REGENERATIVE SYSTEMS 367 



by an ATPase or the utilization of ATP by synthetic or functional systems 

 in the cell. The transformation of A ^ B may be said to be obligatorily 

 coupled to the formation of ATP if ^-' P is present in very small concen- 

 tration, as it would be if the bond were to some enzyme group, because 

 the reaction will rapidly stop if the -^ P is not removed by ADP. The 

 concentration of AJDP may limit the over-all reaction and hence the for- 

 mation of B will depend on the rate of the regenerative reaction 3, as has 

 been demonstrated in the electron-transport sequence (Chance and Wil- 

 liams, 1956). Such systems may be involved in the regulation of cellular 

 metabolism, since the rate of utilization of A will be determined in part 

 by the rate at which ATP is used in synthetic and functional processes. 

 If an uncoupling agent, such as 2,4-dinitrophenol, is added, it may be 

 assumed that ^^ P is split from the enzyme as inorganic phosphate: 



~ P ^ P (7-50) 



This will decrease the formation of ATP but may increase the formation 

 of B if reaction 2 has been limiting. If reaction 7-50 becomes much more 

 rapid than the formation of ATP, the system will be almost completely 

 uncoupled. At the present time it is not possible to treat this system exactly 

 because of the uncertainties in mechanism and the possibility that other 

 reactions may be involved. Another complexity is that most uncoupling 

 agents inhibit the electron-transport in some manner, so that the exper- 

 imental stimulation of A ^ B is not as great as would be expected on the 

 basis of scheme 7-49. Alteration of the rate of reaction 3, either by effects 

 on Eg or on systems removing ATP, may also change the rate of formation 

 of B. Thus inhibition of an ATPase might slow down A -> B since it 

 could reduce (ADP), so that removal of ■^ P from the enzyme is reduced; 

 likewise, activation of such an ATPase could accelerate A ^ B. It may 

 be pointed out that regenerative systems can usually be represented in a 

 cyclic form; thus the sequence 7-49 is equally a cyclic system and obeys 

 the kinetics of cyclic systems. 



1 y \^ 



\ \TP<^ --^P (7-51) 



^\ T 



If the ATP were in equilibrium with a store of creatine phosphate this would 

 provide some buffer to the system with respect to inhibition and would in 

 some instances suj^ply a further means for regeneration of ADP. 



Another type of uncoupling effect may be mentioned. A substance may 

 be capable of accepting the ^-^ P from the enzyme and competing with ADP: 



I + ~P^ I~P (7-52) 



