Coenzyme A is required for rat liver fatty acid synthetase activity

Inhibition of highly purified rat liver fatty acid synthetase occurs when it is assayed in the presence of the ATP citrate lyase reaction components. Citrate, Mg2+, ATP, and ATP citrate lyase were all necessary for the inhibition to take place. Inhibition was prevented by hydroxycitrate, a competitive inhibitor for ATP citrate lyase. The length of time for the onset of inhibition to take place was proportional to the ratio of ATP citrate lyase activity to the fatty acid synthetase activity. The inhibition was reversed by the addition of coenzyme A. This indicates a reaction mechanism for fatty acid synthetase which involves free coenzyme A. Two possible roles for CoA are discussed, one as an allosteric activator and the other in the cleavage of palmitoyl enzyme in the last step of the reaction.