Effect of Dinitrophenol on Oxidation of Tissues

Abstract

The marked acceleration of metabolism of animals injected with small quantities of dinitro α napthol reported by Heymans and Bouchaert, 1 Van Uytvanck, 2 and Euler, 3 and a similar action of dinitrophenol observed by Magne, Mayer and Plantefol 4 and by Tainter and Cutting, 5 make it of interest to learn whether these substances affect the rate of respiration of isolated tissues and cell suspensions in vitro. If that be the case, it may be hoped that a study of the action of these substances will aid in elucidating the mechanism of cellular oxidation and metabolism. We have studied the effect of 2-4 dinitrophenol on the respiration and anaerobic fermentation of yeast and of frog tissues, using Warburg vessels. With muscle, lactic acid was also determined chemically.

Dinitrophenol added to the solutions in which the tissues or yeast are suspended, in concentrations of the same order as perhaps exists in the tissue fluids after administration of toxic or even large therapeutic doses to man or animals, causes a marked increase of respiration of tissues so far examined. With increasing concentrations, the effect rises to a maximum beyond which the rate of respiration is progressively decreased. The optimum for frog tissues at 25° pH 7.5 is 0.5 mg. % and for yeast at 30° pH 4.5 0.36 mg. %.

The effect is most marked with frog muscle, the resting respiration of which is raised about 8 times above the normal, or to a level somewhat above that observed in similar muscles after maximum stimulation or even hashing. The marked increase caused by dinitrophenol is not accompanied by twitching, and the muscle remains irritable for at least 3 hours. A marked acceleration of anaerobic lactate production is caused by dinitrophenol, and reaches levels observed with hashed muscle. The controlling factor of lactic acid production present in normal muscle appears to be removed by the action of dinitrophenol and the process of glycolysis proceeds at nearly the maximum rate. In normal muscle at rest there is no aerobic glycolysis, but in the treated muscles there is an accumulation of lactic acid in spite of the high O₂ consumption. A part of the acceleration in O₂ consumption may therefore be explained by the increase in lactic acid.