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.^[5][6][7][8] This enzyme catalyzes the following chemical reaction, among others:^[8]

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

FMO3
Identifiers
Aliases	FMO3, trimethylamine monooxygenase, flavin-containing monooxygenase 3, Dimethylaniline monooxygenase [N-oxide-forming] 3, FMOII, TMAU, dJ127D3.1, flavin containing monooxygenase 3, flavin containing dimethylaniline monoxygenase 3
External IDs	OMIM: 136132; MGI: 1100496; HomoloGene: 128199; GeneCards: FMO3; OMA:FMO3 - orthologs
EC number	1.14.13.148
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q24.3 Start 171,090,901 bp[1] End 171,117,819 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 H2.1|1 70.34 cM Start 162,781,369 bp[2] End 162,812,097 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver olfactory zone of nasal mucosa nasal epithelium right lung mucosa of paranasal sinus subcutaneous adipose tissue bronchial epithelial cell upper lobe of left lung right uterine tube testicle Top expressed in right lung lobe tunica media of zone of aorta trachea superior surface of tongue olfactory epithelium ascending aorta aortic valve zygote carotid body lacrimal gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function trimethylamine monooxygenase activity oxidoreductase activity N,N-dimethylaniline monooxygenase activity NADP binding flavin adenine dinucleotide binding monooxygenase activity protein binding Cellular component integral component of membrane organelle membrane endoplasmic reticulum membrane intracellular membrane-bounded organelle endoplasmic reticulum membrane Biological process xenobiotic metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2328 14262 Ensembl ENSG00000007933 ENSMUSG00000026691 UniProt P31513 P97501 RefSeq (mRNA) NM_001002294 NM_006894 NM_001319173 NM_001319174 NM_008030 RefSeq (protein) NP_001002294 NP_001306102 NP_001306103 NP_008825 NP_032056 Location (UCSC) Chr 1: 171.09 – 171.12 Mb Chr 1: 162.78 – 162.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

FMO3 is the main flavin-containing monooxygenase isoenzyme that is expressed in the liver of adult humans.^[8][9][10] The human FMO3 enzyme catalyzes several types of reactions, including: the N-oxygenation of primary, secondary, and tertiary amines;^[9][11] the S-oxygenation of nucleophilic sulfur-containing compounds;^[9][11] and the 6-methylhydroxylation of the anti-cancer agent dimethylxanthenone acetic acid (DMXAA).^[9][12]

FMO3 is the primary enzyme in humans which catalyzes the N-oxidation of trimethylamine into trimethylamine N-oxide;^[8][10] FMO1 also does this, but to a much lesser extent than FMO3.^[13][14] Genetic deficiencies of the FMO3 enzyme cause primary trimethylaminuria, also known as "fish odor syndrome".^[8][15] FMO3 is also involved in the metabolism of many xenobiotics (i.e., exogenous compounds which are not normally present in the body),^[9][10] such as the oxidative deamination of amphetamine.^[9][16][17]

Ligands

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

FMO3 substrates	FMO3 inhibitors	FMO3 inducers	FMO3 activators
Endogenous biomolecules Epinephrine[18] Norepinephrine[18] Phenethylamine†[9][18] Trimethylamine†[9][10][18] Tyramine[8][9][18] Notable exogenous xenobiotics Amphetamine† and its hydroxylamine intermediate[9][17] Benzydamine[8][9] Cimetidine[10][11] Clozapine[9][10] N-Deacetyl ketoconazole[9] DMXAA†[9][12] Ethionamide[8][9] Itopride[9][10] Methamphetamine and its hydroxylamine intermediate[9][17] Methimazole[8][10] Nicotine – only the (S)-(−)-nicotine enantiomer[9][11] Olopatadine[9] Phenothiazines – 2-(Trifluoromethyl) analogs[9] Ranitidine[9][11] Sulindac sulfide[8][9] Tamoxifen[9][10] Thiobenzamide[9] Xanomeline[9]	Thiourea[8] Indole-3-carbinol[19]		Chlorpromazine[8] Imipramine[8]
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.^[20] 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.^[20]

See also

• Flavin-containing monooxygenase
• Trimethylaminuria