Pepsin: Structure and Function The digestive en

About 200 years ago, scientists first observed the ability of gastric juice to digest proteins. It wasn't until 1836 though that Schwann demonstrated that the activity required both acid and a "ferment" substance (7:215-221). This ferment material was called pepsin, after, "pepsis," the Greek word for "digestion." Then, about 46 years later, Heidenhain discovered the origins of gastric juice: he observed that the gastric mucosa contained specialized cells which secreted acid and pepsin (4:743-750). Between 1881 and 1886, Langley performed a series of classical experiments describing the cycle of zymogen cells, or peptic cells, and their granules. Moreover, Langley also isolated and crystallized the granules' contents: i.e., the peptide precursor, pepsinogen.

It is now known that the inactive precursor of pepsin, pepsinogen, is synthesized by the gastric mucosa's chief cells (7:215-221). In addition to being secreted into the gastrointestinal lumen, pepsinogen is also released into the circulation. For example, it is typically found in both blood and urine. The secretion of pepsinogen is stimulated by gastrointestinal

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optimally at different pH ranges. For example, optimal digestion of either hemoglobin or albumin occurs within a pH range of 1.8 to 2.3. In contrast, pepsin has maximum milk clotting ability at a pH of 5.5 (4:743-750). Once activated, the enzyme is irreversibly denatured by the following: (a) pH above 7.2; (b) temperatures above 65(C; or (c) high concentrations of urea. The precursor pepsinogen, however, can withstand a pH as high as 10 and temperatures up to boiling for salt-free solutions. In recent decades, scientific investigation has revealed considerable heterogeneity among both pepsin and pepsinogen. For instance, it is now known that there are 2 major types of pepsinogen: pepsinogen I and pepsinogen II (7:215-221). In addition, each of these 2 classes of pepsinogen each consists of molecular variants, or isozymogens, which differ in net ionic charge and immunologic characteristics. In total, there appear to be 7 pepsinogens. Pepsins 1, 2, 3, 3a, and 4 correspond to pepsinogen I (i.e., pepsinogen isozymogens, Pg1-5); whereas, pepsins 5 and 6 derive from pepsinogen II (i.e., pepsinogen isozymogens Pg6 and Pg7) (1:50-54). The isozymogens of pepsinogen I have a more acidic net negative charge than those pepsinogen
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