Protein Digestion and Absorption

Overview & Gastric Digestion - Gastric Gauntlet

• Protein Digestion: Breakdown of dietary proteins into absorbable amino acids & small peptides.
• Key Sites: Stomach (initiation), Small Intestine (completion).
• Gastric Gauntlet (Stomach Phase):
  • Food entry stimulates gastrin release.
  • Parietal Cells: Secrete HCl.
    • Lowers gastric pH to 1.5-2.5.
    • Denatures proteins (unfolds $2^\circ$/$3^\circ$ structures).
    • Activates pepsinogen to pepsin.
  • Chief Cells: Secrete Pepsinogen (inactive zymogen).
    • Activated by HCl (pH < 5) & autocatalysis by pepsin.
    • Pepsin: Endopeptidase, cleaves peptide bonds (prefers aromatic AAs: Phe, Tyr, Trp).
    • Products: Large polypeptides, some oligopeptides.
  • Limited digestion; prepares chyme for duodenum.

  ⭐ HCl not only activates pepsinogen but also provides the acidic environment optimal for pepsin activity (pH 1.5-3.5).

Intestinal Proteolysis - Pancreatic PowerPlay

Acidic chyme in duodenum stimulates S cells to release Secretin (↑ pancreatic $HCO_3^-$ for neutralization) and I cells to release Cholecystokinin (CCK) (↑ pancreatic enzyme secretion, gallbladder contraction). Pancreatic zymogens are crucial.

• Pancreatic Endopeptidases: Hydrolyze internal peptide bonds, producing smaller peptides.
  • Trypsin: Specific for C-terminal of Lysine (Lys), Arginine (Arg).
  • Chymotrypsin: Specific for C-terminal of Phenylalanine (Phe), Tyrosine (Tyr), Tryptophan (Trp), Leucine (Leu), Methionine (Met).
  • Elastase: Specific for C-terminal of small, neutral amino acids like Alanine (Ala), Glycine (Gly), Serine (Ser).
• Pancreatic Exopeptidases: Remove one amino acid at a time from the C-terminus.
  • Carboxypeptidase A: Cleaves C-terminal aromatic (Phe, Tyr, Trp) & neutral aliphatic AAs.
  • Carboxypeptidase B: Cleaves C-terminal basic AAs (Lys, Arg).

⭐ Trypsin is the master activator of pancreatic proteases. Its deficiency (e.g., hereditary pancreatitis, cystic fibrosis) severely impairs protein digestion.

Absorption Mechanisms - Nutrient Gateway

• Location: Duodenum & Jejunum.
• Absorbable forms: Free amino acids (AAs), di- & tri-peptides.
• Amino Acid (AA) Absorption (Lumen → Enterocyte):
  • Secondary active transport, Na⁺-dependent.
  • Apical membrane: Specific carriers for different AA classes (neutral, acidic, basic, imino acids).
    • E.g., SLC transporters (Solute Carrier family).
• Di- & Tri-peptide Absorption (Lumen → Enterocyte):
  • PEPT1 transporter (H⁺-cotransporter); higher capacity & faster than AA transporters.
  • Inside enterocyte: Cytosolic peptidases hydrolyze peptides to free AAs.
• Basolateral Transport (Enterocyte → Portal Blood):
  • Facilitated diffusion & Na⁺-independent carriers transport AAs into portal circulation.

• Clinical Notes:

  ⭐ Hartnup disease: Defective neutral AA transporter (e.g., for tryptophan), leading to pellagra-like symptoms (dermatitis, diarrhea, dementia).

  • Cystinuria: Defective dibasic AA (Cystine, Ornithine, Lysine, Arginine) transporter in kidney & intestine. 📌 Mnemonic: COLA. Leads to cystine kidney stones.

Clinical Tie-ins - Digestion Derailments

• Pancreatic Insufficiency: (Chronic pancreatitis, Cystic Fibrosis)
  • Reduced enzyme (trypsin, chymotrypsin) secretion → protein maldigestion (azotorrhea).
• Celiac Disease:
  • Gluten enteropathy → villous atrophy → impaired nutrient absorption.
• Hartnup Disease:
  • Defect in neutral amino acid transporter (SLC6A19) in intestine & kidney.
  • ↓ Tryptophan absorption → pellagra-like features (dermatitis, diarrhea, dementia).
• Cystinuria:
  • Defect in dibasic amino acid transporter (COLA - Cystine, Ornithine, Lysine, Arginine).
  • Poor cystine reabsorption → cystine kidney stones.

⭐ Hartnup disease: Niacin (B3) supplementation is beneficial as tryptophan, a niacin precursor, is malabsorbed.

High‑Yield Points - ⚡ Biggest Takeaways

• Pepsin (activated by HCl in stomach) initiates protein digestion.
• Enteropeptidase (brush border) activates trypsinogen to trypsin, key pancreatic activator.
• Pancreatic enzymes (e.g., trypsin, chymotrypsin) yield oligopeptides, di- & tripeptides.
• Amino acids are absorbed by Na+-dependent cotransporters; di/tripeptides by PepT1 (H+-dependent, faster).
• Hartnup disease: Defective neutral amino acid (e.g., tryptophan) transport.
• Cystinuria: Defective transport of COLA (Cysteine, Ornithine, Lysine, Arginine).