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-oxidatio n 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 hepato cyte monolayers was determined by titration with 2-[6-(4-chlorophenoxy )hexyl]oxirane-2-carboxylate (Etomoxir), which is converted to Etomoxi r-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 simu late substrate concentrations in fed and fasted states. Rates of beta- oxidation were 4.5-fold higher at 1.0 mM palmitate compared with 0.2mM palmitate. Flux control coefficients of CPT I, estimated by two indep endent methods, were similar: 0.67 and 0.79 for 0.2mM palmitate, and 0 .68 and 0.77 for 1 mM palmitate. It is concluded that the regulatory p otential of CPT I is similar at low and high physiological concentrati ons of palmitate.