Wagenmakers A J, Veerkamp J H, Schepens J T, van Moerkerk H T
Biochem Pharmacol. 1985 Jun 15;34(12):2169-73. doi: 10.1016/0006-2952(85)90413-7.
Clofibric acid inhibited the oxidative decarboxylation of 4-methyl-2-oxopentanoate and 3-methyl-2-oxobutanoate in mitochondria and homogenates of rat liver and quadriceps muscle. In rat hemidiaphragms clofibric acid inhibited the oxidative decarboxylation of 4-methyl-2-oxopentanoate and had no effect on that of 3-methyl-2-oxobutanoate. Clofibric acid displaced branched-chain 2-oxo acids from bovine serum albumin. Clofibrate-treatment of rats decreased the actual activity and activity state of the branched-chain 2-oxo acid dehydrogenase complex in quadriceps muscle, and increased the total activity in heart and liver without a change of the activity state. All interactions of clofibric acid with the metabolism of branched-chain amino acids appear to relate to its structural resemblance to the branched-chain 2-oxo acids. Both reduced plasma and muscle concentrations of branched-chain amino acids and reduced muscle oxidation may play a role in the myopathic side-effects of clofibrate-treatment.
