Alpha-isopropylmalate synthase from Alcaligenes eutrophus H 16. III. Endproduct inhibition and its relief by valine and isoleucine.
The alpha-isopropylmalate synthase (EC 4.1.3.12) from Alcaligenes eutrophus H 16 was inhibited by L-leucine and alpha-ketoisocaproate. The extent of inhibition was influenced by substrate- and inhibitor concentrations as well as by the pH. Intermediary plateaus, which always appeared in the inhibition curves, suggested cooperative effects. The maximal Hill coefficient was found to be two. At low concentrations of leucine the inhibition mechanism was of the competitive type with respect to substrate acetyl coenzyme A and of the noncompetitive type with respect to substrate alpha-ketoisovalerate. The inhibition was specifically relieved by the addition of valine or isoleucine. The anomalous effect of temperature on enzyme activity was diminished by leucine. The Arrhenius energy of the reaction increased from about 11 kcal/mole in the absence of leucine to about 18 kcal/mole in the presence of leucine. The further addition of valine reversed this effect. The physiological relevance of the alpha-ketoisocaproate-mediated inhibition is discussed.
D015079:2-Isopropylmalate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000421:Alcaligenes / Q000201:enzymology*; D002208:Caproates / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007532:Isoleucine / Q000494:pharmacology*; D007651:Keto Acids / Q000494:pharmacology; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D007652:Oxo-Acid-Lyases / Q000378:metabolism*; D013696:Temperature; D014633:Valine / Q000494:pharmacology*
D002208:Caproates; D007651:Keto Acids; D007532:Isoleucine; D006639:Histidine; C013082:alpha-ketoisocaproic acid; D015079:2-Isopropylmalate Synthase; D007652:Oxo-Acid-Lyases; D007930:Leucine; D014633:Valine