Reactome | FMO3:FAD N-oxidises TMA to TMAO

FMO3:FAD N-oxidises TMA to TMAO

Stable Identifier

R-HSA-139970

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum lumen, endoplasmic reticulum membrane

Synonyms

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
5048998	Trimethylamine N-oxide synthesis: a human variant Chaykin, S, Higgins, T, Humbert, JR, Hammond, KB	Biochem Med	1972
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
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