THE ROLE OF CHANGES IN THE SENSITIVITY OF HEPATIC MITOCHONDRIAL OVERTCARNITINE PALMITOYLTRANSFERASE IN DETERMINING THE ONSET OF THE KETOSIS OF STARVATION IN THE RAT

The relationships between the increase in blood ketone-body concentrat ions and several parameters that can potentially influence the rate of hepatic fatty acid oxidation were studied during progressive starvati on (up to 24 h) in the rat in order to discover whether the sensitivit y of mitochondrial overt carnitine palmitoyltransferase (CPTI) to malo nyl-CoA plays an important part in determining the intrahepatic potent ial for fatty acid oxidation during the onset of ketogenic conditions. A rapid increase in blood ketone-body concentration occurred between 12 and 16 h of starvation, several hours after the marked fall in hepa tic malonyl-CoA and in serum insulin concentrations and doubling of pl asma non-esterfied fatty acid (NEFA) concentration. Consequently, both the changes in hepatic malonyl-CoA and serum NEFA preceded the increa se in blood ketone-body concentration by several hours, The maximal ac tivity of CPT I increased gradually throughout the 24 h period of star vation, but the increases did not become significant before 18 h of st arvation. By contrast, the sensitivity of CPT I to malonyl-CoA and the increase in blood ketone-body concentration followed an identical tim e course, demonstrating the central importance of this parameter in de termining the ketogenic response of the liver to the onset of the star ved state.