INHIBITION BY 2,4-DINITRIPHENOL OF REMOVAL OF OXALOACETATE FORMED BY OXIDATION OF SUCCINATE BY RAT-LIVER AND -HEART MITOCHONDRIA

1. The effect of 2,4-dinitrophenol on the oxidation of succinate by isolated mitochondria has been studied in the presence and absence of arsenite. 2. The degree of inhibition by uncoupler of succinate oxidation is correlated with the rate of removal of oxaloacetate formed by malate dehydrogenase. Dinitrophenol inhibits aspartate formation in mitochondria of both rat liver and rat heart, and the formation of phosphoenolpyruvate in rat-liver mitochondria. 3. Arsenite increases the inhibition by dinitrophenol of succinate oxidation, because it blocks another pathway for removal of oxaloacetate, namely citrate synthesis. 4. Addition of ATP and oligomycin together with dinitrophenol prevents inhibition of succinate oxidation by the dinitrophenol, as well as inhibition of the conversion of oxaloacetate into phosphoenolpyruvate. 5. Glutamate prevents the inhibition of succinate oxidation by uncouplers, by enhancing the removal of oxaloacetate by transamination. 6. Oxaloacetate formed from added aspartate and α-oxoglutarate does not inhibit succinate oxidation by intact mitochondria unless dinitrophenol is added. 7. It is proposed that dinitrophenol inhibits an energy-requiring removal of oxaloacetate from the vicinity of succinate dehydrogenase. © 1969.