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.