Trimethylglycine

Trimethylglycine

Names
IUPAC name 2-trimethylammonioacetate
Other names Betaine TMG glycine betaine N,N,N-trimethylglycine
Identifiers
CAS Number	107-43-7 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:17750 N
ChemSpider	242 Y
DrugBank	DB06756 N
ECHA InfoCard	100.003.174
IUPHAR/BPS	4550
MeSH	Betaine
PubChem CID	247
UNII	3SCV180C9W Y
InChI InChI=1S/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3 Y Key: KWIUHFFTVRNATP-UHFFFAOYSA-N Y InChI=1/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3 Key: KWIUHFFTVRNATP-UHFFFAOYAI
SMILES C[N+](C)(C)CC(=O)[O-]
Properties
Chemical formula	C5H11NO2
Molar mass	117.146
Appearance	White solid
Melting point	180 °C (356 °F; 453 K)[1] (decomposes)
Solubility in water	Soluble
Solubility	Methanol
Acidity (pKa)	1.84
Pharmacology
ATC code	A16AA06 (WHO)
Related compounds
Related amino acids	Glycine Methylglycine Dimethylglycine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Trimethylglycine (TMG) is an amino acid derivative that occurs in plants. Trimethylglycine was the first betaine discovered; originally it was simply called betaine because, in the 19th century, it was discovered in sugar beets.^[2] Since then, many other betaines have been discovered, and the more specific name glycine betaine distinguishes this one.

Structure and reactions

Trimethylglycine is an N-trimethylated amino acid. This quaternary ammonium exists as the zwitterion at neutral pH. Strong acids such as hydrochloric acid convert TMG to various salts, with HCl yielding betaine hydrochloride:

(CH₃)₃N⁺CH₂CO−
2 + HCl → [(CH₃)₃N⁺CH₂CO₂H]Cl⁻

Demethylation of TMG gives dimethylglycine. Degradation of TMG yields trimethylamine, the scent of putrefying fish.

Production and biochemical processes

Processing sucrose from sugar beets yields glycine betaine as a byproduct. The value of the TMG rivals that of the sugar content in sugar beets.^[3]

Biosynthesis

In most organisms, glycine betaine is biosynthesized by oxidation of choline in two steps. The intermediate, betaine aldehyde, is generated by the action of the enzyme mitochondrial choline oxidase (choline dehydrogenase, EC 1.1.99.1). Betaine aldehyde is further oxidised in the mitochondria in mice to betaine by the enzyme betaine aldehyde dehydrogenase (EC 1.2.1.8).^[4][5] In humans betaine aldehyde activity is performed by a nonspecific cystosolic aldehyde dehydrogenase enzyme (EC 1.2.1.3) ^[6]

Biological function

TMG is an organic osmolyte that occurs in high concentrations (~10 mM) in many marine invertebrates, such as crustaceans and molluscs. It serves as a potent appetitive attractant to generalist carnivores such as the predatory sea-slug Pleurobranchaea californica.^[7]

TMG is an important cofactor in methylation, a process that occurs in every cell of mammals to synthesize and donate methyl groups (CH₃) for other processes in the body. These processes include the synthesis of neurotransmitters such as dopamine and serotonin. Methylation is also required for the biosynthesis of melatonin and the electron transport chain constituent coenzyme Q₁₀.

The major step in the methylation cycle is the remethylation of homocysteine, a compound which is naturally generated during deamination of the essential amino acid methionine. Despite its natural formation, homocysteine has been linked to inflammation, depression, specific forms of dementia, and various types of vascular disease. The remethylation process that detoxifies homocysteine and converts it back to methionine can occur via either of two pathways. The major pathway involves the enzyme methionine synthase, which requires vitamin B₁₂ as a cofactor, and also depends indirectly on folate and other B vitamins. The minor pathway involves betaine-homocysteine methyltransferase and requires TMG as a cofactor. Betaine is thus involved in the synthesis of many biologically important molecules, and may be even more important in situations where the major pathway for the regeneration of methionine from homocysteine has been compromised by genetic polymorphisms such as mutations in the BHMT gene.

TMG in agriculture and aquaculture

Factory farms supplement fodder with TMG and lysine to increase livestocks' muscle mass (and, therefore, "carcass yield", the amount of usable meat).

Salmon farms apply TMG to relieve the osmotic pressure on the salmon's cells when workers transfer the fish from freshwater to saltwater.^[3][8]

TMG supplementation decreases the amount of adipose tissue in pigs; however, research in human subjects has shown no effect on body weight, body composition, or resting energy expenditure.^[9]

TMG in the human diet

Dietary supplement

Although TMG supplementation decreases the amount of adipose tissue in pigs, research on human subjects has shown no effect on body weight, body composition, or resting energy expenditure when used in conjunction with a low calorie diet.^[9] The Food and Drug Administration of the United States approved anhydrous trimethylglycine (also known by the brand name Cystadane) for the treatment of homocystinuria, a disease caused by abnormally high homocysteine levels at birth.^[10] TMG supplementation may cause diarrhea, stomach upset, or nausea. TMG supplementation lowers homocysteine but also raises LDL-cholesterol.^[11]

Other uses: PCR

Trimethylglycine can act as an adjuvant of the polymerase chain reaction (PCR) process, and other DNA polymerase-based assays such as DNA sequencing. By an unknown mechanism, it aids in the prevention of secondary structures in the DNA molecules, and prevents 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 has been determined under experiment that it is best used at a final concentration of 1 M.^[12]

Speculative uses

Laboratory studies and two clinical trials have indicated that TMG is a potential treatment of non-alcoholic steatohepatitis.^[13][14][15]

TMG has been proposed as a treatment for depression. In theory, it would increase S-adenosylmethionine (SAMe) by remethylating homocysteine. The same homocysteine-to-methionine result could be achieved by supplementing with folic acid and vitamin B12, methionine then serving as a precursor to synthesis of SAMe. SAMe as a dietary supplement has been shown to work as a nonspecific antidepressant.^[16]

IEX Ion Exchange Chromatography

In the book from Amersham Biosciences/GE Healthcare, Ion Exchange Chromatography & Chromatofocusing - Principles and Methods, page 48. "Zwitterionic additives such as betaine can prevent precipitation and can be used at high concentrations without interfering with the gradient elution"

References

External links

• USDA Database for the Choline Content of Common Foods – including the data on choline metabolites, such as betaine, in 434 food items.