Gastric proteolysis in disease. I. The proteolytic activity of gastric juice from patients with pernicious anaemia.

Fenwick (1870) was the first to discover that patients with pernicious anaemia have a deficiency of gastric pepsin, and this observation has been amply confirmed (Stockton, 1904; Levine and Ladd, 1921 ; Teschendorf, 1927; Faber, 1927; Faber and Holst, 1928 ; Johansen, 1929; Polland and Bloomfield, 1930; Castle, Heath, and Strauss, 1931 ; Davies, 1931 ; Wilkinson, 1932; Helmer, Fouts, and Zerfas, 1932; Hartfall, 1933; Maltby, 1934; Griffiths, 1934; Mullins and Flood, 1935; lhre, 1938; Witebsky, Klendshoj, and Vaughan, 1942; Janowitz and Hollander, 1951; Aitken, Spray, and Walters, 1954). Pepsin secretion is usually either absent or slight, whether the gastric juice is obtained in the resting state or after stimulation with histamine or insulin. Low values are still obtained when the stomach is washed with dilute HCI during the collection of juice in order, to prevent the inactivation of pepsin at the neutral pH of gastric secretion in pernicious anaemia (Ihre, 1938). Occasionally patients have been observed who, despite achlorhydria, secrete appreciable though still subnormal amounts of pepsin (Faber, 1927; Davies, 1931 ; Hartfall, 1933 ; Griffiths, 1934; Jones and Wilkinson, 1938; Aitken, Spray, and Walters, 1954; Taylor, 1956). The proteolytic activity of the gastric juice in pernicious anaemia has also been investigated at neutral pH. In contrast to the mild proteolysis observed with normal gastric juice, no activity or decreased activity has been reported by Griffiths (1934), Helmer, Fouts, and Zerfas (1932), Lasch (1937), and Taylor, Castle, Heinle, and Adams (1938). Slight activity, which does not significantly differ from that of normal subjects, has been observed by Maltby (1934), Emerson and Helmer (1936), Jones, Grieve, and Wilkinson (1938), and Gessler, Dexter, Adams, and Taylor (1940). In all this work there has been an underlying assumption that the differences which exist between normal gastric juice and that from patients with pernicious anaemia result from a simple quantitative deficiency of normal proteolytic activity. Usually determinations of proteolytic activity have only been carried out at pH 2.0 or pH 7.4. Only one pH activity curve for proteolysis by gastric juice from a patient with pernicious anaemia has been reported (Jones and Wilkinson, 1938). This showed a single maximum at pH 2.2, but no determinations were made between pH 3 and 4 where a second peak occurs in normal subjects (Taylor, 1959a). The possibility that the gastric juice in pernicious anaemia may contain different enzymes from normal gastric juice or differing proportions of normal enzymes does not seem to have been considered. An investigation of this possibility is now described.