed by pre-treatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference 4.4.1.11 methionine gamma-lyase medicine causes adverse reaction in treatment of amoebiasis with trifluormethionine by degradation 4.4.1.11 methionine gamma-lyase medicine enzyme therapy against various types of methionine-dependent tumors 4.4.1.11 methionine gamma-lyase medicine inhibitory effect of fusion protein on an ovaran cancer cell line, fusion protein produces a dose-dependent inhibition of the proliferation of pancreatic cancer cell lines 4.4.1.11 methionine gamma-lyase medicine utilization for the treatment of cancers 4.4.1.11 methionine gamma-lyase medicine the enzyme is of interest as an anticancer agent, since the growth of malignant cells of various origins (unlike the growth of normal cells) is accompanied by obligatory methionine utilization, and the enzyme is absent in mammalian cells. IC50 of MGL for several tumor cell cultures, overview 4.4.1.11 methionine gamma-lyase medicine encapsulation of enzyme in nanoporous wet silica gels to be delivered at the site of action. Gels exhibit spectroscopic properties very similar to methionine gamma lyase in solution, a higher stability with respect to the soluble enzyme and catalytic activity is 6fold lower than in solution 4.4.1.11 methionine gamma-lyase medicine mice plasma methionine decreases to undetectable level 10 min after methionine gamma lyase 1000 U/kg injection. The enzyme shows a pharmakokinetic half-life of 0.76 h 4.4.1.11 methionine gamma-lyase medicine mice plasma methionine decreases to undetectable level 10 min after methionine gamma lyase 1000 U/kg injection. The enzyme shows a pharmakokinetic half-life of 0.91 h 4.4.1.11 methionine gamma-lyase medicine mice plasma methionine decreases to undetectable level 10 min after methionine gamma lyase 1000 U/kg injection. The enzyme shows a pharmakokinetic half-life of 1.69 h 4.4.1.11 methionine gamma-lyase medicine mutant V358Y selectively inhibits cancer cell growth with a half-maximal inhibitory concentration almost 2fold lower than the wild type 4.4.1.11 methionine gamma-lyase medicine the enzyme significantly inhibits proliferation of leukemia cell lines and induces cellular apoptosis 4.4.1.13 cysteine-S-conjugate beta-lyase medicine considerable interindividual variability in enzyme catalyzed step of degradation of the anesthetic sevoflurane 4.4.1.13 cysteine-S-conjugate beta-lyase medicine renal toxicity of cisplatin is dependent on enzyme activity 4.4.1.13 cysteine-S-conjugate beta-lyase medicine the absence of the enzyme in higher organisms makes it an important target for the development of antibiotics and herbicides 4.4.1.13 cysteine-S-conjugate beta-lyase medicine possible beneficial or useful consequences of cysteine S-conjugate beta-lyase activity include targeting of prodrugs. They can unmask suitably designed prodrugs in target tumors/tissues. Other favorable beta-lyase reactions are associated with activation of S-cysteine conjugates derived from allium foods into reactive persulfide or sulfane sulfur progenitors. Allium-derived S-allylcysteinyl constituents are effective inhibitors of the cancer process. Thus the study of the biochemistry of allium-derived cysteine S-conjugates may lead to new avenues for cancer treatment 4.4.1.13 cysteine-S-conjugate beta-lyase medicine several cysteine S-conjugates that occur in extracts of garlic and other plants of the Allium family possess anti-oxidant properties and are promising anti-cancer agents 4.4.1.13 cysteine-S-conjugate beta-lyase medicine the enzyme is important for bacterial virulence and is therefor a potential target for antibacterial drug development 4.4.1.16 selenocysteine lyase medicine expression of selenocysteine lyase is higher in acute and lower in chronic glomerulonephritis, selenocysteine lyase is upregulated by IL1b in acute nephritis leading to the synthesis of selenoproteins, which act as oxygen radical scavengers and lead to the limitation and resolution of acute glomerular inflammation 4.4.1.17 Holocytochrome-c synthase medicine identification of mutations R217C and DELTA197-268 in female patients with microphthalmia with linear skin defects syndrome. In contrast to wild-type, mutant proteins are unable to complement a Saccharomyces cerevisiae mutant deficient in the yeast enzyme ortholog. Mutation results in disturbance of both oxidative phosphorylation and the balance between apoptosis and necrosis. Upon expression in CHO-K1 cells, mutant DELTA197-268 protein fails to be sorted to mitochondria 4.4.1.17 Holocytochrome-c synthase medicine patient with deletion of the HCCS gene, diagnosis of a microphthalmia with linaer skin defects syndrome. Patient showed bilateral microphthalmia with optic atrophy, a congenital cataract, linear vascular lesions on the cheeks, neck and nose, apparently small, cupped poorly formed ears, anteverted nares, small areolae, a prominent xiphoid, an apparently small phallus, and right cryptorchidism. He had a patent ductus arteriosus, a patent foramen ovale and severe pulmonary hypertension attributed to pulmonary hypoplasia. Head ultrasound showed bilateral ventriculomegaly and agenesis of the corpus callosum. He also had poor tone and diminished reflexes on neurological examination. Patient died at 4 days of age 4.4.1.20 leukotriene-C4 synthase medicine aspirin induced urticaria aggregates in families inheriting the LTC4S -444C allele 4.4.1.20 leukotriene-C4 synthase medicine damaged or inflamed bronchial epithelium may synthesize leukotrienes that contribute directly to bronchoconstriction and leucocytosis in airway inflammation, LTC4 synthase is constitutively expressed in primary bronchial epithelial cells and in the 16-HBE 14o-cell line 4.4.1.20 leukotriene-C4 synthase medicine sodium nitroprusside inhibits leukotriene C4 synthase activity and dwonregulates the protein expression of the enzyme 4.4.1.20 leukotriene-C4 synthase medicine (-1072)GNA and (-444)ANC promoter polymorphisms of LTC4 synthase influence risk of transient ischemic attack and ischemic stroke, but not risk of ischemic heart disease/coronary atherosclerosis, asthma, or chronic obstructive pulmonary disease in a Danish population. The (-1072)A allele has a frequency of 0.07 while the (-444)C allele has a frequency of 0.29. The (-1072)A and (-444)C alleles are on different haplotypes, thus one polymorphism cannot tag the other. Genetically altered leukotriene C4 synthase activity may play a role in thrombi formation rather than the development of atherosclerosis 4.4.1.20 leukotriene-C4 synthase medicine aspirin desensitization may provide effective therapy for aspirin-exacerbated respiratory disease, at least in part, through mitigation of STAT6 expression, thereby downregulating LTC4S pathways 4.4.1.20 leukotriene-C4 synthase medicine the C allele of the A-444C polymorphism is a risk factor for aspirin-induced urticaria in a Venezuelan population and may be a genetic marker for this phenotype. This single-nucleotide polymorphism is mainly associated with the cutaneous clinical pattern and with low skin response to histamine 4.4.1.20 leukotriene-C4 synthase medicine mRNA levels for the three key enzymes/proteins in the biosynthesis of cysteinyl-leukotrienes, 5-lipoxygenase, 5-LO-activating protein, and LTC4 synthase, are significantly increased in the wall of human abdominal aortic aneurysm. Immunohistochemical staining reveals focal expression of 5-lipoxygenase, 5-LO-activating protein, and LTC4 synthase proteins in the media and adventitia, localized in areas rich in inflammatory cells, including macrophages, neutrophils, and mast cells. Challenge of abdominal aortic aneurysm wall tissue with exogenous LTD4 increases the release of matrix metalloproteinases 2 and 9, and selective inhibition of the CysLT1 receptor by montelukast blocks this effect 4.4.1.20 leukotriene-C4 synthase medicine resequencing the gene coding for leukotriene C4 synthase in an population with extreme risk of venous thromboembolism, ischemic stroke and myocardial infarction, among more than 1500 individuals, reveals 17 unknown mutations, of which four are likely to change protein function, i.e. 211G>A, with minor allele frequency, IVS3 + 1G>A, 374G>A and 451_453+10del. Age and sex adjusted odds ratios for venous thromboembolism are 2.0 for IVS3+1G>A heterozygotes versus wild-type, and 1.9 for any mutation heterozygote versus wild-type. Corresponding values are 2.0 and 1.5 for ischemic stroke, and 1.0 and 1.2 for myocardial infarction 4.4.1.21 S-ribosylhomocysteine lyase medicine autoinducer-2 promotes interspecies signaling, the autoinducer-3 activates enterohemorrhagic Escherichia coli virulence genes, knocking out luxS in the enterohemorrhagic human pathogen Escherichia coli reveals a defect in AI-3 production, but not in AI-2 production 4.6.1.1 adenylate cyclase medicine induction of cardiac myocyte apoptosis by high beta-adrenergic receptor stimulation is effectively prevented by type 5 adenylyl cyclase inhibitors. Inhibition of adrenergic signaling at the level of the type 5 adenylyl cyclase isoform by P-site inhibitors may serve as an effective method to prevent cardiac myocyte apoptosis induced by excessive adrenergic stimulation without deleterious effect on cardiac myocyte contraction 4.6.1.1 adenylate cyclase medicine A2bR mediates signaling through AC-6 isoform, therapeutic implications for intestinal inflammation or diarrhea wherein A2bR is upregulated 4.6.1.1 adenylate cyclase medicine AC1 and AC8 involved in long-term memory and in N-methyl-D-aspartate-dependent long-term potentiation, AC1 and AC8 are not required for acute pain response. AC1 is the major Ca2+ sensor for N-methyl-D-aspartate receptor activation and excitotoxicity 4.6.1.1 adenylate cyclase medicine AC5 is the major AC isoform mediating acute beta-adrenergic stimulation, AC5 plays a major role in L-type Ca2+ currents activation 4.6.1.1 adenylate cyclase medicine AC6 improves function in Galphaq-hypertrophic pigs 4.6.1.1 adenylate cyclase medicine AC6, but not AC5, mRNA is decreased in rats with cardiac hypertrophy after myocardial infarction, overexpression of AC6 in cardiac fibroblasts impairs collagen synthesis in response to serum or other activators 4.6.1.1 adenylate cyclase medicine cumulus cells possess multiple active isoforms of adenylyl cyclase, each isoform may have a specific role at a specific time during oocyte growth and maturation 4.6.1.1 adenylate cyclase medicine involved in mediating opioid actions, AC5 is essential for micro, and to a lesser extent, delta, opioid receptor signaling in striatum 4.6.1.1 adenylate cyclase medicine overexpression of AC6 or drug-stimulated cAMP accumulation in WI-38 lung fibroblast attenuates fibrosis 4.6.1.1 adenylate cyclase medicine overexpression of AC6 prevents development of cardiac hypertrophy, restores normal cardiac function, improves mortality rate, and contractile function. Overexpression of AC5 also restores cAMP signaling and contractile deficits, but cardiac hypertrophy still develops. Decreased AC5 expression does not diminish cardiac funcition, may be beneficial in mice experiencing artificial pressure overload 4.6.1.1 adenylate cyclase medicine sAC and the vacuolar proton pumping ATPase have a close association, may be part of a protein complex that is involved in regulating renal distal proton secretion 4.6.1.1 adenylate cyclase medicine sAC plays a critical role in cAMP signaling in spermatozoa, defective cAMP production prevents engagement of multiple components of capacitation resulting in male infertility. sAC and cAMP coordinate cellular energy balance in wild-type sperm. sAC appears to be a promising target for the development of male contraceptives 4.6.1.1 adenylate cyclase medicine inhibition of adenylyl cyclase type 5 is a strategy to treat heart failure 4.6.1.1 adenylate cyclase medicine isoform ACbeta represents a potential target for development of safe and effective antimalarial therapeutics 4.6.1.1 adenylate cyclase medicine isoform Adcy1 catalytic activity can be delicately adjusted by mediating calmodulin activation of Adcy1 by reversible Met oxidation in calmodulin 4.6.1.2 guanylate cyclase medicine antiproliferative mechanisms induced by GCC ligands and exisulind negatively interact in colon cancer cells 4.6.1.2 guanylate cyclase medicine crosstalk occurs between the NO-sGC and atrial natriuretic peptide-pGC pathways to regulate cGMP-dependent vasodilatation in vivo 4.6.1.2 guanylate cyclase medicine different roles of the natriuretic peptide and NO systems. In acute heart failure, the natriuretic peptide system plays a role in maintaining sodium excretion and glomerular filtration rate, while the function of the NO system is in the maintenance of renal blood flow. These two cGMP activating systems function through two distinct GC enzymes, playing a key role in maintaining renal function in acute heart failure 4.6.1.2 guanylate cyclase medicine guanylyl cyclase activity is related to intracellular Ca2+ mobilization and this Ca2+-cGMP cross-talk may in turn be associated with parasite infectivity 4.6.1.2 guanylate cyclase medicine limited species differences in sGC subunit distribution of primates and rodents. NO-cGMP signaling pathway may be involved in important brain functions such as memory formation, sensory processing, and behavior 4.6.1.2 guanylate cyclase medicine NO-sGC pathway in the subnucleus caudalis is involved in mediating orofacial muscle hypersensitivity under acute inflammatory condition 4.6.1.2 guanylate cyclase medicine sensitivity of guanylyl cyclase heme nitrosylation as well as oxygen-dependent NO consumption may be particularly adapted to direct itinerant endothelial cells into hypoxic tissues in the setting of inflammation, wound healing, and cancer 4.6.1.2 guanylate cyclase medicine targeting soluble guanylate cyclase with BAY 41-2272 may represent a therapy in the management of voiding disturbances associated with impaired NO-cGMP signaling 4.6.1.2 guanylate cyclase medicine the enzyme stimulation, e.g. by riociguat, is a strategy in treatment of pulmonary hypertension, moderate-to-severe phenotype, associated with impaired production of the vasodilator nitric oxide, study of safety, tolerability and efficacy in patients 4.6.1.2 guanylate cyclase medicine inhibition of sGC is an approach to restore hypoxic pulmonary vasoconstriction during endotoxemia 4.6.1.2 guanylate cyclase medicine in red blood cells, an intact soluble guanylate cyclaseC/PDE5/PKG-dependent signaling pathway exists, which remains fully responsive to NO and guanylate cyclase stimulators/activators in patients with endothelial dysfunction 4.6.1.12 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase medicine the enzyme is a potential target for antimalarial drugs directed at the nonmevalonate pathway of isoprenoid biosynthesis 4.6.1.13 phosphatidylinositol diacylglycerol-lyase medicine PI-PLC is a virulence factor of the animal and human pathogen causing listeriosis 4.6.1.14 glycosylphosphatidylinositol diacylglycerol-lyase medicine the relegation of short stumpy surface GPI-PLC to a secondary role in differentiation suggests that it may play a more important role as a virulence factor within the mammalian host 4.6.1.14 glycosylphosphatidylinositol diacylglycerol-lyase medicine importance of repeated cell divisions in controlling the steady-state amount of GPI-PLCp during differentiation of the African trypanosome 4.6.1.14 glycosylphosphatidylinositol diacylglycerol-lyase medicine GDE3 overexpression depletes urokinase receptor uPAR from distinct basolateral membrane domains in breast cancer cells, resulting in a less transformed phenotype, it slows tumor growth in a xenograft model and correlates with prolonged survival in patients 4.6.1.18 pancreatic ribonuclease medicine cross-linking of enzyme or its covalently linked dimer to polyspermine using dimethyl suberimidate. The in vitro and in vivo cytotoxic activity of treated monomeric enzyme is not higher than that of free polyspermine, but dimeric suberimidate-treated enzyme proves to be a more efficinet antitumor agent both in vitro and in vivo 4.6.1.18 pancreatic ribonuclease medicine RNase 1 from human healthy pancreas contains only neutral glycans, whereas RNase 1 from pancreas cancer cell lines contains sialylated structures. In serum from patients with pancreatic cancer, there is an increase of 40% in core fucosylation in the main sialylated biantennary glycans of RNase 1 4.6.1.18 pancreatic ribonuclease medicine the chemical conjugation of polyethylene glycol to the RNase A C-dimer, and to two trimers, decreases the aspermatogenic activity of the oligomers while increasing their inhibitory activity on the growth of human UB900518 amelanotic melanoma transplanted in athymic nude mice. The conjugated RNase A oligomers are devoid of any embryotoxic activity 4.6.1.18 pancreatic ribonuclease medicine use of gene duplication to generate tandem enzymes covalently bound by peptide linker. Tandemization has minor effects on the activity and stability in comparison to monomeric RNase A. Relative activity decreases by 10-50%, and melting temperature decreases by less than 2.5 K. Tandemization results in remarkable cytotoxicity, decreasing the IC50 values with K-562 cells to 0.070-0.013 mM 4.6.1.18 pancreatic ribonuclease medicine ribonuclease PE5 is a promising agent for use in anticancer therapy 4.6.1.19 ribonuclease T2 medicine it will be important, for proving advantageous in vaccines, to determine whether mutations in the RNA structure associated with the inhibition of RNAse L attenuate polyviruses or other group C enteroviruses in vivo 4.6.1.23 ribotoxin medicine alpha-sarcin inhibits growth of tumors by inhibition of protein synthesis, protein induces apoptosis in tumor cells after internalization via endocytosis, alpha-sarcin is cytotoxic for normal human cells and for many tumor cell lines, particulary sarcoma and carcinoma, it shows a selective, high level of toxicity against cells with altered or damaged cell membranes, it is a promising candidate for the treatment of cancer and viral infections such as AIDS 4.6.1.23 ribotoxin medicine the recombinant fusion enzyme scFvA33alphasarcin shows high specific toxicity against GPA33-positive tumoral cell lines providing scientific evidence to sustain that scFvA33alphasarcin is a good immunotherapeutic candidate against GPA33-positive colon carcinomas 4.6.1.23 ribotoxin medicine attachment of alpha-sarcin to a monoclonal mouse IgG2 antibody Fib75 to synthesize an immunotoxin. The alpha-sarcin immunotoxin exerts toxic effects in tissue culture against the EJ human bladder carcinoma cell line, expressing the antigen recognised by the Fib75 antibody, inhibiting the incorporation of [3H]leucine by 50% at a concentration of 0.46 nM. The cytotoxic effects of the alpha-sarcin immunotoxin are indistinguishable from those of a Fib75 immunotoxin made with ricin A chain. Fib75-alpha-sarcin is cleared from the circulation of the rat with biphasic kinetics following intravenous administration. The alpha- and beta-phase half-lives are 0.8 h and 6 h, respectively, similar to the serum half-lives of analogous Fib75 immunotoxins made with ribosome-inactivating proteins derived from plants 4.6.1.23 ribotoxin medicine enzyme displays cytotoxity against tumour cells. The ribotoxin dose, able to inhibit by 50% the mitochondrial redox activity of C6 glial cells, is equal to 4.58 microg/ml (0.316 microM). A ribotoxin dose of 8.41 microg/ml inhibits by 50% human SK-N-BE(2)-C