Betaine-homocysteine S-methyltransferase 2 (BHMT2)

Betaine-homocysteine S-methyltransferase 2 (BHMT2) is a zinc-dependent metalloenzyme that catalyzes the transfer of a methyl group from S-methylmethionine (SMM, also known as vitamin U, often derived from plant-based foods) to homocysteine, generating methionine[1][2][5]. Unlike its close homolog BHMT, which uses betaine as a methyl donor, BHMT2 is specific for SMM and is unable to utilize betaine as a substrate[1][2]. The enzyme plays a role in methionine biosynthesis as part of the broader one-carbon metabolic pathway, which is essential for methyl group transfer and regulation of homocysteine, a metabolite associated with cardiovascular and other diseases when dysregulated[3][5]. BHMT2’s tissue expression and physiological details are less well characterized than BHMT, but it is known to be present in the liver[5]. Disease associations for BHMT2 are inferred based on its role in homocysteine/methionine metabolism, with possible links to cardiovascular and metabolic diseases; however, unlike BHMT, direct drug targeting, interacting drugs, or use as a clinical biomarker are not established[5].\n\nKey characteristics:\n- BHMT2 is part of the methyltransferase (specifically, S-methylmethionine-homocysteine methyltransferase) family and shares structural elements with the broader Pfam 02574 family of enzymes[1].\n- It displays high specificity for SMM and does not use betaine, with differences in substrate binding sites explaining selectivity compared to BHMT[1].\n- BHMT2 is a zinc metalloenzyme and may oligomerize, with possible regulatory or evolutionary interactions with BHMT[1].\n- Though it can catalyze the methylation of homocysteine using S-adenosylmethionine (AdoMet) in vitro, its primary physiological function appears centered on SMM[1][2].\n- No known drugs directly target BHMT2, and no safety or toxicology concerns are reported in the literature[5].\n- No clinically established biomarkers or mechanisms of action for drugs targeting BHMT2 are known according to current public biomedical resources.

Other names

S-methylmethionine-homocysteine S-methyltransferase BHMT2SMM-hcy methyltransferasebetaine-homocysteine methyltransferase 2BHMT-2