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Evaluation of inhibitors of fatty acid oxidation in rat myocytes
Authors:S A el-Aleem  H Schulz
Affiliation:Department of Chemistry, City College of the City University of New York, NY 10031.
Abstract:The effects of 4-bromocrotonic acid, 2-bromopalmitic acid, 3-mercaptopropionic acid, 4-pentenoic acid, and 2-tetradecylglycidic acid on the oxidations of palmitate, octanoate, and pyruvate in adult rat myocytes were studied. Since all of these compounds inhibit the oxidation of palmitate but not of pyruvate, they are specific inhibitors of fatty acid oxidation. Fifty percent inhibition of palmitate oxidation was obtained when myocytes were preincubated for 10 min with one of the following: 0.1 microM 2-tetradecylglycidic acid, 60 microM 4-bromocrotonic acid, 60 microM 2-bromopalmitic acid, 100 microM 3-mercaptoproprionic acid, or 100 microM 4-pentenoic acid. Removal of the inhibitors from the medium after preincubation relieved the inhibition caused by 3-mercaptopropionic acid but did not reverse the effects of the other inhibitors. This study leads to the conclusion that 2-tetradecylglycidic acid is the compound of choice for inhibiting the mitochondrial uptake of fatty acids and thereby their oxidation, whereas 4-bromocrotonic acid is the best irreversible inhibitor of the mitochondrial beta-oxidation cycle.
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