Catalytic cycle of mammalian flavin-containing monooxygenases (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
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- 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 Scholia
- Krueger SK, Williams DE; ''Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism.''; Pharmacol Ther, 2005 PubMed Europe PMC Scholia
- Ziegler DM; ''Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity.''; Trends Pharmacol Sci, 1990 PubMed Europe PMC Scholia
- 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 Scholia
- Poulsen LL, Ziegler DM; ''Multisubstrate flavin-containing monooxygenases: applications of mechanism to specificity.''; Chem Biol Interact, 1995 PubMed Europe PMC Scholia
- Phillips IR, Shephard EA; ''Flavin-containing monooxygenases: mutations, disease and drug response.''; Trends Pharmacol Sci, 2008 PubMed Europe PMC Scholia
- Cashman JR; ''Some distinctions between flavin-containing and cytochrome P450 monooxygenases.''; Biochem Biophys Res Commun, 2005 PubMed Europe PMC Scholia
- Cashman JR, Zhang J; ''Human flavin-containing monooxygenases.''; Annu Rev Pharmacol Toxicol, 2006 PubMed Europe PMC Scholia
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
FAD-OH | Metabolite | 4369241 (PubChem-compound) | |
FAD-OOH | Metabolite | Hydroperoxyflavone | |
FADH2 | Metabolite | CHEBI:17877 (ChEBI) | |
FAD | Metabolite | HMDB0001248 (HMDB) | |
FMO1 | GeneProduct | ENSG00000010932 (Ensembl) | |
FMO2 | GeneProduct | ENSG00000094963 (Ensembl) | |
FMO3 | GeneProduct | ENSG00000007933 (Ensembl) | |
FMO4 | GeneProduct | ENSG00000076258 (Ensembl) | |
FMO5 | GeneProduct | ENSG00000131781 (Ensembl) | |
H+ | Metabolite | CHEBI:15378 (ChEBI) | |
H2O | Metabolite | HMDB0002111 (HMDB) | |
NADP+ | Metabolite | HMDB0000217 (HMDB) | |
NADPH | Metabolite | HMDB0000221 (HMDB) | |
O2 | Metabolite | HMDB0001377 (HMDB) |
Annotated Interactions
No annotated interactions