Abstract
Valproic acid and its unsaturated metabolite, 2- n -propyl-4-pentenoic acid, were found to inhibit strongly the metabolism of decanoic acid in homogenates of rat liver. Reductions in decanoate consumption in response to inhibitors were paralleled by decreases in the formation of octanoic and hexanoic acids, two products of decanoate β-oxidation. In contrast, 4-pentenoic acid, an established inhibitor of long-chain fatty acid β-oxidation, had little effect on the metabolism of decanoate. It is concluded that the title compounds are potent, broad-spectrum inhibitors of fatty acid β-oxidation, a property which may be of key toxicological importance in the pathology of valproate-induced liver injury.
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