Human beings and other animals are open systems, since we require the intake of organic matter to obtain energy. 50% of our diet is made up of carbohydrates, 30% of fats and 10-15% of proteins.
All of these macronutrients are broken down through hydrolysis into small biomolecules which cross the plasma membrane of cells and are oxidized in the mitochondrial environment, in order to obtain energy for all tissues and reactions necessary for life.
Digestion, known as the process by which food is transformed in the digestive system into a substance that the body assimilates, is essential so that the food ends up converted into energy and metabolic heat. To do this, the food is ingested through the mouth, subjected to a series of mechanical and chemical changes, transported to the stomach, then to the intestines and, finally, the waste is ejected into the environment in the form of feces.
This general process describes the passage of food through the digestive system in an extremely brief way, but it should be noted that each of these sections of the system is characterized by a series of chemical and physical reactions of great interest. Today we tell you everything about pepsin, one of those essential enzymes to understand digestion at the gastric level
First of all, it is necessary to highlight that pepsin is an endopeptidase, that is, an enzyme that breaks down the proteins obtained in dietary intake into smaller peptides. This type of enzymatic molecules break the peptide bonds between amino acids within the protein chain, following a series of very specific guides. Pepsin is not the only endopeptidase responsible for digestion, since trypsin, chymotrypsin, elastase or thermolysin, among others, also stand out in this group.
Despite the variety of endopeptidases in the gastric environment, pepsin is considered one of the most important, along with trypsin and chymotrypsin Furthermore, its action environment is very clear and delimited: it works at its greatest effectiveness between a pH of 1.5 and 2, the exact ideal conditions of the stomach. Once it reaches the duodenum portion (with a pH of 6), this enzyme is inactivated and its functionality comes to an end (although it maintains its three-dimensional conformation up to a pH of 8).
In any case, it is necessary to clarify that protein digestion also continues at the intestinal level, due to the effects of pancreatic enzymes such as trypsin, chymotrypsin, elastase and carboxypeptidase. Thus, despite its essentiality, pepsin is not essential for life: if this enzyme is missing, others can take care of protein metabolism, with more or less effort.
Curiously, The enzymatic activity of pepsin and other enzymes could self-degrade the body’s own tissue if preventive mechanisms did not exist clear and effective. Luckily, the stomach’s mucosal barrier secretes a mucus-bicarbonate type substance, which gives the gastric wall a nearly neutral pH environment and deactivates pepsin. The stomach itself must be protected from the enzymatic activity taking place within it, as counterintuitive as it may sound.
The synthesis of pepsin
Pepsin is synthesized in the stomach, as we have suggested in previous lines. Anyway, stomach cells (main cells of the gastric glands) do not secrete pepsin itself, but rather pepsinogen This compound is a zymogen or inactive proenzyme, containing 44 “extra” amino acids, compared to the real enzyme.
The hormone gastrin, secreted by the G cells of the gastric apparatus, stimulates the secretion of pepsinogen and hydrochloric acid, which generates a very acidic pH environment within the stomach chamber. When pepsinogen comes into contact with this acidic conglomerate, it undergoes an autocatalytic reaction, in which it is freed from the “tail” of amino acids that kept it inactive. Thus, thanks to the presence of stomach acids, pepsinogen is transformed into its active variant pepsin and this can begin to break down proteins into smaller molecules.
Furthermore, it is necessary to point out that pepsinogen is synthesized thanks to the instructions present in the genes, that is, chromosomes inside cells. In humans, there are 3 different genes that code for the same form of pepsinogen A: PGA3, PGA4 and PGA5. All of them have directions for the synthesis of zymogen, which is then transformed into the enzyme by the stimulation of gastric acids.
On the other hand, some compounds (such as pepstatin) are capable of inhibiting pepsin at very low concentrations Pepstatin was first isolated in cultures of actinomycete fungi, but little else is known about it beyond its activity as a protease.
Pepsin function
At this point, it is essential to highlight that Pepsin is dedicated to breaking down proteins, but since it is made up of amino acids, this enzyme is also a protein in itself Amino acids are the basic unit of all proteins, as they are joined in specific orders through peptide bonds to give rise to peptides (less than 10 amino acids), polypeptides (10 to 50 amino acids) and proteins (more than 50 amino acids).
For its part, pepsin “cuts” the protein chain that is to be degraded at the level of the amino acids leucine (leu), phenylalanine (phe), tryptophan (trp) or tyrosine (tyr), unless one of them is preceded by proline. (pro). We remember that it is an endopeptidase, which means that it cuts “from the inside” (between amino acids that are not part of the terminal protein section).
Proteins only make up 10-15% of our diet (since carbohydrates are the richest source of energy), but they make up 50% of the dry weight of almost all biological tissues, since there is no metabolic process that does not depend in a way of them. This is why pepsin and the rest of the enzymes that degrade proteins are so essential: not only for obtaining energy, but for the integration of amino acids into biological tissues, such as muscles and skin
The role of pepsin in pathologies
Like every element in the human body, pepsin can fail or perform activities at times when it is not necessary, which leads to pathologies. In this case, this and other enzymes play an essential role in the development of symptoms of laryngopharyngeal reflux (LPR) and gastroesophageal reflux (GERD)
A person with a weakened lower esophageal sphincter (LES) may experience these conditions, since the bolus mixed with gastric juices retreats into the esophagus if the stomach environment is not well defined. This causes acids, pepsin and other enzymes to travel backwards through the esophageal tube, even reaching the larynx and, in the worst cases, the lung environment.
To further complicate matters, patients with LPR have altered local neural sensitivity, so they cannot respond with coughs and rales to the presence of acid in the laryngeal environment. Being in its active form and not being excreted, Pepsin begins to break down the laryngeal tissues, which results in chronic dysphagia (inability to swallow), hoarse voice, and repeated coughs The more pepsin is in contact with the laryngeal environment, the worse the damage will be.
Summary
As you may have seen, pepsin is a very interesting enzyme on a physiological level, since it autoactivates itself with the acidic environment of the stomach and its functionality is regulated completely dependent on the environmental pH. If the pH is maintained between 1.5 and 2, the enzyme remains in its active form and does its job. When this value changes, it maintains its three-dimensional conformation, but it does not break down the proteins like inside the stomach.
Thanks to pepsin and many other biomolecules of an enzymatic nature, human beings can transform the proteins we consume into energy and, above all, into amino acids useful for the formation and repair of tissues. Of course, it is clear to us that without our internal metabolism we are nothing.
