Catalytic cycle of mammalian FMOs (Bos taurus)

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1-8Endoplasmic reticulumFMO5H+H2ONADP+FADFMO1NADP+SubstrateNADP+FAD-OHNADPHFADFAD-OOHFMO4NADP+FMO3FMO2O2NADP+Substrate-OFADH2


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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP688(79222) with a 100.0% conversion rate.

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Bibliography

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

History

CompareRevisionActionTimeUserComment
107913view09:44, 10 November 2019EgonwReplaced a sub-optimal PubChem CID with a ChEBI identifier.
106019view11:54, 16 August 2019MaintBotHMDB identifier normalization
80936view15:31, 30 June 2015MkutmonNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
FAD-OHMetabolite
FAD-OOHMetabolite
FADH2MetaboliteCHEBI:17877 (ChEBI)
FADMetaboliteHMDB0001248 (HMDB)
FMO1GeneProductENSBTAG00000021408 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000010932
FMO2GeneProductENSBTAG00000002974 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000094963
FMO3GeneProductENSBTAG00000020597 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000007933
FMO4GeneProductENSBTAG00000016685 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000076258
FMO5GeneProductENSBTAG00000010841 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000131781
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteHMDB0002111 (HMDB)
NADP+MetaboliteHMDB0000217 (HMDB)
NADPHMetaboliteHMDB0000221 (HMDB)
O2MetaboliteHMDB0001377 (HMDB)
SubstrateMetabolite
Substrate-OMetabolite

Annotated Interactions

No annotated interactions
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