Pepsin zymogen

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. 

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. 

The activation of pepsin from its zymogen pepsinogen occurs by a different mechanism. In this case, the pH of the environment plays a decisive role. In the strongly acidic milieu of the stomach cleavage of a 44 amino acid peptide occurs from the inactive precursor pepsinogen. The activation is intramolecular and depends on the pH of the solution. 

Pepsin This acid-stable endopeptidase is secreted by the serous cells of the stomach as an inactive zymogen (or proenzyme), pepsinogen. In general, zymogens contain extra amino acids in... 

Specificity Each of these enzymes has a different specificity for the amino acid R-groups adjacent to the susceptible peptide bond (Figure 19.5). For example, trypsin cleaves only when Ihe carbonyl group of the peptide bond is contributed by arginine or lysine. These enzymes, like pepsin described above, are synthesized and secreted as inactive zymogens. 

In the stomach, hydrochloric acid denatures dietary proteins, making them more susceptible to proteases. Pepsin, an enzyme secreted in zymogen form by the serous cells of the stomach, releases peptides and a few free amino acids from dietary proteins. 

Pepsin (EC 3.4.23.1) is a typical aspartic proteinase produced in the gastric mucosa of vertebrates as a zymogen form [10], This enzyme has been extensively characterized, and its three-dimensional structure has been determined at high resolution. Porcine pepsin, in particular, has been studied as model to analyze the structure-function relationship of the aspartic proteinases. Although the aspartic proteinases including mammalian and fungal enzymes are quite similar in their three-dimentional structures, there are drastic differences in the catalytic properties, especially in substrate specificities. 

The destructive potential of proteases means that their activity has to be tightly regulated to prevent autolysis of protease-producing cells. Thus digestive proteases such as chymotrypsin, pepsin and trypsin are produced as inactive zymogens (proenzymes) and are subsequently activated after secretion. The serine protease-catalysed process of blood clotting involves a cascade of successive proteolytic activations of the blood clotting factor proteases involved [2-6]. 

Aspartic proteases include the gastric proteases pepsin A, pepsin B, gastricsin and chymosin that are secreted as inactive zymogens and are activated through removal of autoinhibitory domains in the low pH conditions of the stomach [7-9]. Oesophagitis is caused by undue... 

The entry of protein into the stomach stimulates the release of a hormone, gastrin, which then causes the release of hydrochloric acid from the parietal cells, and pepsinogen from the chief cells (Fig. 15-5). Pepsinogen is another zymogen (they all start with pro- or end in -ogen) that is converted in the gastric juice to the active enzyme pepsin. 

It is now well known that the mammalian enzymes pepsin, gastricsin, and chymosin are secreted by the respective organisms as zymogens which are activated by the removal of over 40 residues from the N-terminal end. 

Activation of a zymogen. Some enzymes are secreted as inactive precursors, called zymogens. Trypsin and pepsin are two such examples a portion of the zymogen must be cleaved off to form the active enzyme. Again, an on/ off switch more than a tight, variable regulation. 

The activation of pepsinogen is thought to occur by two different mechanisms intramolecular, in which the zymogen acts on itself to generate pepsin, and inter-molecular, in which one molecule of pepsin acts on a molecule of pepsinogen to convert it to pepsin. 

A. Pepsin is produced as pepsinogen (a zymogen), which is initially cleaved by HC1 to form the active protease. Subsequently, pepsin autocatalyses its own activation. 

Protein digestion begins in the stomach, where protein is denatured by the low pH and is exposed to the action of pepsin. The low pH also provides the optimal H+ concentration for pepsin activity. The zymogen precursor pepsinogen (M.W. 40,000) is secreted by the chief cells and is converted to pepsin (M.W. 32,7(K)) in the acid medium by removal of a peptide consisting of 44 amino acid residues. This endopeptidase hydrolyzes peptide bonds that involve the carboxyl group of aromatic amino acid residues, leucine, methionine, and acidic residues (Table 12-5). The products consist of a mixture of oligopeptides. 

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