Catalytic cycle of mammalian flavin-containing monooxygenases (FMOs) (WP688)

Homo sapiens

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.


Pieter Giesbertz , Alex Pico , Kristina Hanspers , Martijn Van Iersel , Egon Willighagen , Chris Evelo , Denise Slenter , and Eric Weitz


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Homo sapiens



Pathway Ontology

cellular detoxification pathway


Label Type Compact URI Comment
H2O Metabolite hmdb:HMDB0002111
NADP+ Metabolite hmdb:HMDB0000217
NADP+ Metabolite hmdb:HMDB0000217
O2 Metabolite hmdb:HMDB0001377
FAD-OH Metabolite pubchem.compound:4369241
NADP+ Metabolite hmdb:HMDB0000217
NADP+ Metabolite hmdb:HMDB0000217
NADP+ Metabolite hmdb:HMDB0000217
NADPH Metabolite hmdb:HMDB0000221
FAD Metabolite hmdb:HMDB0001248
FAD Metabolite hmdb:HMDB0001248
FADH2 Metabolite chebi:17877
H+ Metabolite chebi:15378
FMO2 GeneProduct ensembl:ENSG00000094963
FMO3 GeneProduct ensembl:ENSG00000007933
FMO1 GeneProduct ensembl:ENSG00000010932
FMO5 GeneProduct ensembl:ENSG00000131781
FMO4 GeneProduct ensembl:ENSG00000076258


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