Trimethylglycine

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Trimethylglycine (also commonly known as TMG, betaine, glycine betaine or betaine anhydrous) is more specifically N,N,N-trimethylglycine. Trimethylglycine was originally named betaine after its discovery in sugar beets (Beta vulgaris) in the 19th century. It is a small N-trimethylated amino acid, existing in zwitterionic form at neutral pH. This substance is often called ‘‘glycine betaine’’ to distinguish it from other betaines that are widely distributed in microorganisms, plants and animals. TMG is not to be confused with betaine hydrochloride.

Trimethylglycine is an organic compound with a structure similar to choline and a betaine. The molecular structure is (CH₃)₃NCH₂COOH as a cation with either the carboxylic acid as the anion (loss of proton) or another anion present. The difference is that choline (trimethylaminoethanol) has been reduced from a terminal carboxylic acid to a hydroxyl group. If Trimethylglycine donates one of its methyl groups, then it becomes dimethylglycine.

Alkylated derivates of trimethylglycine have use as quaternary ammonium zwitterionic surfactants.

Contents 1 Sources 2 Functions 3 Therapeutic uses 4 Biochemical mechanisms 5 Trimethylglycine in Molecular Biology 6 References 7 External links

[edit] Sources

Betaine is obtained by humans from foods, either as betaine or choline-containing compounds. Food items with the highest content of betaine are wheat, spinach, shellfish and sugar beets. Estimates of betaine intake are from 0.1 to 1 g/day and as high as 2.5 g/day for a diet high in whole wheat and seafood. Thus, the intake depends on food composition, but is probably also related to production of the food items, including growing and osmotic conditions. Alternatively, betaine is formed from choline.

The conversion of choline to betaine is a two-step enzymic process, which takes place in the liver and kidney. Choline is first oxidised to betaine aldehyde, a reaction catalysed by the mitochondrial choline oxidase (choline dehydrogenase, EC 1.1.99.1), and betaine aldehyde is further oxidised in the mitochondria or cytoplasm to betaine by betaine aldehyde dehydrogenase (EC 1.1.1.8).

[edit] Functions

Betaine has three known functions in mammals. It is an organic osmolyte that accumulates in renal medullary cells and some other tissues to balance extracellular hypertonicity. Secondly, it also acts like a chaperone to stabilise protein structure under denaturing conditions. Finally, it serves as a methyl donor in the betaine homocysteine methyltransferase (BHMT) reaction which converts homocysteine to methionine.

[edit] Therapeutic uses

Trimethylglycine is used to treat high homocysteine levels.^[1] Kilmer S McCully MD theorised that cholesterol and clogged arteries were symptoms rather than causes of heart disease and proposed homocysteine as a more likely culprit. If it were not for his work, homocysteine would not have been thought harmful and so supplements to lower homocysteine would not have been thought necessary.

TMG may also have uses in enhancing mood, as methyl donor it helps increase SAMe levels.

A compound which may be confused with TMG is betaine hydrochloride, or betaine HCl. Betaine HCl is used as a digestive aid; it is particularly helpful for persons with insufficient acid production in the stomach. Betaine HCl has an acidic taste. TMG (anhydrous betaine) tastes sweet with a metallic aftertaste and is usually produced from sugar beets.

After giving off a methyl group TMG becomes dimethylglycine. DMG helps increase oxygenation to cells and athletes have used it to increase performance. TMG is used by the ton in livestock farming, paired with lysine to increase "carcass yield," to help increase muscle mass. It is also used in salmon farming to relieve osmotic pressure in cells as the animals make the switch from saltwater to freshwater.

[edit] Biochemical mechanisms

TMG functions very closely with choline, folic acid, vitamin B12 and S-adenosyl methionine SAMe. All of these compounds function as "methyl donors." They carry and donate methyl functional groups to facilitate necessary chemical processes. The donation of methyl groups is important to proper liver function, cellular replication, and detoxification reactions. TMG also plays a role in the manufacture of carnitine and serves to protect the kidneys from damage.

Methyl donors, DNA and cancer - DNA methylation is central to the establishment and heritability of states of expression. Gene silencing that is dependent on DNA methylation involves histone deacetylation. The relevance of the correct maintenance of these modification patterns is illustrated by cancer, in which alterations in DNA methylation occur. Hypomethylation is associated with chromosomal instability. ^[2] Methionine is formed from Homocysteine and is converted to SAMe, the human body's predominant methyl donor. In 1985, studies were conducted into Methionine metabolism and cancer. One paper summarised the most recent developments linking methionine metabolism and SAMe to DNA methylation and gene expression in relation to cancer. The study stated that "recent evidence suggests that enzymatic DNA methylation is an important component of gene control and may serve as a silencing mechanism for gene function. Some carcinogens interfere with enzymatic DNA methylation, and thus may allow oncogene activation". The author (J van der Westhuyzen) also wrote that demethylation may be a necessary condition for enhanced transcription and pointed out that DNA hypomethylation has been observed in many cancer cells and tumours. ^[3] In 2002 LL Wu and JT Wu of the University of Utah Health Science Centre published a study ^[4] making the claim that circulating total Homocysteine "may be used as a more accurate tumour marker for monitoring cancer patients during treatment, and hyperhomocysteinemia [may be used] as a risk factor for carcinogenesis". Trimethylglycine / betaine donates a methyl group to convert homocysteine to methionine (using Vitamin B6 and Zinc as co-factors) in a reaction catalysed by BHMT (the Betaine-Homocysteine-Methyl-Transferase enzyme). Methionine is then converted to SAMe by Methionine Adenosyl Transferase (MAT) using Magnesium and Adenosine Triphosphate as co-factors.

[edit] Trimethylglycine in Molecular Biology

Trimethylglycine is an adjuvant of the Polymerase Chain Reaction (PCR) and of all DNA polymerisation based assays such as DNA sequencing. By an unknown Function it aids in the prevention of secondary structures in the DNA molecules and prevents the problems associated with the amplification and sequencing of GC rich regions. Trimethylglycine makes Guanosine and Cytidine (Strong binders) behave with thermodynamics similar to those of Thymidine and Adenosine (Weak Binders). It is best used at a final concentration of 1M.

[edit] References

[edit] External links

• USDA Database for the Choline Content of Common Foods - including the data on choline metabolites, such as betaine, in 434 food items.
• Links to external chemical sources