VARIATION OF INTRACELLULAR INHIBITION WITH pH 



737 



Therefore, the curve obtained when log (I), is plotted against i^K^ will 

 have a zero slope at low values of the i>K^ and a slope of — 1 when the 

 piiL^/s are above pH^. A plot of the inhibition against p^^ will also have a 

 zero slope in the low ]-)K^ range but the curve at high y>K,/s will have a 

 sigmoid configuration because the inhibition is not proportional to log (I)^. 

 A typical i-^K^ curve is shown in Fig. 14-26. It will be observed that the 

 inhibition will not be related to the p^^ of the inhibitor if the values of 



Fig. 14-26. Variation of the inliibition with 

 the ipKa for weak acid inhibitors whenall inhi- 

 bitors are used at the same total concentra- 

 tion and external pH (Eq. 14-172 and non- 

 competitive inliibition). 



pK,^ are much lower than the pH^. In other words, if pH^ = 7.4, all inhi- 

 bitors with piiL,/s of 6 or less will produce the same inhibition. In the range 

 of higher piiC,/s the inhibition will be related to piiC,, in a complex manner. 

 The most practical way to determine whether the differences in inhibi- 

 tion observed are related only to the differences in piiC^ is to solve Eq. 

 14-174 for the log (I); that corresponds to each ]iK^ and then to see if the 

 inhibitions conform to the usual equation expressing i in terms of (I). The 

 comparison between inhibitors would be much more accurate and reliable 

 if a simple pH curve for each were obtained. 



Determination of K/ from Cellular Inhibition 



Nonionizing inhibitors that penetrate into cells readily and reach an 

 intracellular concentration which is equivalent to the external concentra- 

 tion may produce inhibitions which are quantitatively quite comparable 



