Mechanism of Oxidative Phosphorylation

THE phenothiazine tranquillizer chlorpromazine has the following actions: (1) It inhibits electron transport between reduced diphosphopyridine nucleotide and cytochrome c in appropriate systems; the efficiency of the coupled phosphorylation is not affected. (2) Chlorpromazine is not effective in mitochondria treated with water or in non-phosphorylating reduced diphosphopyridine nucleotide – cytochrome c reductase systems. (3) Chlorpromazine prevents the stimulation of respiration in systems deficient in adenosine diphosphate by 2 : 4 dinitrophenol (Table 1). (4) It causes some stimulation of respiration in mitochondrial systems deficient in inorganic phosphate, but not a maximal stimulation (Table 1), without causing any detectable increase in the level of inorganic phosphate. (5) It inhibits powerfully the exchange reaction phosphorus-32 – adenosine triphosphate 1 , under conditions in which electron transport cannot be affected (Table 2). (6) It has no effect on succinate – cytochrome c reductase in any system.