Pepsin: Structure, Functions, Production

The  pepsin is an enzyme present in gastric juice powerful to aid in the digestion of proteins. It is actually an endopeptidase whose main task is to break down food proteins into small parts known as peptides, which are then absorbed by the intestine or degraded by pancreatic enzymes.

Although it was isolated for the first time in 1836 by the German physiologist Theodor Schwann, it was not until 1929 that the American biochemist John Howard Northrop, of the Rockefeller Institute for Medical Research, reported its actual crystallization and part of its functions, which would help him receive the Nobel Prize in Chemistry 17 years later.


This enzyme is not unique to humans. It is also produced in the stomach of several animals and acts from the early stages of life, collaborating in the digestion of proteins from dairy products, meats, eggs and grains, mainly.


The main cells of the stomach produce an initial substance called pepsinogen. This proenzyme or zymogen is hydrolyzed and activated by gastric acids, losing 44 amino acids in the process. Ultimately, pepsin contains 327 amino acid residues in its active form, which performs its functions at the gastric level.

The loss of these 44 amino acids leaves an equal number of acid residues free. It is for this reason that pepsin works best in very low pH media.


As already mentioned, the main function of pepsin is the digestion of proteins. Pepsin activity is higher in highly acidic environments (pH 1.5-2) and with temperatures ranging between 37 and 42┬║C.

Only a portion of the proteins that reach the stomach are degraded by this enzyme (approximately 20%), forming small peptides.

The activity of pepsin is mainly focused on the hydrophobic N-terminal bonds present in aromatic amino acids such as tryptophan, phenylalanine and tyrosine, which are part of many proteins from food.

A function of pepsin that has been described by some authors takes place in the blood. Although this claim is controversial, it appears that small amounts of pepsin pass into the bloodstream, where it acts on large or partially hydrolyzed proteins that were absorbed by the small intestine before they were fully digested.

How is it produced?

Pepsinogen secreted by the main cells of the stomach, also known as zymogen cells, is the precursor to pepsin.

This proenzyme is released thanks to impulses from the vagus nerve and the hormonal secretion of gastrin and secretin, which are stimulated after the ingestion of food.

Already in the stomach, pepsinogen mixes with hydrochloric acid, which was released by the same stimuli, rapidly interacting with each other to produce pepsin.

This is carried out after the cleavage of a 44 amino acid segment of the original pepsinogen structure through a complex autocatalytic process.

Once active, the same pepsin is able to continue stimulating the production and release of more pepsinogen. This action is a good example of positive enzyme feedback.

In addition to pepsin itself, histamine and especially acetylcholine stimulate peptic cells to synthesize and release new pepsinogen.

Where does it operate?

Its main site of action is the stomach. This fact can be easily explained by understanding that heartburn is the ideal condition for its performance (pH 1.5-2.5). In fact, when the food bolus passes from the stomach to the duodenum, the pepsin is inactivated by encountering an intestinal medium with basic pH.

Pepsin also works in the blood. Although this effect has already been said to be controversial, certain researchers claim that pepsin passes into the blood, where it continues to digest certain long-chain peptides or those that have not been fully degraded.


When pepsin leaves the stomach and is in an environment with a neutral or basic pH, its function ceases. However, as it is not hydrolyzed, it can be activated again if the medium is reacidified.

This characteristic is important to understanding some of the negative effects of pepsin, which are discussed below.

Gastroesophageal reflux

The chronic return of pepsin into the esophagus is one of the main causes of the damage produced by gastroesophageal reflux. Although the rest of the substances that make up gastric juice are also involved in this pathology, pepsin seems to be the most harmful of all.

Pepsin and other acids present in reflux can cause not only esophagitis, which is the initial consequence, but affect many other systems.

Potential consequences of pepsin activity on certain tissues include laryngitis, pneumonitis, chronic hoarseness, persistent cough, laryngospasm, and even laryngeal cancer.

Asthma due to pulmonary microaspiration of gastric contents has been studied. Pepsin can have an irritating effect on the bronchial tree and favor the constriction of the respiratory tract, triggering the typical symptoms of this disease: respiratory distress, cough, wheezing and cyanosis.

Other effects of pepsin

The oral and dental spheres can also be affected by the action of pepsin. The most frequent signs associated with these damages are halitosis or bad breath, excessive salivation, granulomas and dental erosion. This erosive effect usually manifests itself after years of reflux and can damage the entire teeth.

Despite this, pepsin can be useful from a medical point of view. Thus, the presence of pepsin in saliva is an important diagnostic marker for gastroesophageal reflux.

In fact, there is a rapid test available on the market called PepTest, which detects the presence of pepsin saliva and helps in the diagnosis of reflux.

Papain, an enzyme very similar to pepsin present in papayas or papayas, is useful in hygiene and teeth whitening.

In addition, pepsin is used in the leather industry and classic photography, as well as in the production of cheeses, cereals, snacks, flavored drinks, predigested proteins and even chewing gums.


  1. Liu, Yu et al (2015). Digestion of Nucleic Acids Starts in the Stomach. Scientific Reports, 5, 11936.
  2. Czinn, Steven and Sarigol Blanchard, Samra (2011). Developmental Anatomy and Physiology of the Stomach. Pediatric Gastrointestinal and Liver Disease, Fourth Edition, Chapter 25, 262-268.
  3. Smith, Margaret and Morton, Dion (2010). The Stomach: Basic Functions. The Digestive System, Second Edition, Chapter 3, 39-50.
  4. Wikipedia (last edition May 2018). Pepsin . Recovered from:
  5. Encyclopaedia Britannica (last edition May 2018). Pepsin . Recovered from:
  6. Tang, Jordan (2013). Pepsin A. Handbook of Proteolytic Enzymes, Chapter 3, Volume I, 27-35.

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