How is pepsinogen activated and what is its role in digestion?

• A. Activated to pepsin by pepsin itself (autocatalysis).
• B. Activated by alkaline chyme to pepsin.
• C. Activated by bile acids to pepsin.
• D. Activated by acidic pH created by HCl; pepsin begins proteolysis.

Answer: (D)

Pepsinogen is a zymogen secreted by gastric chief cells, and it must be exposed to the stomach’s acidic environment to become active. The stomach’s hydrochloric acid lowers the luminal pH to about 1.5–2.0, which causes a peptide segment to be cleaved from pepsinogen. This reveals the active site and forms pepsin, an enzyme that begins protein digestion by cleaving peptide bonds, especially after aromatic amino acids. While a small amount of pepsin can help kick off further activation of pepsinogen (autocatalysis), the essential trigger is the acidic pH created by HCl. Activation by alkaline chyme or bile acids would not occur in the stomach and would not produce pepsin.