Why Trypsin Is Inactivated in the Stomach

Trypsin, a pancreatic protease essential for protein digestion in the small intestine, is rapidly inactivated if it enters the stomach. Multiple mechanisms ensure this:

1. Low pH (1–2): Trypsin's optimal pH is 7–9. Gastric acid denatures it, destroying its catalytic structure.
2. Pepsin: The stomach's active protease (optimal at low pH) degrades trypsin directly.
3. Other acidic proteases: Cathepsin D, gastricsin cleave trypsin's peptide bonds.
4. Protease inhibitors: Gastric inhibitors (e.g., pancreatic secretory trypsin inhibitor analogs) bind and block trypsin.
5. Autoactivation risk: High trypsinogen concentration in gastric juice could trigger premature activation, but acidic conditions and inhibitors prevent functional activity.

This safeguard ensures protein digestion occurs sequentially: pepsin in the stomach, then trypsin/chymotrypsin in the alkaline small intestine.