The mechanism of action of chlorpromazine. 2. Reduced diphosphopyridine nucleotide–cytochrome c reductase and coupled phosphorylation

Abstract

The action of chlorpromazine on the respiratory chain has been investigated. Inhibition of electron transport between reduced diphosphopyridine nucleotide and cytochrome c has been demonstrated. This inhibition occurs only in phosphorylating systems and is not observed in succinate-cytochrome c reductase systems. The inhibitory action is due to an effect on the coupled phosphorylation reaction rather than that of an interruption in electron transport. Chlorpromazine acts at a point in the phosphorylation reaction other than that affected by 2,4-dinitrophenol. On the basis of these findings a scheme for the reaction involved in oxidative phosphorylation is proposed.