Betaine-homocysteine S-methyltransferase (BHMT) (BHMT)

Betaine-homocysteine S-methyltransferase (BHMT) is a cytosolic zinc-dependent enzyme primarily localized in the liver and kidneys. It plays a central role in one-carbon metabolism by catalyzing the transfer of a methyl group from betaine (trimethylglycine) to homocysteine, resulting in the formation of methionine and dimethylglycine. This reaction provides an essential folate-independent remethylation pathway, which is critical for maintaining homocysteine homeostasis and supporting universal methylation reactions via S-adenosylmethionine (SAM) production. Dysregulation or genetic deficiency of BHMT activity leads to hyperhomocysteinemia, a significant risk factor for cardiovascular diseases, thrombosis, and atherosclerosis. In clinical practice, anhydrous betaine is utilized as a pharmaceutical agent to drive BHMT-mediated clearance of homocysteine in patients with homocystinuria. Beyond its role in amino acid metabolism, BHMT is a vital regulator of hepatic lipid metabolism and is investigated for its protective role in non-alcoholic fatty liver disease (NAFLD).

Other names

Betaine-homocysteine S-methyltransferase 1BHMT1Trimethylglycine-homocysteine methyltransferase

Exogenous betaine acts as a methyl donor substrate for the BHMT enzyme, which catalyzes the transfer of a methyl group to homocysteine. This enzymatic process remethylates homocysteine into methionine via a folate-independent pathway, effectively reducing toxic systemic homocysteine concentrations in patients with metabolic deficiencies.