ENZYMES 57 



noted that tlie percentages of inhibition of respiration (oxygen uptake) 

 depend upon two conditions, the amount of oxygen available and the 

 concentration of cyanide present. We may assume that the cyanide 

 inhibited one or more respiratory enzymes and that, as the concentration 

 of cyanide increased, more and more of these enzymes were inactivated. 

 When the oxygen tension was reduced, these effects were increased. 



While it is kno^^^l that salts of the heavy metals may denature proteins, 

 and this explanation has been advanced to account for enzyme inactiva- 

 tion by them, recent opinion inclines to the \'iew that the heavy metals 

 inactivate enzymes either by combining with — SH groups, or, under 

 alkaline conditions, by oxidizing thiol sulfur to disulfide. Mercuric ions, 

 especially, may combine with specific metabolites which contain — SH 

 groups (glutathione, thioamino acids), as found by Fildes (1940). Cer- 

 tain metals may inactivate enzymes by replacing the normal metal, ren- 

 dering the enzyme inoperative. It is noteworthy that many enzymes 

 which are inactivated by heavy metals may be either "protected" or 

 restored to activity by the addition of thiol compounds. We may assume 

 for the purpose of illustration that, when a heavy metal combines with an 

 enzyme, an inactive complex or compound is formed as shown in scheme 

 II. Two factors would influence the effectiveness of thiol compounds in 

 preventing or reversing enzyme inactivation, the relative affinity of the 

 enzyme — SH groups and the thiol compound for mercury, and the rela- 

 tive concentration of enzyme and thiol compound. 



Scheme II. A Scheme Illustrating a Possible Mechanism of Inactivation 



OF A Sulfhydril Enzyme by Mercuric Ion and Reactr'ation of the Inactive 



Enzyme-Mercury Complex by the Addition of a Thiol Compound 



Inactivation 



Enzyme — S 



2(Enzyme— SH) + Hg++^ Hg + 2H+ 



Enzyme — S 

 Active enzyme Inactive enzyme complex 



Reactivation 

 Enzyme— S RS 



\ \ 



Hg + 2RSH^ 2 (Enzyme— SH) + Hg 



Enzyme— S RS 



Active enzyme 



Radiation. Many reports are to be found in the literature that radia- 

 tion affects enzymes adversely (see the review of Schomer, 1936). Radia- 

 tion may affect not only the enzymes of an organism but also the sub- 

 strates. Ionizing short-wave radiations may cause the formation of 

 hydrogen peroxide from water. Barron et al. (1947) were able, by adding 



