The Autodestruction of Pepsin in Relation to Its Ionization. By

The irreversible disappearance of the activity of pepsin in alkaline solution was first recorded by Kfihne (1). I t was confirmed by Langley (2), who observed also " tha t the destruction by sodium carbonate solutions goes on very much more slowly at 15°C. than at body temperature." Langley's experiments were carried out with neutralized filtrates of extracts of rabbit gastric mucosa made with 0.1 per cent HC1. He found no especial differences in the pepsins from the cat, dog, mole, newt, and snake. He mentions a possibility of frog pepsin being destroyed more rapidly than that of mammals. Biemacki (3) observed that the proteolytic activity of gastric juice was retained at a higher temperature in acid solution than at neutrality. This author found also that the resistance to destruction by heat was increased by the presence of peptones, and that a pure preparation was accordingly less stable than the pepsin in gastric juice. Grober (4) concluded from the average of a number of determinations that urinary pepsin heated with 0.25 per cent HC1 was destroyed at 66°C., while pepsin from the same source, dissolved in water, was destroyed at 64°C. This difference he interpreted as indicating a chemical combination between the acid and the pepsin. The combination was thought to retard the hydrolysis of the pepsin. This mechanism was considered by Grober to be the cause of the destruction of pepsin by heat. Michaelis and Rothstein (5) investigated the kinetics of the destruction of rennin and pepsin. They were unable to distinguish between these two properties of gastric juice preparations by their behaviour towards alkali. They derived an empirical differential equation in which the velocity of autodestruction was proportional to the fourth power of the hydroxyl ion concentration. They found that 451