Carnitine palmitoyl transferase I and the control of beta-oxidation in heart mitochondria.
Mitochondrial beta-oxidation provides much of the fuel requirements of heart and skeletal muscle despite the malonyl-CoA concentration greatly exceeding the IC(50) of carnitine palmitoyl transferase for malonyl-CoA. To try to explore the relationship between inhibition of carnitine palmitoyl transferase I activity and beta-oxidation flux, we measured the flux control coefficient of carnitine palmitoyl transferase I over beta-oxidation carbon flux in suckling rat heart mitochondria. The flux control coefficient was found to be 0.08 +/- 0.05 and 50% of carnitine palmitoyl transferase I activity could be inhibited before beta-oxidation flux was affected. These observations may help to explain the presence of high rates of beta-oxidation despite the high concentration of malonyl-CoA in rat heart; we hypothesize that although not rate-limiting in vitro, carnitine palmitoyl transferase is rate-limiting in vivo because of the high malonyl-CoA concentration in heart and muscle.
Eaton
S
S
Unit of Paediatric Surgery, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, United Kingdom. s.eaton@ich.ucl.ac.uk
Bartlett
K
K
Quant
P A
PA
D000818:Animals; D000833:Animals, Suckling; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D008293:Malates; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase