A suppressive role of c-kinase for the stimulation of hepatic ketogenesis by glucagon and epinephrine.

The regulatory mechanism of hepatic palmitate oxidation into ketone bodies by c-kinase has been studied in isolated hepatocytes. Glucagon and epinephrine stimulated [U-14C]palmitate oxidation to ketone bodies by 60 and 25% as early as at 1 h. The stimulatory effects were almost totally prevented by the simultaneous presence of vasopressin, phorbol 12-tetradecanoate 13-acetate (TPA), or diacylglycerol (1-oleoyl-2-acetylglycerol). When hepatocytes were treated with glucagon or epinephrine, carnitine palmitoyltransferase (CPT), a key regulatory enzyme of palmitate oxidation, was activated. This hormone-induced activation of CPT was not observed in the presence of TPA. These observations suggest that c-kinase inhibits glucagon- or epinephrine-stimulated palmitate oxidation to ketone bodies, and that this inhibition may be mediated through a covalent modification of CPT.