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Molecular Pharmacology, Vol 3, 333-340, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

The Mechanism of Action of Hypoglycin on Long-Chain Fatty Acid Oxidation

M. ENTMAN 1 and R. BRESSLER 1

1 Departments of Medicine and Physiology and Pharmacology, Duke University Medical Center, Durham, North Carolina 27706

Intravenous administration of hypoglycin (L-agr-amino-beta-methylenecyclopropanepropionic acid) to mice resulted in hypoglycemia, which was preceded by a decrease in palmitate oxidation by myocardial homogenates from treated animals. The homogenates from treated animals carried out normal rates of glucose and hexanoate oxidation, but demonstrated depressed levels of palmityl-CoA:carnitine acyltransferase activity. The addition of carnitine to the myocardial homogenates restored both the depressed palmitate oxidation and palmityl-CoA:carnitine acyltransferase activity to normal levels. The administration of carnitine to hypoglycin-treated animals prevented the decreases in myocardial palmitate oxidation, palmityl-CoA:carnitine acyltransferase activity, and the hypoglycemia.

Note:
ACKNOWLEDGMENT We wish to thank Dr. H. Lebovitz for his help and advice. Supported by U.S.P.H.S. Grants no. HE 7061 and 5TIGM-516.

Submitted on January 23, 1967






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