A new series of S-adenosyl-L-methionine synthetase inhibitors

J Enzyme Inhib. 1998 Aug;13(5):361-7. doi: 10.3109/14756369809021481.

Abstract

A new series of epithio and epoxy amino acid analogues of L-methionine or L-methoxinine were examined as potential inhibitors of the enzyme S-adenosylmethionine (AdoMet) synthetase. The kinetic behaviour of these compounds was studied using recombinant rat liver S-adenosyl-L-methionine sythetase (alpha-isoform) fractionated from E. coli, transformed with the plasmid pSSRL-T7N. All the compounds tested were competitive inhibitors with respect to L-methionine and the (2S, 4S)-2-amino-4,5-epoxy pentanoic acid was found to be a very potent inhibitor of the enzyme compared to those already reported for AdoMet synthetase from other mammalian tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Epoxy Compounds / pharmacology*
  • Homoserine / analogs & derivatives
  • Homoserine / pharmacology
  • Kinetics
  • Liver / enzymology
  • Methionine / analogs & derivatives*
  • Methionine / pharmacology
  • Methionine Adenosyltransferase / antagonists & inhibitors*
  • Rats

Substances

  • 2-amino-4,5-epoxypentanoic acid
  • Enzyme Inhibitors
  • Epoxy Compounds
  • methoxine
  • Homoserine
  • Methionine
  • Methionine Adenosyltransferase