Difference Between Pepsin and Pepsinogen

Pepsin vs Pepsinogen

Both pepsin and pepsinogen are protein in origin and are found in the gastric juice of mammals. Since, pepsinogen is the precursor of pepsin; it is necessary to have pepsinogen with an acidic environment or previously formed pepsin to produce pepsin in the stomach. These two compounds are important to carry out the first digestion steps of protein digestion. When, pepsinogen, a folded single peptide chain, is converted to pepsin, there are some changes in the physical and chemical properties of the protein.


Pepsin is the active form of pepsinogen that hydrolyzes proteins during the digestion process. To form pepsin from pepsinogen, it is necessary to have either an acidic environment (pH< ~5) or presence of previously formed pepsin. Pepsin is a proteolytic enzyme that splits protein into proteoses, peptones, and polypeptides. Porcine pepsin A is the most studied and commercially available pepsin, which is isolated from the gastric mucosa of pigs.

Pepsin is made up with 6 helical sections, and each section contains less than 10 amino acids. Also, it has very few basic amino acid residues and 44 acidic residues. Because of that, it is very stable at extremely low pH. Apart from that, the complex tertiary structure and hydrogen bonds also support to its structure’s acidic stability. A cascade of change in the bond structure in a pepsinogen molecule leads to produce pepsin with the low pH environment. The conversion process has five steps. The first step of the process is reversible while the rest are irreversible. So that, once it passes the second step, the protein cannot revert back to pepsinogen.


Pepsinogen is an inactive proenzyme which is used to form pepsin for digestion of proteins. It has an additional 44 amino acids on its N-terminus that are released during the transformation. There are two forms of pepsinogen, namely; pepsinogen I and pepsinogen II, depending on the site of secretion.

Pepsinogen I is secreted by chief cells, and pepsinogen II is secreted by pyloric glands. The secretion of pepsinogen is stimulated by vagal stimulation, gastrin, and histamine. Pepsinogen I is mainly found in the body of the stomach, where most acid is secreted. Pepsinogen II is mainly found in both body and antrum of the stomach.

What is the difference between Pepsin and Pepsinogen?

• Pepsin is a proteolytic enzyme, whereas pepsinogen is a proenzyme.

• Pepsin is the active form of pepsinogen while pepsinogen is the inactive precursor of pepsin.

• Unlike the pepsin, pepsinogen is secreted by chief cells and pyloric glands.

• Pepsinogen is converted to pepsin by hydrochloric acid or performed pepsin.

• Unlike the pepsin, pepsinogen secretion is stimulated by vagal simulation, gastrin, and histamine.

• Pepsinogen is stable in both neutral and alkaline solutions, whereas pepsin is not.

• Unlike pepsinogen, pepsin can hydrolyze proteins.

• Pepsin can be activated by lowering the pH of the medium, whereas pepsinogen cannot.

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