neuroblastoma cells and of 9.46 microg/ml U-251 glioma cells 4.6.1.24 ribonuclease T1 medicine RNase inhibitors appear to be promising for therapy of cancer 4.98.1.1 protoporphyrin ferrochelatase medicine enzyme is essential for multiplication and intracellular survival as well as for the establishment of chronic disease 4.98.1.1 protoporphyrin ferrochelatase medicine enzyme is not essential for bloodstream survival or nasopharyngeal colonization 4.98.1.1 protoporphyrin ferrochelatase medicine involvement in erythropoietic protoporphyria, overview 4.98.1.1 protoporphyrin ferrochelatase medicine involvement of enzymic defects with erythropoietic protoporphyria, overview 4.98.1.1 protoporphyrin ferrochelatase medicine natural mutant with premature stop codon provides a model for erythropoietic protoporphyria 4.98.1.1 protoporphyrin ferrochelatase medicine role in erythropoietic protoporphyria, deficiency of ferrochelatase 4.98.1.1 protoporphyrin ferrochelatase medicine photodynamic therapy (PDT) for tumors is based on the tumor-selective accumulation of a photosensitizer, protoporphyrin IX (PpIX), followed by irradiation with visible light, PpIX accumulation in 5-aminolevulinic acid, treated U937 cells is increased by the inhibition of ferrochelatase 4.98.1.1 protoporphyrin ferrochelatase medicine siRNA-mediated knockdown of ferrochelatase suppresses heme synthesis and significantly increases intracellular protoporphyrin IX (PpIX) accumulation, this improves the phototoxicity of 5-aminolevulinic acid-based photodynamic therapy in urothelial cancer cell lines 4.98.1.1 protoporphyrin ferrochelatase medicine in bladder cancer cells, the expression of ferrochelatase shows a significant negative correlation with protoporphyrin IX accumulation in vitro. The expression of peptide transporter 1, heme oxygenase-1, and ferrochelatase in resected bladder specimens is correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. The expression of ferrochelatase is a significant factor to predict positive 5-aminolevulinic acid-induced fluorescent cytology 4.99.1.8 heme ligase medicine HDP is a conserved target for future antimalarial development 4.99.1.8 heme ligase medicine involvement of heme detoxification protein in the process of formation of hemozoin suggests that it could be a malaria drug target 5.1.1.1 alanine racemase medicine the requirement for D-Ala as a necessary component of the bacterial cell wall makes the enzyme a logical target for the development of novel antibiotics 5.1.1.1 alanine racemase medicine drug target against Mycobacterium tuberculosis 5.1.1.1 alanine racemase medicine since it is absent in humans, this enzyme is an attractive target for the development of drugs against Streptococcus pneumoniae and other bacterial pathogens 5.1.1.1 alanine racemase medicine Alr might be a potential target for the prevention and treatment of caries 5.1.1.3 glutamate racemase medicine the enzyme may be a viable target for developing new antibacterial agents 5.1.1.3 glutamate racemase medicine MurI is a potentialtarget for controlling dental caries 5.1.1.4 proline racemase medicine potential of the enzyme as a critical target for drug development against Chagas‘ disease. The enzyme is absent in mammalian host, suggesting that inhibition of proline racemase may have therapeutic potential 5.1.1.4 proline racemase medicine potential of the enzyme as a critical target for drug development against Chaga‘s disease. The enzyme is absent in mammalian host, suggesting that inhibition of proline racemase may have therapeutic potential 5.1.1.4 proline racemase medicine proline racemase based PCR can be used, preferably in combination with ITS-1 PCR, as a speciesspecific diagnostic test for Trypanosoma vivax infections worldwide 5.1.1.8 4-hydroxyproline epimerase medicine PrpA can be used as a protein adjuvant in a live Salmonella delivery system, in order to increase humoral responses effectively without major interference on the cell mediated immunity 5.1.1.17 isopenicillin-N epimerase medicine the conversion of isopenicillin N into penicillin N is part of the cephalosporin biosynthesis pathway. Cephalosporin is one of the most potent beta-lactam antibiotics, widely used in the treatment of infectious diseases 5.1.1.18 serine racemase medicine elevated levels of enzyme mRNA in Alzheimer´s disease hippocampus 5.1.1.18 serine racemase medicine serine racemase is the major enzyme for D-serine production in the brain, D-serine is the predominant endogenous coagonist of the NMDA receptor in the forebrain, and D-serine may be involved in controlling the extent of NMDA receptor-mediated neurotoxic insults observed in disorders including Alzheimer's disease. 5.1.1.18 serine racemase medicine targeted disruption of serine racemase results in profoundly altered glutamatergic neurotransmission and subtle but significant behavioral abnormailites that reflect hyperactivity and impaired spatial memory, and that are consistent with elevated anxiety 5.1.3.2 UDP-glucose 4-epimerase medicine drug design 5.1.3.2 UDP-glucose 4-epimerase medicine Galactosylation of one or more glycoprotein(s), most likely in the endosomal/lysosomal system, is essential for the survival of bloodstream form Trypanosoma brucei. GalE-encoded epimerase and the downstream UDP-Gal transporters and UDP-Gal-dependent glycosyltransferases may be exploitable as drug targets. 5.1.3.2 UDP-glucose 4-epimerase medicine The absence of CaGAL10 alone does not significantly reduce virulence in mouse model studies, but since it leads to increased drug sensitivity, it can be explored as a potential drug target in combination with other candidacidal drugs. Thus the UDP-galactose-4-epimerase plays an important role in the biology of the human pathogen, Candida albicans, like in the case of several other pathogens. 5.1.3.2 UDP-glucose 4-epimerase medicine Trypanosoma brucei GalE is a validated drug target for African sleeping sickness. The Trypanosoma brucei enzyme can be selectively inhibited by small molecules that are not substrate analogues in vitro, although the mechanism of cytotoxicity of these inhibitors is unconfirmed. Of the compounds screened, ethacrynic acid displays the best therapeutic index, but is clinically used as a loop diuretic and was found to form multiple covalent adducts with TbGalE in vitro, limiting its potential as a lead compound. 5.1.3.2 UDP-glucose 4-epimerase medicine SjGALE is a potential vaccine against Schistosoma japonicum 5.1.3.7 UDP-N-acetylglucosamine 4-epimerase medicine mutant deficient for gne shows increased surface hydrophobicity, produces deep alterations in the outer membrane architecture, and displays noticeable increases in the sensitivity to microcidal peptides, to eel and human sera, and to phagocytosis/opsonophagocytosis. Significant attenuation of virulence for eels and mice is observed with the mutant, which is correlated with the loss of the O-antigen lipopolysaccharide, while the capsule is maintained 5.1.3.B12 Agrobacterium tumefaciens D-psicose 3-epimerase medicine D-psicose (D-ribo-2-hexulose or D-allulose), a C3 epimer of D-fructose and considered as a rare sugar. It is regarded as a low calorie sweetener, an inhibitor of hepatic lipogenic enzymes, an activator of abdominal lipolysis and intestinal alpha-glycosidase enzymes D-psicose reduces the hyperglycemia, obesity, and hyperlipidemia and decrease the blood glucose level in type-2 diabetes 5.1.3.13 dTDP-4-dehydrorhamnose 3,5-epimerase medicine validated anti-bacterial drug target 5.1.3.14 UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing) medicine UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase interacts with the non-muscle form of alpha-actinin, alpha-actinin-1, in mature skeletal muscle cells. No significant difference in the binding of alpha-actinin-1 with either wild-type or mutant enzyme, and therefore no conclusions wether and how the interaction is relevant to the muscle-restricted pathology of hereditary inclusion body myopathy 5.1.3.17 heparosan-N-sulfate-glucuronate 5-epimerase medicine in 82-84% of human breast tumors there is either downregulation or loss of D-glucuronyl C5-epimerase mRNA expression and significant decrease of the protein content. In 77% of cases, GLCE expression is decreased also in the normal-appearing tissue surrounding the tumor node but the protein amount is comparable to normal breast tissue 5.1.3.17 heparosan-N-sulfate-glucuronate 5-epimerase medicine the anti-tumour effects associated with ectopic GLCE re-expression suggest that it may be a potential tumour-suppressor gene and a possible target for lung cancer diagnosis and treatment 5.1.3.17 heparosan-N-sulfate-glucuronate 5-epimerase medicine the enzyme is a candidate molecular marker for advanced prostate cancer 5.1.99.1 methylmalonyl-CoA epimerase medicine as model to study human methylmalonic aciduria, deletion of the mce gene results in a 80% decreased incorporation of propionate into macromolecules and induces an accumulation of methylmalonic acid 5.1.99.1 methylmalonyl-CoA epimerase medicine point mutation in the methylmalonyl-CoA 2-epimerase gene (C139T) and an insertion polymorphism 41-160-161insT causes methylmalonic aciduria in patients, inhibition of the enzyme by siRNAs in HeLa cells reduces the synthesis of macromolecules 5.1.99.1 methylmalonyl-CoA epimerase medicine point mutation in the methylmalonyl-CoA 2-epimerase gene (C139T) results in an early termination signal and causes methylmalonic aciduria in a patient 5.1.99.4 alpha-methylacyl-CoA racemase medicine the activity of EC 5.1.99.4 may prove to be a valuable parameter for the prenatal diagnosis of general defects of peroxisome biogenesis such as Zellweger syndrome 5.1.99.4 alpha-methylacyl-CoA racemase medicine prognostic indicator in upper urinary tract urothelial cancer 5.1.99.4 alpha-methylacyl-CoA racemase medicine the enzyme potentially can be used as an intermediate endpoint in chemoprevention trials or as a risk stratification tool among patients with negative prostatic biopsies. increased enzyme expression might be a characteristic of high-risk normal tissue 5.1.99.4 alpha-methylacyl-CoA racemase medicine in patients with early Barrett's adenocarcinoma treated with surgery, 91% of cases with low-grade dysplasia show immunoreactivity for alpha-methylacyl-CoA racemase, and 96% of case with high-grade dysplasia and early Barrett's adenocarcinoma are positive for alpha-methylacyl-CoA racemase 5.1.99.4 alpha-methylacyl-CoA racemase medicine in patients with gastric intestinal-type adenocarcinoma and its precursors, staining for alpha-methylacyl-CoA racemase is uniformly negative in samples negative for dysplasia and indefinite for dysplasia. In the groups of high-grade dysplasia and invasive intestinal-type adenocarcinoma, 76% and 34% of samples are positive for alpha-methylacyl-CoA racemase, respectively. Expression of alpha-methylacyl-CoA racemase is not correlated with location, Helicobacter pylori infection, or intestinal metaplasia 5.1.99.4 alpha-methylacyl-CoA racemase medicine in patients with noninvasive bladder cancer, there is a significant positive correlation between alpha-methylacyl-CoA racemase expression and higher tumor grades according to both the the 1973 World Health Organization and the 1998 WHO/International Society of Urological Pathology system 5.1.99.4 alpha-methylacyl-CoA racemase medicine alpha-methylacyl-coenzyme A racemase is a biomarker for prostate cancer and a putative target for the development of therapeutic agents directed against the disease, inhibition of enzyme activity may also act synergistically with androgen ablation therapy 5.1.99.4 alpha-methylacyl-CoA racemase medicine AMACR is a prognostic factor in prostate and colorectal cancer, AMACR expression is significantly associated with poor overall survival 5.1.99.4 alpha-methylacyl-CoA racemase medicine AMACR is used as a diagnostic biomarker for prostate cancer and is a standard biomarker for needle biopsy specimens with ambiguous lesions 5.1.99.4 alpha-methylacyl-CoA racemase medicine reduction of AMACR activity is proposed as a treatment for prostate and other cancers 5.1.99.4 alpha-methylacyl-CoA racemase medicine AMACR is expressed in prostate cancer cell lines but is absent in normal and non-tumour prostate epithelial cell lines. Presence of trifluoroibuprofen induces down-modulation of AMACR expression, suppression of the survival Akt/mTOR signalling pathway and down-modulation of cyclin D1 and survivin with G2/M arrest and apoptosis. Oral administration is associated with acute toxicity at doses >75 mg/Kg/day 5.1.99.4 alpha-methylacyl-CoA racemase medicine immunohistochemistry of cyclin-dependent kinase inhibitor 2A, AMACR, cyclin D1, and E-cadherin show no exclusive staining for nevi or melanomas. A significant overexpression of AMACR is found in malignant melanomas compared to benign nevi and is associated with an increased cyclin-dependent kinase inhibitor 2A staining 5.1.99.4 alpha-methylacyl-CoA racemase medicine The expression of AMACR is an independent factor for the survival of patients with hepatocellular carcinoma. The median survival time is 17 months in the low expression group compared with 45 months in the high expression group 5.1.99.6 NAD(P)H-hydrate epimerase medicine pathogenic biallelic mutations in NAXE in children from four families lead to (sub-)acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate is elevated in cerebrospinal fluid of all affected individuals. Disease onset is during the second year of life and clinical signs as well as episodes of deterioration are triggered by febrile infections. Disease course is rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels are undetectable in fibroblasts from affected individuals of two families. These fibroblasts show highly elevated concentrations of the toxic metabolite cyclic-NADHX 5.2.1.2 maleylacetoacetate isomerase medicine cis and/or trans isomers of 2,4-dioxohept-2-enoic acid might be diagnostic for human deficiency of maleylacetoacetate isomerase 5.2.1.2 maleylacetoacetate isomerase medicine dichloroacetate, a degradation product of chloral hydrate, is further metabolized by glutathione transferase zeta 1, and inhibits its own metabolism through depletion/inactivation of GSTZ1/MAAI with repeated exposure, resulting in lower plasma clearance of the drug and the accumulation of the urinary biomarker maleylacetone. The amount of dichloroacetate produced from clinically relevant doses of chloral hydrate, although insufficient to alter dichloroacetate kinetics, is sufficient to inhibit MAAI and tyrosine catabolism 5.2.1.4 maleylpyruvate isomerase medicine mycothiol as target for clinical treatment 5.2.1.8 peptidylprolyl isomerase medicine Pin1 inhibitors can be used as a novel type of anticancer drug that acts by blocking cell cycle progression 5.2.1.8 peptidylprolyl isomerase medicine cyclophilin B is critical for the efficient replication of the hepatitis C virus genome. enzyme interacts with the viral RNA polymerase NS5B to directly stimulate its RNA binding activity 5.2.1.8 peptidylprolyl isomerase medicine enzyme isoform PPIL1 is frequently overexpressed in colon cancer cells. Wild-type PPIL1 shows a growth-promoting effect on NIH-3T3 and HEK-293 cells. Consistently, transfection with its siRNA reduces gene expression and retards growth of colon cancer cells. Enzyme interacts with SNW1/SKI-binding protein and with stathmin 5.2.1.8 peptidylprolyl isomerase medicine isoform CypA is necessary for the prolactin-induced activation of Janus-activated kinase 2 and the progression of human breast cancer. Direct correlation between the levels of activity of CypA and the extent of prolactin-induced signaling and gene expression. A CypA-mediated conformational change withi the prolactin r/Janus-activated kinase 2 complex is required for prolactin-induced transduction and function 5.2.1.8 peptidylprolyl isomerase medicine isoform Pin1 is a critical regulator of p27kip1 through inhibition of Forkhead box O, FOXO4. Oxidative stress induces binding of Pin1 to FOXO4 thereby attenuating its monoubiquitination. Pin1 prevents nuclear FOXO4 accumulation and acts on FOXO through stimulation of the activity of the deubiquitinating enzyme HAUSP/USP7 5.2.1.8 peptidylprolyl isomerase medicine Pin1 overexpression increases the reporter activities in cells transfected with reporters containing the vascular endothelial growth factor VEGF gene promoter or with minimal reporters of activator protein-1 and hypoxia response element. VEGF reporter gene activity is significantly inhibited by either hypoxia-inducible factor-alpha siRNA or AP-1 decoy ODN. Pin1 stimulates VEGF expression by activating HIF-1alpha and AP-1, and is a potential therapeutic target of angiogenesis during cancer development 5.2.1.8 peptidylprolyl isomerase medicine Pin1 is a target molecule for treating diabetes mellitus 5.2.1.8 peptidylprolyl isomerase medicine CYPJ expression is upregulated in over 60% hepatocellular carcinoma tissues. CYPJ is found in the whole cell of hepatocellular carcinoma tissues with preferential location at the cell nucleus 5.2.1.8 peptidylprolyl isomerase medicine PIN1 inhibition dramatically reduces the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of hypoxia-inducible factor HIF-1alpha 5.3.1.1 triose-phosphate isomerase medicine triosephosphate isomerase is a promising antischistosome vaccine antigen 5.3.1.1 triose-phosphate isomerase medicine 67% of 39 patients suffering from adverse reactions to lychee show allergic reactions resp. IgE binding of their sera to enzyme protein 5.3.1.1 triose-phosphate isomerase medicine analysis of key aspects of triosephosphate isomerase deficiency glycolytic enzymopathy pathogenesis identified using the TPIsugarkill mutation M80T, a Drosophila model of the human disease deficiency. Mutant protein is expressed, capable of forming a homodimer, and is functional. However, the mutant protein is degraded by the 20S proteasome core leading to loss-of-function pathogenesis 5.3.1.1 triose-phosphate isomerase medicine evaluation of the ability of naive monocyte-derived dendritic cells to sensitize peripheral blood mononuclear cells to the Schistosoma vaccine candidate MAP4 using a priming in vitro assay. MAP4 is a multiple antigen peptide containing B- and T-cell epitopes derived from the enzyme triose phosphate isomerase. Cytokine production from activated MAP4 priming in vitro cells is predominantly Th1-like, consisting mainly of IFN-gamma. Naive donor dendritic cells, sensitized with MAP4, thus are able to prime and clonally expand MAP4-specific T cells towards a Th1-type response 5.3.1.1 triose-phosphate isomerase medicine in drug-resistant SGC7901 cells induced by vincristine sulfate, triosephosphate isomerase is downregulated.The sensitivity of TPI-SGC7901/VCR cells to adriamycin, vincristine, 5-fluorouracil and cis-dichlorodiamine platinum, as well as the accumulation and retention to adriamycin, are significantly increased when compared to their control cell lines 5.3.1.1 triose-phosphate isomerase medicine specific polymerase chain reaction protocols used to determine the prevalence of toxigenic Clostridium difficile in Vhembe, South Africa. The study confirms the usefulness of PCR methodologies in the detection of toxigenic Clostridium difficile and suggests that Clostridium difficile is responsible for a small, but underappreciated, proportion of diarrheal cases in the region 5.3.1.1 triose-phosphate isomerase medicine TPI1 expression is greatly decreased