Pepsinogen

Pepsinogen is the inactive precursor (zymogen) of pepsin, a major digestive protease in the human stomach. It is synthesized and secreted by gastric chief cells into the lumen of the stomach, where under acidic conditions (pH < 5), it is autocatalytically converted into active pepsin by cleavage of an N-terminal activation peptide[1][3][5]. Pepsinogen exists in multiple forms in humans, including pepsinogen A (I), pepsinogen B, progastricsin (pepsinogen II), and others; these subfamilies differ in tissue distribution and developmental regulation[3][5]. The conversion mechanism is dependent on the acidic gastric environment, with hydrochloric acid facilitating the transition. Pepsinogen has a bilobal structure with a central active-site cleft containing two catalytic aspartates (Asp32 and Asp215) characteristic of aspartic proteases[5][10]. While pepsin is a critical enzyme for the initial digestion of dietary proteins, pepsinogen itself does not have enzymatic activity until converted. Clinically, blood levels of pepsinogen I and II are used as noninvasive biomarkers for atrophic gastritis and gastric cancer risk stratification[1]. Pepsinogen is not considered a direct therapeutic target, as its physiological and pathological significance is mainly as a precursor and diagnostic biomarker, rather than as an active biologic entity to inhibit or activate[1][8].

Other names

propepsingastric proenzymegastric zymogenproenzyme of pepsin

Drugs like pepstatin act as competitive inhibitors of the active aspartic protease (pepsin) downstream; they prevent protein substrate binding or cleavage by occupying the active site[5][7]