736 



14. EFFECTS OF pH ON ENZYME INHIBITION 



Relation between Inhibitory Activity and the pK^ 



When a series of inhibitors is tested on a system at constant pH^, the 

 problem of how to compare the true potencies arises, and, just as in the 

 study of isolated enzymes, the pH factor must be taken into account. An 

 attempt is often made to relate the different degrees of inhibition to the 

 \)K,,'s of the substances tested. The validity of this procedure must now be 

 examined. Let us assume that several inhibitors have been tested at the 



1.0 



0.8 



0.6 



0.4 



0.2 



A=5yi6^mM 



C-i6^ mM - 

 D=5Xl63mM 



2.5XI0'2mM 



Ot 



pH. 



Fig. 14-25. Variation of the inflection points of i — pH^ curves with 



the concentration of a potent inhibitor. X, = 0.01 m3I, K^ = 10"^, 



and pH, = 6.8. 



same concentration in the medium and that a range of inhibitions has been 

 found. The intracellular concentrations of the inhibitors may be related 

 to their p.K'g's by rewriting Eq. 14-162: 



(H), 



log (I), = log (I,), + pH, - pH„ - log 



1 + 



Ka J 



(14-172) 



For pA^a's significantly less or more than pH^, this simplifies to: 

 Low vKa. log (I), = log {L)„ + pH, - pH, (14-173) 



High vK,: log (I), = log (h), + pH, - vKa (14-174) 



