Effects of sodium 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxylate (POCA) on carbohydrate and fatty acid metabolism in liver and muscle.

In isolated rat hepatocytes, rates of gluconeogenesis, ketogenesis and oleate oxidation to CO2 were measured at various concentrations of lactate, pyruvate and oleate in the presence or absence of sodium 2-[5-(4-chlorophenyl)-pentyl]oxirane-2-carboxylate (POCA). With increasing lactate and pyruvate concentrations, but constant oleate concentration, oleate oxidation to CO2, concomitantly to gluconeogenesis, was accelerated, whereas ketogenesis was decreased. In the presence of POCA, rates of gluconeogenesis, ketogenesis and oleate oxidation to CO2 were diminished; the concentrations for half-maximal inhibition were in the micromolar range for all metabolic processes studied. When octanoate was present instead of oleate, the inhibitory effect of POCA on gluconeogenesis was reduced and that of ketogenesis was nearly abolished, suggesting that POCA specifically inhibits the oxidation of long-chain fatty acids. In addition, the oxidation of glucose and oleate was studied in isolated rat diaphragms. POCA inhibits the oxidation to CO2 of long-chain fatty acids also in muscle tissue; the concentration for half-maximal effect, however, was about one order of magnitude higher than in liver. Concomitantly, glucose oxidation was enhanced by POCA indicating a shift in the substrate preference of energy-yielding metabolism.