The inhibition of citrate synthase by adenosine triphosphate

Abstract

1. 1.Citrate synthase (citrate oxaloacetate-lyase (CoA-acetylating), EC 4.1.3.7) has been partially purified from beef liver, beef heart and Escherichia coli. The beef heart and beef liver enzymes were quite similar in their pH optima, substrate affinities and sensitivity to ATP inhibition. The E. coli enzyme had a lower substrate affinity and had a lower K i for ATP than the mammalian enzymes. The E. coli citrate synthase differed markedly from the mammalian enzymes in its response to pH changes. 2. 2.ATP was competitive with respect to CoASAc with the beef liver and beef heart enzymes. In E. coli, ATP was not competitive with CoASAc but changed both V and K m for oxaloacetate. Mg + also inhibits the activity of the E. coli citrate synthase and tends to relieve the ATP inhibition. 3. 3.The ATP inhibition of citrate synthase may act in concert with AMP and ADP stimulation of isocitrate dehydrogenase and with citrate stimulation of CoASAc carboxylase in partitioning CoASAc between oxidation by way of the citric acid cycle and storage as fat. It may also play a role in regulating liver ketone body formation.