in clinical hepatocellular carcinoma samples, positively correlated with overall survival, and negatively associated with histological differentiation, tumor size and organ metastasis. Forced expression of TPI1 in hepatocellular carcinoma cells inhibits cell growth, migration, and invasion in vitro. Knockdown of TPI1 by shRNA promotes cell growth, migration and invasion. Overexpression of TPI1 leads to slowed tumor growth and decreased tumor weight in vivo. Cell cycle arrest is induced by TPI1 overexpression 5.3.1.6 ribose-5-phosphate isomerase medicine RPIA is significantly elevated in colorectal. RPIA modulates cell proliferation and oncogenicity via activation of beta-catenin in colon cancer cell lines. RPIA enters the nucleus to form a complex with the adenomatous polyposis coli and beta-catenin, the association protects beta-catenin by preventing its phosphorylation, ubiquitination, and subsequent degradation. The C-terminus of RPIA (amino acids 290 to 311) is necessary for RPIA-mediated tumorigenesis 5.3.1.9 glucose-6-phosphate isomerase medicine use as a diagnostic tool in medicine 5.3.1.9 glucose-6-phosphate isomerase medicine frequency of enzyme variants in healthy control subjects with anti-glucoes 6-phosphate antibodies is significantly higher than in antibody-negative healthy subjects. Frequency of enzyme variants in anti-glucose 6-phosphate antibody positive patients suffering from rheumatoid arthritis is more significantly higher than in antibody-negative patients 5.3.1.9 glucose-6-phosphate isomerase medicine mutation A346H is identified in a patient suffering fromchronic nonspherocytic hemolytic anemia. Mutation results in loss of 82% of enzyme activity, loss of enzyme capability to dimerize, and in significant changes in erythrocyte metabolism 5.3.1.9 glucose-6-phosphate isomerase medicine enzyme expression is detected in a major proportion of lung carcinomas, and enzyme may play a part in proliferation and/or progression of the tumours as well as possibly in the differentiation of squamous cell carcinoma. higher enzyme mRNA expression may be related to the high metastatic potential of non-small cell lung carcinomas and to increased protein secretion 5.3.1.9 glucose-6-phosphate isomerase medicine sera and synovial fluids from patients with immune-based inflammatory arthritis contain significantly higher levels of enzyme activity and of enzyme protein both in inactive and active form than healthy control or patients with non-immune based inflammatory arthritis 5.3.1.25 L-fucose isomerase medicine the Streptococcus pneumoniae fucose-processing pathway has a nonmetabolic role in the interaction of this bacterium with its human host 5.3.1.28 D-sedoheptulose 7-phosphate isomerase medicine determination of the three-dimensional structure of GmhA from Burkholderia pseudomallei to provide a structural template for the development of antibiotic adjuvants as antimelioidosis agents 5.3.3.8 DELTA3-DELTA2-enoyl-CoA isomerase medicine decreased levels of 2,3-trans-enoyl-CoA isomerase might have impact on the aberrant behaviour of cancer cells 5.3.3.8 DELTA3-DELTA2-enoyl-CoA isomerase medicine enzyme is involved in controlling host metabolic reprogramming during hepatitis C virus infection. Hepatitis C virus growth and RNA replication in hepatoma cell lines stably expressing dodecenoyl coenzyme A delta isomerase-targeting short hairpin RNA (shRNA) are abrogated, indicating that dodecenoyl coenzyme A delta isomerase is required for productive infection. Pharmacologic inhibition of fatty acid oxidation also blocks hepatitis C virus replication. Production of infectious hepatitis C virus is restored by overexpression of an shRNA-resistant dodecenoyl coenzyme A delta isomerase allele 5.3.3.8 DELTA3-DELTA2-enoyl-CoA isomerase medicine in primary cultures of epithelial cells from 23 breast cancer tissue samples, nucleophosmin is increased in the group with metastases. The levels of 2,3-trans-enoyl-CoA isomerase and glutathione peroxidase 1 are decreased 5.3.3.12 L-dopachrome isomerase medicine levels of enzyme correlate with relative levels of radioresistance and resistance to UV(B) treatment 5.3.3.12 L-dopachrome isomerase medicine use of enzyme as an early differentiation marker for melanoblasts and retinal pigment epithelium 5.3.3.12 L-dopachrome isomerase medicine different sensitivity to inhibition by haematin 5.3.3.12 L-dopachrome isomerase medicine DCT is processed as a melanoma antigen and is a potential target for immunotherapy 5.3.3.12 L-dopachrome isomerase medicine lower enzyme levels on postnatal day 6 are associated with an increased risk of developing bronchopulmonary dysplasia and late-onset neonatal sepsis 5.3.4.1 protein disulfide-isomerase medicine inhibition of isoform procollagen-proline, 2-oxoglutarate-4-dioxygenase beta subunit activity increases apoptosis in response to agents which induce ER-stress such as fenretinide and velcade 5.3.4.1 protein disulfide-isomerase medicine lipopolysaccharide decreases protein disulfide isomerase protein expression by 33% in RAW 264.7 cells. Incubation of the cells with bacitracin significantly decreases tumor necrosis factor alpha gene expression and release. Downregulation of protein disulfide isomerase gene expression by siRNA correlates with a 3.2fold increase in tumor necrosis factor alpha release into the cell supernatant 5.3.4.1 protein disulfide-isomerase medicine overexpression has significant effects on cell-cell fusion mediated by Newcastle disease virus. Overexpression results in increased membrane fusion, and enhanced production of free thiols in Newcastle disease virus fusion protein when expressed without hemagglutinin-neuraminidase protein but drecreased free thiols in Newcastle disease virus fusion protein expressed with hemagglutinin-neuraminidase protein. Overexpression favors a postfusion conformation of surface-expressed Newcastle disease virus fusion protein in the presence of hemagglutinin-neuraminidase protein 5.3.4.1 protein disulfide-isomerase medicine PDI is required in vivo for both fibrin generation and platelet thrombus formation 5.3.4.1 protein disulfide-isomerase medicine presence of protein disulfide isomerase on the surface of platelet-derived microparticles. Enzyme is catalytically active and capable of both promoting platelet aggregation and disrupting insulin signaling. Platelet-derived microparticles increase the initial rates of aggregation by 4fold and the pro-aggregatory activity of micrparticles can be attenuated with an anti-PDI antibody. Anti-PDI antibodies are able to block the degradation of insulin, thereby restoring insulin signaling. Patients with type II diabetes show increased levles of enzyme-containing microparticles in their plasma 5.3.4.1 protein disulfide-isomerase medicine protein disulfide gene expression is significantly decreased by 28% and 69% at 20 h after cecal ligation and puncture or lipopolysaccharide infusion, respectively 5.3.4.1 protein disulfide-isomerase medicine protein disulfide isomerase directly promotes initiator protein tissue factor-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of carotid artery, enzyme is released at the injury site from adherent platelets and disrupted vessel walls. Inhibition of the enzyme decreases initiator protein tissue factor-triggered fibrin formation. Enzyme infusion increases fibrin generation at the injury site 5.3.4.1 protein disulfide-isomerase medicine protein disulfide isomerase PDI directly interacts with thiol-containing fibrinogen receptor alphaIIbbeta3. PDI has greater ability to isomerize disulfide bonds than the alphaIIbbeta3 integrin. Anti-PDI antibodies inhibit signalling-independent activation of the thiol-containing fibrinogen receptor alphaIIbbeta3 by Mn2+ 5.3.4.1 protein disulfide-isomerase medicine PDI represents a potential drug target for anti-amebic therapy 5.3.4.1 protein disulfide-isomerase medicine protein disulfide isomerase upregulation is e.g. associated with cancer, attention-deficite hyperactivity disorder, Alzheimer disease, amyotrophic lateral sclerosis, perinatal asphyxia, brain ischemia, sporadic Creutzfeldt-Jacob disease, major depression, brain injury, tuberous sclerosis, endothelial function, acute coronary syndrome, iscemic heart disease, hepatosteatosis, varioliform gastritis, preeclampsia, obesity, insulin resistance, diabetes, congenital hypothyroid goiter, Helicobacter pylori infection, peridontitis, dehydration, aging, or pregnancy 5.3.4.1 protein disulfide-isomerase medicine the enzyme is a therapeutic target for preventing and treating inappropriate neutrophil sequestration 5.3.99.2 Prostaglandin-D synthase medicine the enzyme may be a potential marker that may aid in the differential diagnosis of obstructive and non-obstructive azoospermia 5.3.99.2 Prostaglandin-D synthase medicine enzyme mRNA is up-regulated in mouse model of globoid cell leukodystrophy or Krabbe’s disease, of Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis and Niemann-Pick type C1 disease,. Oligodendrocytes of all these mouse models show strong immunoreactivity for enzyme, but not astrocytes or microglia 5.3.99.2 Prostaglandin-D synthase medicine hematopoietic prostaglandin D2 synthase derived prostaglandins may protect against inflammatory diseases, where T-lymphocytes play a pathogenic role, as in rheumatoid arthritis, atopic eczema, and chronic rejection 5.3.99.2 Prostaglandin-D synthase medicine hematopoitic prostaglandin synthase controls an inhibitory effect on intestinal tumours 5.3.99.2 Prostaglandin-D synthase medicine lipocalin-type prostaglandin D synthase may have the ability to improve progressive motility of sperm and, in seminal plasma and on sperm surface, may impact male fertility in the female reproductive tract 5.3.99.2 Prostaglandin-D synthase medicine prostaglandin synthase and testicular factor SOX9 are expressed at both RNA and protein levels in different types of ovarian tumors, while treatment of these cells with prostaglandin D2 can inhibit their growth and induce apoptosis 5.3.99.2 Prostaglandin-D synthase medicine the lipocalin-type prostaglandin D synthase, prostaglandin D2, and prostaglandin D receptor system plays a pivotal role in the regulation of physiological sleep 5.3.99.2 Prostaglandin-D synthase medicine transgenic mice overexpressing the enzyme improve clearance of Pseudomonas from the lung compared with nontransgenic mice, as does intratracheal instillation of prostaglandin D2. Enzyme knock-out mice show impaired ability to remove Pseudomonas from the lung. Potential therapeutic use of enzyme or prostaglandin D2 against Pseudomonas pneumoniae 5.3.99.2 Prostaglandin-D synthase medicine apoptosis induced by chemotherapeutics paclitaxel, cisplatin and 5-fluorouracil is prevented by siRNA targeting lipocalin-type prostaglandin synthase-D 5.3.99.2 Prostaglandin-D synthase medicine both hematopoietic- and lipocalin-type prostaglandin-D synthase are present in cartilage from healthy donors as well as from patients with osteoarthritits. Level of lipocalin-type prostaglandin-D synthase is more than 20fold higher than hematopoietic-type enzyme. Levels of lipocalin-type prostaglandin-D synthase mRNA and protein are increased in cartilage from aptients with osteoarthritis. Treatment of chondrocytes with IL-1beta upregulates lipocalin-type prostaglandin-D synthase mRNA and protein expressions as well as prostaglandin D2 production in a dose- and time-dependent manner. The upregulation of lipocalin-type prostaglandin-D synthase by IL-1beta is blocked by the translational inhibitor cycloheximide. Specific inhibitors of the MAPK p38 and c-jun N-terminal kinase and of the NF-kappaB and Notch signalling pathways suppress IL-1beta-induced upregulation of lipocalin-type prostaglandin-D synthase expression. An inhibitor of the extracellular signal-regulated kinase ERK/MAPK demonstrates no significant influence. Prostaglandin D2 prevents IL-1beta-induced upregulation of lipocalin-type prostaglandin-D synthase expression 5.3.99.2 Prostaglandin-D synthase medicine in patients receiving long-term intravenous administration of gentamicin for the treatment of infective endocarditis, systemic clearance of gentamicin is reduced by 10% from the early to late treatment phase, wherease urinary lipocalin-type prostaglandin synthase excretion shows a significant increase. No significant changes are observed for urinary beta2-microglobulin and N-acetyl-beta-D-glucosaminidase concentrations 5.3.99.2 Prostaglandin-D synthase medicine in patients with acute inflammatory demyelinating polyneuropathy, concentration of prostaglandin-D synthase is significantly increased in cerebrospinal fluid, due to a blood-cerebrospinal fluid barrier dysfunction. The intrathecal synthesis of prostaglandin-D synthase is significantly decreased in these patients. Changes of the ratio of cerebrospinal fluid prostaglandin-D synthase to albumin are only observed in patients with acute inflammatory demyelinating polyneuropathy, but not in Miller Fisher Syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, or multiple sclerosis patients 5.3.99.2 Prostaglandin-D synthase medicine in patients with HIV infection who have progressive neurocognitive decline over the next 6 months and in patients with a history of intravenal drug use, 3-nitrotyrosine modified proteins are significantly elevated. Among the 13 different proteins with 3-nitrotyrosine modification identified, lipocalin-type prostaglandin-D synthase is the most abundant, and the modification results in loss of enzymatic activity 5.3.99.2 Prostaglandin-D synthase medicine in patients with stabel coronary artery disease who underwent diagnostic coronary angiography, the most powerful independent predictor of the coronary severity score is the level of lipocalin-type prostaglandin-D synthase 5.3.99.2 Prostaglandin-D synthase medicine level of seminal plasma lipocalin-type prostaglandin-D synthase is significantly lower in groups with obstruction of the male seminal tract. Men with nonobstructive azoospermia have less homogenity of lipocalin-type prostaglandin-D synthase levels. Lipocalin-type prostaglandin-D synthase can be a potential biomarker for assessing patency in the seminal tract in men with azoospermia. In men with azoospermia and high seminal lipocalin-type prostaglandin-D synthase levels, the diagnosis of nonobstructive azoospermia can be potentially made without biopsy 5.3.99.2 Prostaglandin-D synthase medicine orally administered AT-56, i.e. 4-dibenzo [a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)-butyl]-piperidine, below 30 mg/kg body weight decreases the prostaglandin D2 production to 40% in the brain of H-PGDS-deficient mice after a stab-wound injury in a dose-dependent manner without affecting the production of prostaglandin E2 and prostaglandin F2alpha, and also suppresses the accumulation of eosinophils and monocytes in the bronco-alveolar lavage fluid from the antigen-induced lung inflammation model of human L-PGDS-transgenic mice 5.3.99.2 Prostaglandin-D synthase medicine prostaglandin D2 stimulates food intake after intracerebroventricular administration in mice. Central administration of an antagonist or antisense oligodeoxynucleotide for the DP1 receptor remarkably decreases food intake, body weight and fat mass. Hypothalamic mRNA levels of lipocalin-type PGD synthase are up-regulated after fasting 5.3.99.2 Prostaglandin-D synthase medicine study on the pharmacokinetics of recombinant human lipocalin-type prostaglandin-D synthase in canines. After an intravenous bolus injection, the serum concentration decreases biexponentially with a half-life of the terminal line phase of 0.77 h. L-PGDS is distributed mainly in the blood. Only 10.3% of the administered enzyme is excreted to the urine, suggesting that L-PGDS is actively degraded within the body 5.3.99.2 Prostaglandin-D synthase medicine based on the observations it is speculated that PGD2 acts as one of the immuno-modulating molecules in gastric mucosa infected with Helicobacter pylori, PGD2 might be involved in the pathophysiology of other gastric diseases, such as gastric ulcers or erosion 5.3.99.2 Prostaglandin-D synthase medicine dendritic cells in the epidermis and dermis are capable of functioning as an important source of PGD2 in the skin, thereby contributing to or regulating innate and/or acquired immune responses of the skin 5.3.99.2 Prostaglandin-D synthase medicine induction of L-PGDS expression in the heart as a response to hemodynamic stress 5.3.99.2 Prostaglandin-D synthase medicine L-PGDS is beneficial for protecting the brain against transient and permanent cerebral ischemia, these results provide a better understanding of the role played by the enzymes that control eicosanoid synthesis and how they can be utilized as potential targets to prevent damage following either acute or potentially chronic neurological disorders 5.3.99.2 Prostaglandin-D synthase medicine prostaglandin D2 produced by hematopoietic prostaglandin D synthase contributes to lipopolysaccharide-induced fever 5.3.99.2 Prostaglandin-D synthase medicine prostaglandin D2 synthesized by the hematopoietic prostaglandin D2 synthase has a pro-inflammatory effect in allergic asthma, regulating many hallmark characteristics of the disease 5.3.99.2 Prostaglandin-D synthase medicine the results demonstrate that the neuroprotective effects of hematopoietic prostaglandin D synthase in the model are mediated by suppression of activation and infiltration of inflammatory cells 5.3.99.2 Prostaglandin-D synthase medicine elevated enzyme levels in the cervicovaginal secretions of women are a potential biomarker for preterm birth 5.3.99.2 Prostaglandin-D synthase medicine the enzyme is a biomarker for the assessment of cerebrospinal fluid leaks 5.3.99.3 prostaglandin-E synthase medicine a considerable increase of mPGES-2 expression is observed in human colorectal cancer 5.3.99.3 prostaglandin-E synthase medicine antiinflammatory drug target, deletion of microsomal mPGES-1 abrogates inflammation 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 is involved in various types of pathology including inflammation, pain hyperalgesia, fever, and cancer 5.3.99.3 prostaglandin-E synthase medicine in enzyme knock-out mice, the infarction, edema, apoptotic cell death, and caspase-3 activation in the cortex ischemia cell are all reduced. the behavioral neurological dysfunctions observed after ischemia in wild-type animals are significantly ameliorated in knock-out animals. Microsomal enzyme mPGES-1 may be a critical determinant of postischemic neurological dysfunctions and a therapeutic target for treatment of stroke 5.3.99.3 prostaglandin-E synthase medicine prostaglandin E2 derived from COX-2 and isoform mPGES-1 plays a significant role in the pathogenesis of chronic acid reflux oesophagitis, and possibly in basal hyperplasia and persistent inflammatory cell infiltration 5.3.99.3 prostaglandin-E synthase medicine use of isoform mPGES-1 as a target for the treatment of inflammatory bone disease 5.3.99.3 prostaglandin-E synthase medicine 17beta-estradiol and proinflammatory cytokines can act together to up-regulate PTGES, the finding supports a model whereby estrogens and inflammatory factors orchestrate a complex network of cross talk and feedback mechanisms that can contribute to hormone-dependent breast tumor growth and progression 5.3.99.3 prostaglandin-E synthase medicine induction of various inflammatory cytokines in addition to overexpression of COX-2 and mPGES-1 could be risk factors of gastric