Effects of sodium 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxylate (POCA) on intermediary metabolism in isolated rat-liver cells

Abstract

In hepatocytes isolated from meal-fed rats, sodium 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) decreased the rate of lipogenesis measured as incorporation of 3H from 3H2O into glycerolipids and cholesterol. Moreover, POCA inhibited the oxidation of added oleate, whereas oleate esterification was stimulated. In hepatocytes from 24-hr-starved rats, inhibition of gluconeogenesis by POCA was observed only with gluconeogenic precursors which require pyruvate carboxylation. This inhibition was secondary to impaired oxidation of long-chain fatty acids by POCA. It is concluded that, in addition to its inhibition of long-chain fatty acid oxidation, POCA interferes with de novo synthesis of cholesterol and fatty acids. On the other hand, neither fatty acid esterification nor the conversion of oxaloacetate into glucose are affected by POCA.