THE SIGNIFICANCE OF THE HYDROGEN ION CONCEN- 

 TRATION FOR THE DIGESTION OF PROTEINS 

 BY PEPSIN. 



By JOHN H. NORTHROP. 



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



(Received for publication, September 25, 1920.) 



One of the most striking peculiarities of enzyme action is the fact 

 that the activity of the enzyme is limited to a definite range of acidity. 

 If the solution is more or less acid than this the enzyme is practically 

 inactive. Sorensen^ showed that for a number of enzjones the 

 determining factor was the hydrogen ion concentration and not the 

 total acidity of the solution. 



In attempting to account for this phenomenon it has usually been 

 assumed that the influence of the hydrogen ion concentration was 

 exerted upon the enzyme. Michaelis^ pointed out, in the case of 

 many enzymes, that if the activity of the enzyme was plotted against 

 the hydrogen ion concentration of the solution the curve resembled 

 strikingly that obtained when the ionization of a salt of a weak base 

 and a strong acid was plotted in the same way. He concluded there- 

 fore that enzymes were weak bases or acids which formed salts with 

 the acids or bases of the solution. These salts then dissociated into 

 ions and the ions so formed were the active agents in the reaction. 

 A similar explanation had already been proposed independently by 

 Loeb^ and by Nasse.^ Michaelis' work rendered the hypothesis 

 quite plausible. In the case of pepsin, however, it meets with several 

 serious objections. In the first place, one of the strongest points of 

 Michaelis' experiments was the fact that pepsin was found to have 

 an isoelectric point at about pH 3.0 which agreed fairly well with the 



^ Sorensen, S. P. L., Biochem. Z., 1909, xxi, 131. 

 ^ Michaelis, L., Die Wasserstoffionenkonzentration, Berlin, 1914, 58. 

 ^Loeb, J., Biochem. Z., 1909, xix, 534. 

 ^ Nasse, 0., Malys Jahrb., 1894, xxiv, 718. 



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