carcinogenesis and may serve as a better gastric carcinogenesis model 5.3.99.3 prostaglandin-E synthase medicine licofelone suppresses inflammatory PGE2 formation preferentially by inhibiting mPGES-1 at concentrations that do not affect COX-2 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 could be a potential therapeutic target of novel inhibitors for treatment of inflammatory diseases 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 expression is significantly elevated in Alzheimer's disease tissue 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 inhibitors have therapeutic potential in syndromes of cardiovascular inflammation, cancer and perhaps neurodegenerative disease 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 is a potential target for inhibitors, pathological conditions, such as inflammation, pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis are related to elevated levels of PGE2 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 is a potential target of anti-inflammatory drugs 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 is a promising target for the development of anti-inflammatory drugs 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 plays a role in atherosclerosis, stroke, inflammation, pain and fever 5.3.99.3 prostaglandin-E synthase medicine MPGES1 has been implicated in a number of human diseases or pathological conditions, such as rheumatoid arthritis, fever, and pain, and is therefore regarded as a primary target for development of novel antiinflammatory drugs 5.3.99.3 prostaglandin-E synthase medicine the selective inhibition of mPGES-1 generates anti-inflammatory effects without unwanted side effects involving homeostasis 5.3.99.3 prostaglandin-E synthase medicine MPGES-1 is an alternative therapeutic target in cancer cells expressing this enzyme 5.3.99.3 prostaglandin-E synthase medicine inhibition of mPGES-1 may have clinical utility in the management of bone cancer pain 5.3.99.3 prostaglandin-E synthase medicine mPGES-1 is a therapeutic target for endometriosis 5.3.99.3 prostaglandin-E synthase medicine enzyme inhibition can be useful for treating pain, fever, and anorexia 5.3.99.4 prostaglandin-I synthase medicine formation of monoclonal antibodies against prostacyclin synthase 5.3.99.4 prostaglandin-I synthase medicine manipulation of prostaglandin production distal to cyclooxygenase significantly reduces lung carcinogenesis in a tobacco smoke exposure model 5.3.99.4 prostaglandin-I synthase medicine overexpression of PGIS is highly effective in controlling vascular diseases and ischemia-reperfusion tissue injury, gene transfer of bicistronic COX-1/PGIS has the potential for treatment of diverse clinical disorders including vascular diseases, pulmonary hypertension, and ischemia-reperfusion cerebral and cardiac injury 5.3.99.4 prostaglandin-I synthase medicine prostaglandin-I synthase protects the brain by enhancing prostaglandin I2 synthesis and creating a favorable prostaglandin I2/thromboxane A2 ratio, prostaglandin-I synthase expression after ischemic insult is important in promoting neuronal cell survival 5.3.99.4 prostaglandin-I synthase medicine the enzyme acts as a regulator of thyroid papillary carcinoma proliferation, increased expression levels may play a role in the pathogenesis of these tumors 5.3.99.4 prostaglandin-I synthase medicine exposure of isolated coronary arteries to high glucose switches angiotensin II-stimulated prostacyclin-dependent relaxation into a persitent vascoconstriction. High glucose, but not mannitol, significantly increases superoxide and nitration of tyrosine in prostacyclin synthase. Concurrent administration of polyethylene-coated superoxide dismutase, L-nitroarginine methyl ester, or sepiapterin abolishes enzyme nitration, as well as its association with endothelial nitric oxide synthase 5.3.99.4 prostaglandin-I synthase medicine significant suppression of enzyme activity in parallel with increased superoxide and enzyme nitration in the aortas of diabetic C57BL6 mice, but less effect in diabetic mice either lacking endothelial nitric oxide synthase or overexpressing human superoxide dismutase 5.3.99.4 prostaglandin-I synthase medicine study on involvement of enzyme polymorphism in adenomatous or hyperplastic colorectal polyps. The enzyme promoter polymorphism may affect risk of colorectal polyps and modify the effects of nonsteroidal anti-inflammatory drug use on polyp risk 5.3.99.4 prostaglandin-I synthase medicine synthesis of prostaglandin by enzyme contributes to renal protection against endotoxemia-related acute kidney injury 5.3.99.4 prostaglandin-I synthase medicine upregulation of prostaglandin I2 synthesis by expression of a fusion protein linking cyclooxygenase COX-2 and prostacyclin synthase shows strong activity in inhibiting platelet aggregation induced by arachidonic acid in vitro and may be used for therapeutic inventions for strokes and heart attacks 5.3.99.4 prostaglandin-I synthase medicine after culture of embryos in presence of the selective cyclooxygenase-1 inhibitor SC560, the selective cyclooxygenase-2 inhibitor NS398, or the selective prostacyclin synthase inhibitor U51605 in a 48-h culture, the implantation rate decreases with exposure to either the cyclooxygenase-2 inhibitor of the prostaglandin-I synthase inhibitor, which is increased further after supplementation with prostaglandin I2. The level of prostaglandin I2 is also higher at the 8-16 cell stage, compaction and blastocyst stage than prostaglandin E2 5.3.99.4 prostaglandin-I synthase medicine by impairing prostacyclin synthase function, and thus PGI2 release, C-reactive protein, CRP, could promote endothelial dysfunction and participate in the development of coronary artery disease 5.3.99.4 prostaglandin-I synthase medicine it is hypothesized that the combination of prostacyclin synthase overexpression and epidermal growth factor receptor tyrosine kinase inhibitor, EGFR TKI, would lead to augmented chemoprevention for lung cancer 5.3.99.4 prostaglandin-I synthase medicine prostacyclin synthase may be chemopreventive in cancer 5.3.99.4 prostaglandin-I synthase medicine prostacyclin synthase overexpression apparently protects insulin-producing cells against cytokine toxicity via suppression of endoplasmic reticulum and mitochondrial stress-mediated cell death pathways 5.3.99.4 prostaglandin-I synthase medicine sustained release of prostaglandin I2 enhances the proangiogenic function of mesenchymal stem cells and subsequent muscle cell regrowth in the ischemic tissue suggesting potential therapeutic benefits of cell-based gene therapy for critical limb ischemia 5.3.99.4 prostaglandin-I synthase medicine tyrosine nitration of prostacyclin synthase is correlated with an excessive inflammatory response in atherosclerotic carotid arteries from patients with type 2 diabetes 5.3.99.4 prostaglandin-I synthase medicine co-adjuvant therapy with enzyme enhancers, such as retinoids, has therapeutic value for head and neck squamous cell carcinoma treatment 5.3.99.5 thromboxane-A synthase medicine the thromboxane A2 synthetase inhibitor/thromboxane A2-receptor antagonist (5Z)-6-[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridylmethyl)-2-pyrrolidinyl]-5-hexenoic acid hydrochloride may be of clinical relevance for the prevention or treatment of th 5.3.99.5 thromboxane-A synthase medicine thromboxane A2 may somehow mediate coughing induced by the angiotensin converting enzyme inhibitors. Patients on angiotensin converting enzyme inhibitors who develop cough may benefit from thromboxane A2 synthetase inhibitors 5.3.99.5 thromboxane-A synthase medicine improvement of the renal function with the selective thromboxane A2 synthetase inhibitor (+/-)-6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate 5.3.99.5 thromboxane-A synthase medicine possible role in the regulation of prostate cancer cell migration 5.3.99.5 thromboxane-A synthase medicine TXAS mRNA expression was found to be an independent prognostic marker for patients with bladder cancer 5.3.99.5 thromboxane-A synthase medicine in addition to inhibitory activity, application of ONO-1301, i.e. ([5-[2-([[(1E)-phenyl(pyridin-3-yl)methylidene]amino]oxy)ethyl]-7,8-dihydronaphthalen-1-yl]oxy)acetic acid, significantly attenuates the development of pulmonary fibrosis and improves survival after treatment with bleomycin 5.3.99.5 thromboxane-A synthase medicine thromboxane-A synthase protein is consistently upregulated in the cancer tissues from patients with colorectal carcinoma and also highly expressed in colonic cancer cell lines. Depletion of enzyme protein by antisense oligonucleotide inhibits proliferation of cancer cells 5.3.99.5 thromboxane-A synthase medicine TBXAS1 gene polymorphisms are a marker for development of cerebral infarction, especially small-artery occlusion type in Korean population 5.3.99.5 thromboxane-A synthase medicine the targeted inhibition of TXSA activity improves the efficiency of conventional alkylation chemotherapy in vivo 5.4.2.2 phosphoglucomutase (alpha-D-glucose-1,6-bisphosphate-dependent) medicine inhibition of phosphoglucomutase activity by chronic treatment with Li+ causes compensatory elevation of phosphoglucomutase activity in Li+-treated bipolar patients due to increased expression of PGM1 gene 5.4.2.4 Bisphosphoglycerate mutase medicine BPGM deficiency can cause erythrocytosis 5.4.2.8 phosphomannomutase medicine analysis of clinically important mutations involved in congential disorder of glycosylation type 1a 5.4.2.10 phosphoglucosamine mutase medicine phosphoglucosamine mutase could be a a novel drug target 5.4.2.10 phosphoglucosamine mutase medicine the glmM gene may have a constructive role in the virulence properties of Streptococcus mutans 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) medicine analysis of enzyme mutations found in some patients 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) medicine both in erythroblasts and reticulocytes, increase in enzyme activity and mRNA level after application of triiodothyronine or induction of hypoxia by 90% nitrogen/10% oxygen. Propylthiouracil produces a decrease in enzyme activity 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) medicine mutation M230I identified in a patient with non-spherocytic anemia. Enzyme activity is reduced by 50%, with normal levels of enzyme protein. Mutation results in decrease of glycolytic metabolites, with the exception of hexose phosphates. In contrast, lactate levels are increased 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) medicine mutation M230I is identified in a patient with hereditary sperocytosis and 50% deficiency of enzyme activity in red blood cells. Enzyme shows abnormal behaviour on ion-exchange chromatography and is more thermo-labile than wild-type 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) medicine PGAM1 may have a pathological role of vascular invasion into cancerous tissue 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) medicine PGAM1 plays an important role in hepatocarcinogenesis, is a potential diagnostic biomarker as well as an attractive therapeutic target for hepatocellular carcinoma 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) medicine the anti-PGAM1 antibody is a marker of autoimmune hepatitis and a nonspecific marker of central nervous system autoimmune diseases 5.4.2.12 phosphoglycerate mutase (2,3-diphosphoglycerate-independent) medicine drug target for novel anti-filarial therapies that selectively target the Wolbachia endosymbiont of Brugia malayi 5.4.2.12 phosphoglycerate mutase (2,3-diphosphoglycerate-independent) medicine the enzyme is a potential vaccine candidate against visceral leishmaniasis 5.4.99.2 methylmalonyl-CoA mutase medicine lentiviral delivery of enzyme gene into fibroblasts derived from a patient with mut0 class methylmalonic acidemia can partially restore propionate flux 5.4.99.2 methylmalonyl-CoA mutase medicine method for separation of methylmalonyl-CoA and succinyl-CoA by capillary electrophoresis suitable for evaluation of total and holo-enzyme activity in biological matrices. Application of method for the differential diagnosis of methylmalonic acidemia, in relation to protein or coenzyme defects 5.4.99.7 Lanosterol synthase medicine target for the development of new hypocjolesterolemic drugs 5.4.99.7 Lanosterol synthase medicine S23515 can exert hypolipidemic effects in addition to its hypotensive activities 5.4.99.7 Lanosterol synthase medicine since the Shumiya cataract rat model represents a new example of hereditary cholesterol deficiency-associated cataracts, it should be useful in the development of therapeutic and/or preventive measures for cataracts 5.4.99.9 UDP-galactopyranose mutase medicine the UDP-galactopyranose mutase is an appealing adjunct therapeutic target in combination with other drugs against Aspergillus fumigatus 5.4.99.16 maltose alpha-D-glucosyltransferase medicine trehalose synthase from Pyrococcus horikoshii can be applied to the sugar nucleotide cycling process for the synthesis of functional alpha-galactosyl oligosaccharides, alpha-galactose epitopes and globotriose, using the effective regeneration of UDP-Gal. The alpha-Gal epitope III with galactulose acceptor shows the most inhibitory activity of anti-adhesion of Escherichia coli cells to human Caco-2 cells. The alpha-galactosyl oligosaccharides may be alternative anti-adhesion molecules that overcome antibiotic resistance 5.5.1.4 inositol-3-phosphate synthase medicine anticonvulsants valnoctamide and valrocemide drastically reduce enzyme activity in crude brain homogenate 5.5.1.4 inositol-3-phosphate synthase medicine the common inositol-reversible effects of mood stabilizers lithium, valproate and carbamazepine on neurons are independent of enzyme and of sodium-dependent myo-inositol transporters 5.6.1.1 microtubule-severing ATPase medicine a major fraction of autosomal dominant cases of hereditary spastic paraplegia (HSP) is caused by mutations in SPG4 encoding spastin 5.6.1.1 microtubule-severing ATPase medicine hereditary spastic paraplegias (HSPs) are most commonly caused by mutations in the spastin gene 5.6.1.1 microtubule-severing ATPase medicine mutations cause an autosomal dominant form of hereditary spastic paraplegia 5.6.1.1 microtubule-severing ATPase medicine mutations in the SPG4 gene, spastin is the SPG4 gene product, are the most common cause of autosomal dominant hereditary spastic paraplegia, HSP 5.6.1.1 microtubule-severing ATPase medicine tauopathies 5.6.1.1 microtubule-severing ATPase medicine the most frequently mutated gene causing autosomal dominant hereditary spastic paraplegias is SPG4, which encodes spastin 5.6.1.1 microtubule-severing ATPase medicine KSPA-1 inhibits the proliferation of tumor cells 5.6.1.1 microtubule-severing ATPase medicine spastin is frequently mutated in hereditary spastic paraplegia 5.6.1.1 microtubule-severing ATPase medicine spastin is mutated in the neurodegenerative disease hereditary spastic paraplegia 5.6.1.1 microtubule-severing ATPase medicine spastin is the most commonly mutated protein in hereditary spastic paraplegia 5.6.1.1 microtubule-severing ATPase medicine spg4, the gene encoding for spastin, is mutated in around 40% of cases of autosomal dominant hereditary spastic paraplegia 5.6.1.1 microtubule-severing ATPase medicine the analysis provides insights into the structural defects in spastin that arise from mutations identified in hereditary paraplegia patients 5.6.1.2 dynein ATPase medicine redistribution of endoplasmic reticulum during oocyte maturation is dynein-driven and cell cycle-dependent. Role for dynein in the cytoplasmic changes that prepare the oocyte for fertilization 5.6.1.3 plus-end-directed kinesin ATPase medicine appears tempting to test whether blocking KIF2beta expression in host cells may inhibit parasite entry without affecting host cell viability, KIF2beta antisense oligonucleotides could act as preventive agents for parasite infection 5.6.1.3 plus-end-directed kinesin ATPase medicine inhibition of mitotic spindles is a pharmaceutically validated strategy for cancer therapeutics, human Eg5 in addition to microtubules represents an attractive target molecule for novel clinical therapies in the treatment of human malignancies, kinesin spindle protein Eg5 is a target for anticancer therapies 5.6.1.5 proteasome ATPase medicine molecular analysis of this parasite, new means to combat drug resistance in malaria, PSF4 may be a target for the development of new antimalarial drugs that will be effective against chloroquine-resistant parasites 5.6.1.5 proteasome ATPase medicine the finding that the disassembly of the 26S proteasome is an old-age event could explain the presence of protein deposits containing ubiquitinated proteins and oxidatively modified proteins in nonpathologic aging, as well as in a variety of aging-related neurodegenerative disorders 5.6.1.5 proteasome ATPase medicine the human orthologue of yeast Rpt3, S6 ATPase, interacts with the oncoprotein gankyrin, gankyrin is commonly overexpressed in hepatocellular cancer cells 5.6.1.5 proteasome ATPase medicine the enzyme serves as a prognostic indicator for radiotherapy and molecular targeted therapy in lung cancer patients 5.6.1.6 channel-conductance-controlling ATPase medicine CFTR is a phamacological target for activators and inhibitors, acivators are useful for phamacotherapy of cystic fibrosis, conversely, inhibitors are useful to treat secretory diarrhoea caused by enterotoxins 5.6.1.6 channel-conductance-controlling ATPase medicine CFTR is involved in the pathogenesis of ovarian hyperstimulation syndrome by reproduction treatments, upon ovarian hyperstimulation enhanced CFTR expression and channel activity 5.6.1.6 channel-conductance-controlling ATPase medicine novel mechanism for regulation of the vascular tone by cAMP-dependent CFTR chloride channels in vascular smooth muscle cells 5.6.1.6 channel-conductance-controlling ATPase medicine role of CFTR in pathological cases, metabolic labelling of CFTR ex vivo in human tissue 5.6.1.6 channel-conductance-controlling ATPase medicine SB-300, which targets the CFTR Cl- channel, is a low cost extract from Croton lechleri and may present a complementary and alternative medicine approach for the treatment of fluid loss in watery diarrhea 5.6.1.6 channel-conductance-controlling ATPase medicine analysis of patients with hypertriglyceridemia for mutations in the CFTR gene. 13 out of 126 patients carried a mutation in CFTR, all carrying I556V. Multivariate analysis indicates that triglycerides, CFTR mutation 470V, and TNF promoter 863A are independent risk markers for hypertriglyceridemia 5.6.1.7 chaperonin ATPase medicine the Hsp60-p.V98I mutation is associated with Hereditary Spastic Paraplegia 5.6.1.7 chaperonin ATPase medicine the enzyme can be used as a vaccine candidate against Mycoplasma gallisepticum, a common and widespread cause of chronic respiratory disease in poultry 5.6.1.8 myosin ATPase medicine Ca2+-activated myosin ATPase activity is reduced with age in semimembraneous muscle, one mechanism that contributes to age-related slowing of contraction in that muscle 5.6.1.8 myosin ATPase medicine decrease of enzyme activity in hearts of idiopathic and ischemic cardiomyopathic individuals, MCI-154 and caffeine increased enzyme activity 5.6.2.1 DNA topoisomerase medicine TopoI is very important for the antitumor efficacy of many drugs, through the regulating the circadian clock genes and cell cycle control genes 