The Mechanism of Substrate Inhibition of Palmityl Coenzyme A:Carnitine Palmityltransferase by Palmityl Coenzyme A

The substrate inhibition of palmityl coenzyme A:carnitine O-palmityltransferase (EC 2.3.1.-) by palmityl-CoA has been studied. Beside being a substrate for the enzyme, palmityl-CoA was found to behave as a competitive inhibitor for the second substrate (carnitine). The Ki was found to be approximately 3 x 10-6 m, while the Km for palmityl-CoA was found to be approximately 10-5 m. Thus, the affinity of palmityl-CoA as an inhibitor for the enzyme was at least as high as its affinity as substrate. These results explain the pronounced substrate inhibition by palmityl-CoA. The Km values for the other substrates were found to be: l-carnitine, 2.5 x 10-4 m; l-palmitylcarnitine, 4 x 10-5 m; and CoA, 5 x 10-5 m. The possible physiological importance of the reaction kinetics of carnitine palmityltransferase is discussed.