Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase.

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Szegedi SS, Castro CC, Koutmos M, Garrow TA

Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase.

J Biol Chem. 2008 Apr 4;283(14):8939-45. doi: 10.1074/jbc.M710449200. Epub 2008 Jan 29.

PubMed ID

18230605 [ View in PubMed

]

Abstract

We demonstrate that purified recombinant human betainehomocysteine methyltransferase-2 (BHMT-2) is a zinc metalloenzyme that uses S-methylmethionine (SMM) as a methyl donor for the methylation of homocysteine. Unlike the highly homologous betaine-homocysteine methyltransferase (BHMT), BHMT-2 cannot use betaine. The K(m) of BHMT-2 for SMM was determined to be 0.94 mm, and it has a turnover number similar to BHMT. Several compounds were tested as inhibitors of recombinant human BHMT and BHMT-2. The SMM-specific methyltransferase activity of BHMT-2 is not inhibited by dimethylglycine and betaine, whereas the former is a potent inhibitor of BHMT. Methionine is a stronger inhibitor of BHMT-2 than BHMT, and S-adenosylmethionine does not inhibit BHMT but is a weak inhibitor of BHMT-2. BHMT can use SMM as a methyl donor with a k(cat)/K(m) that is 5-fold lower than the k(cat)/K(m) for betaine. However, SMM does not inhibit BHMT activity when it is presented to the enzyme at concentrations that are 10-fold greater than the subsaturating amounts of betaine used in the assay. Based on these data, it is our current hypothesis that in vivo most if not all of the SMM-dependent methylation of homocysteine occurs via BHMT-2.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Methionine	S-methylmethionine--homocysteine S-methyltransferase BHMT2	Protein	Humans	Unknown	Product of	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Methionine	S-methylmethionine--homocysteine S-methyltransferase BHMT2	Protein	Humans	Unknown	Product of	Details

Polypeptides

Name	UniProt ID
S-methylmethionine--homocysteine S-methyltransferase BHMT2	Q9H2M3	Details