5.6.2.1 DNA topoisomerase medicine bacterial topoisomerase I is a therapeutic target 5.6.2.1 DNA topoisomerase medicine the enzyme is an anti-cancer target 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) medicine a candidate procedure for the study to topoisomerase II in patient-derived blood samples 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) medicine the enzyme is a target for cancer chemotherapy 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) medicine the isozyme alpha is a target for many chemotherapeutic agents in clinical use 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) medicine both isoforms IIalpha and IIbeta are present in pre-integration complexes of HIV-1. Enzyme inhibitors azalactone ferrocene, thiomorpholide amido methyl ferrocene and ruthenium benzene amino pyridine show singificant anti-HIV-1 activity at nanomolar concentrations in Sup-T1 cells 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) medicine mouse skin carcinogenesis model, the incidence of VP-16-induced melanomas in the skin of 7,12-dimethylbenz[a]anthracene-treated mice is found to be significantly higher in wild-type than in skin-specific isoform 2beta-knockout mice. Etoposide-induced DNA sequence rearrangements and double-strand breaks are found to be isoform 2beta-dependent and preventable by cotreatment with a proteasome inhibitor. The cytotoxicity of etoposide in wild-type cells is mainly dependent on enzyme isoform 2alpha 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) medicine topoisomerase II alpha is a marker predicting anthracyclines activity in early breast cancer patients 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) medicine catalytic inhibitors of DNA topoisomerase II suppress the androgen receptor signaling and prostate cancer progression 5.6.2.3 DNA 5'-3' helicase medicine modulation the function of HELQ helicase may be used in the treatment of ovarian cancer 5.6.2.4 DNA 3'-5' helicase medicine UvrD helicase is a potential drug targets for chemotherapy of malaria. As Plasmodium falciparum contains only one homologue of UvrD helicase and human lacks this helicase, detailed studies including cloning and characterization of UvrD helicase of malaria parasite may be helpful in identifying a compound that has no effect on the cellular machinery of the host and consequently could be used as the potential drug for the treatment of malaria 6.1.1.1 tyrosine-tRNA ligase medicine enzyme inhibitors can be used as antibacterial agents 6.1.1.1 tyrosine-tRNA ligase medicine high-dose mini-TyrRS (600 microgram/kg/day) augments while low-dose mini-TyrRS (3 microgram/kg/day), inhibits angiogenesis in the ischemic mouse ear. Enhanced angiogenesis is associated with increased CD45- and CD4-positive leukocyte accumulation. Mini-TyrRS also has biphasic actions on both basal and mustard oil-evoked and VEGF-evoked leakage of Evan's blue dye-albumin in nonischemic ear and in endothelial cell monolayers, that is, low-dose inhibited and high-dose augmented leakage. Mini-TyrRS has dose-dependent biphasic effects on ischemic angiogenesis and vascular permeability in vivo, that is, antiangiogenic and antipermeability activities at low concentration and proangiogenic, propermeability activities at high concentrations 6.1.1.1 tyrosine-tRNA ligase medicine it is shown that mini-TyrRS is exported from endothelial cells when they are treated with tumor necrosis factor-alpha. Mini-TyrRS binds to vascular endothelial cells and activates an array of angiogenic signal transduction pathways. Mini-TyrRS-induces angiogenesis requires the activation of VEGF receptor-2. Mini-TyrRS stimulates VEGFR2 phosphorylation in a VEGF-independent manner, suggesting VEGFR2 transactivation 6.1.1.1 tyrosine-tRNA ligase medicine dominant-intermediate Charcot-Marie-Tooth neuropathy, DI-CMT, is characterized by axonal degeneration and demyelination of peripheral motor and sensory neurons, three dominant mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, have so far been associated with DI-CMT type C 6.1.1.1 tyrosine-tRNA ligase medicine it has been suggested that bone metabolism disorders are one of the major complications of diabetes mellitus, glucose could affect bone metabolism by regulating the expression of tyrosyl-tRNA synthetase genes 6.1.1.1 tyrosine-tRNA ligase medicine some mammalian synthetases develop cytokine functions possibly linked to disease-causing mutations in tRNA synthetases 6.1.1.1 tyrosine-tRNA ligase medicine recombinant hTyrRS might be a useful therapeutic agent for chemotherapy-induced thrombocytopenia. Intraperitoneal administration of at least 0.01 mg/day recombinant hTyrRS for 7 days significantly prevents the decrease in platelets 8 days after cyclophosphamide injection 6.1.1.2 tryptophan-tRNA ligase medicine enzyme is the target for antibacterial activity of chuangximycin and chuangximycin lactone 6.1.1.2 tryptophan-tRNA ligase medicine as producers of nearly half of the 10000 known antibiotics, Streptomyces bacteria have been particularly important in drug discovery and are a major source of drug resistance genes 6.1.1.2 tryptophan-tRNA ligase medicine human mini, but not full-length, TrpRS has angiostatic activity 6.1.1.2 tryptophan-tRNA ligase medicine TrpRS is differentially expressed in colorectal cancer and thus a potential prognostic marker 6.1.1.4 leucine-tRNA ligase medicine LARS1 plays roles in migration and growth of lung cancer cells, which suggest its potential implication in lung tumorigenesis 6.1.1.4 leucine-tRNA ligase medicine pretreatment of mice with zinc sulfate solution favors to protection of protein synthesis and acceptor activity of tRNALeu against cadmium-induced inhibition. Under co-exposure of mouse liver to cadmium and zinc, activity of the leucyl-tRNA synthetase is at the level of control. Zinc does not influence TUNEL-positive cell number in cadmium-exposed mouse liver 6.1.1.4 leucine-tRNA ligase medicine suppression of a tRNA gene mutation by increasing the steady-state levels of its cognate aminoacyl-tRNA synthetase is a model for potential therapies for human pathogenic tRNA mutations 6.1.1.4 leucine-tRNA ligase medicine the A3243G mutation of the tRNALeu gene causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and 2% of cases of type 2 diabetes. The alteration of aminoacylation of tRNALeu(UUR) caused by the A3243G mutation leads to mitochondrial translational defects and thereby reduces the aminoacylating efficiencies of tRNALeu(UUR) as well as of tRNAAla and tRNAMet. The transfer of human mitochondrial leucyl-tRNA synthetase into the cybrid cells carrying the A3243G mutation improve the efficiency of aminoacylation and stability of mitochondrial tRNAs and then increase the rates of mitochondrial translation and respiration, consequently correcting the mitochondrial dysfunction 6.1.1.5 isoleucine-tRNA ligase medicine four hundred nine methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates collected in 2006 and 2007 at Madigan Army Medical Center are screened for mupirocin resistance by E test and polymerase chain reaction. No trend of increased mupirocin resistance is found when compared with subsequent years. These results show that mupirocin remains a valid infection control measure due to its unique mechanism of action and the high susceptibility rate of MRSA isolates 6.1.1.5 isoleucine-tRNA ligase medicine inhibition of the enzyme constitutes a potential treatment for African sleeping sickness 6.1.1.6 lysine-tRNA ligase medicine KRS is released from the multi-tRNA synthetase complex (MSC) and translocates to the plasma membrane, where it binds to p67LR, resulting in cell migration and metastasis. Modulation of KRS-67LR interaction by an inhibitor BC-KYH16899 may offer a strategy with which to control metastasis 6.1.1.9 valine-tRNA ligase medicine a C25U point mutation in the MTTV gene, gene encoding tRNAVal, is associated with a metabolic disorder resulting in the neonatal deaths of numerous siblings. In primary myoblasts and transmitochondrial cybrids established from the proband and offspring, the steady-state levels of the mutated mt-tRNAVal are greater than in the biopsy material, but are still lower than in control myoblasts. Decrease in steady-state mt-tRNAVal observed cell lines is caused by a rapid degradation of the deacylated form of the abnormal mt-tRNAVal. By both establishing the identity of the human mitochondrial valyltRNA synthetase then inducing its overexpression in transmitochondrial cell lines, steady-state levels of the mutated mt-tRNAVal can be partially restored 6.1.1.10 methionine-tRNA ligase medicine REP3123 is a fully synthetic methionyl-tRNA synthase inhibitor in pre-clinical development as a novel agent to treat Clostridium difficile infection, CDI 6.1.1.10 methionine-tRNA ligase medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug 6.1.1.10 methionine-tRNA ligase medicine REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug to combat Clostridium difficile infections 6.1.1.10 methionine-tRNA ligase medicine REP8839 is a selective inhibitor of methionyl-tRNA synthetase with antibacterial activity against a variety of gram-positive organisms 6.1.1.10 methionine-tRNA ligase medicine methionyl-tRNA synthetase overexpression is associated with poor clinical outcomes in non-small cell lung cancer 6.1.1.12 aspartate-tRNA ligase medicine for designing selective inhibitors of yeast AspAS, well distinguished from mammalian AspRS, the understanding of the structural features is necessary 6.1.1.12 aspartate-tRNA ligase medicine the adaption of pathogens to antibiotics calls for new target macromolecules and new types of inhibitors 6.1.1.14 glycine-tRNA ligase medicine the distribution of mutations in the seven genes identified for hereditary motor neuropathy (HMN) is investigated in a cohort of 112 familial and isolated patients with a diagnosis of HMN. Nine different disease-causing mutations are found in small heat shock 22 kDa protein 8, small heat shock 27 kDa protein 1, Berardinelli-Seip congenital lipodystrophy and senataxin in 17 patients. No mutations are found in glycyl-tRNA synthetase, dynactin 1 and VAPB(VAMP)-associated protein B and C 6.1.1.14 glycine-tRNA ligase medicine Charcot-Marie-Tooth disease, CMT, type 2D, a hereditary axonal neuropathy, is caused by mutations in glycyl-tRNA synthetase 6.1.1.16 cysteine-tRNA ligase medicine in order to evaluate genetic associations between candidate genes involved in oxidative stress and multiple system atrophy (MSA) 119 Japanese patients with MSA and 123 controls are examined and single-nucleotide polymorphisms are genotyped. Results revealed genetic associations of cysteinyl-tRNA synthetase, solute carrier family 1A4, sequestosome 1, and eukaryotic translation initiation factor 4E-binding protein 1 with MSA 6.1.1.21 histidine-tRNA ligase medicine purified Jo-1 antigen will be useful in determining the role of anti-Jo-1 in the pathogenesis of polymyositis 6.1.1.21 histidine-tRNA ligase medicine the autoantibody anti-Jo-1 is a useful diagnostic tool since the antibody is very specific for polymyositis 6.1.1.21 histidine-tRNA ligase medicine patients suffering from autoimmune-disease myositis develop antibodies against a histidyl-tRNA synthetase. Cytoplasm is the sole localization of enzyme-green fluorescent protein or green fluorescent protein-enzyme construct in T24 cell, HeLa cell and L6 cell 6.1.1.22 asparagine-tRNA ligase medicine filariasis caused by the nematode, Brugia malayi, is an important worldwide tropical disease in which parasites disappear from the bloodstream during daylight hours, thus hampering standard microscopic diagnostic methods 6.1.1.22 asparagine-tRNA ligase medicine homozygous missense mutation c.822G>C affects the 3 splice site of exon 7, leading to skipping of the whole exon 7 and a part of exon 8 in the NARS2 mRNA. Upon expression in fibroblasts a specific decrease in the amount of charged mt-tRNAAsn is found. Mutation was found in in two siblings born to consanguineous parents, one presenting with mild intellectual disability and epilepsy in childhood, whereas the other had severe myopathy 6.2.1.1 acetate-CoA ligase medicine acetyl-CoA synthetase appears to be important in acetate uptake and acetate-dependent lipid synthesis for the growth of cancer cells with a low-glycolysis phenotype 6.2.1.1 acetate-CoA ligase medicine cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells 6.2.1.2 medium-chain acyl-CoA ligase medicine involvement of the MACS2 Leu513Ser polymorphism in the development of the metabolic syndrome 6.2.1.45 E1 ubiquitin-activating enzyme medicine in a mouse model of leukemia, intraperitoneal administration of inhibitor 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione, i.e. PYZD-4409, decreases tumor weight and volume compared with control without untoward toxicity 6.2.1.45 E1 ubiquitin-activating enzyme medicine knockdown of E1 decreases the abundance of ubiquitinated proteins in leukemia and myeloma cells and induces cell death. Inhibitor 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione, i.e. PYZD-4409, induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells compared with normal hematopoietic cells. Mechanistically, genetic or chemical inhibition of E1 increases expression of E1 stress markers. ER membrane protein BI-1 overexpression blocks cell death after E1 inhibition 6.2.1.45 E1 ubiquitin-activating enzyme medicine functional foods, e.g. ginsenoside Rg1 in Panax ginseng root, targeting the ubiquitin-activating enzyme (E1) of the ubiquitin-proteasome pathway as anti-tumour agents are considered to be important for cancer chemoprevention 6.2.1.45 E1 ubiquitin-activating enzyme medicine the ubiquitin-activating enzyme E1 is a therapeutic target for the treatment of restenosis 6.2.1.59 long-chain fatty acid adenylase/transferase FadD26 medicine a FadD26 mutant has impaired synthesis of phthiocerol dimycocerosates and is attenuated in BALB/c mice. The FadD26 mutant induces less pneumonia and larger delayed-type hypersensitivity reactions. It induces lower but progressive production of interferon-gamma, interleukin-4 and tumour necrosis factor-alpha. Used as a subcutaneous vaccine, the mutant induces a higher level of protection than does strain Bacille Calmette-Guérin (BCG). There is less tissue damage (pneumonia) and lower colony-forming units in the mice vaccinated with the FadD26 mutant compared to the findings in mice vaccinated with BCG 6.2.1.59 long-chain fatty acid adenylase/transferase FadD26 medicine a SigE/FadD26 double mutant is more attenuated and more efficacious than wild-type strain BCG BCG in a mouse model of infection, and equivalent to BCG in a Guinea pig model of infection 6.2.1.59 long-chain fatty acid adenylase/transferase FadD26 medicine comparison of parental virulent clinical isolate MT103 with its mutant FadD26, lacking phthiocerol dimycocerosates. Upon airways infection both mycobacteria behave similarly regarding T cell stimulation kinetics. They differ in the magnitude of these responses, in the bacterial load within tissues, and to trigger in vivo cytotoxicity in lungs and regional lymph nodes 6.3.1.2 glutamine synthetase medicine potential target for anti-mycobacterial therapy 6.3.1.2 glutamine synthetase medicine glutamine synthetase is a target for disruption in the development of vaccines against both bovine and human tuberculosis. Glutamine synthetase is also a potential target for tuberculosis chemotherapy 6.3.1.2 glutamine synthetase medicine restoration of glutamine synthetase may represent an approach to therapeutic intervention in mesial temporal lobe epilepsy 6.3.1.2 glutamine synthetase medicine treatment with methionine sulfoximine of transgenic mice that overexpresses the mutant human superoxide dismutase SOD1G93A gene, an animalmodel for the primary inherited form of the human neurodegenerative disease amyotrophic lateral sclerosis. This treatment in vivo reduces glutamine synthetase activity measured in vitro by 85% and reduces brain levels of glutamine by 60% and of glutamate by 30% in both the motor cortex and the anterior striatum, while also affecting levels of GABA and glutathione. Methionine sulfoxime treatment significantly extends the lifespan of these mice by 8% 6.3.1.2 glutamine synthetase medicine expression of glutathione synthetase is observed in 70% of hepatocellular carcinoma patients, 46.7% of chronic hepatitis B stage 4 patients and 38% of chronic hepatitis B stage 1-3 patients. There is significant difference between hepatocellular carcinoma samples and non-tumor tissues. Serum glutathione synthetase levels are increased in hepatocellular carcinoma and chronic hepatitis B stage 1-4 patients. There are significant differences among all samples, except chronic hepatitis B stage 1-3 versus chronic hepatitis B stage 4. Hepatocellular carcinoma, chronic hepatitis B stage 1-4 and AFP are significantly associated with serum glutathione synthetase levels. In hepatocellular carcinoma group, TNM and Child-Pugh are significantly associated with glutathione synthetase levels. Expression of glutathione synthetase is increased in hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis B 6.3.1.2 glutamine synthetase medicine in brain, no significant changes in the enzyme activity between morphine-treated and control samples 6.3.1.4 aspartate-ammonia ligase (ADP-forming) medicine the first intron of the gene ASNS contains two 14-bp tandem repeat sequences, i.e. 2R. Approximately 75% of acute lymphoblastic leukemia samples have the 2R sequence in both alleles, 20% and 3% acute lymphoblastic leukemia samples have three and four 14-bp tandem repeats in one allele, respectively. The other allele has 2R. The tandem repeat sequence is not specific to the leukemia cells but represents a novel germline polymorphism. The 14-bp sequence functions as a transcriptional enhancer element as shown by reporter analysis and forms a protein-DNA complex in vitro 6.3.1.12 D-aspartate ligase medicine the enzyme appears as an attractive target for the development of narrow spectrum antibiotics active against multiresistant Enterococcus faecium 6.3.1.12 D-aspartate ligase medicine the enzyme is a potential target for specific antimicrobials 6.3.2.2 glutamate-cysteine ligase medicine enzyme inhibitor L-buthionine-S-sulfoximine is used to modulate GSH levels in cancer patients, overview 6.3.2.2 glutamate-cysteine ligase medicine the enzyme is a target for development of potential therapeutic agents 6.3.2.2 glutamate-cysteine ligase medicine the enzyme may be a key factor in the chemopreventive potential of coffee components kahweol and cafestol 6.3.2.2 glutamate-cysteine ligase medicine gamma-GCS gene is the downstream target of c-Myc oncoprotein, driving the response to ROS-inducing drugs. gamma-GCS impairment might specifically sensitize high c-Myc tumor cells to chemotherapy 6.3.2.2 glutamate-cysteine ligase medicine activation of glycogen synthase kinase 3beta is a key mediator of the initial phase of acetaminophen-induced liver injury through modulating GCL and Mcl-1 degradation, as well as JNK activation in liver. The silencing of glycogen synthase kinase 3beta decreases the loss of hepatic GCL, and promotes greater GSH recovery in liver following acetaminophen treatment 6.3.2.2 glutamate-cysteine ligase medicine mice lacking the glutamate-cysteine ligase modifier subunit are susceptible to myocardial ischaemia-reperfusion injury partly through an increased vulnerability of mitochondria to oxidative damage owing