20 JOHN H. NORTHROP 



value of the constant is 14.6, i.e. with unit concentration of trypsinogen 

 the active trypsin would increase 14 times per hour. As in the case of 

 chymo-trypsin there is no evidence for the sphtting off of any part of 

 the molecule during this activation reaction, nor is there any marked 

 change in chemical composition so that the change from the inactive 

 protein to the enzyme is probably due to some internal rearrangement 

 in the structure of the molecule. However, the work on this question is 

 still in the preliminary stage. The autocatalytic nature of this reaction 

 was correctly described by Vernon but subsequently denied by Bayliss, 

 Starling, and others. 



Kunitz (1938) has recently found that trypsin is also formed from 

 trypsinogen at pH 5.0 by a proteolytic enzyme secreted by a mold 

 (penicillium). Trypsin is only slightly active at this pH, so that the 

 activation curve is no longer autocatalytic but simply logarithmic as is 

 the activation of chymo-trypsinogen. Trypsin obtained in this way is 

 identical with that formed by autocatalytic activation. The mold enzyme, 

 therefore, must attack the trypsinogen molecule at the same place as does 

 trypsin. 



The formation of trypsin from trypsinogen is also accelerated by 

 enterokinase. The reaction trypsinogen -^trypsin is therefore cata- 

 lyzed by three different catalysts — trypsin itself, mold kinase, and 

 enterokinase. 



Activation of Trypsin by Enterokinase. Pancreatic juice as 

 secreted is inactive and becomes active in vivo only when mixed with 

 the contents of the small intestine. The subject has been controversial 

 for many years. Kunitz (1939b) has reinvestigated the problem with 

 purified materials and has found that the conflicting results are due to 

 the fact that an inert protein, as well as the active enzyme, are formed 

 simultaneously during the reaction. The relative amounts of the two 

 substances obtained depend on the acidity of the solution. In slightly 

 acid solution nearly all the precursor is transformed into the active 

 enzyme and very little inert protein is formed. In neutral or slightly 

 alkaline solution considerable amounts of inert protein are formed. 



The entire reaction may be quantitatively predicted on the assump- 

 tion that the rate of formation of the active enzyme is proportional to 

 the concentration of precursor and of activator, while the rate of forma- 

 tion of the inert protein is proportional to the concentration of trypsin 

 and of the precursor. The relative rates of the two reactions are deter- 

 mined by the acidity. 



Pepsin from Pepsinogen (Herriott, 1938). The reaction at /'H4.65 



