Pepsin A-5 (PGA5)

Pepsin A-5 is an aspartic-type endopeptidase encoded by the human PGA5 gene, synthesized and secreted by chief cells in the stomach in the inactive precursor form pepsinogen-5. Under acidic conditions (pH 1.5–2.5), pepsinogen-5 is auto-catalytically converted to Pepsin A-5, which then cleaves dietary proteins into peptides and amino acids, facilitating nutrient absorption. Pepsin A-5 has broad substrate specificity but prefers peptide bonds next to phenylalanine and leucine. While primarily involved in digestion, abnormally localized pepsin contributes to reflux disorders and mucosal damage, and can be detected in saliva as a biomarker for laryngopharyngeal reflux. Inhibitors such as pepstatin block its active site, and pepsin may be used supplements for patients with pancreatic insufficiency.

Other names

Pepsinogen-5PGA5Pepsinogen A5

Inhibition of enzyme activity — small molecules (e.g. pepstatin) bind the aspartyl active site, preventing protein cleavage. Enzyme replacement therapy — administered exogenously to aid in protein digestion when endogenous pepsin is deficient.