Where is pepsinogen produced

Pepsinogen II is produced primarily in the Oxyntic gland mucosa of the stomach, the gastric antrum and the duodenum. It is secreted mainly into the gastric lumen and into circulation.

Pepsinogen II has little or no biological activity but in acid is converted to the active enzyme Pepsin which exhibits proteolytic actions. Patients with pernicious anemia have low to non-detectable levels of Pepsinogen I but normal levels of Pepsinogen II. Pepsinogen II levels are slightly elevated in gastric ulcer. Patients with Zollinger-Ellison's syndrome exhibit greatly elevated levels.

The mature, active enzymes are roughly amino acids with a mass of approximately 35 kDa. Pepsins are synthesized as inactive pre-proenzymes, consisting of a signal peptide, activation peptide and active enzyme.

The signal peptide is cleaved as the protein is inserted into endoplasmic reticulum and the resulting proenzyme - pepsinogen - is transported to the Golgi and condensed into secretory granules. Pepsinogens are secreted in a form such that the activation peptide assumes a compact structure that occludes the active site. On exposure to an acidic pH the activation peptide is cleaved, thereby unmasking the active site and generating catalytically-active pepsin.

Optimal activity of pepsins is at pH of 1. They are reversibly inactivated at about pH 5 and irreversibly inactivated at pH 7 to 8. In general, secretion of pepsinogens is coupled to secretion of acid from the parietal cell.