Control of Rate of Intracellular Respiration 79 



chain below cytochrome a, and the reduction of cytochrome a. 

 Chance and Baltscheffsky (1958) have found that rat heart 

 sarcosomes behave similarly. It is, therefore, of very con- 

 siderable interest that Chance and Connelly (1957) have 

 found that stimulation of frog sartorius muscle causes the 

 oxidation of the DPNH and that Weber (1957) has found 

 that cytochrome h was oxidized and cytochrome a^ reduced. 

 This is very suggestive that the increased respiration brought 

 about by muscular stimulation proceeds through the same 

 type of mechanism as formulated in equations (l)-(36). In 

 fact, Chance and Connelly calculated the amount of ADP 

 reaching the sarcosome, on the assumption that the two 

 processes were completely analogous. 



However, it must be emphasized that the fact that stimu- 

 lation of the muscle has the same type of effect as addition of 

 ADP to liver mitochondria is no proof that ADP is indeed 

 formed by a muscular contraction. The same result would be 

 obtained if muscular contraction were associated with a 

 hydrolysis of A /^ I, X /^ I or X /^ P, instead of the hydroly- 

 sis of ATP to ADP. Indeed, Chance and WiUiams (1956) have 

 demonstrated that the uncoupling agent, dicoumarol, which 

 is believed to promote the hydrolysis of X '^ I, has the same 

 sort of effect as the addition of ADP. This is an important 

 point, because the chemical studies of Fleckenstein and 

 co-workers (1954) and Mommaerts (1954) have not demon- 

 strated the breakdown of ATP during muscular contraction. 

 The very close topographical arrangement between the sarco- 

 some and the myofibril (Cleland and Slater, 1953) suggests the 

 possibility that A'-^I, Xz-^I orX-^P might be directly 

 utilized for the energy of muscular contraction, without the 

 intermediate formation of ATP (see above). This question 

 will no doubt be settled by direct chemical analysis of the 

 changes in muscle which occur on muscular contraction. 



In any case, there is no essential disagreement between 

 the results of Fleckenstein and co-workers (1954) and Mom- 

 maerts (1954), on the one hand, and Chance and Connelly 

 (1957) on the other, since the amount of ADP calculated by 



