ANTI-ENZYME IMMUNITY 279 



proteins by the action of the enzyme thrombin. Coagulation by heat 

 and chemical agents involves denaturation reactions. Clotting of 

 fibrinogen by thrombin is a specific enzyme reaction involving none of 

 the denaturation reactions. Coagulation by denaturation is "any non- 

 proteolytic modification of the unique structure of a native protein, 

 giving rise to definite changes in chemical, physical, or biological 

 properties" (Neurath, et al. 1944). Fibrin clot formation by the action 

 of thrombin, in contrast, is an enzyme process involving the linkage of 

 inter-molecular bonds leading to the formation of fibrin of higher 

 structure from the fibrinogen molecules. Coagulation of a protein by 

 denaturation, as we know now, presents hydrophobic compact protein 

 aggregates devoid of elastic and other physical properties characteristic 

 of fibrin clots. It would, therefore, be more precise to avoid the use of 

 the non-specific term coagulation in describing the conversion of 

 fibrinogen specifically into fibrin clot. 



b. Factors Responsible for the Formation of Plasma Clot. The 

 available information regarding the mechanism of blood clotting in- 

 structs us that the blood plasma factor, prothromhin, is activated by 

 calcium ion and platelets, or tissue extracts, or simply by purified 

 thromho'plastin (lipo-protein) to form thrombin, which catalyzes the 

 conversion of fibrinogen in plasma into fibrin clot. Other substances of 

 animal and vegetable origin have been reported to exercise thrombic 

 activity. Eagle and Harris (1937) reported that trypsin, which has no 

 direct clotting action on purified fibrinogen, converts prothrombin to 

 thrombin; and this thrombin then acts on blood fibrinogen to form 

 fibrin. With an excess of trypsin, no thrombin formation was demon- 

 strated, because of the digestion of prothrombin, thrombin, or both. 

 They also reported that papain, unlike trypsin, did not activate pro- 

 thrombin to thrombin but acted directly on fibrinogen in changing it 

 to fibrin. The reaction between trypsin and prothrombin, as well as 

 the action of papain on fibrinogen in changing it to fibrin, according 

 to them, is independent of calcium ion, platelets or tissue extracts. 

 Trypsin and the Ca-tissue (or Ca-platelet) system were looked upon 

 as mutually supplementary. Both systems affect the same substrate, 

 prothrombin, to form as end products clots which are qualitatively 

 indistinguishable.* 



* Studies dealing with the mechanism of blood clotting, and of the interaction of 

 various factors leading to or inhibiting blood clotting, constitute a vast array of 



