Pepsinogens

The proteases are secreted as inactive zymogens the active site of the enzyme is masked by a small region of its peptide chain, which is removed by hydrolysis of a specific peptide bond. Pepsinogen is activated to pepsin by gastric acid and by activated pepsin (autocatalysis). In the small intestine, trypsinogen, the precursor of trypsin, is activated by enteropeptidase, which is secreted by the duodenal epithelial cells trypsin can then activate chymotrypsinogen to chymotrypsin, proelas-tase to elastase, procarboxypeptidase to carboxypepti-dase, and proaminopeptidase to aminopeptidase. 

Alterations in other gastric secretions, such as pepsinogens and blood group substances also take place in chronic atrophic gastritis. The secretion of pepsinogen I has been used as an indicator of intestinal metaplasia and gastric cancer (21, 22). 

Gastrin G cells in pyloric region of the stomach Protein in stomach vagal stimulation Stimulates parietal cells (HC1) and chief cells (pepsinogen) in stomach enhances gastric motility... 

Pepsinogen is produced by the chief cells. Within the lumen of the stomach, this precursor molecule is split by HCl to form the active enzyme pepsin. Optimally active at an acidic pH (pH = 2), pepsin begins protein digestion by fragmenting proteins into smaller peptide chains. 

Gastrin is a hormone produced by gastric endocrine tissue — specifically, the G cells in the pyloric gland area. It is released into the blood and carried back to the stomach. The major function of gastrin is to enhance acid secretion by directly stimulating parietal cells (HC1) and chief cells (pepsinogen). Gastrin also stimulates the local release of histamine from enterochromaf-fin-like cells in the wall of the stomach. Histamine stimulates parietal cells to release HC1. 

The gastric phase is elicited by the presence of food in the stomach. Distension of the stomach wall, as well as the presence of protein, caffeine, and alcohol, enhances gastric secretion. This phase is mediated by the intrinsic nerves, the vagus nerve, and gastrin. Each of these mechanisms promotes secretion of HC1 and pepsinogen. 

Sagar, M., et al., "Omeprazole and CYP2C19 Polymorphism Effects of Long-Term Treatment on Gastrin, Pepsinogen I, and Chromogranin A in Patients with Acid Related Disorders," Aliment. Pharmacol. Then, 14, 1495-1502 (2000). 

Pepsinogen appears to be excreted in characteristic amounts by each individual. The range in excretion of pepsinogen by normals was found to be from 0 to 136 units per hour.32 The acid phosphatase activities of male urines show a range of 5 to 310 units. Women excrete less, 5 to 70 units.33... 

Consider what happens to pepsinogen near its optimal Tm of 339.4°K (66.2°C), when 20% ethanol is added to the solution (Figure 13.9). The temperature of maximum stability occurs near 300°K (26.9°C). When 20% ethanol is added, the Tm is lowered to 329.0°K (55.9°C) as expected, suggesting some destabilization of the protein between the two solution conditions. However, the temperature of maximum stability occurs at a lower temperature near 273°K... 

Figure 13.8 Temperature response trace (at optimal Tm solution conditions) of the free energy of unfolding (AGu), calculated from Equation 1. Pgen = pepsinogen, Ctsin = a-chymotrypsin, Ctgen = a-chymostrypsinogen, and papain. Note the pH conditions are listed in parentheses and the thermodynamic parameters used in Equation 1 are from those listed in Table 13.2.

Figure 13.9 Temperature response trace (at optimal Tm solution conditions) of AGu, for pepsinogen at pH 6, with and without 20% ethanol (EtOH). Labels shown are identified as Ted = cold denaturation temperature, Tms = temperature of maximum stability, and Tra...

Makarov, A.A., I.I. Protasevich, N.P. Bazhulina, and N.G. Esipova. 1995. Heat denaturation of pepsinogen in a water-ethanol mixture. FEBS Lett 357 58-61. 

The stomach secretes pepsinogens, which are inactive proteolytic enzymes, and protons - the high concentration of which initiates hydrolysis of the pepsinogens to form active pepsins, which then continue their own activation, via an autocatalytic, hydrolysis (Appendix 4.1). 

Gastric juice is the product of several cell types. The parietal cells produce hydrochloric acid, chief cells release pepsinogen, and accessory cells form a mucin-containing mucus. 

The hydrochloric acid in gastric juice is important for digestion. It activates pepsinogen to form pepsin (see below) and creates an optimal pH level for it to take effect. It also denatures food proteins so that they are more easily attacked by proteinases, and it kills micro-organisms. 

The self-activating process for converting an inactive catalyst, I, to its active form, A. Such processes typically display a discernible lag-phase followed by accelerated conversion of I to A. Zymogen activation can display autocatalysis, as exemplified by the conversion of pepsinogen to active pepsin at low pH. Many growth processes can also be described via an autocatalysis curve. 

CONTROL COEFFICIENT Convergence-point method, POINT-OF-INTERSECTION Conversion of pepsinogen to active pepsin, AUTOCATALYSIS Cooperative oxygen binding,... 

RIBULOSE-5-PHOSPHATE 3-EPIMERASE PEPSINS and PEPSINOGENS Peptide bond(s),... 

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