Defective FMO3 does not N-oxidise TMA

Stable Identifier
Reaction [transition]
Homo sapiens
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Trimethylamine (TMA) is present in the diet (in fish) but primarily formed in vivo from the breakdown of choline. It is N-oxidised by FMO3 in the liver, the major isoform active towards TMA. Defects in FMO3 can cause trimethylaminuria (TMAU; MIM:602079, fish-odour syndrome), a human genetic disorder characterised by an impaired ability to convert the malodourous TMA to its odourless N-oxide (Treacy et al. 1998). Mutations that cause TMAU include M66I, P153L, R492W, N61S and E32K (Zhang et al. 2003, Yeung et al. 2007).

Literature References
PubMed ID Title Journal Year
9536088 Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication

Knight, M, Treacy, EP, Chow, LM, Cashman, JR, Danks, DM, Youil, R, Lin, J, Bibeau, C, Bruce, AG, Akerman, BR, Forrest, SM

Hum. Mol. Genet. 1998
12893987 Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) gene causing trimethylaminuria

Tran, Q, Lattard, V, Zhang, J, Cashman, JR

Pharmacogenetics 2003
17531949 Functional characterization of genetic variants of human FMO3 associated with trimethylaminuria

Rettie, AE, Adman, ET, Yeung, CK

Arch. Biochem. Biophys. 2007
Catalyst Activity

N,N-dimethylaniline monooxygenase activity of FMO3 mutants:FAD [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of FMO3 mutants:FAD [endoplasmic reticulum membrane]

Name Identifier Synonyms
inherited metabolic disorder DOID:655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
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