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

Sandra S. Szegedi, Carmen C. Castro, Markos Koutmos, Timothy A. Garrow

Research output: Contribution to journalArticlepeer-review

Abstract

We demonstrate that purified recombinant human betaine-homocysteine 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 Km 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 kcat/Km that is 5-fold lower than the k cat/Km 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.

Original languageEnglish (US)
Pages (from-to)8939-8945
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number14
DOIs
StatePublished - Apr 4 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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