Inhibition of acetohydroxy acid synthase by leucine.
The enzymatic reaction of acetohydroxy acid synthase in crude extracts of Escherichia coli K-12 is inhibited by leucine. Inhibition is most pronounced at low pH values and is low at pH values higher than 8.0. Both isoenzymes of acetohydroxy acid synthase present in E. coli K-12 (isoenzyme I and isoenzyme III) are inhibited by leucine. Isoenzyme I, which is responsible for the majority of acetohydroxy acid synthase activity in E. coli K-12 at physiological pH, is inhibited almost completely by 30 mM leucine at pH 6.25-7.0 and is not affected at all at pH values higher than 8.4. Inhibition of isoenzyme I by leucine is a mixed noncompetitive process. Leucine inhibition of isoenzyme III is pH-independent and reaches only 40% at 30 mM leucine. The inhibition of acetohydroxy acid synthase by leucine at physiological pH, observed in vitro in this study, correlates with the idea that acetohydroxy acid synthase is a target for the toxicity of the abnormally high concentrations of leucine in E. coli K-12.
D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D005838:Genotype; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology*; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors*; D010641:Phenotype; D013045:Species Specificity
D007527:Isoenzymes; D000095:Acetolactate Synthase; D007652:Oxo-Acid-Lyases; D007930:Leucine