The action of 2:4-dinitrophenol on oxidative phosphorylation

Abstract

Oxidative phosphorylation by mitochondria from liver and kidney of rats and rabbits was studied. The inhibition by 2,4-dimtrophenol (DNP) of the oxidation of pyruvate was reversed by adenosine triphosphate [ ATP], coenzyme I and dicarboxylic acids of the citric acid cycle. Phosphorus/oxygen ratios for pyruvate, 2-ketoglutarate, L-glutamate and beta-hydroxybutyrate at 15[degree] approached 4.0 for the first 3 and 3.0 for the last. Coenzyme I was probably required for alpha-ketoglutarate oxidation. DNP and azide did not affect the phosphorylation coupled with the anaerobic dismutation of alpha-ketoglutarate and NH3. Phosphorylation accompanied the oxidation of reduced cytochrome c in the presence of ascorbic acid by anomalous results were obtained with cysteine. Phosphorylation during anaerobic oxidation of various substrates in the presence of cyanide was also studied. It was suggested that DNP acted on all transphosphorylations from pyridine nucleotide level upwards. The "replacement" of inorganic orthophosphate by DNP was reinvestigated and it was suggested that "replacement" was the consequence of a sparing of inorganic phosphate. The synthesis of ATP from coenzyme I and inorganic pyrophosphate by mitochondria was demonstrated. The action of thyroxine on oxidative phosphorylation, pyruvate oxidation, and fatty acid oxidation was investigated and it was concluded that its action was entirely different from DNP both in vivo and in vitro.