80 E. C. Slater and W. C. Hulsmann 



the latter (and this amount might be overestimated, but not 

 underestimated) was less than the sensitivity of the methods 

 used by Fleckenstein and co-workers (1954) or Mommaerts 

 (1954). The three groups agree that the amount of ADP 

 formed was only a very small fraction of the value expected 

 on the assumption that the hydrolysis of ATP provides the 

 energy for the contraction of the muscle. 



Although Chance and Connelly's (1957) results cannot yet 

 be taken to establish that the respiration of muscle is con- 

 trolled by the concentration of ADP, they do provide good 

 support for the view that either the breakdown of ATP, or of 

 intermediates in the oxidative phosphorylation reaction, are 

 an important mechanism for the control of respiration, in 

 vivo. 



Other evidence pointing in the same direction is: (1) The 

 increased metabolism of animals after administration of DNP 

 or related compounds (Cazeneuve and Lepine, 1885; Mathews 

 and Longfellow, 1910; Heymans and Bouchaert, 1928). 

 Ehrenfest and Ronzoni (1933) found that DNP stimulated 

 the respiration of isolated frog muscle sevenfold. According 

 to the formulation of equations (l)-(3b), DNP might not be 

 expected to have very much effect on the rate of respiration, 

 if it is added to a system already supplied with ADP as in 

 actively metabolizing muscle, even though it will stop the 

 synthesis of ATP. Under these circumstances, the rate of 

 respiration is governed by the activity of the enzymic system 

 bringing about reaction (1). If, however, DNP is added to a 

 system corresponding to a resting muscle, in which respiration 

 is largely blocked by the fact that X '^ I is not broken down, 

 it will cause the same stimulus of respiration as is brought 

 about by muscular activity. Since, however, the energy made 

 available by respiration is not utilized under these conditions, 

 it will appear as heat. In fact, it was known to pharma- 

 cologists, long before the biochemical site of action of DNP 

 was known, that animals receiving a toxic dose of dinitro- 

 phenols developed a very high temperature (Cazeneuve and 

 Lepine, 1885). 



