Regulation of the activity of acetyl coenzyme A carboxylase by palmitoyl coenzyme A and citrate.

Pahnitoyl-CoA (100 PM), in the presence of albumin (24 mg per ml), inhibited the incorporation of [14C]citrate into fatty acids in a cytosol fraction of chick liver and inhibited the activity of acetyl-CoA carboxylase purified from chick liver. Under similar incubation conditions, pahnitoyl-CoA (ZOO PM) did not inhibit fatty acid synthetase, ATP-citrate lyase, malic enzyme, NADP-linked isocitrate dehydrogenase, pyruvate kinase, or glutamate dehydrogenase. The high concentration of albumin was used to ensure that the free concentration of pahnitoyl-CoA was very low and relatively independent both of the concentration of the enzyme tested and of its aflinity for palmitoyl-CoA. In the presence of 0.26 mg of albumin per ml and 1 fzl~ citrate, 1 PM palmitoyl-CoA inhibited the activity of the partially purified acetyl-CoA carboxylase by about 75%. This inhibition was reversed after 9 min of incubation by increasing the albumin concentration to 11 mg per ml or by increasing the citrate concentration to 6 ells or by adding 10 PM (+) -pahnitoylcamitine. At both high and low albumin concentrations, inhibition by pahnitoyl-CoA was competitive with respect to citrate. Inhibition of acetylCoA carboxylase by pahnitoyl-CoA occurred immediately and did not increase with time of incubation. It is concluded that pahnitoyl-CoA inhibition of acetylCoA carboxylase is reversible and competitive with citrate and, therefore, may play an important role in the regulation of fatty acid synthesis in vivo.