Two important factors that determine the flux of hepatic β-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 β-oxidation at 0.2 mM and 1.0 mM palmitate to simulate substrate concentrations in fed and fasted states. Rates of β-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.
The flux control coefficient of carnitine palmitoyltransferase I on palmitate β-oxidation in rat hepatocyte cultures
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Tracey D. SPURWAY, H. Stanley A. SHERRATT, Christopher I. POGSON, Loranne AGIUS; The flux control coefficient of carnitine palmitoyltransferase I on palmitate β-oxidation in rat hepatocyte cultures. Biochem J 1 April 1997; 323 (1): 119–122. doi: https://doi.org/10.1042/bj3230119
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