Tration for the Digestion of Proteins by Pepsin. by John H. Northrop

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. SSrensen 1 showed that for a number of enzymes the determiuing 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 therefore 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 3 and by Nasse. 4 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