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evolution
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genes ldh, ldhB and ldhX, are transcribed to some extent in Lactococcus lactis strain MG1363. The product of the ldhX gene has little nLDH activity as well as ldhB which exhibits only leaky transcription and plays a minor role in lactate yield. LDHA encoded by ldh has been found to perform major L-nLDH activity, with the contribution of other alternate L-nLDHs being small
evolution
sequence identity between the Enterococcus mundtii LDH-1 and LDH-2 is 44.9%
evolution
there are two types of L-nLDHs, non-allosteric L-nLDHs and allosteric L-nLDHs
evolution
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sequence identity between the Enterococcus mundtii LDH-1 and LDH-2 is 44.9%
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evolution
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genes ldh, ldhB and ldhX, are transcribed to some extent in Lactococcus lactis strain MG1363. The product of the ldhX gene has little nLDH activity as well as ldhB which exhibits only leaky transcription and plays a minor role in lactate yield. LDHA encoded by ldh has been found to perform major L-nLDH activity, with the contribution of other alternate L-nLDHs being small
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evolution
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there are two types of L-nLDHs, non-allosteric L-nLDHs and allosteric L-nLDHs
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malfunction
LDH-5 inhibitors decrease mitochondrial membrane potential and elevate intracellular oxidative stress that diminishes the ability of cells to proliferate, reduces their metastatic potential, and increases sensitivity to chemotherapeutic drugs. Inhibitors can also act as a blocker of the LDH-5ssDNA interactions to prevent RNA synthesis. miR-34a is a direct repressor of LDHA gene expression. Inhibiting LDHA expression may reduce the invasive and metastatic potential of cancer cells by decreasing their proliferation ability and reversing their resistance to chemotherapy. Enzyme inhibitors NHI-1 and -2 used together with gemcitabine enhance the antiproliferative and anti-invasive activities of the chemotherapeutic drug, under both normoxia and hypoxia, in pancreatic ductal adenocarcinoma (PDAC) cell lines. Inhibitor NIH-2, combined with the redox-dependent bioreductive anticancer prodrug EO9, synergistically induces p53-positive cancer cell death
malfunction
loss of water-forming NADH oxidase NOX activity in Streptococcus mutans leads to Rex-mediated overcompensation in NAD+ regeneration by lactate dehydrogenase. The altered transcriptome and metabolome of the DELTAnox strain are sufficient to impair its ability to compete with commensal peroxigenic oral streptococci during growth under aerobic conditions, phenotype, overview
malfunction
silencing LDHB selectively inhibits the proliferation of both oxidative and glycolytic cancer cells over normal cells, targeting LDHB selectively blocks autophagy in oxidative and glycolytic cancer cells, but siLDHB does not affect the subcellular distribution pattern of lysosomes and their distance to the cell nucleus. siLDHB induces lysosomal inhibition in oxidative cancer cells. Overexpression of LDHB decreases the number of acidic vesicles per cell. LDHB overexpression increases mature autolysosome formation and intracellular proteolysis in SiHa and in HeLa cells. LDHB reaction substrate lactate and product pyruvate do not metabolically restore autophagy and intracellular proteolysis in LDHB-depleted SiHa cells, but LDHB-depleted cells switch to a glycolytic metabolism
malfunction
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loss of water-forming NADH oxidase NOX activity in Streptococcus mutans leads to Rex-mediated overcompensation in NAD+ regeneration by lactate dehydrogenase. The altered transcriptome and metabolome of the DELTAnox strain are sufficient to impair its ability to compete with commensal peroxigenic oral streptococci during growth under aerobic conditions, phenotype, overview
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metabolism
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LDH plays a central role in several metabolic pathways, e.g. in energy production in glycolysis, in gluconeogenesis. Glycolytic process, overview
metabolism
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the enzyme catalyzes the first step in L-lactate catabolism
metabolism
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L-lactate dehydrogenase is an important enzyme involved in the last step of glycolysis that catalyzes the reversible conversion of pyruvate to L-lactate with the simultaneous oxidation of NADH to NAD+
metabolism
lactate dehydrogenase (LDH) is a glycolytic enzyme that catalyzes the final step of glycolysis and produces NAD+
metabolism
lactate dehydrogenase-5 (LDH-5) is a central player in theWarburg effect which catalyzes the formation of lactate in the final step of the glycolytic pathway
metabolism
NAD-dependent L-lactate dehydrogenases (L-nLDHs) catalyze the last step of anaerobic glycosis, the reduction of pyruvate to L-lactate, concomitantly oxidizing NADH into NAD+
metabolism
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NAD-dependent lactate dehydrogenase catalyses the first step in respiratory utilization of lactate by Lactococcus lactis
metabolism
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since the mitochondrial metabolism of (S)-lactate results in synthesis and export of oxaloacetate, malate and citrate into the extramitochondrial phase, an anaplerotic role for the mitochondrial (S)-lactate metabolism is proposed
metabolism
L-lactate dehydrogenase (LDHA) is a substrate of protein tyrosine phosphatase PTP1B. LDHA enrichment ias significantly lower in PTP1B knockdown cell lysate compared to untreated and scrambled siRNA controls
metabolism
