Trimethylglycine (TMG)

Trimethylglycine (TMG), also known as betaine, is a naturally occurring quaternary ammonium compound and a metabolite of choline that serves as a critical methyl donor and osmolyte in human physiology [PubChem, CID 670]. In the methionine cycle, TMG donates a methyl group to homocysteine to regenerate methionine, a reaction catalyzed by the enzyme betaine-homocysteine S-methyltransferase (BHMT) primarily in the liver and kidneys [UniProt, P11308]. This pathway provides an alternative to the folate-dependent remethylation route and is essential for maintaining low systemic homocysteine levels. Elevated homocysteine is a known risk factor for cardiovascular disease and is the hallmark of homocystinuria, a genetic metabolic disorder [NIH, StatPearls]. Therapeutically, TMG is administered as betaine anhydrous (Cystadane) to reduce toxic homocysteine concentrations in patients with various forms of homocystinuria [FDA, Cystadane Label]. Beyond its role in methylation, TMG acts as a cytoprotectant by stabilizing protein conformation and maintaining cellular fluid balance under osmotic stress [PubMed, PMID: 15121016].

Other names

BetaineGlycine betaineBetaine anhydrousTrimethylammonioacetateOxyneurineAbromine

Trimethylglycine acts as a substrate and methyl donor for the enzyme betaine-homocysteine S-methyltransferase (BHMT), which converts homocysteine into methionine, thereby lowering plasma homocysteine levels [FDA, Cystadane Label; UniProt, P11308].