704 



14. EFFECTS OF pH ON ENZYME INHIBITION 



groups in the vicinity of the ionizing group are evident. Such variation of 

 the p^a with the environment must always be taken into account in in- 

 terpreting the data. Table 14-5 presents the p^^'s of certain important 

 protein groups as determined from the titrations of amino acids, polypep- 

 tides, and proteins, and the values are eclectic and somewhat arbitrary. 



Table 14-5 

 Dissociation Constants of Enzymically Important Groups " 



" The pA'„ given is considered to be the most hkcly vahie to be found in proteins 

 taking into account the net charge of the average protein in the pH range near the 

 pKa- The actual value in a particular protein may vary from this, depending not only 

 on the over-all net charge of the protein but on vicinal ionizing groups and steric fac- 

 tors; the most probable ranges to be found are given in the last column. 



Variation of the Rate of Inhibition with pH 



The rate at which the inhibition of an enzyme develops may also depend 

 on the pH. Two basic mechanisms may be involved: changes in the con- 

 centration of the active form of the inhibitor and changes in the rate con- 

 stants for the inhibition. In other words, the situation is the same as in the 

 variation of K^ with pH. Similarly, we may define a true rate constant, k^ 

 or k_i, as expressing the rates of formation or dissociation of the EI complex 

 when the enzyme and the inhibitor are in their active forms, and an apparent 

 rate constant, k^ or k'_j^, which is experimentally derivable by plotting pro- 

 cedures. Thus, a change in pH may i)roduce a change in the apparent rate 

 constants either by affecting the concentrations of active forms or by di- 

 rectly altering the true rate constants. Of course, the rate constants and 

 K^ are closely related and a change in K^ implies some modifications of 

 k^ and k^^. 



