VARIATION OF ENZYME INHIBITION WITH pH 



697 



Shookhoff (1939) and the development has been summarized in Edsall 

 and Wyman's recent book (1958, Chapt. 11). The interactions of car- 

 boxyl groups in dicarboxylic acids of varying chain length and the 

 interactions between carboxyl and amino groups in amino acids lead to 

 shifts in the p^^'s of comparable magnitudes to those given in Fig. 14-14. 

 Thus in the series from malonic to azelaic acids, where the inter-carboxyl 

 distance varies roughly from 5 to 12 A, the J])KJs vary from 2.26 to 0.26 

 (Westheimer and Shookhoff. 1939). The microscopic ionization constants 



Fig. 14-14. Expected changes in pi^,- due to a charged vicinal group at the distance 

 d from the active center. Interaction energy between groups calculated from eq. 6-109 



with r„ = 10.2 A. 



of glutamic acid (Edsall and Wyman, 1958. p. 496). cysteine (Edsall and 

 Wyman, 1958, p. 503), and tyrosine derivatives (Martin et al., 1958) also 

 indicate that pii,^ shifts of 0.4 to 2.1 arise from charged groups distant 5 

 to 10 A. Although there is undoubtedly some difference between the dis- 

 sociation of an inhibitor from the active center and the dissociation of a 

 proton from a single group, one might expect changes in piiC^ and piiTj 

 at least of a similar order of magnitude. 



It has been shown that the inhibition can be quite sensitive to small 

 changes in the binding energy (Eq. 6-102, Fig. 6-15) and it is clear that 



