FMO3:FAD N-oxidises TMA to TMAO

Stable Identifier
Reaction [transition]
Homo sapiens
Trimethylamine N-oxidised to Trimethylamine-N-oxide
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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, to form trimethylamine-N-oxide (TMAO). Trimethylaminuria (fish-odour syndrome) is a human genetic disorder characterised by an impaired ability to convert the malodourous TMA to the odourless N-oxide form TMAO (Higgins et al. 1972, Humbert et al. 1970, Treacy et al. 1998). L-carnitine is an abundant component of red meat and contains a trimethylamine structure similar to that of choline. Gut microbiota is able to produce TMAO from L-carnitine. If high levels of L-carnitine via high red meat intake or dietary supplements is achieved, Koeth et al. have shown the resultant TMAO produced in the gut can accelerate atherosclerosis in mice and increase the risk of cardiovascular disease (CVD) (Koeth et al. 2013).
Literature References
PubMed ID Title Journal Year
23563705 Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

Smith, JD, DiDonato, JA, Lewis, JD, Koeth, RA, Britt, EB, Chen, J, Org, E, Bushman, FD, Levison, BS, Sheehy, BT, Buffa, JA, Tang, WH, Warrier, M, Wang, Z, Fu, X, Hazen, SL, Krauss, RM, Wu, GD, Li, L, Wu, Y, Li, H, Lusis, AJ, Brown, JM

Nat. Med. 2013
4195988 Trimethylaminuria: the fish-odour syndrome

Humbert, JA, Hathaway, WE, Hammond, KB

Lancet 1970
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
5048998 Trimethylamine N-oxide synthesis: a human variant

Chaykin, S, Higgins, T, Humbert, JR, Hammond, KB

Biochem Med 1972
Catalyst Activity

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

Orthologous Events
Cross References
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