When is pepsin active

Pepsin is one of the three main proteases in the human digestive system. It is produced in the stomach and helps digest proteins in food. The other two are chymotrypsin and trypsin.

Each digestive enzyme can cut off the relationship between specific types of amino acids, in which pepsin can effectively break down the peptide bond between hydrophobic amino acids and aromatic amino acids.

These digestive enzymes work together to break down food proteins into peptides and amino acids, which are eventually absorbed by the small intestine. Pepsinogen is the precursor of pepsin, which is released by chief cells of intestinal wall.

Its primary structure is composed of 44 amino acids. Compared with pepsin, pepsinogen is stable in neutral and weak alkaline environment, but when exposed to hydrochloric acid in gastric juice, these 44 amino acids are removed in an autocatalytic manner and activated into pepsin. Parietal cells of the gastric wall release hydrochloric acid HCl , pepsinogen can be activated by hydrochloric acid.

Gastrin and vagus nerves trigger the release of pepsinogen and hydrochloric acid from the gastric wall when eating. Hydrochloric acid produces acidic environment, which makes pepsinogen unfold and cleave in an autocatalytic manner, thus producing pepsin. Pepsin cuts 44 amino acids in pepsinogen into more pepsin. Pepsin is a chain protein monomer composed of two similar folding domains separated by a deep cleft. The catalytic site of pepsin is formed at the junction of the domain, each domain contains two aspartic acid residues, Asp32 and Asp Under the catalysis of pepsin, the water molecule helps the active carboxyl group to bear positive and negative charges with aspartic acid and aspartic acid 32, respectively, which breaks the peptide bond in the protein.

The activity of pepsin was the highest in pH2. Therefore, in the solution below pH8. The stability of pepsin at high pH value is of great significance to the diseases caused by pharynx and larynx reflux. Pepsin is one of the main causes of mucosal injury in pharynx and larynx reflux. Pepsin still stays in the pharynx and larynx after pharyngeal reflux. Although the enzyme is in a neutral environment, it can be reactivated in the subsequent acid reflux event.

The enzyme must be constructed inside the cell, but controlled in some manner so that it doesn't immediately start digesting the cell's own proteins. To solve this problem, pepsin and many other protein-cutting enzymes are created as inactive "proenzymes," which may then be activated once safely outside the cell.

Pepsin is constructed with an extra 44 amino acids, shown in green in the lower illustration from entry 3psg , which block the large active site groove and hobble the enzyme. In the stomach, this extraneous chain is clipped off and the enzyme begins its destructive campaign. For several reasons, digestive enzymes are attractive candidates for scientific study. They are easily isolated and present in large amounts in digestive juices.

They are also extraordinarily stable, because they perform their jobs under the harsh conditions present in the digestive system. The reactions catalyzed by digestive enzymes are also easily followed: you can add them to a protein such as gelatin and watch it lose its gel-like consistency.

In the 18th century, pepsin was the first enzyme to be discovered, and later, pepsin was the second enzyme to be crystallized after urease. These crystals played an important role in showing that enzymes were proteins and that they had a defined structure.

Today, the structure of pepsin, determined from similar crystals, is available in PDB entry 5pep and several others. Acid proteases: pepsin upper left , chymosin upper right , cathepsin D lower left , and endothiapepsin lower right.

Pepsin is one example of a group of enzymes termed "acid proteases. Pepsin works its best in strong hydrochloric acid. But the similarity with the other enzymes pictured here refers to a second type of acid.

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Pepsin Chymosin Renin Signal peptide peptidase Beta secretase 1 2. Plasmepsin HIV-1 protease.