<P> Pepsin is expressed as a zymogen called pepsinogen, whose primary structure has an additional 44 amino acids . </P> <P> In the stomach, chief cells release pepsinogen . This zymogen 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 (the active form). Pepsin cleaves the 44 amino acids from pepsinogen to create more pepsin . </P> <P> Pepsin is most active in acidic environments between 37 ° C and 42 ° C. Accordingly, its primary site of synthesis and activity is in the stomach (pH 1.5 to 2). Pepsin will digest up to 20% of ingested amide bonds by cleaving preferentially at the C - terminal side of aromatic amino acids such as phenylalanine, tryptophan, and tyrosine . Pepsin exhibits preferential cleavage for hydrophobic, preferably aromatic, residues in P1 and P1' positions . Increased susceptibility to hydrolysis occurs if there is a sulfur - containing amino acid close to the peptide bond, which has an aromatic amino acid . Pepsin cleaves Phe Val, Gln His, Glu Ala, Ala Leu, Leu Tyr, Tyr Leu, Gly Phe, Phe in the insulin B chain . Pepsin exhibits maximal activity at pH 2.0 and is inactive at pH 6.5 and above, however pepsin is not fully denatured or irreversibly inactivated until pH 8.0 . Therefore, pepsin in solution 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 resulting in damage to local tissues . </P> <P> Pepsin is one of the primary causes of mucosal damage during laryngopharyngeal reflux . Pepsin remains in the larynx (pH 6.8) following a gastric reflux event . While enzymatically inactive in this environment, pepsin would remain stable and could be reactivated upon subsequent acid reflux events . 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 . </P>

Where is pepsin most active in the body