Control of isoleucine, valine and leucine biosynthesis

Abstract

Acetohydroxy acid synthetase, which catalyzes the synthesis of α-acetolactate and α-acetohydroxybutyrate, the first 5- and 6-carbon precursors of valine and isoleucine, respectively, has been studied in extracts of Salmonella typhimurium. Required for enzyme activity are thiamine pyrophosphate, Mg2+ and an unidentified factor which can be supplied by boiled extracts of Salmonella or yeast. The activity of the enzyme is inhibited by l-valine and a group of related compounds. Valine inhibition is noncompetitive with respect to pyruvate and thiamine pyrophosphate and is rigidly dependent on pH. Inhibition is greatest at pH 8.0, also the optimal pH for activity, and is non-existent at values less than 6.5. The sensitivity of the enzyme to valine can be removed by heat, Hg2+ or urea treatments. Glutathione is effective in restoring valine sensitivity to the Hg2+-treated enzyme. These properties indicate that this enzyme belongs to the class of proteins recently described as “allosteric” in nature.