FMO3
FMO3 (flavin-containing monooxygenase 3, also known as FMOII) is the major hepatic flavin-containing monooxygenase in adults. It oxygenates nitrogen- and sulfur-containing drugs and dietary compounds, and converts trimethylamine to trimethylamine N-oxide. Browse Assay Genie's current range of FMO3 research reagents below, or read on for the biology behind the target.
FMO3 is an essential hepatic enzyme that catalyses the NADPH-dependent oxygenation of a wide variety of nitrogen-, sulfur- and phosphorus-containing compounds. These include therapeutic drugs, dietary compounds, pesticides and other xenobiotics, which places the flavin-containing monooxygenase 3 enzyme firmly within drug metabolism research. It also has a defined role in the metabolism of trimethylamine (TMA). Gut microbiota generate TMA from dietary precursors such as choline, choline-containing compounds, betaine and L-carnitine, and FMO3 oxidises it to trimethylamine N-oxide (TMAO). By regulating TMAO concentration, FMO3 directly affects platelet responsiveness and the rate of thrombus formation.
The FMO3 gene belongs to the FMO family; the human family comprises five genes and several pseudogenes, with distinct developmental and tissue-specific expression patterns. FMO3 is the major FMO expressed in adult liver, and its expression can vary up to 20-fold between individuals. This variation is likely to influence the rate at which xenobiotics are metabolised, and is therefore of considerable interest to the pharmaceutical industry. The protein is a transmembrane enzyme located in the endoplasmic reticulum membrane (microsomes) of many tissues. Alternative splicing produces multiple transcript variants that encode different isoforms. HGNC classes the gene among flavin-containing monooxygenases and flavoproteins, and also lists it as a microRNA protein-coding host gene.
Mutations in FMO3 cause trimethylaminuria (TMAu), characterised by accumulation and excretion of unmetabolised trimethylamine and a distinctive body odour. In healthy individuals, trimethylamine is mainly converted to the non-odorous TMAO. Mouse and rat both carry an Fmo3 ortholog. The previous HGNC name for the gene was flavin containing monooxygenase 3.
FMO3 oxygenates many therapeutic drugs and other xenobiotics, and its variable hepatic expression affects how quickly they are metabolised.
FMO3 converts microbiota-derived trimethylamine from choline, betaine and L-carnitine into TMAO, linking diet, microbial metabolism and host enzyme activity.
By regulating TMAO concentration, FMO3 directly influences platelet responsiveness and the rate of thrombus formation.
FMO3 mutations cause trimethylaminuria, with unmetabolised trimethylamine accumulating and being excreted, making the gene a focus for studies of this disorder.
FMO3 is a hepatic enzyme that catalyses oxygenation of nitrogen- and sulfur-containing drugs and dietary compounds. It also oxidises trimethylamine to trimethylamine N-oxide (TMAO), and through TMAO levels it affects platelet responsiveness and thrombus formation.
FMO3 is also known as FMOII, and its UniProt name is flavin-containing monooxygenase 3. The enzyme activities are assigned EC 1.14.13.148, 1.14.13.32 and 1.14.13.8. Alternative splicing of the gene results in multiple transcript variants encoding different isoforms.
Mutations in FMO3 cause trimethylaminuria, in which unmetabolised trimethylamine accumulates and produces a distinctive body odour. Mouse and rat each have an Fmo3 ortholog; check the datasheet of any product for its validated reactivity.
Other flavin-containing monooxygenase family members and related targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P31513; product specifications from Assay Genie datasheets.