pH stability and activity curves of pepsin with special reference to their clinical importance.

In the past the maintenance of the pH of the gastric contents above pH 7 has been discouraged by British Pharmacopoeia (1963). The Pharmaceutical Press, London. pp. 33.

Card, W. I. (1952). Aetiology (of peptic ulcer). In Modern Trends in the concept of acid rebound. Recent investigations have, however, shown that this phenomenon does not occur (Pereira-Lima and Hollander, 1959a and b; Gastroenterology, 1st series, edited by F. Avery Jones, pp. 380-

Butterworth, London. and Sircus, W. (1958). Anacidity. In Modern Trends in Gastroenterology, 2nd series, edited by F Avery Jones, pp. 177-192. Gillespie, 1959). Probably too, in deference to this concept, some methods of antacid assay have Butterworth, London.

Christensen, L. K. (1955). Concerning the pH optimum of peptic hydrolysis. Arch. Biochem., 57, 163-173.

stipulated that the pH of the reaction mixture must not be elevated above 5 by the antacid (Brit. Pharm., Ege, R. (1923). Eine Modifikation des Fuldschen Verfahrens zur Bestimmung von Pepsin. Hoppe-Seylers Z. physiol. Chem., 127, 125-136.

). The observations in this study show that elevation of the pH of the gastric contents above 8, even if transiently, not only inhibits peptic activity but leads to irreversible denaturation of pepsin. This is clearly an effect which antacid therapy should aim

-and Menck-Thygesen, P. (1933). Ober die Aktivierung des

Fruton, J. S., and Simmons, S. (1958). General Biochemistry, 2nd ed., p. 272. Wiley, New York.

Gillespie, I. E. (1959). Influence of antral pH on gastric acid secretion in man. Gastroenterology, 37, 164-168.

Hollander, F. (1939). What constitutes effective neutralization of to achieve, assuming this effect can be attained without systemic effects.

Kahn, J. R. (1937). Absence of peptic ulcer in pernicious anemia.

The pH activity curve constructed in this study shows that the pH of the reaction mixture (or gastric juice) must be above pH 55 if complete inactivation of pepsin is to be produced. This is higher than thepH level usually considered essential; Hollander in 1939

Klotz, A. P., and Duvall, M. R. (1957). The laboratory determination of pepsin and gastric juice with radioactiveiodinated albumin.

Langley, J. N. (1881a). On the histology of the mammalian gastric glands, and the relation of pepsin to the granules of the chief-cells. J. Physiol. (Lond.), 3, 269-291.

Langley, J. N. (1881b). On the destruction of ferments in the alimentary canal.

LeVeen, H. H. (1947). Chemical, physiological, and pathological observations on the role of pepsin and hydrochloric acid in the findings of considerable peptic activity in the pH range of pH 4-5 are consistent with the observations of Taylor (1959a, b and c) who found that in many preparations containing pepsin considerable peptic activity was still present in the pH range above 4.5.

Michaelis, L. (1918). Die Bestimmung und Bedeutung der Fermente im Magensaft. Dtsch. med. Wschr., 44, 685-689.

Northrop, J. H., Kunitz, M., and Herriott, R. M. (1948). Crystalline

Enzymes, 2nd ed., Columbia University Press, New York. Pereira-Lima, J., and Hollander, F. (1959a). Gastric acid rebounda review. Gastroenterology, 37, 145-153.

Enzymes, 2nd ed., Columbia University Press, New York. Pereira-Lima, J., and Hollander, F. (1959b). Basal secretion of gastric acid following administration of alkali (acid rebound). Ibid., 37, 154-157. PEPTIC ACTIVITY IN ACHLORHYDRIC STATES Pepsin is Piper, D. W. (1960). The estimation of peptic activity in gastric secreted as pepsinogen; the conversion of pepsinogen to pepsin begins slowly at pH 6 and is almost instantaenous atpH 2-0 (Ege, 1923; Ege and MenckThygesen, 1933). Accepting achlorhydria as defined by Card and Sircus (1958) as failure of the pH to drop below 6-0 after maximal histamine stimulation, pepsinogen would only be converted to pepsin to a juice using radioiodinated serum albumin as substrate. Ibid., 38, 616-621.

Schiffrin, M. J. (1940). Production of experimental jejunal ulcer. Proc. Soc. exp. Biol. (N. Y.), 45, 592-594.

Schiffrin, M. J. and Warren, A. A. (1942). Some factors concerned in the production of experimental ulceration of the G-I tract in cats. Amer. J. dig. Dis., 9, 205-209.

Taylor, W. H. (1959a). Studies on gastric proteolysis. I. The proteolytic activity of human gastric juice and pig and calf gastric mucosal extracts below pH 5. Biochem. J., 71, 73-83.

-(1959b). Gastric proteolysis in disease. II. The proteolytic activity of gastric juice and gastric mucosal extracts from patients with chronic gastric and duodenal ulcer. J. clin. Path., 12, 338-343.

-(1959c). Gastric proteolysis in disease. III. The proteolytic activity of gastric juice in chronic hypochromic anaemia and in idiopathic steatorrhoea. Ibid., 12, 473476.