642 13. REVERSAL OF INHIBITION 



Removal of the Inhibitor by an Inactivator 



If the free inhibitor reacts with a substance that is present in the test 

 medium and, as a result, is inactivated, the following reactions may be 

 written for an irreversible inhibition: 



k, 

 E + I -^ EI (13-69) 



1 + A ^ Q (13-70) 



where Q represents a product or products resulting from the inactivation 

 of the inhibitor. Since the inhibitor concentration will decrease with time 

 according to: 



(I) = (I)oe-*2<^'* (13-71) 



the differential equation for the rate of change of the inhibition is: 



dildt = A-i(l - i){l)oe-h^^^' (13-72) 



which may be integrated directly for the situation in which there is suffici- 

 ent inhibitor present to inhibit the enzyme completely: 



1 — exp 



^''(I)«'^(,-.,U)*^1] 



k-AA) 



(13-73) 



If all of the inhibitor is inactivated before the inhibition has reached 

 100%, the final inhibition will depend on (I)^. 



REVERSAL OF INHIBITIONS IN CELLS 

 AND WHOLE ANIMALS 



The rise and fall of the intracellular inhibitor concentration during pen- 

 etration and destruction have been discussed in Chapter 8 and expressed 

 in equations such as 8-8 and 8-9. It was assumed there that the equilibrium 

 between the enzyme and the inhibitor was achieved rapidly, and thus the 

 variation of the inhibition with time could be directly calculated. If the 

 formation or dissociation of the EI complex lags behind the changes in 

 inhibitor concentration, the kinetics of inhibition may become quite com- 

 plex. Better than following this approach is an examination of the occur- 

 rence of the types of reversal discussed above as they are modified in cel- 

 lular or tissue preparations. It must be borne in mind that there are many 

 possible reasons for the recovery of some cell metabolic process or function 

 that has been depressed by an inhibitor, as listed at the beginning of this 

 chapter, and that such reversal does not necessarily imply recovery of 

 the activity of the primary enzyme inhibited. 



