COMPARISON OF SH REAGENTS 817 



petitive component. These potencies may actually have a physical inter- 

 pretation if a state approaching equilibrium was achieved in the inhibition, 

 if mutual depletion of enzyme and inhibitors did not appreciably occur, 

 and if secondary inactivation has not contributed significantly to the 

 measured inhibition. Since these conditions are seldom realized, the po- 

 tencies should be taken only as figures giving very approximate relative 

 inhibitory potencies. They should not be used for comparisons between 

 different enzymes because the experimental conditions are likely to be 

 quite different. If an inhibition is given as 0%, it is assumed that the inhi- 

 bition is less than 1%, and if it is given as 100%, it is assumed that it is 

 more than 99%, for the purpose of calculating the potencies. Inhibitions 

 given as close to 50% have been chosen when a range of values is given 

 in the reports in order to increase the reliability of the values for comparison. 

 Only a few general remarks relative to the data in the table will be made 

 and those particularly interested in this type of inhibitor may find some 

 profit in a more detailed perusing of the results. Perhaps it will be only 

 by some such wide comparisons that an understanding of the differences 

 between the various enzyme SH groups will be reached. The fact most 

 immediately apparent from inspecting the table is the tremendous varia- 

 tion in the susceptibilities of single enzymes to different SH reagents, 

 which implies a similar variation in the reactivity or accessibility of SH 

 groups involved in some way in the catalysis. Some enzymes are inhibited 

 strongly by one or more substances but scarcely at all by others, although 

 all these inhibitors are classed as SH reagents. This reflects, of course, 

 the marked differences between the reactivities and other properties of the 

 inhibitors, as well as the differences in the SH groups. Some of the char- 

 acteristics of enzyme SH groups possibly responsible for their different 

 reactivities were examined in Chapter II-4; these include the electric 

 field surrounding the SH group, steric factors such as would exist if the 

 SH group is buried within the protein structure, the occurrence of disulfide 

 linkages, complexes of the SH group with surrounding groups, and whether 

 there is a single SH group or two vicinal SH groups. One becomes more 

 and more unsatisfied with the common explanation for unreactivity with 

 a particular SH reagent, namely, that the SH group, or groups, is sterically 

 inaccessible, being within some pocket or crevice. First, if the SH group 

 is indeed so situated, then one has the problem of how it is functionally 

 involved in the catalytic process, although of course it is always possible 

 to provide some theory. Second, if the SH group is sterically inaccessible 

 to a certain inhibitor, why does it often react readily with other inhibitors 

 of equal or greater size ? It seems that the only valid evidence for a troglo- 

 dytic SH group is the demonstration that it does not react with any of the 

 many SH reagents, and even this can be explained in other ways. This 

 problem is only one reason of many why studies on enzyme SH groups 



