656 



14. EFFECTS OF pH ON ENZYME INHIBITION 



Expressions for the pH Depencence of Enzymic Rate 



A complete and rigorous steady-state treatment of even relatively simple 

 enzyme systems with respect to their response to pH changes is laborious 

 and the resultant exx;)ressions are too unwieldly to apply to experimental 

 data (Laidler, 1955 b, 1958, p. 125). In most cases it seems that the data 

 can be adequately interpreted by simpler kinetics and for the ijresent pur- 

 pose it will suffice to outline a basic api^roach and to illustrate this with 

 some examples. Extensions to cover various complications may readily 

 be made on this basis. 



Equilibrium kinetics rather than steady-state kinetics will be used for 

 several reasons. Firstly, as mentioned above, a rigorous steady-state anal- 

 ysis is complex and in the present state of our knowledge it is not profitable. 

 Secondly, proton association and dissociation reaction rates are generally 

 very rapid compared with enzyme reaction rates and hence would seldom 

 be of significance in the over-all rate expression. Thirdly, it is usual to 

 express the results in terms of changes in iiL„, or F,„; in most cases these 

 cannot be broken down satisfactorily into rate constants at any pH, so 

 it is useless to attempt to interpret pH effects on these rate constants at 

 present. Lastly, it will be evident later that the extension of the treatment 

 to enzyme inhibition, which is our primary concern, is completely satis- 

 factory. 



A further word may be said regarding the rates of proton association and 

 dissociation, inasmuch as these rates, relative to the rates of the other 

 reactions occurring in the inhibition, determine whether ionization rates 

 must be included in the treatment or not. The rate constants for the reac- 

 tion: 



H + B 



HB 



for some acids are given by Bell (1959) (see tabulation below). Average 

 values for the carboxyl group would be: log k,^ = 10.1 and log k^ = 6.7. 



