INTERPRETATION OF INHIBITIONS BY SH REAGENTS 647 



It is quite possible that many or all of these mechanisms contribute in 

 various situations to the differential reactivity of SH groups, and that we 

 should not be too eager to argue for a single dominant factor. After all, 

 there is a graded scale of reactivity, which in itself implies multiple mecha- 

 nisms. It would probably aid in the characterization of SH groups if some 

 standard method for designating the reactivity could be used, rather than 

 designating them by terms such as "sluggish," etc. The time for 50% reac- 

 tion, where determinable, might be the simplest and most useful, although 

 some form of reaction rate constant would be preferable. 



INTERPRETATION OF INHIBITIONS BY SH REAGENTS 



The SH reagents are used most commonly to determine whether a parti- 

 cular enzyme is an "SH enzyme" or not. What this means depends on one's 

 definition of "SH enzyme." If we take the definition proposed earlier (page 

 635) that an SH enzyme is one that is inhibited by SH reagents, not a great 

 deal has been achieved by proving that an enzyme belongs to this class. 

 In the past, many workers have been satisfied to stop at this distinction, 

 and the designation of an enzyme as an SH enzyme has been deemed suffi- 

 cient without further discussion as to the significance of the observation. 

 On the other hand, some have assumed immediately that inhibition by SH 

 reagents indicates a catalytically functional role for an SH group at the 

 active center, and this, as we have seen, is entirely unjustifiable. It is thus 

 important to determine as far as possible what such inhibition means and 

 what valid conclusions may be drawn from the use of SH reagents. 



The various mechanisms by which SH reagents can inhibit pure enzymes 

 may be classified in the following way. 



(A) The SH group reacted is at the active center and is functional. The SH 

 group may be involved in the binding of substrate, coenzyme, or activator 

 to the apoenzyme, or it may participate in the transfer of groups of elec- 

 trons. 



(B) The SH group reacted is at the active center but is nonfunctional. It is 

 possible that an SH group occurs at the active center but is unrelated to 

 the catalytic process. 



(C) The SH group reacted is vicinal to the active center. The SH reagent 

 introduces a new structure on the enzyme, and if this is near enough to 

 the active center it may either sterically or electrostatically modify the 

 reactions proceeding at the active center. 



(D) Reaction of the SH groups alters the enzyme protein structure. This 

 could also apply to reaction with disulfide groups or other complexes form- 

 ed by SH groups. The change in protein structure would then reduce the 



