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malfunction
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enzyme-deficient mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals
malfunction
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mutations in isoform FMO3 are causative of the disorder trimethylaminuria
malfunction
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a sidechain at position Gly74 can have interactions with the substrate. Despite being a pre-Pro residue, the phi-psi angles (-130,175°) will also fit non-Glycine residues. Mutation of Cys78 can fill up a cavity in the active site making binding of indole more productive. Tyr207 and Asp317 form part of the entrance to the substrate binding cavity while residues Trp319, Phe397, and Trp400 limit the size of the substrate binding cavity
malfunction
FMO1 malfunction causes taurine deficiency, which is implicated in a number of pathologic conditions, including cardiomyopathy, muscular abnormalities, and renal dysfunction
malfunction
FMO1 malfunction causes taurine deficiency, which is implicated in a number of pathologic conditions, including cardiomyopathy, muscular abnormalities, and renal dysfunction
malfunction
genetic mutations in FMO3 can cause trimethylaminuria (or fish-odor syndrome) as a result of impaired N-oxygenation of food-derived trimethylamine
malfunction
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genetic mutations in FMO3 can cause trimethylaminuria (or fish-odor syndrome) as a result of impaired N-oxygenation of food-derived trimethylamine
malfunction
naturally occurring polymorphic enzyme variants demonstrate differences in rates of turnover of its substrates: xenobiotics including drugs as well as dietary compound
malfunction
the hFMO3 gene contains many naturally occuring single SNPs and these mutations can severely affect the activity of the enzyme resulting in lower or abolished activity
metabolism
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FMOs are involved in Phase I metabolism catalyzing the NADPH-dependent oxygenation of drugs, xenobiotics and endogenous compounds containing a soft nucleophilic heteroatom, typically nitrogen or sulfur, but in some cases also selenium or phosphorous
metabolism
the enzyme is involved in metabolism of the anti-tuberculosis drug ethionamide in lung and liver, overview
metabolism
the enzyme is involved in metabolism of the anti-tuberculosis drug ethionamide in lung and liver, overview
metabolism
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the flavin monooxygenase FMO1 contributes to metabolism of anti-tumor triazoloacridinone C-1305 (5-[[3-(dimethylamino)propyl]amino]-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one) in liver microsomes
metabolism
the flavin monooxygenase FMO1 contributes to metabolism of anti-tumor triazoloacridinone, C-1305 (5-[[3-(dimethylamino)propyl]amino]-8-hydroxy-6H-[1,2,3]triazolo[4,5,1-de]acridin-6-one), in liver microsomes and Hep-G2 cells
metabolism
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isoform FMO3 contribute a major part in busulphan metabolic pathway
metabolism
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isoform FMO3 contribute a major part in busulphan metabolic pathway
metabolism
flavin-containing monooxygenase (FMO) 3 is a member of a family of NADPH-dependent enzymes that oxygenate a range of highly polarizable soft nucleophilic heteroatom-containing substances. Human liver FMO3 potentially forms a complementary enzyme system to the NADPH-dependent cytochrome P450 enzymes (P450s, EC 1.14.14.1) responsible for drug metabolism
physiological function
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FMO catalyzes the oxidation at nucleophilic, heteroatom centers and is important for drug, xenobiotic, and endogenous substrate metabolism
physiological function
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FMO catalyzes the oxidation at nucleophilic, heteroatom centers and is important for drug, xenobiotic, and endogenous substrate metabolism
physiological function
FMO3 plays an important role in kidney metabolism of xenobiotics containing sulfur and selenium atoms
physiological function
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the flavin-containing monooxygenase family of enzymes oxygenates nucleophilic xenobiotics and endogenous substances
physiological function
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flavin-containing monooxygenase 3 reduces endoplasmic reticulum stress in palmitate-treated hepatocytes. The enzyme can contribute to the regulation of glucose metabolism in the liver by reducing lipid-induced endoplasmic reticulum stress and the expression of phosphoenolpyruvate carboxykinase, independently of insulin signal transduction
physiological function
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flavin-containing monooxygenase 3 reduces endoplasmic reticulum stress in palmitate-treated hepatocytes. The enzyme can contribute to the regulation of glucose metabolism in the liver by reducing lipid-induced endoplasmic reticulum stress and the expression of phosphoenolpyruvate carboxykinase, independently of insulin signal transduction
