Flavin-containing monooxygenase 3

Flavin-containing monooxygenase 3 (FMO3), also known as dimethylaniline monooxygenase [N-oxide-forming] 3 and trimethylamine monooxygenase, is a flavoprotein enzyme (EC 1.14.13.148) that in humans is encoded by the FMO3 gene. This enzyme catalyzes the following chemical reaction, among others:

trimethylamine + NADPH + H⁺ + O₂ $\rightleftharpoons$ trimethylamine N-oxide + NADP⁺ + H₂O

FMO3 is the main flavin-containing monooxygenase isoenzyme that is expressed in the liver of adult humans. The human FMO3 enzyme catalyzes several types of reactions, including: the N-oxygenation of primary, secondary, and tertiary amines; the S-oxygenation of nucleophilic sulfur-containing compounds; and the 6-methylhydroxylation of the anti-cancer agent dimethylxanthenone acetic acid (DMXAA).

FMO3 is the primary enzyme in humans which catalyzes the N-oxidation of trimethylamine into trimethylamine N-oxide; FMO1 also does this, but to a much lesser extent than FMO3. Genetic deficiencies of the FMO3 enzyme cause primary trimethylaminuria, also known as "fish odor syndrome". FMO3 is also involved in the metabolism of many xenobiotics (i.e., exogenous compounds which are not normally present in the body), such as the oxidative deamination of amphetamine.

Ligands

List of human FMO3 substrates, inhibitors, inducers, and activators

FMO3 substrates	FMO3 inhibitors	FMO3 inducers	FMO3 activators
Endogenous biomolecules Epinephrine Norepinephrine Phenethylamine† Trimethylamine† Tyramine Notable exogenous xenobiotics Amphetamine† and its hydroxylamine intermediate Benzydamine Cimetidine Clozapine N-Deacetyl ketoconazole DMXAA† Ethionamide Itopride Methamphetamine and its hydroxylamine intermediate Methimazole Nicotine – only the (S)-(−)-nicotine enantiomer Olopatadine Phenothiazines – 2-(Trifluoromethyl) analogs Ranitidine Sulindac sulfide Tamoxifen Thiobenzamide Xanomeline	Thiourea Indole-3-carbinol		Chlorpromazine Imipramine
A † indicates moderate to complete selectivity for FMO3 relative to other FMO isoenzymes.

Cancer

The FMO3 gene has been observed progressively downregulated in human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, FMO3 is likely to be associated with tumorigenesis and may be a potential prognostic marker for progression of uterine cervical preneoplastic lesions.

See also

• Flavin-containing monooxygenase
• Trimethylaminuria

External links

• Trimethylamine+monooxygenase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Primary Trimethylaminuria (FMO3 Deficiency) – NCBI bookshelf GeneReviews entry