Catalytic cycle of mammalian FMOs (Sus scrofa)

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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.


This pathway was inferred from Homo sapiens pathway WP688(r34638) with a 60% conversion rate.

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  1. Cashman JR, Zhang J; ''Human flavin-containing monooxygenases.''; Annu Rev Pharmacol Toxicol, 2006 PubMed Europe PMC
  2. Ziegler DM; ''Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity.''; Trends Pharmacol Sci, 1990 PubMed Europe PMC
  3. Poulsen LL, Ziegler DM; ''Multisubstrate flavin-containing monooxygenases: applications of mechanism to specificity.''; Chem Biol Interact, 1995 PubMed Europe PMC
  4. Elfarra AA, Krause RJ; ''Potential roles of flavin-containing monooxygenases in sulfoxidation reactions of l-methionine, N-acetyl-l-methionine and peptides containing l-methionine.''; Biochim Biophys Acta, 2005 PubMed Europe PMC
  5. Phillips IR, Shephard EA; ''Flavin-containing monooxygenases: mutations, disease and drug response.''; Trends Pharmacol Sci, 2008 PubMed Europe PMC
  6. Krueger SK, Williams DE; ''Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism.''; Pharmacol Ther, 2005 PubMed Europe PMC
  7. Cashman JR; ''Some distinctions between flavin-containing and cytochrome P450 monooxygenases.''; Biochem Biophys Res Commun, 2005 PubMed Europe PMC
  8. Hines RN, Cashman JR, Philpot RM, Williams DE, Ziegler DM; ''The mammalian flavin-containing monooxygenases: molecular characterization and regulation of expression.''; Toxicol Appl Pharmacol, 1994 PubMed Europe PMC


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107034view13:48, 17 September 2019MaintBotHMDB identifier normalization
89161view03:35, 23 August 2016AriuttaOntology Term : 'classic metabolic pathway' added !
68431view18:55, 5 July 2013MaintBotUpdated to 2013 gpml schema
59000view20:01, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
41928view05:03, 2 March 2011MaintBotRemoved redundant pathway information and comments
37712view20:23, 28 June 2010MaintBotNew pathway

External references


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NameTypeDatabase referenceComment
FADH2Metabolite25244872 (PubChem)
FADMetaboliteHMDB0001248 (HMDB)
FMO1GeneProductENSSSCG00000015268 (Ensembl)
FMO2GeneProductENSSSCG00000015267 (Ensembl)
FMO5GeneProductENSSSCG00000006702 (Ensembl)
H+MetaboliteHMDB0001362 (HMDB)
H2OMetaboliteHMDB0002111 (HMDB)
NADP+MetaboliteHMDB0000217 (HMDB)
NADPHMetaboliteHMDB0000221 (HMDB)
O2MetaboliteHMDB0001377 (HMDB)

Annotated Interactions

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