THE INACTIVATION OF TRYPSIN. 

 HI. Spontaneous Inactivation. 



By JOHN H. NORTHROP. 

 {From the Laboratories of The Rockefeller Institute for Medical Research^ 



(Received for publication, November 15, 1921.) 



In addition to the inactivation of trypsin caused by its combination 

 with some of the products of the hydrolysis, which has been discussed 

 in the first part of this series, trypsin undergoes a second or spontane- 

 ous inactivation. This inactivation is independent of the action 

 of the enzyme, irreversible and distinct from the reversible retarda- 

 tion of the action of the enzyme by the products formed during the 

 reaction. Tammann^ clearly recognized this complicating factor and 

 attempted to correct for it, and there has since been considerable 

 discussion as to the nature and course of this reaction. The rate of 

 destruction of a number of enzymes has been studied, especially by 

 Madsen and Walbum- who found in general that the reaction was 

 monomolecular. 



The inactivation of trypsin was studied by Vernon' who found that 

 the reaction was not monomolecular but became progressively slower 

 than the rate predicted by the monomolecular formula. He con- 

 cluded therefore that the solution must contain a nimiber of dif- 

 ferent forms of the enzyme some of which were more stable than 

 others. He also found that, as is generally the case, the purity of 

 the solution had a marked influence on the rate of decomposition. As 

 will be seen from the experiments in this paper it is this factor which 

 causes the divergence from the monomolecular formula so that it is 

 unnecessary to assume the existence of a series of enzymes differing 

 in their degree of stability. 



^ Tammann, G., Z. physik. Chem., 1889, iii, 25. 

 ^ See Arrhcnius, S., Immunochemie, Leipsic, 1907. 

 3 Vernon, II. M., /. Physiol., 1904, xxx, 330. 



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