Catalytic cycle of mammalian FMOs (Homo sapiens)

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Description

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.

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Bibliography

View all 8 references
  1. Krueger SK, Williams DE; ''Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism.; ''Pharmacol Ther, 2005 - PubMed
  2. Poulsen LL, Ziegler DM; ''Multisubstrate flavin-containing monooxygenases: applications of mechanism to specificity.; ''Chem Biol Interact, 1995 - PubMed
  3. 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
  4. Cashman JR; ''Some distinctions between flavin-containing and cytochrome P450 monooxygenases.; ''Biochem Biophys Res Commun, 2005 - PubMed
  5. Cashman JR, Zhang J; ''Human flavin-containing monooxygenases.; ''Annu Rev Pharmacol Toxicol, 2006 - PubMed
  6. Phillips IR, Shephard EA; ''Flavin-containing monooxygenases: mutations, disease and drug response.; ''Trends Pharmacol Sci, 2008 - PubMed
  7. 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
  8. Ziegler DM; ''Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity.; ''Trends Pharmacol Sci, 1990 - PubMed

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CompareRevisionActionTimeUserComment
63157view20:18, 8 May 2013MaintBotUpdating gpml version
59115view22:27, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
48246view06:16, 17 May 2012MaintBotUpdating PubChem xrefs
44984view14:33, 6 October 2011MartijnVanIerselOntology Term : 'cellular detoxification pathway' added !
41065view23:18, 1 March 2011MaintBotRemoved redundant pathway information and comments
34638view19:41, 7 January 2010KhanspersModified categories
33407view14:49, 30 November 2009MaintBotRemoved group label
30258view04:47, 25 July 2009AlexanderPicoModified categories
29954view06:26, 15 June 2009Pieter GiesbertzSpecify description
29591view11:49, 19 May 2009Pieter GiesbertzAdded datanodes
29590view10:26, 19 May 2009Pieter GiesbertzModified description
29507view07:54, 11 May 2009Pieter GiesbertzAdded literature reference
29506view07:26, 11 May 2009Pieter GiesbertzAdded literature references
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29280view07:38, 22 April 2009Pieter GiesbertzSpecify description
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29234view07:57, 17 April 2009Pieter GiesbertzSpecify description
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29096view09:32, 2 April 2009Pieter GiesbertzPeriodical save, work in progress
29095view09:22, 2 April 2009Pieter GiesbertzPeriodical save, work in progress
29094view09:10, 2 April 2009Pieter GiesbertzPeriodical save, work in progress
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29090view07:31, 2 April 2009Pieter GiesbertzPeriodical save, work in progress
29081view14:56, 31 March 2009Pieter GiesbertzCatalytic cycle of mammalian FMOs
29080view14:48, 31 March 2009Pieter GiesbertzPeriodical save, work in progress
29079view14:38, 31 March 2009Pieter GiesbertzNew pathway

External references

View all 16...

Name Type Database reference
FAD-OHMetabolite
SubstrateMetabolite
FMO2GeneProductENSG00000094963 (Ensembl)
H2OMetaboliteHMDB02111 (HMDB)
FMO3GeneProductENSG00000007933 (Ensembl)
FAD-OOHMetabolite
FMO5GeneProductENSG00000131781 (Ensembl)
FMO1GeneProductENSG00000010932 (Ensembl)
FMO4GeneProductENSG00000076258 (Ensembl)
NADP+MetaboliteHMDB00217 (HMDB)
H+MetaboliteHMDB01362 (HMDB)
Substrate-OMetabolite
NADPHMetaboliteHMDB00221 (HMDB)
FADH2Metabolite25244872 (PubChem)
O2MetaboliteHMDB01377 (HMDB)
FADMetaboliteHMDB01248 (HMDB)
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