The Mechanism of the Influence of Acids and Alkalies on the Digestion of Proteins by Pepsin or Trypsin. By

I t has long been known that pepsin digestion occurs only in acid solution while trypsin digestion takes place in neutral or alkaline solutions. This marked influence of the reaction on the rate of hydrolysis is a characteristic property of enzymes in general. A great advance in the explanation of this phelaomenon was made by SSrensen (1) who was able to show in the case of a number of enzymes that the controlling factor was the hydrogen ion concentration, and that the other ions present were of secondary importance. Michaelis (2) found that the curves expressing the rate of hydrolysis as a function of the pH could be accurately calculated on the assumption that the enzyme was a weak acid or base, and that the activity was due either to the ion or to the undissociated molecule, depending on the nature of the enzyme. Michaelis' experiments leave little doubt that the experimental curve is very similar to a dissociation curve. The weak point in the hypothesis is the lack of direct or independent evidence for the ionic character of the enzymes and the fact that migration experiments (3) on pure pepsin appear to contradict some of the assumptions used in the calculations. I t had been suggested by Euler (4) and by Arrhenius (5) that the ett.ect of the acid was upon the substrate rather than on the enzyme, The writer was able to show (6) that in the case of pepsin this mechanism served very well to explain the results, since it was found that the rate of hydrolysis could be quite accurately predicted from a measurement of the concentration of ionized protein and also that the pH for minimum digestion shifted with the isoelectric point of the protein. This indicates that the effect is primarily on the protein. The present paper contains 263