Control of Rate of Intracellular Respiration 81 



Vitamin E-deficient animals also show an increased rate 

 of respiration and heat production. This can also be demon- 

 strated in the dystrophic muscles, isolated from the deficient 

 animals (Victor, 1934). It appears that the dystrophic 

 muscle has lost its respiratory-control mechanism. This may 

 possibly reflect structural damage to the mitochondria. How- 

 ever, the fact that the increase of respiration occurs well in 

 advance of the morphological degeneration during the course 

 of avitaminosis E, and the rapidity with which the heightened 

 respiration of the isolated muscle is suppressed soon after the 

 administration of vitamin E suggest the possibility that the 

 vitamin might be involved more specifically. This is currently 

 under investigation. 



(2) The studies of Mcllwain and his co-workers (see Mcllwain, 

 1955) have shown that the increase of the rate of respiration 

 and glycolysis which occurs when brain slices are electrically 

 stimulated is accompanied by the hydrolysis of creatine 

 phosphate. Stimulation caused no increase in the rate of 

 respiration in the presence of DNP (Mcllwain and Gore, 1951). 

 Kratzing (1952) obtained similar results with rat diaphragm. 



Conclusion 



There is now good reason to conclude that respiration in 

 vivo is to a large extent controlled by the concentration of 

 energy-rich intermediates of oxidative phosphorylation, 

 named here A '^ I, X -^^ I and X ^^ P (or I '^-' P). Respira- 

 tion cannot proceed unless A, the respiratory-chain compon- 

 ent, is liberated from its inhibited form, A ^' I. This can 

 be brought about by reaction of X '^ I with ADP, or by 

 hydrolysis of any of the intermediates. The symbol I was 

 introduced by Chance and Williams (1956), replacing C in the 

 earlier formulation (Slater, 1953), in order to emphasize this 

 inhibition. This was a useful change of nomenclature, since 

 it directed attention to the analogies between inhibition of 

 respiration associated with phosphorylation and the more 

 commonly studied respiratory inhibitors, such as antimycin. 



