Evidence for direct methyl transfer in betaine: homocysteine S-methyl-transferase.

W. M. Awad, P. L. Whitney, W. E. Skiba, J. H. Mangum, M. S. Wells

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20 Scopus citations

Abstract

We described recently the purification and preliminary characterization of human hepatic betaine: homocysteins S-methyltransferase (Skiba, W. E., Taylor, M. P., Wells, M. S., Mangum, J. H., and Awad, W. M., Jr. (1982) J. Biol. Chem. 258, 14944-14948) where it was shown that isovalerate and 3,3-dimethylbutyrate, analogs of dimethylglycine and betaine, respectively, were good inhibitors. The present study demonstrates that butyrate is a modest competitive inhibitor, binding at the betaine site. This led to the consideration and synthesis of a putative dual-substrate analog, S(delta-carboxybutyl)-DL-homocysteine, which bound with high affinity to the active site of the methyltransferase; presumably this effect is due to the L-isomer only. Homologs, S(gamma-carboxypropyl)-DL-homocysteine and S(beta-carboxyethyl)-DL-homocysteine, do not inhibit at concentrations 100-fold higher than where inhibition is noted with the dual-substrate analog, indicating the latter's specificity. These findings support the hypothesis that methyl transfer in this enzyme occurs directly from one substrate to the other.

Original languageEnglish (US)
Pages (from-to)12790-12792
Number of pages3
JournalJournal of Biological Chemistry
Volume258
Issue number21
StatePublished - Nov 10 1983

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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