Pepsin is an endopeptidase that breaks down proteins into smaller peptides.
It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive system.
It helps digest the proteins in food.
It is an aspartic protease.
One of three principal proteases in the human digestive system, the other two being chymotrypsin and trypsin.
These enzymes, sever links between particular types of amino acids, collaborate to break down dietary proteins into their components: peptides and amino acids.
Peptides and amino acids can then be readily absorbed by the small intestine.
Pepsin’s proenzyme, is pepsinogen zymogen.
Pepsinogen is released by the gastric chief cells in the stomach wall, and upon mixing with the hydrochloric acid of the gastric juice, pepsinogen activates to become pepsin.
The zymogen pepsinogen, whose primary structure has an additional 44 amino acids compared to the active enzyme pepsin.
The gastric chief cells release pepsinogen, the zymogen, which is activated by hydrochloric acid (HCl), which is released from parietal cells in the stomach lining.
The hormone gastrin and the vagus nerve trigger the release of both pepsinogen and HCl from the stomach lining when food is ingested.
Hydrochloric acid creates an acidic environment, which allows pepsinogen to unfold and cleave itself in an autocatalytic fashion, thereby generating pepsin, its active form.
Pepsin cleaves the 44 amino acids from pepsinogen to create more pepsin.
Pepsinogens are grouped in 5 different structural group:
pepsinogen A (also called pepsinogen I)
pepsinogen B, progastricsin (also called pepsinogen II
pepsinogen C, prochymosin (also called prorennin)
pepsinogen F (also called pregnancy-associated glycoprotein).
Pepsin is most active in an acidic environment, between pH 1.5 to 2.5.
The concentration of pepsin in the stomach reaches 0.5 – 1 mg/mL.
It is inactivated at pH 6.5 and above, and fully denatured or irreversibly inactivated at pH 8.0.
Pepsin in solutions of up to pH 8.0 can be reactivated upon re-acidification.
The stability of pepsin at high pH has significant implications on disease attributed to laryngopharyngeal reflux.
Pepsin remains in the larynx following a gastric reflux event.
At the mean pH of the laryngopharynx (pH = 6.8) pepsin would be inactive but could be reactivated upon subsequent acid reflux events,
Pepsin digests up to 20% of ingested amide bonds: the P1 and P1′ positions are most important in determining cleavage probability.
Pepsin is one of the primary causes of mucosal damage during laryngopharyngeal reflux.
It remains in the larynx at pH 6.8,
, following a gastric reflux event.
Pepsin remains stable and could be reactivated upon subsequent acid reflux events.
The exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in reduced expression of protective proteins and thereby increases laryngeal susceptibility to damage.
It may also cause mucosal damage during weakly acidic or non-acid gastric reflux.
Under non-acid conditions pepsin is internalized by cells of the upper airways such as the larynx and hypopharynx by receptor-mediated endocytosis.
The cellular pepsin uptake is stored in intracellular vesicles of low pH which restores its enzymatic activity
Intracellular pepsin is retained within the cell for up to 24 hours.
It is the exposure to pepsin at a neutral pH and it’s endocytosis that causes gene expression alterations associated with the inflammation, which underlies the findings and symptoms of reflux.
It also explains the implication of pepsin in carcinogenesis attributed to gastric reflux.
Pepsin in airway specimens is considered to be a sensitive and specific marker for laryngopharyngeal reflux.
Testing (Peptest) is available to determine the presence of pepsin in saliva samples.
Pepsin may be inhibited by high pH or by inhibitor compounds.
Pepstatin is a low molecular weight compound and potent inhibitor specific for pepsin.
Pepstatin inhibition of pepsin is reversible.
Sucralfate, also inhibits pepsin activity.
Pepsin is used in food manufacturing, providing whipping qualities to soy protein and gelatin, to modify vegetable proteins for snack items, to make precooked cereals into instant hot cereals, and to prepare animal and vegetable protein hydrolysates for use in flavoring foods and beverages.
Pepsin is used in the leather industry to remove hair and residual tissue from hides and in the recovery of silver from discarded photographic films by digesting the gelatin layer that holds the silver.
Pepsin is used in the preparation of F(ab’)2 fragments from antibodies by digesting IgG.
The following three genes encode identical human pepsinogen A enzymes:
pepsinogen 3, group I (pepsinogen A)
A fourth human gene encodes gastricsin also known as pepsinogen C: