712 14. EFFECTS OF pH ON ENZYME INHIBITION 



taken into account, each rate must now be written with the proper pH 

 functions included. For examj)le, in a two-step monolinear chain: 



El E2 



A -> B ^ C (14-141) 



if both A and B ionize but the enzyme does not over the range studied: 



- - "' WtW <"-'*^' 



"' - ''' WtW '"-^«' 



where the same conventions are used as in Eq. 7-2. The concentration 

 of B in the steady state will be given by setting i\ — v^\ 



'^'' = (A,)(F,-F.)+/.F.y. <"-"*' 



which may be compared with 7-3. 



If an ionizable inhibitor competitively inhibits Eg, the rate of reaction 

 2 must now be written as: 



V. = F, ^?i r^-^ (14-145) 



(B,), +AK, 



fiK,\ 



so that the change in the intermediate concentration induced by the in- 

 hibitor will be given by: 



which differs from Eq. 7-8 only in the /, factor. Thus the effect of the inhi- 

 bitor on (B,) will not depend on the ionizations of the substrate or inter- 

 mediate but only on the ionization of the inhibitor. 



When the enzyme also ionizes, the rate expressions for the inhibited 

 step will depend on the type of inhibition, as discussed previously in this 

 chapter. Let us assume that each enzyme conforms to scheme 14-31 and 

 the inhibition on E2 is of the type IV a shown in scheme 14-52. The indi- 

 vidual rate expressions will be: 



^^ = ^^ ,A^ ^/ fjr (1^-1*'^) 



(A,) + fefaKi 



V, = F. ^^ ^--^ (14-148) 



{^t)i + feMK, 



/.+ ^'^ 





