Trimethylamin-N-Oxid: the pathway in the body

Trimethylamin-N-Oxid is part of the pathway “TMAO”. This page shows the whole pathway; the station of Trimethylamin-N-Oxid is highlighted.

Where this laboratory value sits: Trimethylamine (TMA) — made by gut bacteria. Certain gut bacteria split off this group with their own enzymes: from choline with choline TMA-lyase, from carnitine with an oxygenase. Human cells cannot do this. Source 2, 3

In brief

Trimethylamine N-oxide (TMAO) is a small, water-soluble molecule. It is formed in the liver from trimethylamine, which gut bacteria split off from choline and carnitine, and it leaves the body through the kidneys.

The pathway step by step

1. Choline and carnitine → Trimethylamine (TMA) CutC/D, CntA/B Certain gut bacteria split off this group with their own enzymes: from choline with choline TMA-lyase, from carnitine with an oxygenase. Human cells cannot do this. Source 2, 3
2. Trimethylamine (TMA) → TMA in portal blood Uptake in the gut Trimethylamine is absorbed from the gut into the blood. The portal vein carries it to the liver first, before it reaches the rest of the circulation. Source 1
3. TMAO → TMAO in the blood From the liver, TMAO enters the circulation. It is a small, water-soluble molecule and is not converted any further in the body. Source 1
4. TMAO from fish → TMAO in the blood From the liver, TMAO enters the circulation. It is a small, water-soluble molecule and is not converted any further in the body. Source 1
5. TMAO in the blood → TMAO in the urine Filtration The kidneys filter TMAO from the blood into the urine. Most of it leaves the body within a day; the amount therefore closely follows what was eaten most recently. Source 4, 1

Cofactors in this pathway

• Choline — Starting material from which the bacterial choline TMA lyase splits off trimethylamine Source 2, 1
• Carnitine — Starting material from which the bacterial enzyme CntA/B splits off trimethylamine Source 3, 1In the ORY catalogue as a laboratory value: Carnitin
• Vitamin B2 (FAD) — Flavin cofactor of FMO3, which makes TMAO from trimethylamine in the liver Source 1
• NADPH — Electron donor of FMO3 Source 1
• Oxygen — Provides the oxygen atom that FMO3 attaches to the nitrogen Source 1
• Iron — Sits in the Rieske centre of the bacterial enzyme CntA Source 3

Sources

1. Fennema D, Phillips IR, Shephard EA. Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease. Drug Metab Dispos 2016 · PubMed 27190056
2. Craciun S, Balskus EP. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc Natl Acad Sci U S A 2012 · PubMed 23151509
3. Zhu Y, Jameson E, Crosatti M et al. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc Natl Acad Sci U S A 2014 · PubMed 24591617
4. Krüger R, Merz B, Rist MJ et al. Associations of current diet with plasma and urine TMAO in the KarMeN study: direct and indirect contributions. Mol Nutr Food Res 2017 · PubMed 28755411

Whole pathway: TMAO

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert approval pending
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