Abstract
Summary In isolated rat diaphragms, the stimulation of pyruvate decarboxylation by oxfenicine but not by its metabolite, 4-hydroxyphenylglyoxylate (HPG), was blocked by aminooxyacetate. However, when administered intravenously to fat-fed rats, HPG was only poorly transported into the heart and did not activate cardiac pyruvate dehydrogenase. Oxfenicine (2mM) was a more potent inhibitor of the oxidation of palmitate (52%) by rat diaphragm than of palmitylcarnitine (17%) or octanoate (20%). In mitochondria incubated with palmitate, CoA, ATP and [ 14 C]carnitine, oxfenicine did not inhibit palmityl-[ 14 C]carnitine formation. However, HPG was a potent inhibitor in heart mitochondria (46% at 50μM, 61% at 1mM) but not in liver mitochondria (24% at 5mM). We conclude that oxfenicine (via HPG) stimulates myocardial carbohydrate oxidation by cardioselective inhibition of long-chain fatty acid oxidation at the level of fatty acyl-CoA synthetase or carnitine acyltransferase.
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