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

Article Details

Citation

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
DrugTargetKindOrganismPharmacological ActionActions
MethionineS-methylmethionine--homocysteine S-methyltransferase BHMT2ProteinHumans
Unknown
Product of
Details
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
MethionineS-methylmethionine--homocysteine S-methyltransferase BHMT2ProteinHumans
Unknown
Product of
Details
Polypeptides
NameUniProt ID
S-methylmethionine--homocysteine S-methyltransferase BHMT2Q9H2M3Details