LDH activity with free NADH and GAPDH-NADH complex always take place in parallel. NADH-channeling from D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to L-lactate dehydrogenase (LDH) is observed only in assays that mimic cytosolic conditions where free NADH concentration is negligible and the GAPDH-NADH complex is dominant. LDH and GAPDH can form a leaky channeling complex only at the limiting NADH concentrations. A positive electric field between the NAD(H) binding sites on LDH and GAPDH tetramers can merge in the LDH-GAPDH complex
metabolism
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predominantly the conformational changes in the T to R transition start from the region near the active site, comprised of helix alphaC, helix alpha1/2G, helix alpha3G, and helix alpha2F, and proceed to other structural units, thus completing the global motion. The bottleneck for assembly is the formation of the correct orientational registry between the subunits, requiring contacts between the interface residues. These residues are part of the allostery wiring diagram
metabolism
the substrate binding and product states are stabilized only in the open-loop conformation of LDH and the reaction occurs in the closed-loop conformation, i.e., before and after the chemical reaction, a large-scale structural transition from the open-loop conformation to the closed-loop conformation and vice versa occurs. The closed-loop conformation stabilizes the transition state of the reaction. In contrast, the open-loop conformation stabilizes the substrate binding and final states
metabolism
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NAD-dependent lactate dehydrogenase catalyses the first step in respiratory utilization of lactate by Lactococcus lactis
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metabolism
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NAD-dependent L-lactate dehydrogenases (L-nLDHs) catalyze the last step of anaerobic glycosis, the reduction of pyruvate to L-lactate, concomitantly oxidizing NADH into NAD+
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metabolism
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predominantly the conformational changes in the T to R transition start from the region near the active site, comprised of helix alphaC, helix alpha1/2G, helix alpha3G, and helix alpha2F, and proceed to other structural units, thus completing the global motion. The bottleneck for assembly is the formation of the correct orientational registry between the subunits, requiring contacts between the interface residues. These residues are part of the allostery wiring diagram
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metabolism
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the enzyme catalyzes the first step in L-lactate catabolism
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physiological function
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although Ldh-2 contributes to lactate production, Ldh-1 plays the major role in energy metabolism in Enterococcus faecalis
physiological function
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LADH-A is a key enzyme that couples L-lactate production to reoxidation of NADH formed during glycolysis
physiological function
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LDH-A deficiency causes myoglobinuria
physiological function
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the enzyme catalyzes the stereospecific conversion of lactate to pyruvate and converts NAD+ to NADH, which is an important way of regenerating NAD+, enabling the continuation of glycolysis
physiological function
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the parasite's ATP production is almost completely dependent on the glucose metabolism and the glycolytic pathway, that is absent in normal human host cells, overview. PfLDH plays the essential role in NAD+ regenration needed for the continuity of the glycolytic cycle
physiological function
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Inactivation of the lactate dehydrogenase gene results in a metabolic shift predominantly towards ethanol production. Formic and acetic acids are still produced, the latter in lower amounts than with the wild-type, but, unlike the wild-type strain, significant quantities of pyruvic acid accumulate
physiological function
alternative allosteric regulation mechanism of an acidophilic L-lactate dehydrogenase, overview. LDH-1 mainly plays a role in L-lactate production in Enterococcus mundtii, while LDH-2 plays another, different role
physiological function
lactate dehydrogenase (LDH) is a critical enzyme during aerobic glycolysis as it is typically responsible for the production of lactate and regeneration of NAD+, which allows for the continued functioning of glycolysis even in the absence of oxygen. LDH is the final enzyme in glycolysis pathway that catalyzes interconversion of pyruvate and lactate and it also regenerates NAD+, which is necessary for continued high glycolysis rate in cancer cells
physiological function
lactate dehydrogenase 5 (LDH-5) catalyzes the reduction of pyruvate by NADH to form lactate, thus determining the availability of NAD+ to maintain the continuity of glycolysis.Direct phosphorylation of LDHA at Y10 and Y83 strongly enhances LDH-5 tetramer formation and cofactor binding, resulting in significantly increased LDH enzymatic activity and promoting cancer cell metabolism and tumor growth. LDH-5 tyrosine phosphorylation might be an extra regulatory mechanism underlying the Warburg effect and lactate production. LDHA tyrosine phosphorylation decides about the translocation of LDH-5 to the nucleus, where it acts as a single-stranded DNA-binding protein, stimulating transcription and/or DNA replication. LDH-5 plays a crucial role in tumor maintenance and elevated LDHA gene expression characterizes many human tumors
physiological function
lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD+ to pyruvate, NADH and H+, controls lysosomal acidification, vesicle maturation, and intracellular proteolysis. LDHB activity is necessary for basal autophagy and cancer cell proliferation not only in oxidative cancer cells but also in glycolytic cancer cells. Lactate supports lysosomal acidification and autophagy in cancer. Lactate oxidation by LDHB yields protons that fuel lysosomal V-ATPase. LDHB is critical for lysosomal activity and autophagy in cancer cells. LDHB controls early tumor progression and the number of cancer cells, and negatively affects patient survival. Lactate promotes LDHB-dependent autophagy in oxidative cancer cells
physiological function
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lactate dehydrogenase is the terminal enzyme of anaerobic glycolysis, and has a crucial role in sustaining ATP production by glycolysis during periods of anoxia via regenerating NAD+ through the production of lactate. Anoxia-induced modifications of crayfish muscle LDH may contribute significantly to modulating enzyme function under anoxic conditions
physiological function
the stereospecific L-LDH is a fructose 1,6-diphosphate-activated NAD-dependent lactate dehydrogenase, L-nLDH
physiological function
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both the single-gene deletion mutants of isoforms LDHL1 or LDHL2 exhibit phenotypic defects in vegetative growth, sporulation, spore germination, L-lactate biosynthesis and activity. The two L-lactate dehydrogenases are involved in the utilization of carbon sources and maintenance of redox homeostasis during spore germination. The LDHL1 deletion mutant exhibits reduced virulence on wheat spikelets and on corn stigmas
physiological function
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lactate can fuel the bioenergetics of heart, muscle, and liver mitochondria. Lactate is just as effective as pyruvate at stimulating mitochondrial coupling efficiency. Inclusion of LDH and pyruvate dehydrogenase inhibitors abolishes respiration in mitochondria energized with lactate. Lactate also fueled mitochondrial ROS generation and is just as effective as pyruvate at stimulating H2O2 production. Lactate-induced ROS production is inhibited by both LDH and PDH inhibitors
physiological function
Q5F885; Q5F884; Q5F883
the growth of the LutACB mutants is similar to that of the wild-type strain on L-lactate. The isoforms LutACB/LldD double mutant fails to grow on L-lactate, and complementation of this strain with LutACB restores growth to wild-type levels. LutACB contributes to L-lactate dehydrogenase activity under iron-replete conditions, and the LutACB deletion mutant is impaired in its ability to survive within human primary cervical epithelial cells
physiological function
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Inactivation of the lactate dehydrogenase gene results in a metabolic shift predominantly towards ethanol production. Formic and acetic acids are still produced, the latter in lower amounts than with the wild-type, but, unlike the wild-type strain, significant quantities of pyruvic acid accumulate
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physiological function
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alternative allosteric regulation mechanism of an acidophilic L-lactate dehydrogenase, overview. LDH-1 mainly plays a role in L-lactate production in Enterococcus mundtii, while LDH-2 plays another, different role
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physiological function
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the stereospecific L-LDH is a fructose 1,6-diphosphate-activated NAD-dependent lactate dehydrogenase, L-nLDH
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physiological function
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the growth of the LutACB mutants is similar to that of the wild-type strain on L-lactate. The isoforms LutACB/LldD double mutant fails to grow on L-lactate, and complementation of this strain with LutACB restores growth to wild-type levels. LutACB contributes to L-lactate dehydrogenase activity under iron-replete conditions, and the LutACB deletion mutant is impaired in its ability to survive within human primary cervical epithelial cells
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physiological function
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both the single-gene deletion mutants of isoforms LDHL1 or LDHL2 exhibit phenotypic defects in vegetative growth, sporulation, spore germination, L-lactate biosynthesis and activity. The two L-lactate dehydrogenases are involved in the utilization of carbon sources and maintenance of redox homeostasis during spore germination. The LDHL1 deletion mutant exhibits reduced virulence on wheat spikelets and on corn stigmas
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additional information
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ldhA expression is primarily repressed by SugR in the absence of sugar. In the presence of sugar, SugR-mediated repression of ldhA is alleviated, and ldhA expression is additionally enhanced by LldR inactivation in response to L-lactate produced by LdhA
additional information
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the enzyme is involved in development of cancer, especially of hypoxic cancer cells, since the cancer cells relay on LDH-A for the energy supply. The glycolytic phenotype is responsible for the tumorigenicity of hypoxic cells
additional information
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the ldh-1 mutants detoxifies excess pyruvate by converting it to acetoin
additional information
the key catalytic residues Arg109, Asp168, Arg171, and His 195, are conserved in Bacillus coagulans strain NL01 L-nLDH
additional information
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the key catalytic residues Arg109, Asp168, Arg171, and His 195, are conserved in Bacillus coagulans strain NL01 L-nLDH
additional information
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the key catalytic residues Arg109, Asp168, Arg171, and His 195, are conserved in Bacillus coagulans strain NL01 L-nLDH
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