Carnitine palmitoyl transferase I and the control of beta-oxidation in heart mitochondria

Mitochondrial beta -oxidation provides much of the fuel requirements of hea rt and skeletal muscle despite the malonyl-CoA concentration greatly exceed ing the IC50 of carnitine palmitoyl transferase for malonyl-CoA. To try to explore the relationship between inhibition of carnitine palmitoyl transfer ase I activity and beta -oxidation flux, we measured the flux control coeff icient of carnitine palmitoyl transferase I over beta -oxidation carbon flu x in suckling rat heart mitochondria. The flux control coefficient was foun d to be 0.08 +/- 0.05 and 50% of carnitine palmitoyl transferase I activity could be inhibited before beta -oxidation flux was affected. These observa tions may help to explain the presence of high rates of beta -oxidation des pite the high concentration of malonyl-CoA in rat heart; we hypothesize tha t although not rate-limiting in vitro, carnitine palmitoyl transferase is r ate-limiting in vivo because of the high malonyl-CoA concentration in heart and muscle. (C) 2001 Academic Press.