to mitochondrial glutathione reduction 6.3.2.2 glutamate-cysteine ligase medicine model to explain adenosine triphosphate depletion during cystinosis. In the absence of cysteine, enzyme gamma-glutamyl cysteine synthetase forms 5-oxoproline, and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. Thus, in cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and this is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells. The model is also compatible with the differences seen in the human patients and the mouse model of cystinosis, where renal failure is not observed 6.3.2.2 glutamate-cysteine ligase medicine the presence of at least one T allele in the -129 C/T polymorphism of the GCL catalytic subunit gene is independently associated with non-alcoholic steatohepatitis 6.3.2.2 glutamate-cysteine ligase medicine study on recombinant Leishmania donovani gammaglutamyl cysteine synthetase protein alone or incorporated into a non-ionic surfactant vesicle delivery system to protect against Leishmania donovani infection in a BALB/c mouse model. Immunization with gammaglutamyl cysteine synthetase alone or gammaglutamyl cysteine synthetase-NIV induces specific IgG1 and IgG2a antibodies compared to controls, with gammaglutamyl cysteine synthetase-NIV inducing significantly higher titers of both antibody classes. Both formulations induce similar increases in splenocyte IFN-gamma production following ex vivo antigen stimulation with gammaglutamyl cysteine synthetase compared with cells from control mice. Similar levels of protection against infection are induced by gammaglutamyl cysteine synthetase alone and gammaglutamyl cysteine synthetase-NIV, based on their ability to suppress liver parasite burdens compared to control values 6.3.2.2 glutamate-cysteine ligase medicine suitability of treatment of humans with exogenous enzyme gamma-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases 6.3.2.2 glutamate-cysteine ligase medicine the enzyme is a target for development of a vaccination against ancylostomiasis 6.3.2.3 glutathione synthase medicine the enzyme is a target for therapy of disease like diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells, since manipulation of the GSH synthetic capacity is beneficial in treatment of many of these disorders 6.3.2.6 phosphoribosylaminoimidazolesuccinocarboxamide synthase medicine phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is an important bifunctional enzyme in de novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (SAICARs) activities. It is an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway 6.3.2.10 UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase medicine MurF is a potential target for antibacterial design because it is unique to bacteria and performs an essential non-redundant function in the bacterial cell 6.3.2.12 dihydrofolate synthase medicine study on therapeutic efficacy of sulfadoxine-pyrimethamine at two locations in the Peruvian Amazon in order to correlate the presence of polymorphisms in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase to in vitro parasite susceptibility to sulfadoxine and pyrimethamine and to in vivo treatment outcomes. A single mutation present in the isolate obtained at the time of enrollment from either dihydrofolate reductase, 164L, or dihydropteroate synthase, 540E, predicts treatment failure as well as any other single gene alone or in combination. Patients carrying parasites with the dihydrofolate reductase 164L mutation are 3.6times as likely to be treatment failures while patients carrying parasites with the dihydropteroate synthase 540E mutation are 2.6times as likely to fail treatment. Patients with both dihydrofolate reductase 164L and dihydropteroate synthase 540E mutations are 4.1times as likely to be treatment failures compared to patients having both wild forms I164 and K540 6.3.2.12 dihydrofolate synthase medicine target for antimalarial therapy 6.3.2.17 tetrahydrofolate synthase medicine the enzyme inhibition can be useful for cancer chemotherapy 6.3.2.17 tetrahydrofolate synthase medicine pemetrexed shows potent cytotoxicity in 211-H cells compared to A-549 cells and H-1299 cells, accompanied by significantly higher expression of foloylpolyglutamate synthase and reduced folate carrier 1. Simulltaneous exposure of pemtrexed and gemcitabine is antagonistic in all cell lines tested, while strong synergism is observed in 211-H cells when pemetrexed precedes gemcitabine 6.3.2.17 tetrahydrofolate synthase medicine reduced folate carrier-1 and folylpolyglutamate synthase gene expression levels are significantly correlated in patients lacking p16 promoter hypermethylation in mucosa, but not at all correlated in patients having hypermethylation in mucosa. p16 Hypermethylation in mucosa of colorectal cancer patients is an independent prognostic parameter for cancer-specific survival as well as an independent predictor of disease-free survival 6.3.2.17 tetrahydrofolate synthase medicine siRNA transfected into DLD-1 cells to downregulate folylpolyglutamate synthase reduces the basal level of reduced folate, the folate level after leucovorin treatment, and the enhancement of 5-fluoro-2'-deoxyuridine-induced cytotoxicity elicited by leucovorin. Folylpolyglutamate synthase and gamma-glutamyl hydrolase expression levels in tumors are determinants of the efficacy of leucovorin in enhancing the antitumor activity of 5-fluorouracil 6.3.2.17 tetrahydrofolate synthase medicine target for antimalarial therapy 6.3.2.17 tetrahydrofolate synthase medicine FPGS rs1544105 alleles are demonstrated to be an indicator for poor prognosis 6.3.2.26 N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase medicine production of penicillin 6.3.2.35 D-alanine-D-serine ligase medicine of 7271 Enterococcus-containing clinical samples collected between 2004 and 2009, 16 vancomycin resistant enterococci were identified. The vanC1 resistance gene was found in 14 Enterococcus gallinarum and the vanC2 resistance gene in two Enterococcus casseliflavus strains. Except for two samples, the isolates have different pulsed-field gel electrophoresis types, suggesting sporadic emergence of the resistant bacteria 6.3.2.35 D-alanine-D-serine ligase medicine emergence of vancomycin resistance in Clostridium argentinense due to decryptification of the vanGCar gene cluster could occur 6.3.2.35 D-alanine-D-serine ligase medicine the distribution of Enterococcus faecium and Enterococcus faecalis containing vanC2/3 is observed in sewage and urban river water samples 6.3.2.43 [amino group carrier protein]-L-2-aminoadipate ligase medicine in the presence of antimicrobial peptides produced by epithelial cells and macrophages, lysX expression increases significantly. Strains with higher lysX expression show increased levels of intracellular survival in vivo and in vitro and induce more severe lesion related with pneumonia. The ability of Mycobacterium tuberculosis to replicate intracellularly is directly correlated to the level of lysX expression 6.3.3.2 5-formyltetrahydrofolate cyclo-ligase medicine the enzyme is important in cancer treatment to rescue cells from high dose levels of the anti-folate methotrexate, and to potentiate the antitumor activity of 5-fluorouracil 6.3.3.2 5-formyltetrahydrofolate cyclo-ligase medicine identification of four patients from two different families, due to a missense mutation (c.806C>T, p.Thr296Ile) and a splice site mutation (c.1674G>A) leading to exon skipping,while the other three patients harboured a missense mutation (c.146C>T, p.Ser49Phe) and a premature stop mutation (c.673G>T, p.Glu225*). Patient fibroblasts show severely reduced methionine formation from [14C]-formate, which does not increase in cobalamin supplemented culture medium but is responsive to folic and folinic acid 6.3.4.2 CTP synthase (glutamine hydrolysing) medicine the enzyme is an target for treatment of African sleeping sickness because the trypanosomes, unlike mammalian cells, cannot compensate for the inhibition of CTP synthetase by the salvage of cytidine. The CTP synthetase inhibitors 6-diazo-5-oxo-L-norleucine and alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid reduce the parasite CTP level even further and inhibit trypanosome proliferation in vitro and in Trypanosoma brucei-infected mice 6.3.4.2 CTP synthase (glutamine hydrolysing) medicine glutamine deficiency induces CTPS cytoophidia in human Huh-7 cells. CTPS cytoophidia are found in various human cancers and some noncancerous tissues. Among 203 tissue samples of hepatocellular carcinoma, 28% exhibited many cytoophidia, whereas no cytoophidia are detected in adjacent noncancerous hepatocytes for all samples 6.3.4.3 formate-tetrahydrofolate ligase medicine MTHFD1L may be involved in OSCC progression via the c-MYC gene and p53 signaling and may serve as a target and orientation for tumor therapy 6.3.4.4 adenylosuccinate synthase medicine enzymes of the salvage pathway are good targets for anti-parasitic drugs 6.3.4.4 adenylosuccinate synthase medicine most parasitic protozoa lack the de novo purine biosynthetic pathway and rely exclusively on the salvage pathway for their purine biosynthetic pathway, enzymes of the salvage pathway are candidate drug targets 6.3.4.4 adenylosuccinate synthase medicine target of drugs 6.3.4.4 adenylosuccinate synthase medicine the adenylosuccinate synthase gene is not associated with susceptibility for schizophrenia 6.3.4.4 adenylosuccinate synthase medicine genetic variation of inosine triphosphatase causing an accumulation of inosine triphosphate protects patients against ribavirin-induced anemia during treatment for chronic hepatitis C infection. ITP can be used for ATP biosynthesis via adenylosuccinate synthase in place of guanosine triphosphate. With ribavirin challenge, erythrocyte ATP reduction is more severe in the wild-type inosine triphosphatase ITPA genotype than in the hemolysis protective ITPA genotype. The alleviation of ATP reduction by the hemolysis protective ITPA genotype is canceled by the adenylosuccinate synthase inhibitor 6-mercaptoethanol 6.3.4.5 argininosuccinate synthase medicine AS and GTP cyclohydrolase I are intimately associated with inflammatory arthritis, they may be important modulators of arthritis and may represent novel targets for modulation of disease activity 6.3.4.5 argininosuccinate synthase medicine citrulline-arginine recycling enzyme, intervention in the supply of arginine may represent a new therapeutic approach to the treatment of NO-mediated neurodegenerative damage in the brain 6.3.4.5 argininosuccinate synthase medicine neuronal and glial ASS expression is increased in brains of patients with Alzheimer disease 6.3.4.5 argininosuccinate synthase medicine a case of late-onset CTLN1 (citrullinemia) in a patient is described by biochemical analyses and ASS gene mutation confirmation. This is the first report of a Korean patient with late-onset CTLN1 confirmed by ASS gene mutation identification 6.3.4.5 argininosuccinate synthase medicine argininosuccinate synthetase is inhibited by endotoxin, implying that bacterial products might potentially regulate the arginine metabolism in the host and perturb NO synthesis 6.3.4.5 argininosuccinate synthase medicine the downregulation of tumor necrosis factor-alpha is an added insult to endothelial function because of its important role in NO production and in endothelial viability 6.3.4.5 argininosuccinate synthase medicine transient ischemia induces changes in nitric oxide synthase, argininosuccinate synthetase and argininsuccinate lyase co-expression in the rat striatal neurons. At 24 h after reperfusion in the animals with a longer survival and better motor-sensory performances there is an increase in these neuronal populations. It is hypothesized that the elevated expression of argininosuccinate synthetase and argininsuccinate lyase protects ischemic striatal neurons from tissue damages by maintaining a correct NO production 6.3.4.5 argininosuccinate synthase medicine novel target for the therapy of hypertension-related disorders 6.3.4.5 argininosuccinate synthase medicine potential novel therapeutic strategies for ovarian cancer 6.3.4.5 argininosuccinate synthase medicine potential target in platinum sensitive tumours 6.3.4.5 argininosuccinate synthase medicine argininosuccinate synthase 1 is upregulated in primary human colorectal tumors and pharmacological inhibition or genetic ablation of ASS1 impairs colorectal cancer pathogenicity. ASS1 inhibition leads to reductions in the levels of oncogenic metabolite fumarate, leading to impairments in glycolytic metabolism that supports colorectal cancer cell pathogenicity 6.3.4.5 argininosuccinate synthase medicine argininosuccinate synthase Ass contributes to ethanol plus Fas/CD95 agonistic antibody Jo2-mediated liver injury. NOS2 induction, 3-nitrotyrosine adducts formation and elevated nitrites, nitrates and S-nitrosothiols are higher in livers from wild-type mice than from Ass+/- mice 6.3.4.5 argininosuccinate synthase medicine argininosuccinate synthase ASS1 is significantly downregulated in the urine of 30 depressed subjects while remaining unchanged in the plasma. ASS1 displays strong efficacy in distinguishing major depressive disorder subjects from healthy controls 6.3.4.5 argininosuccinate synthase medicine unclassified hepatocellular carcinomas display specific up-regulation of the arginine synthesis pathway associated with overexpression of argininosuccinate synthase (ASS1) and arginosuccinate lyase. All the unclassified hepatocellular carcinomas tested could be identified by ASS1 immunohistochemistry, and 64.7% of these carcinomas presented clinical bleeding manifestations. The significance of ASS1 also encompasses certain hemorrhagic cases, particularly inflammatory hepatocellular carcinomas 6.3.4.10 biotin-[propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase medicine HCS deficiency results in biotin-responsive multiple carboxylase deficiency 6.3.4.10 biotin-[propionyl-CoA-carboxylase (ATP-hydrolysing)] ligase medicine identifaction of patients with holocarboxylase synthetase deficiency by newborn screening 6.3.4.13 phosphoribosylamine-glycine ligase medicine high GART expression is observed in glioma and is related to the grade of malignancy. GART overexpression is significantly associated with overall survival. Transfecting cells with GART-siRNA suppresses proliferation and enhances temozolomide-induced apoptosis in glioma cells 6.3.4.14 biotin carboxylase medicine the three biotin carboxylase mutants M169K, R338Q and R338S are used for study in order to mimic the disease-causing mutations M204K and R374Q of propionyl-CoA carboxylase and R385S of 3-methylcrotonyl-CoA carboxylase, which are mutations found in propionic acidemia or methylcrotonylglycinuria patients 6.3.4.14 biotin carboxylase medicine identification of mutations of the pyruvate carboxylase gene that cause pyruvate carboxylase deficiency. Deficiency form A results from association of two missense mutations located in biotin carboxylase or carboxyltransferase N-terminal part domains. Although most pyruvate carboxylase mutations are suggested to interfere with biotin metabolism, none of the pyruvate carboxylase-deficient patients tested is biotin-responsive 6.3.4.16 carbamoyl-phosphate synthase (ammonia) medicine human hepatocellular carcinoma cells do not express CPS1, whereas cultured human primary hepatocytes express abundant levels. CPS1 is silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues. The expression of CPS1 in human hepatocellular carcinoma cells is restored with demethylation agent, 5-azacytidine. Two CpG dinucleotides, located near the transcription start site, and a CpG-rich region in the first intron are hypermethylated in human hepatocellular carcinoma cells 6.3.4.16 carbamoyl-phosphate synthase (ammonia) medicine upregulation of CPS1 gene most significantly predicts poor response to neoadjuvant concurrent chemoradiotherapy. CPS1 overexpression is significantly related to advanced posttreatment tumor and nodal status, and inferior tumor regression grade. CPS1 overexpression is significantly associated with shorter disease-specific survival and metastasis-free survival. CPS1 protein expression is more abundant in colon cancer cells than nonneoplastic HCoEpiC 6.3.4.18 5-(carboxyamino)imidazole ribonucleotide synthase medicine observed only in microorganisms, target for antimicrobial drug 6.3.4.18 5-(carboxyamino)imidazole ribonucleotide synthase medicine target for antimicrobial agents 6.3.4.19 tRNAIle-lysidine synthase medicine lysidine/TilS is a eubacterial-specific system of AUA decoding. Therefore, TilS is an ideal target for a broad-spectrum antibacterial agent 6.3.4.21 nicotinate phosphoribosyltransferase medicine NAPRT is amplified and overexpressed in a subset of common types of cancer, including ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression signature. Both NAPRT and nicotinamide phosphoribosyltransferase NAMPT increase intracellular NAD+ levels. NAPRT silencing reduces energy status, protein synthesis, and cell size in ovarian and pancreatic cancer cells. NAPRT silencing sensitizes cells to NAMPT inhibitors both in vitro and in vivo. Reducing NAPRT levels in a BRCA2-deficient cancer cell line exacerbates DNA damage in response to chemotherapeutics 6.3.5.1 NAD+ synthase (glutamine-hydrolysing) medicine erythrocyte NAD synthetase is activated by lead, and the activity is a sensitive indicator of lead exposure in human 6.3.5.2 GMP synthase (glutamine-hydrolysing) medicine the enzyme is a viable target for development of antimalarial chemotherapy 6.3.5.3 phosphoribosylformylglycinamidine synthase medicine in fibroblasts infected with the human pathogen herpes simplex virus 1, FGAMS immunolabeling shifts from a diffuse cytoplasmic location to a mainly perinuclear localization by 12 hours post infection. In infected rat neurons, FGAMS localization shows no discernable changes. There are no changes in total FGAMS protein levels in either cell type 6.3.5.4 asparagine synthase (glutamine-hydrolysing) medicine analysis of asparagine synthetase mRNA expression in 19 ovarian cancer cell lines. L-Asparaginase activity is only weakly correlated with asparagine synthetase mRNA expression, while asparagine synthetase protein expression measured by liquid-phase immunoassay exhibits a much stronger correlation 6.3.5.4 asparagine synthase (glutamine-hydrolysing) medicine mass spectrometry-based procedure for the direct quantification of asparagine synthetase protein concentration in complex sample mixtures. Assay is able to distinguish samples from transformed cell lines that express the enzyme over a wide dynamic range of concentration. The method directly detects asparagine synthetase protein, use in blast samples from patients with acute lymphoblastic leukemia 6.3.5.5 carbamoyl-phosphate synthase (glutamine-hydrolysing) medicine serum samples from patients with acute liver failure due to acetaminophen, Wilson disease, or ischemia show readily detectable CPS1 that i not observed in patients with chronic viral hepatitis or in control donors. CPS1 rapidly decreases to undetectable levels in sera of patients with acetaminophen-related acute liver failure who ultimately recover 6.4.1.1 pyruvate carboxylase medicine A610T mtation leads to type A pyruvate carboxylase deficiency, no import of the enzyme into mitochondria 6.4.1.1 pyruvate carboxylase medicine pyruvate decarboxylase deficiency is an autosomal, recessively inherited disease, patients