INHIBITION OF ENZYMES 



797 



rapidly and unrelated to the enzyme activity and the other reacting slowly 

 to produce inactivation; altering the pH from 5.2 to 7.2 modifies the rates 

 of reaction of these groups with p-MB in quite different ways (Gilbert, 

 1963). 



Increase of any ligand capable of complexing the mercurials should re- 

 duce the inhibition, but this has been studied very little. Fernley (1962) 

 noted that raising the CI" concentration suppresses the inhibition of /?- 

 glucuronidase by Hg++. It is very difficult in such cases to separate a direct 

 complexing action from an ionic strength effect. Green and Neurath (1953) 



-6 -5 -4 



LOG CONCENTRATION (mM) 



Fig. 7-17. Concentration-inhibition curves for the actions of Hg++ 

 and PM on pancreatic amylase. (From Owens, 1953 b.) 



varied the ionic strength with NaCl, SrClg, and (NH4)2S04 and found the 

 inhibition of trypsin by Hg++ to be suppressed at high ionic strengths 

 (Fig. 7-18). Since all the salts had essentially the same effect, they assumed 

 that this is not due to specific ions, but certainly part of the reduction 

 must be due to increasing formation of the Hg++ complexes with CI", NH4+, 

 and 864=. The nature of the inhibition of trypsin is not clear since free SH 

 groups are generally not considered to play a role in the active center. 

 The inhibition of pancreatic amylase by Hg++ and PM was postulated by 

 Owens (1953 a) to involve phosphate ion, and the unusual configuration of 

 the PM inhibition curve was attributed, at least in part, to the formation 

 of phosphate complexes, although it is strange that Hg++ is not similarly 

 affected. It is also not clear to me why the curve should assume this shape, 

 particularly why increase in PM from 0.1 to 1 vaM should bring about a 



