Control Points in Phosphorylating Respiration 143 



DNP and that its action is prevented by the presence of ADP, 

 possibly in a competitive manner. It may,- in fact, be neces- 

 sary to modify the scheme by adding an additional reaction 

 or reactions. It also appears certain that the crude factor 

 may represent a mixture of factors, which may titrate each 

 other out under certain circumstances. Actually, z^ooctane 

 extraction removes some but not all activity from the pre- 

 paration, suggesting that it contains the factor described by 

 Hiilsmann, Elhott and Rudney (1958), among others. The 

 separation and identification of these factors is in progress. 



TIGHT 



NORMAL / +ADP 



UNCOUPLED 



P/0 = 1.8 



ADP 



TYPES OF RESPIRATORY COUPLING 



Fig. 3. Types of respiratory coupling and action of R 

 factor and DNP. 



It appears quite clear that R factor activity may be a major 

 element in a rather elusive problem, namely the mechanism 

 of "tight" versus "loose" coupling in phosphorylating mito- 

 chondrial systems. Figure 3 shows opposite poles of respira- 

 tory control produced by ADP and R factor activity. The 

 normal tightly coupled system is shown at the left, with high 

 P/0 ratio and a large ADP stimulation of respiration. Addition 

 of R factor produces a "loosely coupled" system in which 

 respiration may proceed at the .same rates in the absence or 

 presence of ADP and with nearly normal phosphorylation. 

 The "loosely coupled" respiration shown may very likely be a 

 physiological event. It will be recalled that Hoch and Lip- 

 mann (1954) have shown that mitochondria isolated from 

 livers of hyperthyroid rats have normal P/0 ratios but 