physiological function
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the enzyme plays a role in sensing or responding to gut bacteria and is a regulator of body weight and of glucose disposal and insulin sensitivity
physiological function
flavin-containing monooxygenases (FMOs) are a family of phase I enzymes involved in metabolism of numerous drugs (e.g. benzydamine, methimazole, and albendazole) and environmental toxicants (e.g. insecticides, fonfos, and aldicarb). Flavin-containing monooxygenase 5 (FMO5) is a phase I enzyme that plays an important role in xenobiotic metabolism. Analysis of the diurnal rhythms of Fmo5 expression and activity in mouse liver and of the potential roles of clock genes (Bmal1, Rev-erba, and E4bp4) in the generation of diurnal rhythms. Fmo5 mRNA and protein show robust diurnal rhythms, with peak values at zeitgeber time (ZT) 10/14 and trough values at ZT2/22 in mouse liver. Bmal1 (a known Rev-erba activator) activates Fmo5 transcription via direct binding to an E-box (21822/21816 bp) in the promoter, whereas E4bp4 (a known Rev-erba target gene) inhibits Fmo5 transcription by binding to two D-boxes (21726/21718 and 2804/2796 bp). In conclusion, circadian clock genes control diurnal expression of Fmo5 through transcriptional actions on E-box and D-box cis-elements. Circadian time-dependent in vivo activity of Fmo5, molecular mechanism for generation of rhythmic Fmo5 expression, detailed overview. Human FMO5 specifically catalyzes the formation of an oxidized metabolite (PTX-M) from PTX, also known as a Baeyer-Villiger oxidation reaction
physiological function
human flavin-containing monooxygenase 3 (FMO3) is a highly polymorphic membrane-bound, phase I drug metabolizing enzyme. Human FMO3 catalyzes the monooxygenation of nucleophilic heteroatom containing chemicals (drugs, pesticides, and xenobiotics) through an unusual mechanism of activation of molecular oxygen via a stable FAD intermediate in the absence of the bound substrate. This mechanism accounts for the broad substrate range as well as uncoupling of this enzyme, i.e. the wastage of electrons without oxygenation of the substrate leading to the formation of reactive oxygen species (ROS) such as the superoxide radical and hydrogen peroxide. FMO3 is the primary catalyst of benzydamine N-oxygenation with minimal contribution from cytochrome P450 enzymes and that N-oxygenation is the major pathway of benzydamine biotransformation in various species in vitro. FMO3 catalyzes the formation of tamoxifen N-oxide. Tamoxifen N-oxide represents a detoxification pathway, after the metabolic activation carried out by cytochrome P450 (tamoxifen alpha-hydroxylation) that leads to products capable of DNA adduction, with potentially significant toxicological consequences. Administered orally, sulindac is a prodrug which is reduced by the gut flora to the active sulfide form before absorption. In vivo, the sulfide form is re-oxidized to sulindac, the latter compound is relatively inactive compared to the sulfide form: this oxidation step leading from sulindac sulfide to sulindac is carried out by FMO3
physiological function
human flavin-containing monooxygenase 3 (hFMO3) is a drug-metabolizing enzyme capable of performing N- or S-oxidation using the C4a-hydroperoxy intermediate. Importance of the involvement of hFMO3 in the production of radicals in the endoplasmic reticulum
physiological function
human flavin-containing monooxygenases (hFMOs) comprise a family of five isoenzymes and are the second most important phase 1 drug-metabolizing enzymes after cytochromes P450. Its isoform 3 (hFMO3) is predominantly expressed in the liver where substrates containing nitrogen-, sulphur- and phosphorous-containing soft nucleophiles are transformed into more polar and excretable metabolites. Wild-type hFMO3 contributes to the metabolism of several important drugs such as ranitidine, cimetidine, tamoxifen, clozapine, benzydamine
physiological function
human FMO isozymes FMO1 and FMO3 are the most relevant to Phase I drug metabolism of all human isozymes. They are involved in the oxygenation of xenobiotics including drugs and pesticides
physiological function
human FMO3 protein exhibits marked individual variability in oxygenation activities, analysis of in vivo pharmacokinetics of itopride and trimethylamine-d9 and their N-oxygenated metabolites after co-administrations in humanized-liver mice, modeling of physiologically based pharmacokinetic (PBPK) and formation of models for itopride and its N-oxide consisting of receptor (gut), metabolizing (liver), and central compartments, overview
physiological function
