Trimethylglycine

Biosynthesis

In most organisms, glycine betaine is biosynthesized by oxidation of choline. The intermediate, betaine aldehyde, is generated by the action of the enzyme mitochondrial choline oxidase (choline dehydrogenase, EC 1.1.99.1). In mice, betaine aldehyde is further oxidised in the mitochondria by the enzyme betaine-aldehyde dehydrogenase (EC 1.2.1.8).^[15][16] In humans betaine aldehyde activity is performed by a nonspecific cystosolic aldehyde dehydrogenase enzyme (EC 1.2.1.3) ^[17]

Trimethylglycine is produced by some cyanobacteria, as established by ¹³C nuclear magnetic resonance. It is proposed to protect for some enzymes, against inhibition by NaCl and KCl.^[18]

Osmolyte

Trimethylglycine is an osmolyte, a water-soluble salt-like substance. Sugar beet was cultivated from sea beet, which requires osmolytes in order to survive the salty soils of coastal areas. Trimethylglycine also occurs in high concentrations (~10 mM) in many marine invertebrates, such as crustaceans and molluscs. It serves as a appetitive attractant to generalist carnivores such as the predatory sea slug Pleurobranchaea californica.^[19]

Methyl donor

Trimethylglycine is a cofactor in methylation, a process that occurs in all mammals. Methylation is required for the biosynthesis of the neurotransmitters dopamine and serotonin, as well as for the synthesis of melatonin and coenzyme Q₁₀. DNA methylation is also involved in epigenetics.

The methylation cycle involves the remethylation of homocysteine, which occurs via either of two pathways. One pathway, present in virtually all cells, involves the enzyme methionine synthase (MS), which requires vitamin B₁₂ as a cofactor, and also depends indirectly on folate and other B vitamins. The second pathway is restricted to the liver and kidneys in most mammals and involves betaine-homocysteine methyltransferase (BHMT), requiring trimethylglycine as a methyl donor. During normal physiological conditions, the two pathways contribute equally to removal of homocysteine in the human body.^[20]

Dimethylglycine dehydrogenase also uses betaine to produce folate, contributing back to methionine synthase.

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 MS gene.

In foods

Trimethylglycine is a popular dietary supplement for athletes.^[27]

In 2017, the European Food Safety Authority concluded that betaine was safe "as a novel food to be used at a maximum intake level of 6 mg/kg body weight per day in addition to the intake from the background diet."^[28] Trimethylglycine supplementation may cause diarrhea, bloating, cramps, dyspepsia, nausea or vomiting.^[12][8] Although rare, it can also cause excessive increases in serum methionine concentrations in the brain, which may lead to cerebral edema, a life-threatening condition.^[8]

Biochemistry

The addition of betaine to polymerase chain reactions improves the amplification of DNA by reducing the formation of secondary structure in GC-rich regions. The addition of betaine may enhance the specificity of the polymerase chain reaction by eliminating the base pair composition dependence of DNA melting.^[29][30]