Reversal by Nicotinamide Adenine Dinucleotide of the Inhibitory Action of Salicylate on Mitochondrial Malate Dehydrogenase
SALICYLATE causes an increased incorporation of carbon-14 in fumarate and malate in rat liver mitochondria incubated with radioactive succinate1. This effect is explicable in terms of a direct action of the drug on the mitochondrial malate dehydrogenase because salicylate inhibits the activity of the purified enzyme from pig heart2. The mechanism of inhibition of the isolated enzyme involves competition with nicotinamide adenine dinucleotide (NAD)2 and the presence of excess of the coenzyme prevents the accumulation of labelled malate in mitochondria incubated with salicylate and radioactive succinate3. We have now shown that the addition of NAD will reverse the inhibitory action of salicylate on mitochondrial malate dehydrogenase after this inhibition has become established.