ANTI-ENZYME IMMUNITY 285 



bin failed. Sodium cyanide and arsenates inhibited clotting. Quantita- 

 tive determinations were carried out by the use of the reaction 

 2NaN3+l2^2NaI+3N2 which is catalyzed by -SH and blocked-SH 

 groups and showed that all reactions and properties of fibrinogen A 

 are typical of the blocked protein-SH which is later converted to 

 protein-SH or fibrinogen B. The latter is oxidized by a thrombin com- 

 ponent (possibly a naphthoquinone complex) to a protein-S-S-protein 

 form. A large number of these linkages combining fibrinogen B mole- 

 cules would give the typical fibrin structure. 



On the basis of the results discussed above, it would seem that throm- 

 bin exposes the blocked protein-SH in fibrinogen molecules in fresh 

 plasma, and the naphthoquinone, or vitamin K-like component of 

 thrombin oxidizes the exposed protein-SH to a R-S-S-R structure yield- 

 ing the fibrin structure. Fibrinogen prepared from aged plasma which 

 possesses the protein-SH groups already in an exposed form, can directly 

 be oxidized to the disulfide linkage, yielding the fibrin structure. 



The above interpretation of the mechanism of the conversion of 

 fibrinogen to fibrin structure may explain also the unique role of 

 papain among the proteolytic enzymes in clotting fibrinogen molecules. 

 It has been known that papain is activated by hydrocyanic acid, hydro- 

 gen sulfide, glutathione, cysteine, sodium thiosulfate and other reduc- 

 ing agents. It is inactivated by hydrogen peroxide and iodoacetic acid. 

 In an active state papain may be considered as a SH-protein. In an 

 inactive state it would contain the -S-S- linkage which can oxidize -SH 

 groups of fibrinogen molecules yielding the fibrin structure. Thus 

 the clotting of fibrinogen by papain may be referred to its oxidative- 

 reductive properties through its thiol groupings. Papain may also bring 

 out the blocked -SH groupings in the fibrinogen molecules for their 

 conversion to -S-S- linkages, yielding the fibrin structure. 



3. Antibody Against Thrombin. Neutralization of Throm- 

 bin of Rabbit Serum by Anti-Rabbit Guinea Pig Immune 

 Serum 



Bordet and Gengou (1901) showed that a neutralizing antibody 

 against the enzyme of rabbit blood responsible for clotting of the blood 

 or plasma could be produced in guinea pigs. 



