102 PROTEIN THERAPY 



The Serum Enzymes. In the blood stream several proteolytic 

 enzymes are known to occur. These include the leukoproteases : (a) 

 one that acts in a slightly alkaline or neutral reaction and is capable of 

 splitting native proteins largely to the proteose stage; (b) one that acts 

 in a reaction slightly acid, with a digestive range similar to the first; 

 (c) an erepsin-like enzyme active in a neutral medium and freely hy- 

 drolyzing proteins from the intermediate stages (albumoses and pep- 

 tones) to the amino acid forms. These enzymes seem to be derived 

 from disintegrating but not from living polymorphonuclear leukocytes 

 and fluctuations in the peripheral leukocyte count are not indicative of 

 the relative titer of the enzyme concentration. (Hedin, Jobling and 

 Petersen, etc.) 



Apart from the leukocytes as sources of proteolytic enzymes we 

 must consider those derived from the gastro-intestinal tract, the large 

 abdominal organs and from areas pathologically altered, either by 

 infection or by trauma, burns, toxins, etc. These enzymes include a 

 tryptase or protease a polyvalent trypsin-like ferment active in a 

 neutral or slightly alkaline reaction. In the human this enzyme is 

 normally present in only a very slight amount, but under certain 

 conditions (pneumonia, leukemia) may be markedly increased. In cer- 

 tain animals one can also increase the amount by moderate stimulation 

 of the liver (by Roentgen irradiation, etc.). In many of the smaller 

 laboratory animals these enzymes are present in a considerable 

 amount in the serum, especially in those that have no leukoprotease 

 present in the leukocytes (guinea pigs, rabbits, etc.). 



Serum ereptase or peptidase is an enzyme able to digest partly 

 hydrolyzed proteins to the animo acid stage. It is normally present 

 in human serum in small amount. But after feeding it is increased, 

 probably entering the blood stream from the gastro-intestinal tract 

 via the lymph current. It can also be augmented by stimulating the 

 gastro-intestinal tract by means of short Roentgen ray exposure. In 

 smaller animals this enzyme is present in relatively large amounts. 



We have to deal in general with two types of proteolytic enzymes, 



(a) the true proteases capable of digesting the native proteins, and 



(b) the erepsin-like enzymes (peptldases) that are able to digest 

 only partly hydrolyzed proteins ; both active in neutral or at the most 

 in a reaction varying from the neutral to only a slight extent. The 

 enzymes of the first variety are, however, not active under normal 

 conditions in the blood serum because their activity is inhibited or 

 checked by the antiferment of the serum. In small localized areas the 

 amount of true protease liberated by disintegrating leukocytes or by 

 other causes may be sufficient to saturate the antiferment and in 

 this case digestion may go the entire stage from native protein to 

 amino-acids. As a general rule the protease derived from the leu- 

 kocytes, active in the slightly acid reaction, is more active than the 

 alkaline acting protease and autolysis therefore goes on much more 



