The flux control coefficient of carnitine palmitoyltransferase I on palmitate beta-oxidation in rat hepatocyte cultures.
Two important factors that determine the flux of hepatic beta-oxidation of long-chain fatty acids are the availability of fatty acid and the activity of carnitine palmitoyltransferase I (CPT I). Using Metabolic Control Analysis, the flux control coefficient of CPT I in rat hepatocyte monolayers was determined by titration with 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir), which is converted to Etomoxir-CoA, an irreversible inhibitor of CPT I. We measured CPT I activity and flux through beta-oxidation at 0.2 mM and 1.0 mM palmitate to simulate substrate concentrations in fed and fasted states. Rates of beta-oxidation were 4.5-fold higher at 1. 0 mM palmitate compared with 0.2 mM palmitate. Flux control coefficients of CPT I, estimated by two independent methods, were similar: 0.67 and 0.79 for 0.2 mM palmitate, and 0.68 and 0.77 for 1 mM palmitate. It is concluded that the regulatory potential of CPT I is similar at low and high physiological concentrations of palmitate.
Spurway
T D
TD
Department of Pharmacological Sciences, Medical School University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK.
Sherratt
H A
HA
Pogson
C I
CI
Agius
L
L
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D019308:Palmitic Acid; D002334:Carnitine O-Palmitoyltransferase; C054207:etomoxir