742 

 and 



so that 



14. EFFECTS OF pH EN ENZYME INHIBITION 



(I). (H): 



(Do (H)^ 



ihh = (I). 



(H): 



(H): ^ K." ^ K^'K. 



(14-185) 



(14-186) 



If the I, or doubly charged ion, is assumed to be the active inhibitor, a 

 plot of log (I^)o against pH^ will have the following characteristics: 



Low pH„: log (I,),, - log (I), - 2pH, + p^,' + pZ„" (14-187) 



Intermediate pH„: log (!,)„ = log (I), - 2pH, + P^a" + pH^ (14-188) 



High pH„: log (I,)„ = log (I), - 2pH, -f 2pH<, (14-189) 



As the pHg increases, the slope will change from zero, through + 1 to 

 -f 2. If HI is the active inhibitor: 



(I.)o = (I). 



(H)« 



1 + 



(H), 

 K' 



+ 



(H)J 



(14-190) 



and the log (I;)o — pH^ plot will show the same slopes as when I is the 

 inhibitor. From this type of plot it is impossible to determine the active 

 form of the inhibitor within the cells. If both Hgl and HI penetrate into 

 the cells, the inhibitor will behave as if it were monobasic with a p^^ equal 

 to the vKJ' of the dibasic acid. It may be noted that if pK^ and p^a" 

 are close together, the slope will change from zero to + 2 without any in- 

 termediate slope of -f 1, as long as only the Hgl form penetrates. 



Intracellular Competitive Inhibition 



If both the substrate and the inhibitor are introduced into the medium 

 and both are weak acids or bases, the competitive inhibition on an enzyme 

 within the cells will depend upon the intracellular concentrations of S and 

 I, and hence upon the degrees to which they penetrate. The usual expres- 

 sion for the inhibition may be written: 



at)o 



{h)o + K,' 



1 + 



K 



V J 



(14-191) 



