Protein Digestion in the Stomach: HCl, Pepsin, and Enzymatic Breakdown

Gastric Protein Digestion: Acid and Enzyme Action

Stomach Environment

• Parietal cells secrete HCl → pH 1.5-3.5.
• Chief cells secrete pepsinogen (inactive zymogen).
• HCl converts pepsinogen → pepsin (autocatalytic).

Mechanism

1. Denaturation: HCl unfolds protein tertiary/quaternary structure → exposes peptide bonds.
2. Pepsin cleavage: Endopeptidase – hydrolyzes interior peptide bonds, preferentially at aromatic (Phe, Tyr, Trp) and hydrophobic (Leu, Met) residues. Produces large peptides.
3. Gastric lipase/rennin: Minor fat/coagulation roles.

Gastric Output → Duodenum

• Chyme (partially digested proteins + acid) enters duodenum.
• Secretin/CCK → pancreatic bicarbonate (neutralizes acid) + proteases (trypsin, chymotrypsin, carboxypeptidases).
• Brush border enzymes (aminopeptidases, dipeptidases) → free amino acids, di/tripeptides.
• Absorption via amino acid transporters (SGLT1, PAT1, etc.) and PEPT1 (di/tripeptides).

Clinical Relevance

• Achlorhydria (PPIs, atrophic gastritis, H. pylori) → impaired protein digestion, B12 malabsorption (needs acid for IF release).
• Pancreatic insufficiency → maldigestion despite gastric phase.
• Protein-losing gastropathy (hypertrophic gastropathy, Ménétrier's).

Stomach initiates protein digestion; pancreas and small intestine complete it.