have less than 5% of normal enzyme activity. Four single point mutations are responsible for some forms of the disease: V145A, R451C, A610T and M743I 6.4.1.1 pyruvate carboxylase medicine identification of mutations of the pyruvate carboxylase gene, in five unrelated patients. Pyruvate deficiency form B is consistently associated with at least one truncating mutation, mostly lying in the C-terminal part of carboxyltransferase or BCCP domains, whereas form A always results from association of two missense mutations located in biotin carboxylase or N-terminal part of carboxyltransferase domains. Although most pyruvate carboxylase mutations are suggested to interfere with biotin metabolism, none of the newly identified pyruvate carboxylase-deficient patients is biotin-responsive 6.4.1.1 pyruvate carboxylase medicine in lung tumor tissue, pyruvate carboxylase shows increased levels of protein and mRNA 6.4.1.1 pyruvate carboxylase medicine in mildly hyperglycemic type 2 diabetic Agouti-K mice, islet pyruvate carboxylase activity, but not protein level, is increased 1.7fold. In severely hyperglycemic type 2 diabetic Agouti-K mice, islet pyruvate carboxylase activity and protein level are reduced. all other changes including insulin secretion and islet morphology in diabetic Agouti K mice are similar to those of obese Agouti mice 6.4.1.1 pyruvate carboxylase medicine treatment of cultured 3T3-L1 adipocytes with inhibitor phenylacetate. Inhibiting the enzyme over several days does not alter the adipocyte differentiation program. The main metabolic effects are to up-regulate intracellular lipolysis and decrease triglyceride accumulation. Inhibition also up-regulates glycolysis. The reduction in triglycerides is due to decreased de novo fatty acid synthesis. Exogenous addition of free fatty acids dose-dependently increases the cellular triglyceride level in the inhibitor-treated adipocytes, but not in untreated control cells 6.4.1.1 pyruvate carboxylase medicine induction of pyruvate decarboxylase during chronic suppression of glutamine metabolism is a mechanism of resistance to therapies targeting glutaminolysis 6.4.1.1 pyruvate carboxylase medicine cancerous tissues of patients with early-stage non-small-cell lung cancer display enhanced pyruvate carboxylase activity. Pyruvate carboxylase overexpression is found in cancer cells rather than in stromal cells of tumor tissues. Pyruvate carboxylase knockdown induces multinucleation, decreases cell proliferation and colony formation in human non-small-cell lung cancer cells, and reduces tumor growth in a mouse xenograft model 6.4.1.1 pyruvate carboxylase medicine pyruvate carboxylase is expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. There is a statistical association between the levels of pyruvate carboxylase expression and tumor size and tumor stage. The abundance of both pyruvate carboxylase mRNA and protein in MDA-MB-231 and MDA-MB-435 cells is 2-3fold higher than that in MCF-7 and SKBR-3 cells. siRNA-mediated knockdown of expression in MDA-MB-231 and MDA-MB-435 cells results in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of pyruvate carboxylase in MCF-7 cells results in a 2fold increase in their proliferation rate, migration and invasion abilities 6.4.1.2 acetyl-CoA carboxylase medicine possible use of ACC inhibitors for diabetes therapy 6.4.1.3 propionyl-CoA carboxylase medicine propionyl-CoA carboxylase is a sensitive indicator of biotin status 6.4.1.3 propionyl-CoA carboxylase medicine stringent model of propionyl CoA carboxylase subunit A deficiency, where homozygous knock-out mice are born, but die within 36 hours. Injection of vectors expressing propionyl CoA carboxylase subunit A significantly increases the lifespan for both unmodified and polyethylene glycol modified vectors, but the rescue is transient 6.4.1.3 propionyl-CoA carboxylase medicine living-donor liver transplantation is an effective treatment modality in patients with congenial metabolic liver disease, i. e., propionic acidemia caused by deficiency in propionyl-CoA carboxylase 6.4.1.3 propionyl-CoA carboxylase medicine treatment of propionic acidemia by import of a biologically active, fully assembled propionyl-CoA carboxylase dodecamer, posttranslationally chemically conjugated with the HIV TAT peptide. TAT-propionyl-CoA carboxylase is transferred into isolated mitochondria, as well as into mitochondria of patient fibroblasts . A single-dose intraperitoneal injection into propionyl-CoA carboxylase-deficient mice decreases the propionylcarnitine/acetylcarnitine (C3/C2) ratio toward the normal level 6.4.1.4 methylcrotonoyl-CoA carboxylase medicine studies of the c.1054G3A mutation in exon 11 of subunit MCCB detected in the homozygous state in a patient with 3-methylcrotonyl-CoA carboxylase deficiency. Sequence analysis of MCCB cDNA revealed two overlapping transcripts, one containing the normal 73 bp of exon 11 including the missense mutation c.1054G3A, i.e. p.G352R, the other with exon 11 replaced by a 64-bp sequence from intron 10, i.e. cryptic exon 10a that maintains the reading frame and is flanked by acceptable splice consensus sites. Both transcripts lack detectable 3-methylcrotonyl-CoA carboxylase activity. The reduction in utilization of exon 11 associated with the c.1054G3A mutation is due to alteration of this exon splice enhancer 6.4.1.4 methylcrotonoyl-CoA carboxylase medicine study of a family with 3-methylcrotonyl-CoA carboxylase deficiency with different clinical features. The three patients display elevated urinary 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, elevated 3-hydroxyisovalerylcarnitine and decreased free carnitine levels. Methylcrotonyl-CoA carboxylase activity in cultured fibroblasts displays a low residual activity of 2.2% of the median control value while propionyl-CoA carboxylase activity is normal in the index patient. Mutation analysis reveals a large homozygous deletion of 2264 bp, i.e. c.873þ4524_6787de12264 in the subunit MCCA gene 6.4.1.6 acetone carboxylase medicine inactivation of operon acxABC encoding acetone carboxylase with a chloramphenicol resistance cassette. In mouse colonization studies the numbers of Helicobacter pylori recovered from mice inoculated with the acxB:cat mutant are generally one to two orders of magnitude lower than those recovered from mice inoculated with the parental strain 6.5.1.2 DNA ligase (NAD+) medicine potential target for antibiotics 6.5.1.2 DNA ligase (NAD+) medicine potential target for antibiotics due to the fact that eukaryotic cells use ATP instead of NAD+ as cofactor for DNA-ligase 6.5.1.2 DNA ligase (NAD+) medicine potential target for antiobiotics 6.5.1.2 DNA ligase (NAD+) medicine although NAD+-dependent DNA ligase is essential for mycobacterial viability, only low levels of protein are required for growth. very efficient inhibition of enzyme activity would be required if NAD+-dependent DNA ligase is to be useful as an antibiotic target in mycobacteria 6.5.1.2 DNA ligase (NAD+) medicine NAD+-dependent ligases can serve as a valuable target in the development if chemotherapeutics for the treatment of numerous human ailments 6.5.1.2 DNA ligase (NAD+) medicine NAD+-dependent ligases can serve as a valuable target in the development of chemotherapeutics for the treatment of numerous human ailments 6.5.1.3 RNA ligase (ATP) medicine regulated repression of the enzyme blocks editing, this repression is lethal in bloodforms of the parasite, indicating that editing is essential in the mammalian stage of the life cycle, the editing complex, which is present in all kinetoplastid parasites, may thus be a chemotherapeutic target 7.1.1.1 proton-translocating NAD(P)+ transhydrogenase medicine after 20 weeks on a high-fat diet, Nnt-/- mice exhibit a higher prevalence of steatohepatitis and content of liver triglycerides compared to Nnt+/+ mice on an identical diet. Under a a high-fat diet, the aggravated non-alcoholic fatty liver disease phenotype in the Nnt-/- mice is accompanied by an increased H2O2 release rate from mitochondria, decreased aconitase activity and higher susceptibility to Ca2+-induced mitochondrial permeability transition. A high-fat diet leads to the phosphorylation (inhibition) of pyruvate dehydrogenase and markedly reduces the ability of liver mitochondria to remove peroxide in Nnt-/- mice. Compared to mice that are chow-fed, a high-fat diet does not impair peroxide removal nor elicit redox imbalance in mitochondria from Nnt+/+ mice 7.1.1.1 proton-translocating NAD(P)+ transhydrogenase medicine in cardiac mitochondria from NNT-competent mice, H2O2 emission is equally low with pyruvate/malate or 2-oxoglutarate as substrates. In NNT-deficient mitochondria, H2O2 emission is higher with 2-oxoglutarate than with pyruvate/malate as substrate, and further potentiated by complex I blockade. NADH from 2-oxoglutarate dehydrogenase selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. In heart failure, 2-oxoglutarate dehydrogenase/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade 7.1.1.1 proton-translocating NAD(P)+ transhydrogenase medicine in peripheral blood mononuclear cells, palmitate decreases immune cell expression of NNT, NADPH, and anti-oxidant glutathione, but increases reactive oxygen and proinflammatory Th17 cytokines. Oleate has no effect on these outcomes. Genetic inhibition of NNT recapitulates the effects of palmitate. Peripheral blood mononuclear cells from obese (BMI >30) compared to lean subjects have lower NNT and glutathione expression, and higher Th17 cytokine expression, none of which are changed by exogenous palmitate 7.1.1.1 proton-translocating NAD(P)+ transhydrogenase medicine NNT activity is about 30% lower in cystic fibrosis cells than healthy cells. The cellular redox state, together with the low mitochondrial membrane potential, pushes to drive NNT reverse reaction, at the expense of its antioxidant potential, thus consuming NADPH to support NADH production. At the same time, the reduced NNT activity prevents the NADH, produced by the reaction, from causing an explosion of ROS by the damaged respiratory chain, in accordance with the reduced level of mitochondrial ROS in NNT-loss cells 7.1.1.1 proton-translocating NAD(P)+ transhydrogenase medicine NNT expression significantly enhances tumor formation and aggressiveness in mouse models of lung tumor initiation and progression 7.1.1.1 proton-translocating NAD(P)+ transhydrogenase medicine transient knockdown of NNT in NCI-H295R cells increases intracellular levels of oxidative stress, resulting in a pronounced suppression of cell proliferation, higher apoptotic rates, and sensitization of cells to chemically induced oxidative stress. Steroidogenesis is stimulated by NNT loss. In a stable NNT knockdown model in the same cell line, after long-term culture, cells adapt metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remains suppressed. This is associated with higher rates of oxygen consumption 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine a deficient activity of the NADH:ubiquinone oxidoreductase enzyme complex is frequently observed in clinical heterogeneous group of mitochondrial disorders with Leigh (-like) disease as the main contributor. Enzyme complex activity measurement in skeletal muscle is the mainstay of the diagnostic process. Fibroblast studies are a prerequisite whenever prenatal enzyme diagnostic is considered 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine the NDI1 gene provides a potentially useful tool for gene therapy of mitochondrial diseases caused by complex I deficiency 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine the doxorubicin-inhibited NADH-quinone-reductase may provide a target for the anthracycline antitumor agents 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine a systemic defect in complex I activity is not present in early Huntington's disease when striatal neuronal degeneration is already present 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine complex I deficient patients show a specific increase in superoxide dismutase activity. Reactive oxygen species production remains significantly elevated in complex I deficient patients compared to controls, whereas glutathione peroxidase, catalase and glutathione-S-transferase are significantly reduced. Information on the status of reactive oxygen species and marking the alteration of reactive oxygen species scavenging enzymes in peripheral lymphocytes or lymphoblast cell lines will provide a better way to design antioxidant therapies for such disorders like complex I deficiency 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine correlation between peripheral complex I activity and cerebral glucose metabolism in regions implicated in schizophrenia, may be a pathological factor that is differentially expressed in subgroups of schizophrenic patients 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine enzymes activated by DNA damage, e.g. mediated by complex I inhibition, are an important feature in the process of neuronal apoptosis 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine identification of a NDUFS7 mutation in a consanguineous family with Leigh syndrome and isolated complex I deficiency 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine inhibition of complex I may elicit enhanced formation of reactive oxygen species and contribute thus to neuronal injury 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine mitochondrial complex I plays an important role in modulating Toll-like receptor 4-mediated neutrophil activation. Metformin, as well as other agents that inhibit mitochondrial complex I, may be useful in the prevention or treatment of acute inflammatory processes in which activated neutrophils play a major role, such as acute lung injury 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinson’s disease in rodents. Cell vulnerability in the rotenone model of partial complex I deficiency is primarily determined by spare respiratory capacity rather than oxidative stress 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine radiolabeled MC-I inhibitors as potential myocardial perfusion imaging agents 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine superoxide production is increased in children with inherited complex I deficiency, which is primarily a consequence of the reduction in cellular complex I activity and not of a further leakage of electrons from mutationally malformed complexes 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine cellular levels of reactive oxygen species are significantly increased in cells of patients with DNA-inherited isolated complex I deficiency. This increase is associated with variable decreases in the amount and intrinsic catalytic activity of complex I. Chronic treatment with a vitamin E derivative (Trolox) increases the amount of complex I and might provide an experimental basis for the use of antioxidants to treat complex I deficient patients 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine cellular levels of reactive oxygen species are significantly increased in cells of patients with nDNA-inherited isolated complex I deficiency. This increase is associated with variable decreases in the amount and intrinsic catalytic activity of complex I. Chronic treatment with a vitamin E derivative (Trolox) increases the amount of complex I and might provide an experimental basis for the use of antioxidants to treat complex I deficient patients 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine mutations in NADH dehydrogenase ND subunits of complex I are an important genetic cause of childhood mitochondrial encephalopathies 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine NADH dehydrogenase activity in the platelets of patients with Parkinson's disease from an Indian population is lower than that in healthy age and gender-matched controls. The study contribute to the evidence of mitochondrial dysfunction playing a major role in the disease mechanism of Parkinson's disease and opens avenues for therapeutic intervention 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine gene therapy approaches involving Ndi1p may offer substantial clinical benefits in cases of complex I deficiency 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine alterations in mitochondrial membrane complex MMC-I may constitute an inheritable risk factor for endometriosis. MMC-I expression in eutopic endometria of patients is elevated compared to controls. Haplotype 10398A/10400C/13603AG and haplogroup N show higher endometriosis risk 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine in rats subjected to left descending artery occlusion followed by reperfusion, treatment with 3,4-dihydroxyl-phenyl lactic acid ameliorates myocardial structure and function disorder, blunts the impairment of Complex I activity and mitochondrial function after ischemia/reperfusion. 