TOXICITY (IF l:\y.V MES 61 



cell, but after the death of an or^aii it may result from tin; decom- 

 position products tliat are formed. I'lider i)hysiolo<rical conditions 

 this activation appears to be brouj^ht about by special activating,' sub- 

 stances. In the case of tlie pancreas it is the enterokinase, which is 

 furnished by tlie epithelial cells of the intestine. Enterokinase ap- 

 pears to unite with trypsinogen to fonn an active enzyme, which re- 

 minds one of the way that complement and the intermediary l)ody 

 unite to form hemolytic and bacteriolytic substances.-" Kinases, hav- 

 ing the same action as enterokinase upon the trypsinogen, are found 

 in various tissues and organs, but generally much less active than the 

 enterokinase. Pepsinogen is probably activated by the IICl of the 

 gastric juice. It is very probable that it is through this mechanism 

 that the rate of enzyme action is modified, and perhaps it is a means 

 of defense of the body against its own enzymes; as the prozymes are 

 more resistant to harmful agencies than the enzymes, it also may be 

 a method of storage. The activity of various enzymes is greatly in- 

 creased by certain more or less specific substances, referred to usually 

 as "co-enzymes"; thus bile-salts act as co-enzymes for lipase 

 (Loevenhart). 



THE TOXICITY OF ENZYMES 



Although present normally in greater or less amounts in all the 

 cells in the body, when artificially isolated and injected directly into 

 animals nearly all enzymes seem to be extremely toxic. As foreign 

 proteins, especially extracts of tissues, are generally more or less 

 toxic, it is difficult to state how much of the toxicity of a given enzyme- 

 containing solution depends on the enzyme and how much on the 

 admixt proteins. The following statements are taken at the face 

 value placed on them by the several investigators quoted, and are 

 subject to discount until the enzymes have been isolated and investi- 

 gated in a pure condition, if such a thing shall ever become possible. 



The first thorough study of the toxicity of enzymes was made by 

 Hildebrandt,-^ who found that pepsin, invertase, diastase, emulsin, 

 myrosin, and rennin were all toxic. The symptoms produced in dogs 

 were trembling, uneasiness, difficulty in walking, and finally coma. 

 The anatomical changes observed w^ere : numerous hemorrhages 

 throughout the body, fatty degeneration of the liver and myocardium, 

 renal congestion, and numerous thromboses. Considerable fever re- 

 sults, and ]Mayer considers this responsible for the relative harmless- 

 ness of rennin, the action of which is impaired above 40°, That these 

 effects are due to the enzymes themselves rather than to contaminating 



20 Bayliss and Starlinp: (.Tour, of Physiol.. Ifl05 (32). 120), quoslioii tlu> 

 analogy of zymogen-kinase combinations to coniplement-amboceptor eomliination. 

 Walker, however, finds evidence that many enzymes consist of a specitic ambo- 

 ceptor and a non-specific complement or kinase (Jour, of Physiol.. IKiKl (.3.3), 

 p. xxi.). 



2iVircho\v's Archiv, 1800 (121), 1. 



