Trimethylamine ''N''-oxide (TMAO) is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the formula . It is in the class of amine oxides. Although the anhydrous compound is known, trimethylamine ''N''-oxide is usually encountered as the dihydrate. Both the anhydrous and hydrated materials are white, water-soluble solids. TMAO is found in the tissues of marine crustaceans and marine fish, where it prevents water pressure from distorting proteins and thus killing the animal. The concentration of TMAO increases with the depth at which the animal lives; TMAO is found in high concentrations in the deepest-living described fish species, '' Pseudoliparis swirei'', which was found in the

Mariana Trench The Mariana Trench is an oceanic trench located in the western Pacific Ocean, about east of the Mariana Islands; it is the deep sea, deepest oceanic trench on Earth. It is crescent-shaped and measures about in length and in width. The maxi ...

, at a recorded depth of . In animals, TMAO is a product of the oxidation of trimethylamine, a common metabolite of trimethyl quaternary ammonium compounds, like choline, trimethylglycine, and L-carnitine. High TMAO concentrations are associated with an increased risk of all-cause mortality and cardiovascular disease.

Marine animals

Trimethylamine ''N''-oxide is an osmolyte found in molluscs, crustaceans, and all marine fishes and bony fishes. It is a protein stabilizer that serves to counteract the protein-destabilizing effects of pressure. In general, the bodies of animals living at great depths are adapted to high pressure environments by having pressure-resistant biomolecules and small organic molecules present in their cells, known as piezolytes, of which TMAO is the most abundant. These piezolytes give the proteins the flexibility they need to function properly under great pressure. TMAO decomposes to trimethylamine (TMA), which is the main

odorant An aroma compound, also known as an odorant, aroma, fragrance, flavoring or flavor, is a chemical compound that has a smell or odor. For an individual chemical or class of chemical compounds to impart a smell or fragrance, it must be sufficien ...

that is characteristic of degrading seafood.

TMAO in diet

TMAO levels increase with consumption of

animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...

protein such as eggs, red meat, shellfish and total

fish A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...

consumption. Plant-based diets such as vegan, vegetarian and the

Mediterranean diet The Mediterranean diet is a concept first proposed in 1975 by the American biologist Ancel Keys and chemist Margaret Keys. The diet took inspiration from the eating habits and traditional food typical of Crete, much of the rest of Greece, and s ...

lower TMAO levels.

Chemistry

TMAO can be synthesized from trimethylamine by treatment with

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...

: : The dihydrate is dehydrated by azeotropic distillation from dimethylformamide.

Laboratory applications

Trimethylamine oxide is used in

protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...

experiments to counteract the unfolding effects of

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

. In the

organometallic chemistry Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and so ...

reaction of nucleophilic abstraction, is employed as a decarbonylation agent according to the following

stoichiometry Stoichiometry () is the relationships between the masses of reactants and Product (chemistry), products before, during, and following chemical reactions. Stoichiometry is based on the law of conservation of mass; the total mass of reactants must ...

: : where M is a metal. This reaction is used to decomplex organic ligands from metals, e.g. from . It is used in certain oxidation reactions, e.g. the conversion of alkyl iodides to the corresponding aldehyde.

Effects on protein stability

The effects of TMAO on the backbone and charged residues of peptides are found to stabilize compact conformations, whereas effects of TMAO on nonpolar residues lead to peptide swelling. This suggests competing mechanisms of TMAO on proteins, which accounts for hydrophobic swelling, backbone collapse, and stabilization of charge-charge interactions. These mechanisms are observed in Trp cage.

Disorders

Trimethylaminuria

Trimethylaminuria is a rare defect in the production of the enzyme flavin-containing monooxygenase 3 (''FMO3''). Those suffering from trimethylaminuria are unable to convert choline-derived trimethylamine into trimethylamine oxide. Trimethylamine then accumulates and is released in the person's sweat, urine, and breath, giving off a strong fishy odor.

Health effects

Mortality

High circulating TMAO concentrations are associated with an increased risk of all-cause mortality.

Cardiovascular disease

High circulating TMAO concentrations are associated with an increased risk of cardiovascular events and

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

s in particular.

Hypertension

High circulating TMAO concentrations are associated with an increased risk of

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

Potential toxicity

Exposure limit guidelines with a detailed description of toxicity are available such as "Recommendation from the Scientific Committee on Occupational Exposure Limits" by the European Union Commission.

References

{{Reflist, 30em Amine oxides Lipid disorders Nutrition Oxidizing agents Quaternary ammonium compounds Microbiomes Methyl compounds