The digestive enzyme, pepsin, has received considerable attention for hundreds of years. Recent analyses have led to an increased understanding of the molecule's biochemical, physicochemical, and immunochemical characteristics. Many currently believe that the enzyme plays an etiologic role in ulcer development.
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 distension whenever there is food in the stomach (6:268). This physiological mechanism is mediated through parasympathetic pathways located in the vagus nerve (2:419). In the presence of acidic pH, pepsinogen undergoes a multistage activation process, or "autocatalysis." Intramolecular cleavage by the pepsin active site converts the pepsinogen to proteolytic pepsin. This transformation essentially involves splitting about nine peptide bonds. There is a loss of a variable number of amino a...