Abstract
Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported. The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways and promotion foam cell formation. TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease. A number of therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that utilize TMAO as substrate and the development of target-specific molecules with varying level of success. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies examining the cellular signaling in physiology and pathological states in order to establish the role of TMAO in health and disease in humans.
Highlights
Trimethylamine N-oxide (TMAO) is a small organic compound in the class of amine oxides with a molecular mass 75.1 Daltons. It is frequently found in the tissues of a variety of marine organisms [1] including marine elasmobranch, in which TMAO is known to protect against the adverse effects of temperature, salinity, high urea and hydrostatic pressure
TMAO is formed from trimethylamine (TMA), which is generated by the action of gut microbiota from dietary choline and phosphatidylcholine [8,9]
L-carnitine is first converted into the intermediate metabolite γ-butyrobetaine and into TMA, which is subsequently converted into TMAO by host hepatic flavin monooxygenases 3 (FMO3) [10]
Summary
Trimethylamine N-oxide (TMAO) is a small organic compound in the class of amine oxides with a molecular mass 75.1 Daltons. It is frequently found in the tissues of a variety of marine organisms [1] including marine elasmobranch, in which TMAO is known to protect against the adverse effects of temperature, salinity, high urea and hydrostatic pressure. Toxins 2016, 8, 326 structural arrangement of TMAO allows it to form H bonds with water and preferentially exclude or interact with certain protein functional groups [7]
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