The Inhibition of Malic Dehydrogenase by Salicylate and Related Compounds

Abstract

Salicylate and γ-resorcylate affected the distribution of radioactivity incorporated from labelled succinate into the soluble intermediates of rat liver mitochondria in a manner consistent with an inhibitory action of the drugs on malic dehydrogenase. The addition of nicotinamide adenosine dinucleotide to the mitochondrial preparations reversed the effects of salicylate and γ-resorcylate. A general structural requirement for inhibitory activity against malic dehydrogenase in vitro in salicylate congeners appears to be a phenolic hydroxyl group in the ortho position to a carboxyl group except that 2-hydroxyphenylacetate also inhibited the enzyme.