REVERSAL BY A SUBSTANCE BINDING THE INHIBITOR 



617 



deal greater than that of the inhibitor. In those situations where the reversor 

 is not depleted, (R,) must of necessity be higher than (I^) if an appreciable 

 reduction in inhibition is to be expected. Thus only those portions of the 

 curves at least above 10 mM reversor are valid under these conditions. If 

 one wishes to reduce an inhibition to l/^?th of the initial value, the concen- 

 tration of reversor that must be added is given by: 



(R,) = (n - 1! 



K^ 



K, 



[(I) + K,) 



(13-23) 



The ratio of the concentration of reversor to that of inhibitor required to 

 produce a specified reduction in the inhibition has often been considered 

 an important factor in describing an inhibition reversal quantitatively. 



0.8 



06 



0.4- 



0.2 - 



10 



100 



1000 



(R|)mM- 



Fig. 13-5. Reversal of the inhibition by a substance binding the inhibitor (Eq. 13-21). 



Ki = 1 mM, (I) = 5 mM, and (E() = 1 mM. Curve A: K^ = 0.1 mM; curve B: K^ = 



1 mM; curve C: K^ = 10 mM; curve D: K^ = 100 mM. 



and in some instances (R,)/(I,) is specified rather than (R^). Under the pres- 

 ent assumptions, this ratio is not a constant for each inhibition reversal 

 but depends on the initial degree of inhibition: 



(R.) 

 (I.) 



in 



1] 





1 + 



{It) 



n — 1 





(13-24) 



The less the original inhibition, the greater must be the ratio of reversor 

 to inhibitor for the inhibition to be reduced a chosen amount. A hypotheti- 

 cal example will serve to illustrate this; we shall assume that K^ = K^= 1 

 and that the inhibition is to be reduced to one-tenth its initial level. 



