ENZYME INHIBITION AND CHANGES IN CELL FUNCTION 



469 



the internal concentration of agonist is given by: 



(A,)^ + [{V,„lk) + K, - (A,)] (A,) - /i,(AJ - 



(9-17) 



which is identical with Eq. 7-11, where k is the diffusion constant of the 

 agonist through the membrane. The behavior of such a diffusion-limited 

 monolinear chain has been discussed. Figure 9-7 shows the variation in 



Fig. 9-7. Concentration of an agonist in the receptor region as it depends on the 

 rate of its destruction (scheme 9-16 and Eq. 9-17). (AJ = 10-^ mM, K, = 1 mM, 



and k = IQ-^. 



(Aj) with the rate of inactivation and Fig. 9-8 illustrates how the effect of 

 the agonist on the tissue increases with rising inhibitor concentration. 

 As the activity of the enzyme becomes less, the agonist concentration rises 

 in a sigmoidal fashion and eventually becomes equal to (Ap). It is interest- 

 ing to note that it requires a fair degree of inhil^ition of the enzyme before 

 there is an appreciable increase in the activity of the agonist. The change 

 in the functional activity occurs mainly between 90% and complete in- 

 hibition of the enzyme. It may be observed that an inhibitor of an inac- 

 tivating enzyme will have its greatest effect on function when the rates 

 of entrance and destruction of the agonist are comparable; if either one is 

 much larger than the other, such inhibition will have very little effect 

 on the agonist concentration. If the receptors are in the membrane, the 

 partition coefficient of the agonist between medium and membrane would 

 have to be introduced; this would be the same as assigning different rates 

 to the inward and outward diffusion across the membrane in scheme 9-16. 

 It is quite possible that the kinetics for the situation in which the en- 

 zyme is forming a screen between the source of agonist and the receptors 



