INHIBITION OF ENZYMES 861 



trations being used, or statements that both at certain concentrations in- 

 hibit 100%. Of the remaining reports, Hg++ is more potent in 65%, p-MB 

 in 29%, and in 6% they are of equal potency. One must admit that Hg++ 

 is generally more effective. In some cases it is of much greater inhibitory 

 potency than p-MB or the other organic mercurials. One might expect Hg++ 

 to be more potent than p-MB because (1) it is smaller and might be able 

 to penetrate and react with SH groups inaccessible to the larger molecule, 

 and (2) it could possibly in some instances induce dimerization of the en- 

 zyme (or even polymerization), since it is bifunctional. On the other hand, 

 p-MB might be considered to shield off, sterically or electrostatically, a 

 greater area on the enzyme surface once it has combined with the SH groups, 

 due to its greater size and the charged COO" group. The result in any case 

 is probably a balance of these and other factors. The fact that Hg++ is 

 often more inhibitory than p-MB does not immediately imply that it is a 

 better or more reliable inhibitor to use for the purpose of detecting SH 

 groups on enzymes, but it does, I think, suggest that Hg++ has been un- 

 necessarily neglected by many workers. It might be proposed that both 

 mercurials be used, since not only will the detection of SH groups be made 

 more certain, but occasionally interesting information on the nature of the 

 inhibition may be obtained. 



The organic mercurials themselves have not often been used in the same 

 investigation, but in 19 reports using both p-MB and PM, I have found PM 

 to be more potent in 79%. The differences between them are seldom very 

 marked, however. One would not expect much difference between p-MB 

 and 2?-MPS, and examination of the eight reports using both bears this out, 

 in two p-MB being the more potent, in two p-MPS being the more potent, 

 and in four the potencies being the same. There is some reason for believ- 

 ing that the smaller uncharged alkyl mercurials, such as MM, might be 

 better for enzyme study than any of the other mercurials, but there has 

 been so little comparison that nothing can be said definitely about their 

 relative effectiveness at this time. 



Meaning of K,- and Methods of Expressing Inhibition by the Mercurials 



The values for Kj have occasionally been reported for mercurial inhibi- 

 tion; e.g., for the inhibition of phosphoribosyl-ATP pyrophosphorylase by 

 p-MB, pZ, = 5.15 (Martin, 1963), and for the inhibition of heart lactate 

 dehydrogenase by p-MB, pK^ = 4.10 (Gruber et al., 1962). In the latter case 

 the binding of the mercurial to the noncatalytic SH groups, causing the 

 spontaneous reversal of the inhibition, is characterized by a p^j of 5.40. 

 Most of the values given for p^, are in the range 4-6. However, these values 

 were obtained by simply taking the concentration to produce 50% inhibi- 

 tion, which would be valid if (1) the inhibition is classically noncompetitive 

 (which in most cases probably it is not), and (2) the system is in zone A 



