SPECIFICITY OF INHIBITION 865 



ficiencies. Another way of stating the problem is that the apparent speci- 

 ficity is always greater than the absolute specificity. However, the more 

 we know about the actions of an inhibitor, the more able are we to use it 

 properly and to achieve true specificity if this is possible. The subject of 

 specificity has been a very neglected aspect of inhibition and the attempt 

 will be made in this chapter to i)ut specificity on a simple quantitative basis 

 that may be a steppingstone for the more detailed analyses that will 

 undoubtedly be made in the future. 



Definition of Enzyme Specificity of Inhibition 



It is necessary to express the specificity in some definite way if the 

 phenomenon is to be amenable to quantitative treatment. This is difficult 

 to do in a completely satisfactory manner. The most important element in 

 specificity is the difference in the inhibitions produced by a concentration 

 of a inhibitor on two enzymes, and this we can express simply as: 



a = ii — ii (16-1) 



where o is the specificity, ^\ is the inhibition on the enzyme of interest, 

 and *2 is the inhibition on a second enzyme. For absolute specificity, cr = 1, 

 and complete inhibition of one enzyme may be achieved without any inhi- 

 bition of the other; partial specificity occurs when o < \ and there will 

 be some overlap in the inhibitions of the two enzymes. The sioecificity as 

 thus defined will generally depend on the concentration of the inhibitor. 



This definition of specificity is not entirely applicable to all situations 

 because it omits the other factor that is important in the practical use 

 of an inhibitor, namely the requirements with regard to the absolute 

 levels of the inhibitions. As an example we may take a case in which the 

 specificity is designated as 0.7. Now this degree of specificity could occur 

 with ij = 1.0 and i.^ = 0.3, or ?\ = 0.9 and ^2 = 0.2, or i^ = 0.8 and i^ = 

 0.1, or t'l = 0.7 and rg = 0- Which set of values would be appropriate for 

 a particular situation? In some cases, it is more important to inhibit the 

 enzyme being studied completely, even though the other enzyme is inhi- 

 bited to some extent, and in other cases, it is more important that the sec- 

 ond enzyme is not inhibited at all. Thus a determined specificity does not 

 immediately tell one the correct inhibitor concentration to use, but does 

 provide limits. 



Let us first consider two enzymes inhibited noncompetitively, for which 

 the individual inhibitions may be written as: 



'' = (i)T^ '' = (i)T^ ^''-'^ 



