The effects of 2,4-dinitrophenol on mitochondrial oxidations

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Abstract
With rat-liver mitochondria glutamate is oxidized mainly by the transaminase pathway of Krebs and Bellamy (1960). However, in the presence of malonate or 3-fluoromalate, glutamate is oxidized through the dehydro-genase pathway. In the presence of 3-fluoromalate the rate is 50% of that of the normal observed rate of adenosine diphosphate-stimulated glutamate oxidation. The rate-limiting reaction in the oxidation of glutamate by rat-liver and pigeon-heart mitochondria is possibly the rate at which a[alpha]-oxoglutarate is converted into succinate, when oxidation occurs through the transaminase pathway, and the glutamate de-hydrogenase when oxidation occurs through the dehydrogenase pathway. The rate of oxidation of succinate or of malate in the presence of glutamate appears to be limited by the rate at which adenosine tri-phosphate can be synthesized. 2,4-Dinitrophenol caused higher rates of oxygen uptake than adenosine diphosphate and phosphate, with these substrates. The extent to which the malate derived from succinate oxidation is further metabolized with both liver and pigeon-heart mitochondria depends on both the activity of the succinate dehydrogenase and the rate of flux of electrons through the respiratory chain. At low dinitrophenol concentrations, or with liver mitochondria with adenosine diphosphate, the malate was not oxidized to any significant extent. At higher dinitrophenol concentrations, and with pigeon-heart mitochondria with adenosine diphosphate, the malate derived from succinate oxidation was oxidized. In the absence of suitable systems for removal of oxaloacetate this resulted in an inhibition of succinate oxidation.