Inhibition of mitochondrial carnitine palmitoyl transferase by 2-tetradecylglycidic acid (McN-3802) (Preliminary Communication)

The oral hypoglycemic agent, 2-tetradecylglycidic acid (McN-3802), which has been reported to inhibit the oxidation of long chain but not short chain fatty acids in isolated rat hepatocytes and muscle preparations, inhibited the oxidation of palmitoyl CoA and palmitic acid by rat liver mitochondria. The drug itself, which is a fatty acid analog, was not oxidized by mitochondria. Evidence is presented that 2-tetradecylglycidic acid (or its coenzyme A ester) inhibits fatty acid oxidation by irreversibly inhibiting mitochondrial carnitine palmitoyltransferase. The drug did not inhibit mitochondrial palmitoyl-CoA synthetase.