Catalytic cycle of mammalian FMOs (WP3281)
Flavin-containing monooxygenases are a group of enzymes that catalyze the oxygenation of substrates, mostly soft nucleophiles via the cofactor flavin. In the catalytic cycle, FMO binds to NADPH and to FAD, causing the reduction of FAD to FADH2. Next, molecular oxygen binds to the complex and is reduced to a hydroperoxide form, called 4a-hydroperoxyflavin. This complex is stable in the absence of a substrate. When a substrate is present, the distal O-atom of the complex is transferred to the substrate yielding an oxygenated product and leaving the flavincomplex 4a-hydroxyflavin that breaks down releasing water. At the end of the cycle, NADP+ is released resulting in FAD as the flavin form to start a next cycle. In contrast to cytochrome P450 enzymes, FMOs are generally not induced or inhibited by xenobiotic substances. The five human FMOs are tissue specific: FMO1 is present in the human fetal liver and the adult kidney, FMO2 is present in the lung and FMO3 is present in the adult liver.
AuthorsMartina Summer-Kutmon and Egon Willighagen
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Pathway Ontologycellular detoxification pathway
|FMO2||GeneProduct||ensembl:ENSBTAG00000002974||HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000094963|
|FMO3||GeneProduct||ensembl:ENSBTAG00000020597||HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000007933|
|FMO1||GeneProduct||ensembl:ENSBTAG00000021408||HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000010932|
|FMO5||GeneProduct||ensembl:ENSBTAG00000010841||HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000131781|
|FMO4||GeneProduct||ensembl:ENSBTAG00000016685||HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000076258|
- Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity. Ziegler DM. Trends Pharmacol Sci. 1990 Aug;11(8):321–4. PubMed Europe PMC Scholia
- Multisubstrate flavin-containing monooxygenases: applications of mechanism to specificity. Poulsen LL, Ziegler DM. Chem Biol Interact. 1995 Apr 28;96(1):57–73. PubMed Europe PMC Scholia
- The mammalian flavin-containing monooxygenases: molecular characterization and regulation of expression. Hines RN, Cashman JR, Philpot RM, Williams DE, Ziegler DM. Toxicol Appl Pharmacol. 1994 Mar;125(1):1–6. PubMed Europe PMC Scholia
- Potential roles of flavin-containing monooxygenases in sulfoxidation reactions of l-methionine, N-acetyl-l-methionine and peptides containing l-methionine. Elfarra AA, Krause RJ. Biochim Biophys Acta. 2005 Jan 17;1703(2):183–9. PubMed Europe PMC Scholia
- Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism. Krueger SK, Williams DE. Pharmacol Ther. 2005 Jun;106(3):357–87. PubMed Europe PMC Scholia
- Some distinctions between flavin-containing and cytochrome P450 monooxygenases. Cashman JR. Biochem Biophys Res Commun. 2005 Dec 9;338(1):599–604. PubMed Europe PMC Scholia
- Human flavin-containing monooxygenases. Cashman JR, Zhang J. Annu Rev Pharmacol Toxicol. 2006;46:65–100. PubMed Europe PMC Scholia
- Flavin-containing monooxygenases: mutations, disease and drug response. Phillips IR, Shephard EA. Trends Pharmacol Sci. 2008 Jun;29(6):294–301. PubMed Europe PMC Scholia