INHIBITION OF ENZYMES 621 



arsenite to inhibit 50% (Albers and Koval, 1961). This was interpreted 

 as indicating the presence of a dithiol group. It is useless to try to decide 

 between the conclusions from such results until we know exactly why 

 the thiol potentiates the inhibition. We shall discuss this matter in a later 

 section, but it is interesting to speculate here that such behavior may 

 point to a monothiol type of enzyme, since now reaction A above may be 

 modified to: 



S— E 



R— As=0 + HS— E + HS— T ^ R— As + H^O 



S— T 



where T — SH is a simple thiol, which may to some extent stabilize the 

 complex and make unnecessary another SH group on the enzyme. If this 

 explanation is true, inhibition by R2=As — CI should never be potentiated 

 by thiols, but I know of no experiments on this point. 



Summarizing the situation, it is likely that the original criterion applied 

 by Lotspeich and Peters (1951), namely, the relative susceptibilities of 

 enzymes to monosubstituted (R — As==0) and disubstituted (Rg^As — CI) 

 arsenicals, is the most valid to judge whether an enzyme possesses single 

 or paired SH groups, but from what we have said it is clear that even 

 this is not an infallible test. What shall we say about those enzymes which 

 are inhibited approximately equally by these two types of arsenical? This 

 is the case with urease (Rona and Gyorgy, 1920), cholinesterases (Mounter 

 and Whittaker, 1953), liver succinate oxidase (Aldridge and Cremer, 

 1955), and several other enzymes. Should we conclude that possibly there 

 are two SH groups but farther apart than would provide maximal stability 

 for a cyclic structure? Or that reaction E above can lead to as stable a 

 complex as reaction D due to interactions with the rest of the molecule? 

 These questions cannot be certainly answered until we have more infor- 

 mation of the relative inhibitions produced not only by series of arsenicals 

 but also by other inhibitors reacting with SH groups. Unfortunately not 

 a single enzyme has been subjected to an extensive group of arsenicals 

 under the same experimental conditions, as may be seen from perusal 

 of Table 6-3, and the answers we are looking for cannot be found from 

 simple comparisons of the effects of arsenite or an arsenoxide with those 

 of (p2=As — CI. 



Stimulation of Enzymes by Arsenicals 



Arsenicals in common with other SH reagents occasionally increase en- 

 zyme activity. In addition to the instances cited in Table 6-3, catalase 

 is stimulated 45% by 5.5 mM cacodylate and initially by 7.4-11 mM 

 arsenite (Santesson, 1915), dihydrofolate reductase is stimulated 17% by 

 10 mM arsenite (Blakley and McDougall, 1961), and the oxidation of a- 



