2-Keto-4-methylthiobutyrate, an intermediate in the methionine salvage pathway, is a good substrate for CtBP1

Biochem Biophys Res Commun. 2007 Jan 26;352(4):903-6. doi: 10.1016/j.bbrc.2006.11.111. Epub 2006 Dec 4.


In the present work, we have studied the kinetic properties of the catalytic domain of CtBP1, a co-repressor belonging to the d-2-hydroxyacid dehydrogenase family and known to reduce pyruvate in the presence of NADH. CtBP1 acted on a variety of alpha-keto acids, for which it displayed biphasic curves with inhibition at elevated concentrations, as observed with other dehydrogenases of the same family. Based on catalytic efficiencies, the best substrate was 2-keto-4-methylthiobutyrate, an intermediate of the methionine salvage pathway. It was about 20-fold better than 2-ketoisocaproate and glyoxylate, and 80-fold better than pyruvate. From these data we conclude that 2-keto-4-methylthiobutyrate may be an important regulator of CtBP activity, possibly linking gene repression to the activity of the methionine salvage and spermine synthesis pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Catalysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Methionine / analogs & derivatives*
  • Methionine / metabolism*
  • Substrate Specificity


  • DNA-Binding Proteins
  • 2-keto-4-methylthiobutyric acid
  • Methionine
  • Alcohol Oxidoreductases
  • C-terminal binding protein