trimethylamine oxide
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Trimethylamine ''N''-oxide (TMAO) is an
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
with the formula (CH3)3NO. It is in the class of
amine oxide In chemistry, an amine oxide, also known as an amine ''N''-oxide or simply ''N''-oxide, is a chemical compound that contains the functional group , a nitrogen-oxygen coordinate covalent bond with three additional hydrogen and/or substituent-grou ...
s. Although the anhydrous compound is known, trimethylamine ''N''-oxide is usually encountered as the
dihydrate In chemistry, a hydrate is a substance that contains water or its constituent elements. The chemical state of the water varies widely between different classes of hydrates, some of which were so labeled before their chemical structure was understo ...
. 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 deepest oceanic trench on Earth. It is crescent-shaped and measures about in length and in width. The maximum known ...
, at a recorded depth of . TMAO is a product of the oxidation of
trimethylamine Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a colorless, hygroscopic, and flammable tertiary amine. It is a gas at room temperature but is usually sold as a 40% solution in water. (It is also sold in pressurized ...
, a common metabolite of
choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but r ...
in animals.


Marine animals

Trimethylamine ''N''-oxide is an
osmolyte Osmolytes are low-molecular weight organic compounds that influence the properties of biological fluids. Their primary role is to maintain the integrity of cells by affecting the viscosity, melting point, and ionic strength of the aqueous solution. ...
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 Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a colorless, hygroscopic, and flammable tertiary amine. It is a gas at room temperature but is usually sold as a 40% solution in water. (It is also sold in pressurized ...
(TMA), which is the main
odorant An aroma compound, also known as an odorant, aroma, fragrance or flavoring, 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 sufficiently vol ...
that is characteristic of degrading seafood.


Chemistry

TMAO can be synthesized from trimethylamine by treatment with hydrogen peroxide:A. J. Pearson "Trimethylamine N-Oxide" in ''Encyclopedia of Reagents for Organic Synthesis'', John Wiley & Sons, 2001: New York. :H2O2 + (CH3)3N → H2O + (CH3)3NO The dihydrate is dehydrated by azeotropic distillation from
dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the maj ...
.


Laboratory applications

Trimethylamine oxide is used in
protein folding Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduc ...
experiments to counteract the unfolding effects of
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...
. In the organometallic chemistry reaction of
nucleophilic abstraction Nucleophilic abstraction is a type of an organometallic reaction which can be defined as a nucleophilic attack on a ligand which causes part or all of the original ligand to be removed from the metal along with the nucleophile.Spessard, Gary; Mie ...
, Me3NO is employed as a decarbonylation agent according to the following stoichiometry: :M(CO)''n'' + Me3NO + L → M(CO)''n''−1L + Me3N + CO2 This reaction is used to decomplex organic ligands from metals,
e.g. Eg or EG may refer to: In arts and media * ''E.G.'' (EP), an EP by Goodshirt * ''EG'' (magazine), a journal dedicated to chess endgame studies * Eg White (born 1966), a British musician, songwriter and producer * E.G. Records, a music record l ...
from (diene)Fe(CO)3. It is used in certain oxidation reactions, e.g. the conversion of alkyl iodides to the corresponding
aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
.


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 Trimethylaminuria (TMAU), also known as fish odor syndrome or fish malodor syndrome, is a rare metabolic disorder that causes a defect in the normal production of an enzyme named flavin-containing monooxygenase 3 (''FMO3''). When ''FMO3'' is not w ...
is a rare defect in the production of the enzyme
flavin-containing monooxygenase 3 Flavin-containing monooxygenase 3 (FMO3), also known as dimethylaniline monooxygenase -oxide-forming3 and trimethylamine monooxygenase, is a flavoprotein enzyme () that in humans is encoded by the ''FMO3'' gene. This enzyme catalyzes the foll ...
(''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.


Cardiovascular disease

High TMAO concentrations are associated with an increased risk of cardiovascular disease and all-cause mortality.


Potential toxicity

Due to its widespread use in industry, various 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.Pospischil, E.; Johanson, G.; Nielsen, G.; Papameletiou, D.; Klein, C. SCOEL/REC/179 Trimethylamine. Publ. Sci. Comm. Occup. Expo. Lim. Eur. Union 2017.


References


See also

*
Greenland shark The Greenland shark (''Somniosus microcephalus''), also known as the gurry shark, grey shark, or by the Kalaallisut name ''eqalussuaq'', is a large shark of the family Somniosidae ("sleeper sharks"), closely related to the Pacific and souther ...
{{DEFAULTSORT:Trimethylamine N-Oxide Amine oxides Lipid disorders Nutrition Oxidizing agents Quaternary ammonium compounds Microbiomes