ANTI-ENZYME IMMUNITY 283 



proteinase converting fibrinogen into insoluble fibrin with very little, 

 if any, proteolytic action on the fibrinogen molecule, seems to require 

 consideration. Since theoretically all actions are fundamentally re- 

 versible, and also since a catalyst accelerates both directions of a reac- 

 tion at equal rate to attain equilibrium, it may, therefore, at first, seem 

 reasonable to assume that papain functions as a synthetic as vv^ell as a 

 digestive enzyme. If we assume that thrombin catalyzes the conversion 

 of fibrinogen to fibrin in a similar manner, it would necessitate that we 

 accord to thrombin the role of a specific proteinase. In view of the fact, 

 however, that thrombin has not been shown to possess proteolytic 

 activity, it would seem necessary that the action of this enzyme be 

 explained in another manner. 



In connection with the nature of the primary chemical bonds in- 

 volved in the conversion of fibrinogen to fibrin a discussion by Chargaff 

 (1945), and, particularly, a study by Lyons (1945), are of interest. In 

 a critical review, ChargafF pointed out that fibrinogen solution free 

 from prothrombin forms clots when acted upon by a number of simple 

 organic substances such as sodium N-chloro-p-toluenesulfonamide or 

 chloramine T, potassium l,4-naphthoquinone-2-sulfonate, sodium 1,2- 

 naphthoquinone-4-sulfonate, ninhydrin ( 1 ,2,3-indenetrionehydrate) 

 and, much less markedly, alloxan and salicylaldehyde. The clots were 

 coherent and rapidly retracting. Discussing various reactions as possible 

 mechanisms or alterations in the fibrinogen molecule forming the 

 fibrin structure, he stated that the activity of these clotting agents was 

 found to parallel their ability to decarboxylate amino acids of the 

 fibrinogen molecule. The possibility of oxidation of susceptible group- 

 ings, such as sulfhydryl, was also considered. From the fact that re- 

 ducing substances, such as sodium bisulfite and glutathione, inhibited 

 the action of the clotting agents, an oxidative reaction appeared to be 

 responsible for clotting. Though there was some indication of the evo- 

 lution of carbon dioxide from the action of thrombin on fibrinogen in 

 an oxygen-free atmosphere, Chargaff was non-committal regarding 

 the relationship of these reactions to the mechanism of true clot forma- 

 tion. The question of whether the clots formed by the action of organic 

 substances were comparable to normal fibrin, or were similarly 

 susceptible to the fibrinolytic action of serum lytic factor was not dis- 

 cussed. 



Chargaff and Ziff (1941) reported that "ninhydrin" would clot 



