Effect of clofibrate on branched-chain amino acid metabolism.
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.
D050645:2-Oxoisovalerate Dehydrogenase (Acylating); D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D003653:Decarboxylation; D066298:In Vitro Techniques; D007658:Ketone Oxidoreductases / Q000032:analysis; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D012709:Serum Albumin; D007658:Ketone Oxidoreductases; D050645:2-Oxoisovalerate Dehydrogenase (Acylating); D002994:Clofibrate