role of human flavin-containing monooxygenase (FMO) 5 in the metabolism of (4-(6-methoxynaphthalen-2-yl)butan-2-one, NAB): Baeyer-Villiger oxidation in the activation of the intermediate metabolite, 3-hydroxy-nabumetone, to the active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA) in vitro. The reaction involves carbon-carbon cleavage catalyzed by the Baeyer-Villiger oxidation (BVO) of a carbonyl compound, the BVO substrate, such as a ketol, by FMO5. Further in vitro inhibition experiments show that multiple non-CYP enzymes are involved in the formation of 6-MNA from 3-OH-NAB in human hepatocytes. NAB is a substrate for CYP1A2, CYP3A4, and CYP2J2. In the extract obtained from 3-hydroxy-nabumetone (3-OH-NAB) by a combined incubation of recombinant human FMO5 and human liver S9
physiological function
the formation of taurine from hypotaurine is catalyzed by an FMO in vivo, it is the terminal step of the biosynthetic pathway of taurine production from cysteine
physiological function
the formation of taurine from hypotaurine is catalyzed by an FMO in vivo, it is the terminal step of the biosynthetic pathway of taurine production from cysteine
physiological function
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flavin-containing monooxygenases (FMOs) are a family of phase I enzymes involved in metabolism of numerous drugs (e.g. benzydamine, methimazole, and albendazole) and environmental toxicants (e.g. insecticides, fonfos, and aldicarb). Flavin-containing monooxygenase 5 (FMO5) is a phase I enzyme that plays an important role in xenobiotic metabolism. Analysis of the diurnal rhythms of Fmo5 expression and activity in mouse liver and of the potential roles of clock genes (Bmal1, Rev-erba, and E4bp4) in the generation of diurnal rhythms. Fmo5 mRNA and protein show robust diurnal rhythms, with peak values at zeitgeber time (ZT) 10/14 and trough values at ZT2/22 in mouse liver. Bmal1 (a known Rev-erba activator) activates Fmo5 transcription via direct binding to an E-box (21822/21816 bp) in the promoter, whereas E4bp4 (a known Rev-erba target gene) inhibits Fmo5 transcription by binding to two D-boxes (21726/21718 and 2804/2796 bp). In conclusion, circadian clock genes control diurnal expression of Fmo5 through transcriptional actions on E-box and D-box cis-elements. Circadian time-dependent in vivo activity of Fmo5, molecular mechanism for generation of rhythmic Fmo5 expression, detailed overview. Human FMO5 specifically catalyzes the formation of an oxidized metabolite (PTX-M) from PTX, also known as a Baeyer-Villiger oxidation reaction
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additional information
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although maltose-binding-protein-FMO enzymes afford lower rates of turnover than the corresponding commercial recombinant FMOs, both types of FMO show identical substrate dependencies and similar responses to changes in assay conditions. Comparison of commercial recombinant enzymes with recombinant MBP-FMOs expressed in Escherichia coli, overview
additional information
chromatin immunoprecipitation assays do not detect recruitment of aryl hydrocarbon receptor or ARNT to Fmo3 regulatory elements after exposure to 3-methylcholanthrene in liver or in Hepa-1 cells. However, in Hepa-1, 3-methylcholanthrene and benzo[a]pyrene , but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, cause recruitment of p53 protein to a p53 response element in the 5'-flanking region of the Fmo3 gene. Although FMO3 mRNA is highly induced by 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse liver and in Hepa-1 cells, FMO protein levels and FMO catalytic function show only modest elevation
additional information
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chromatin immunoprecipitation assays do not detect recruitment of aryl hydrocarbon receptor or ARNT to Fmo3 regulatory elements after exposure to 3-methylcholanthrene in liver or in Hepa-1 cells. However, in Hepa-1, 3-methylcholanthrene and benzo[a]pyrene , but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, cause recruitment of p53 protein to a p53 response element in the 5'-flanking region of the Fmo3 gene. Although FMO3 mRNA is highly induced by 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse liver and in Hepa-1 cells, FMO protein levels and FMO catalytic function show only modest elevation
additional information
enzyme hFMO3 structural modeling with NADP-binding domain and FAD-binding domain with bound cofactors, overview
additional information
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enzyme hFMO3 structural modeling with NADP-binding domain and FAD-binding domain with bound cofactors, overview
additional information
enzyme protein structure homology-modelling using the PDB ID 6SE3 structure as the template
additional information
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enzyme protein structure homology-modelling using the PDB ID 6SE3 structure as the template
additional information
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enzyme structure and active site structure analysis using the structure with PDB ID 2VQ7, overview
additional information
heat-induced changes in the secondary structure in the presence and absence of NADP+, overview
additional information
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heat-induced changes in the secondary structure in the presence and absence of NADP+, overview