Betaine-homocysteine S-methyltransferase, BHMT (IPR017226)

Short name: Betaine-hCys_S-MeTrfase_BHMT

Overlapping homologous superfamilies

Family relationships



Betaine-homocysteine methyltransferase (BHMT) is involved in the regulation of homocysteine metabolism. It converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline. BHMT requires a thiol reducing agent for its activity. The catalytic zinc of BHMT is bound by three thiolates and one hydroxyl group. A disulphide bond is formed between two of the three zinc-binding ligands when BHMT is inactive [PMID: 18262489].

BHMT regulates homocysteine levels in the liver. The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury, but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death. It also has a generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine [PMID: 17705221]. However, the peripheral metabolism of homocysteine protects the liver without the direct action of BHMT in the liver [PMID: 18498552].

The human betaine-homocysteine methyltransferase-2 is also a zinc metalloenzyme that uses S-methylmethionine (SMM) as a methyl donor for the methylation of homocysteine. Unlike the highly homologous BHMT, BHMT-2 cannot use betaine as a substrate [PMID: 18230605].

This entry also includes homocysteine S-methyltransferase (EC:, which converts S-adenosylmethionine to methionine [PMID: 11013242]; selenocysteine Se-methyltransferase (EC:, which methylates DL- and L-selenocysteine, DL-homocysteine, and DL- and L-cysteine [PMID: 15863700]; and S-methylmethionine--homocysteine S-methyltransferase BHMT2 (also EC:, which converts converts homocysteine to methionine [PMID: 18230605].

GO terms

Biological Process

GO:0009086 methionine biosynthetic process

Molecular Function

GO:0047150 betaine-homocysteine S-methyltransferase activity
GO:0008270 zinc ion binding

Cellular Component

GO:0005737 cytoplasm

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.