Hepatic hydrolysis of octanoyl-CoA and valproyl-CoA in control and valproate-fed animals.
1. Medium-chain acyl-CoA hydrolase activities were determined in liver from control and valproate-fed rats and rabbits. 2. Octanoyl-CoA was readily hydrolyzed by all control liver preparations. 3. Animals that had been fed diets containing 0.5 or 1.0% (w/w) valproic acid had significantly elevated octanoyl-CoA hydrolase activities. 4. The CoA ester of valproic acid, a branched-chain isomer of octanoic acid, was poorly hydrolyzed by liver preparations from both control and valproate-fed animals. 5. Livers from the valproate-fed animals contained high levels of medium-chain acyl-CoA; total CoA content was also increased. 6. The inefficiency of hepatic valproyl-CoA hydrolysis may play a role in the toxicity of valproic acid.
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D004032:Diet; D005260:Female; D006868:Hydrolysis; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013869:Thiolester Hydrolases / Q000378:metabolism*; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000214:Acyl Coenzyme A; C045335:valproyl-coenzyme A; C034681:octanoyl-coenzyme A; D014635:Valproic Acid; D013869:Thiolester Hydrolases; D010170:Palmitoyl-CoA Hydrolase