CELLULAR METABOLISM III 



is known. However, as this combination is irreversible, it is difficult to 

 establish definitely whether enzyme inhibition is due to this reaction or 

 to combination with some other group of the protein. Very little is 

 known about the role of these — SH groups. Protection of the — SH 

 groups of the protein moiety of succinoxidase by succinate and by 

 malonate {2,7) would suggest that the substrate is anchored in close 



TABLE VI 



Inhibition of Crystalline Urease b}' Radium Radiation 

 Effect of Glutathione, Glycine, and p-Cl-Hg Benzoic Acid. 



vicinity to the — SH groups. The proximity of the carboxyl electronega- 

 tive groups would decrease the activity of the — SH groups and thus 

 render them less susceptible to the action of sulfhydryl reagents. Some 

 other proteins require the presence of a metal (Mg, Mn, Zn, Co) for 

 enzyme activity; the metal does not participate in the reaction. Their 

 role is still more obscure than that of the — SH groups. It is known, 

 however, that — SH groups and metals contribute to increase the stability 

 of the native protein. 



The combination of the substrate with the protein brings forth the 

 "activation" of the substrate. It is not yet clear what is meant by activa- 

 tion of the substrate. It is plausible, however, to postulate with Michaelis 

 that activation consists in the formation of a radical, the first step in the 

 process of oxidation of organic substances with a loss of two electrons. 

 This is implicit in Michaelis' theory of compulsory univalent oxidation 

 (6o). 



