Abstract
The effects of the hypoketonaemic and hypoglycaemic compound 2[5(4-chlorophenyl)pentyl] oxirane-2-carboxylate (POCA) on fatty acid synthesis and fatty acid oxidation in rat hepatocytes were examined. Two μM-POCA caused a small stimulation of fatty acid synthesis which might be due to an increased flux through pyruvate dehydrogenase. Ten to one hundred μM-POCA inhibited (40–70%) fatty acid synthesis. At low concentrations (⩽5 μM) POCA was a more powerful inhibitor of fatty acid oxidation than of synthesis, but at higher concentrations (10–100 μM) the inhibition of synthesis and oxidation was similar. One hundred μM POCA-CoA inhibited acetyl-CoA carboxylase by about 22% and 100 μM-palmitoyl-CoA by about 33%. Since POCA was a more potent inhibitor of fatty acid synthesis than palmitate, but POCA-CoA did not inhibit acetyl-CoA carboxylase more strongly than palmitoyl-CoA, it is suggested that POCA-CoA may inhibit fatty acid synthase directly.
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