3,4-Dihydroxyl-phenyl lactic acid DLA is able to prevent ischemia/reperfusion-induced decrease in NDUFA10 expression, improve complex I activity and mitochondrial function, eventually attenuate cardiac structure and function injury after ischemia/reperfusion 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) medicine metformin used in treatment for type II diabetes mellitus, inhibits activity of NADH:ubiquinone oxidoreductase (complex I) 7.1.1.7 quinol oxidase (electrogenic, proton-motive force generating) medicine cytochrome bd-I respiratory oxidase is the main contributor to NO tolerance and host colonisation under microaerobic conditions. Uropathogenic Escherichia coli strains have acquired a host of specialized mechanisms to evade nitrosative stresses 7.1.1.8 quinol-cytochrome-c reductase medicine complex III deficiency in the muscle mitochondria 7.1.1.8 quinol-cytochrome-c reductase medicine peripheral arterial disease 7.1.1.8 quinol-cytochrome-c reductase medicine test of respiratory-chain dysfunction in human mitochondrial myopathies 7.1.1.8 quinol-cytochrome-c reductase medicine serum ubiquinol cytochrome c reductase hinge is a diagnostic biomarker for lung adenocarcinoma 7.1.1.8 quinol-cytochrome-c reductase medicine the enzyme is a potential independent favorable prognostic factor for recurrence and survival of patients with clear cell renal cell carcinoma after nephrectomy 7.1.1.9 cytochrome-c oxidase medicine at therapeutic concentrations used for asthma relief, theophylline causes inhibition of the lung enzyme and decreases cellular ATP levels, suggesting a mechanism for its clinical action 7.1.1.9 cytochrome-c oxidase medicine A122T, i.e. m.6267G>A is a recurrent missense mutation in mitochondrially encoded cytochrome oxidase I specifically associated with cancer 7.1.1.9 cytochrome-c oxidase medicine amyloid beta which is involved in Alzheimer’s disease, specifically inhibits cytochrome-c oxidase 7.1.1.9 cytochrome-c oxidase medicine enzyme isoform cytochrome oxifdase III interacts with hepatitis B virus X protein 7.1.1.9 cytochrome-c oxidase medicine in skeletal muscle and brain of patients with mutations in genes SCO2 or SURF1, cytochrome-c oxidase holoenzyme is reduced to 10-20%, and to 10-30% in heart, whereas liver contains normal levels of enzyme. Heart, brain, and skeletal muscle of patients contain accumulated levels of enzyme subcomplexes of different subunits, but lacking subunit COX2. SCO2 is presumably involved in formation of the CuA centre of the COX2 subunit, and the lack of the CuA centre may result in decreased stability of COX2 7.1.1.9 cytochrome-c oxidase medicine 6W/Kg GSM 900MHz microwaves may affect brain metabolism and neuronal activity (cytochrome c oxidase activity) in rats 7.1.1.9 cytochrome-c oxidase medicine a single injection of exogenous cytochrome c 24 h post-cecal ligation and puncture repletes mitochondrial substrate levels for up to 72 h, restores myocardial COX activity, and significantly improves survival 7.1.1.9 cytochrome-c oxidase medicine antipsychotic drugs do not alter COX 7.1.1.9 cytochrome-c oxidase medicine CO histochemistry, which reflects neuronal activity, is altered at all levels of the auditory system in Relnrl-Orl mutants (with Orleans mutation, which selectively affects cell migration, cell orientation, and to a more limited extent, cell number in the brain tissue) 7.1.1.9 cytochrome-c oxidase medicine COX deficiency is a common cause of human mitochondrial disease 7.1.1.9 cytochrome-c oxidase medicine cytochrome oxidase deficiency is a result of heme deficiency that may be relevant to the demyelinating phenotype of the neurodegenerative disease Friedreich's ataxia. Heme-based stimulation of iron–sulfur cluster biogenesis is a rational strategy for the neurodegenerative disease Friedreich's ataxia 7.1.1.9 cytochrome-c oxidase medicine cytochrome oxidase is a metabolic target of caffeine. Stimulation of Cox activity by caffeine via blockade of A2AR signaling may be an important mechanism underlying the therapeutic benefits of caffeine in Parkinson’s disease 7.1.1.9 cytochrome-c oxidase medicine evidence of secondary loss of electron transport chain function (loss of complex II-III activity) resulting from a primary electron transport chain deficiency (of complex IV), which provides a possible mechanism for the progressive nature of mitochondrial encephalomyopathies and why in some patients multiple patterns of electron transport chain deficiencies may be demonstrated 7.1.1.9 cytochrome-c oxidase medicine hypoxia synergises with NO from neuronal nitric oxide synthase to induce neuronal death via cytochrome oxidase inhibition causing neuronal depolarisation. Neuronal nitric oxide synthase activity sensitises the cells to hypoxic-inhibition of cytochrome oxidase 7.1.1.9 cytochrome-c oxidase medicine in HIV-associated dementia, cortical neurons demonstrate decreased respiration upon HIV-1 neurotoxin trans activator of transcription proteint treatment, consistent with inhibition of the enzyme 7.1.1.9 cytochrome-c oxidase medicine lack of energy after traumatic brain injury caused by inhibition of CcO may be an important aspect of trauma pathology 7.1.1.9 cytochrome-c oxidase medicine low prenatal Cu intake by dams is the determinant of CCO activity in cardiac mitochondria of 21-d-old offspring and may lead to the assembly of a less-than-fully active holoenzyme 7.1.1.9 cytochrome-c oxidase medicine myocardial CcOX impairment can underlie CO induced cardiac dysfunction 7.1.1.9 cytochrome-c oxidase medicine protein kinase C epsilon is activated by hypoxia, which results in the activation of the mitochondrial protein CytCOx, which can protect the lens from mitochondrial damage under naturally hypoxic conditions observed in this tissue 7.1.1.9 cytochrome-c oxidase medicine recovery of enhanced cytochrome-c oxidase activity may play a role in ischemic preconditioning protection 7.1.1.9 cytochrome-c oxidase medicine relationship between the allosteric ATP-inhibition and phosphorylation of CcO subunit I, which apparently occurs in living cells, but is lost under stress (e.g. hypoxic stress) 7.1.1.9 cytochrome-c oxidase medicine simultaneous decrease in 2-deoxyglucose uptake and increase in COI mRNA expression are difficult to reconcile with the current model of basal ganglia function and suggest that the mechanisms by which high-frequency stimulation of the subthalamic nucleus exerts its clinical benefits are more complex than a simple reversal of abnormal activity in the subthalamic nucleus and its targets 7.1.1.9 cytochrome-c oxidase medicine the cholinesterase and monoamine oxidase inhibitor ladostigil may have a beneficial effect on cognitive deficits in Alzheimer's disease patients that have a reduction in cortical COx activity and cholinergic hypofunction 7.1.1.9 cytochrome-c oxidase medicine mutations in various mitochondrial enzymes can result in Leigh syndrome, among them cytochrome c oxidase 7.1.1.9 cytochrome-c oxidase medicine the copper-enzyme cytochrome c oxidase has been indicated as a primary molecular target of mutant copper, zinc superoxide dismutase in familial amyotrophic lateral sclerosis 7.1.2.2 H+-transporting two-sector ATPase medicine ATP hydrolysis by F1FO-ATPase is well preserved after hypoxia/reoxygenation as long as Mg2+ is available, indicating that function of the enzyme is largely intact, but ATP hydrolysis by F1FO-ATPase does not restore mitochondrial membrane potential as much as expected from the rate of ATP utilization, it is likely that uncoupling plays a major role in the mitochondrial dysfunction in proximal tubules during hypoxia/reoxygenation 7.1.2.2 H+-transporting two-sector ATPase medicine F0F1 ATP synthase activity transiently increases during nonpreconditioned coronary reactive hyperemia, decreases 4 min after nonpreconditioned coronary reactive hyperemia and returns to control 2 min later, it is lower after ischemic preconditioning and does not change during and after preconditioned coronary reactive hyperemia, postischemic long-lasting inhibition of the enzyme activity may be a feature of the preconditioned heart 7.1.2.2 H+-transporting two-sector ATPase medicine when hyperemia is induced before ischemic preconditioning, a steep increase in synthase capacity, followed by a deep decrease can be observed, hyperemia does not affect synthase capacity when applied after ischemic preconditioning, similar effects in vitro by treatment of heart biopsy samples with anoxia, which down-regulates, or high salt or high pH buffers, which up-regulates 7.1.3.1 H+-exporting diphosphatase medicine enzyme might serve as effective drug target 7.2.1.1 NADH:ubiquinone reductase (Na+-transporting) medicine about 50% of all mitochondrial disorders affecting the energy metabolism can be traced to mutations in complex 1 7.2.1.1 NADH:ubiquinone reductase (Na+-transporting) medicine Vibrio cholerae Na+-NQR is significant for the induction of virulence factors. Thus, this enzyme can be used as a target in the treatment or prevention of many infectious diseases 7.2.2.3 P-type Na+ transporter medicine - 7.2.2.3 P-type Na+ transporter medicine ATP hydrolysis 7.2.2.3 P-type Na+ transporter medicine ATP hydrolysis and synthesis, H+ and Na+ transport 7.2.2.3 P-type Na+ transporter medicine ATP synthesis, Na+ pump 7.2.2.3 P-type Na+ transporter medicine enzyme is involved in vascular tone regulation 7.2.2.8 P-type Cu+ transporter medicine ATP7A protein is markedly downregulated in vessels isolated from high-fat diet-induced or db/db type 2 diabetes mellitus mice. Downregulation of ATP7A in type 2 diabetes mellitus mice vessels is restored by constitutive active Akt or in protein-tyrosine phosphatase 1B-deficient type 2 diabetes mellitus mice. Insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at residues Ser1424/1463/1466. Superoxide dismutase SOD3 activity is reduced in Akt2-/- vessels or vascular smooth muscle cells, which is rescued by ATP7A overexpression 7.2.2.8 P-type Cu+ transporter medicine ATP7A protein is markedly downregulated in vessels isolated from type 2 diabetes mellitus patients. Akt2 (protein kinase B beta) activated by insulin promotes ATP7A stabilization via preventing ubiquitination/degradation as well as translocation to plasma membrane in vascular smooth muscle cells 7.2.2.8 P-type Cu+ transporter medicine cisplatin-resistant cell sublines show cross-resistance to carboplatin and oxaliplatin. ATP7A expression in cisplatin-resistant cell sublines is much higher than in cisplatin-sensitive cell lines at both mRNA and protein levels. ATP7A-targeted siRNA in cisplatin-resistant cancer cells partially reverses cisplatin-resistance. It also increases cell apoptosis at different cisplatin concentrations 7.2.2.8 P-type Cu+ transporter medicine deletion of isoform ATP7A in H-RAS transformed tumorigenic mouse embryonic markedly suppresses tumorigenesis relative to wild type parental cells, associated with hyperaccumulation of copper and sensitivity to reactive oxygen species and hypoxia. Tumor grafts lacking ATP7A are markedly more sensitive to cisplatin chemotherapy compared to ATP7A-expressing control tumors 7.2.2.8 P-type Cu+ transporter medicine mutation T994I is located in the sixth transmembrane domain of ATP7A, and is associated with the an adult-onset isolated distal motor neuropathy, and with an abnormal interaction with p97/valosin-containing protein. T994I substitution results in conformational exposure of the UBX domain in the third lumenal loop of ATP7A, which then binds the N-terminal domain of p97/VCP. This abnormal interaction occurs at or near the cell plasma membrane 7.2.2.9 P-type Cu2+ transporter medicine the overexpression of ATP7B in hepatocellular carcinoma might be associated with unfavorable clinical outcome in patients treated with cisplantin-based chemotherapy. Analysis of ATP7B expression might be clinically relevant for the choice of therapy 7.2.2.9 P-type Cu2+ transporter medicine molecular mechanisms of copper deficiency (Menkes disease) or copper overload (Wilson disease) 7.2.2.9 P-type Cu2+ transporter medicine studies on copper deficiency during pregnancy, Menkes and Wilson disease 7.2.2.9 P-type Cu2+ transporter medicine studies on diseases of copper deficiency or excess 7.2.2.9 P-type Cu2+ transporter medicine studies on pathogenesis and treatment of Menkes disease 7.2.2.9 P-type Cu2+ transporter medicine enzyme overexpression might be useful in gene therapy 7.2.2.10 P-type Ca2+ transporter medicine isoform SERCA2-mediated Ca2+-regulation decreases in the failing heart, isoform SERCA2a overexpression can potentially reduce arrhythmias and is a therapy for heart failure and cardiac hypertrophy 7.2.2.10 P-type Ca2+ transporter medicine isoform SERCA3f may account for the mechanism of endoplasmic reticulum stress in vivo in heart failure 7.2.2.10 P-type Ca2+ transporter medicine PMCA4b overexpression significantly reduces cardiac hypertrophy following pressure overload 7.2.2.10 P-type Ca2+ transporter medicine SERCA2 expression and activity are decreased in cycstic fibrosis airway epithelium resulting in enhanced susceptibility to oxidants, reduced SERCA2 expression may alter calcium signalling and apoptosis in cystic fibrosis 7.2.2.10 P-type Ca2+ transporter medicine plasmalemmal Ca2+ pump isoform 2 mRNA levels are a potential tool in identifying poor responders to therapy in women with basal breast cancer 7.2.2.13 Na+/K+-exchanging ATPase medicine analysis of mutations F785L and T618M associated with familial rapid-onset dystonia parkinsonism 7.2.2.13 Na+/K+-exchanging ATPase medicine in induced hyperthyroidism, Na+K+-ATPase activity is significantly decreased, whereas acetylcholinesterase activity is increased in the hippocampus. Na+K+-ATPase activity of the frontal cortex remains unchanged in hyperthyroidism. In hypothyroid rat, Na+K+-ATPase activity is significanlty decreased in both the frontal cortex and the hippocampus, whereas acetylcholinesterase activity is decreased in the frontal cortex and increased in the hippocampus. Mg2+-ATPase activity remains unchanged in both hyper- and hypothyroid rat brain 7.2.2.13 Na+/K+-exchanging ATPase medicine neonatal hypothyroidism results in a generalized decrease in Vmax with ATP, Na+, K+ and Mg2+ together with an increase in the Km value for ATP, appearance of a low affinity component for Na+ and allosteric characteristic for the Mg2+-dependent activity at high concentrations of Mg2+ 7.2.2.13 Na+/K+-exchanging ATPase medicine study on enzyme isoforms in muscle in three consecutive days of exercise followed by 3 days of recovery. Increases in subunit isoforms alpha1, alpha2, alpha3 by 46%, 42%, and 31% are observed at recovery day 1, respectively. Subunit isoforms beta1 and beta2 increase by 19% and 28% at recovery day 1, whereas isoform beta3 increase by 18% at recovery day 2. with exception of isoforms alpha 2 and alpha 3, the increases persisted at recovery day 3. The increases in subunit expression are not accompanied by increases in the maximal catalytic activity 7.2.2.13 Na+/K+-exchanging ATPase medicine the positive inotropic effect produced by Na+/K+-ATPase inhibition is used for the treatment of heart failure 7.2.2.13 Na+/K+-exchanging ATPase medicine in the aging kidney, quantitative changes in axial distribution of Na+-K+-ATPase occur at the level of gene expression, protein abundance, and activity in the nephrons. The animals maintain Na/K balance, however with a steady state elevated serum K+ 7.2.2.14 P-type Mg2+ transporter medicine Mg2+ transport 7.2.2.19 H+/K+-exchanging ATPase medicine nongastric H-K-ATPase is required for acidification of luminal prostate fluids, operates as a proton pump, beta1 is an authentic subunit of nongastric H-K-ATPase in vivo, apical localization of beta1 in the prostate is completely dependent on its association with the enzyme alpha-subunit 7.4.2.1 ABC-type polar-amino-acid transporter medicine identification of genus-specific motifs in amino acid permeases, which might be useful to better understand parasite physiology within its hosts, close relationship between the Leishmania donovani and Trypanosma brucei amino acid permeases 7.4.2.1 ABC-type polar-amino-acid transporter medicine the enzyme is used as a target for Leishmania identification and diagnosis of leishmaniases 7.4.2.3 mitochondrial protein-transporting ATPase medicine import of the enteropathogenic Escherichia coli effector protein Map into mitochondria, which alters organelle morphology, is dependent on mtHsp70 7.4.2.3 mitochondrial protein-transporting ATPase medicine in vivo binding of mortalin/mtHsp70 with HSP60, involvment in tumorigenesis, functional distinction in pathways involved in senescence 7.4.2.3 mitochondrial protein-transporting ATPase medicine mtHsp70 forms complexes with wild-type DJ-1 and its mutants, DJ-1 is an oncogene and causative gene for familial form of the Parkinson's disease, translocation of DJ-1 to mitochondria after oxidative stress is carried out in association with chaperones like mtHsp70 7.4.2.8 protein-secreting ATPase medicine pilD-dependent mechanism for promoting Legionella pneumophila intracellular infection of human cells 7.6.2.1 P-type phospholipid transporter medicine The enzyme gene is an interesting candidate for chromosome 15-associted autism and it can contribute to the Angelman syndrome phenotype. 7.6.2.1 P-type phospholipid transporter medicine ATP8B1 deficiency leads to reduced PS flipping and impaired farnesoid X receptor signaling via impaired PKCgamma-mediated nuclear translocation of farnesoid X receptor, resulting in reduced bile salt export pump and enhanced apical sodium-dependent bile salt transporter activation 7.6.2.1 P-type phospholipid transporter medicine some ATP8B1 mutants found in patients of progressive familial intrahepatic cholestasis type 1 (PFIC1), a severe liver disease caused by impaired bile flow, fail to translocate phosphatidylcholine despite their delivery to the plasma membrane. Incorporation of phosphatidylcholine mediated by ATP8B1 can be reversed by simultaneous expression of ABCB4, a phosphatidylcholine floppase mutated in PFIC3 patients 7.6.2.1 P-type phospholipid transporter medicine spontaneous loss of lipid asymmetry, not corrected by aminophospholipid translocase activity, is the mechanism for ribavirin-induced phosphatidylserine exposure that may contribute to ribavirin-induced anemia 7.6.2.2 ABC-type xenobiotic transporter medicine ATP-driven pumping of a variety of drugs out of cells by P-glycoprotein poses a serious problem to medical therapy 7.6.2.2 ABC-type xenobiotic transporter medicine MRP1 confers resistance to a wide variety of anticancer drugs 7.6.2.2 ABC-type xenobiotic transporter medicine Pgp plays a central role in compromising cancer chemotherapy and in modulating the bioavailability and distribution of therapeutic agents 7.6.2.2 ABC-type xenobiotic transporter medicine specific inhibitors of MRP4 can be a valuable asset for enhancing the brain penetration and therapeutic efficacy of adefovir and tenofovir 7.6.2.2 ABC-type xenobiotic transporter medicine development of a method for predicting the risk of drug-drug interactions involving inhibition of P-glycoprotein 7.6.2.2 ABC-type xenobiotic transporter medicine lovastatin increases the absorption of verapamil (used as an antiarrhythmic agent to control supraventricular tachyarrhythmias) by inhibiting P-glycoprotein 7.6.2.2 ABC-type xenobiotic transporter medicine procyanidine is a potent inhibitor of P-glycoprotein on blood-brain barrier and can improve the therapeutic effects on cerebral tumors of some drugs which are difficult to accumulate in the brain 7.6.2.2 ABC-type xenobiotic transporter medicine rosemary phytochemicals, such as carnosic acid, have inhibitory effects on anticancer drug efflux transporter P-glycoprotein and may become useful to enhance the efficacy of cancer chemotherapy 7.6.2.2 ABC-type xenobiotic transporter medicine the direct inhibitory effects of indomethacin and SC236 on P-gp may contribute to their ability to increase the intracellular retention of doxorubicin and thus enhance its cytotoxicity. The combination of indomethacin or SC236 with doxorubicin may have significant potential clinical application, especially in the circumvention of P-gp-mediated multidrug resistance in cancer cells 7.6.2.2 ABC-type xenobiotic transporter medicine the human multidrug resistance transporter P-glycoprotein (P-gp) prevents the entry of compounds into the brain by an active efflux mechanism at the blood-brain barrier. In treatment of neurodegenerative diseases the development of new reversible inhibitors of P-gp is pertinent to overcome this problem. Design and synthesis of a crosslinked agent based on the Alzheimer’s disease treatment galantamine (Gal-2, bis[(4aS,6R,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-yl] decanedioate) that inhibits P-gp-mediated efflux from cultured cells. Gal-2 inhibits the efflux of the fluorescent P-gp substrate rhodamine 123 in cancer cells that over-express P-gp. It inhibits the efflux of therapeutic substrates of P-gp, such as doxorubicin, daunomycin and verapamil. Potential role of Gal-2, as inhibitors of P-gp at the blood-brain barrier to augment treatment of neurodegenerative diseases 7.6.2.2 ABC-type xenobiotic transporter medicine the presence of P-gp in various drug-resistant cancer cells can cause failure in chemotherapy, as it is able to transport a variety of anticancer drugs out of the cell 7.6.2.4 ABC-type fatty-acyl-CoA transporter medicine a correction of the biochemical defect of X-linked adrenoleukodystrophy could be possible by drug-induced overexpression or ectopic expression of adrenoleukodystrophy-related protein 7.6.2.4 ABC-type fatty-acyl-CoA transporter medicine mutations in the gene encoding ALDP result in a devasting neurodegenerative disorder, X-linked adrenoleukodystrophy, X-ALD 7.6.2.4 ABC-type fatty-acyl-CoA transporter medicine the finding that PMP70 over-expression partially corrected very long-chain fatty acid oxidation defects in fibroblasts of X-linked adrenoleukodystrophy patients, has unveiled its potential clinical relevance