Overview
This lecture explains the processes of protein digestion and absorption in the human gastrointestinal (GI) tract, detailing the key enzymes, mechanisms, and cellular transporters involved.
Protein Digestion Basics
- Protein digestion is a catabolic process that breaks down large polypeptides (proteins) into amino acids.
- Digestion occurs through hydrolysis, breaking peptide bonds by adding water.
- Proteins are polymers composed of amino acid monomers.
Gastric Digestion (Stomach)
- Protein digestion begins in the stomach, NOT the mouth or esophagus.
- Chief cells secrete pepsinogen, which is activated to pepsin by acidic conditions (low pH from hydrochloric acid).
- Pepsin cleaves large polypeptides into smaller polypeptides, targeting bonds near aromatic amino acids (tyrosine, phenylalanine, tryptophan).
- Pepsin can auto-activate more pepsinogen.
Pancreatic Digestion (Small Intestine)
- In the duodenum, cholecystokinin (CCK) stimulates the pancreas to release inactive proteases (trypsinogen, chymotrypsinogen, procarboxypeptidase, proelastase).
- Enterokinase (on duodenal cells) activates trypsinogen to trypsin.
- Trypsin activates additional trypsinogen, chymotrypsinogen, procarboxypeptidase, and proelastase to their active forms.
- Trypsin cleaves peptide bonds after lysine and arginine; chymotrypsin targets aromatic amino acids; carboxypeptidase and elastase act on the carboxy end.
Brush Border Digestion and Absorption
- Brush border enzymes (aminopeptidases and dipeptidases) on enterocytes further break down di- and tripeptides to amino acids.
- Aminopeptidase cleaves peptides from the amino (N) end; dipeptidase breaks dipeptides into amino acids.
- Remaining di- and tripeptides, as well as amino acids, are transported into enterocytes by specific transporters.
Transport and Final Absorption
- Di- and tripeptides enter enterocytes via proton-coupled cotransport; amino acids use sodium-coupled cotransport.
- Intracellular peptidases convert absorbed di- and tripeptides to amino acids.
- Amino acids exit enterocytes via facilitated diffusion into the intestinal capillaries, entering the hepatic portal vein to the liver.
Intact Protein Uptake & Immunity
- Rarely, intact proteins can be absorbed by enterocytes and M cells via endocytosis, important for mucosal immunity.
- M cells present intact proteins to immune cells, which may trigger immune responses (e.g., in celiac disease with gluten proteins).
Key Terms & Definitions
- Catabolism — metabolic pathway that breaks down molecules into smaller units.
- Hydrolysis — chemical breakdown using water to split bonds.
- Pepsinogen/Pepsin — inactive/active enzyme from chief cells digesting proteins in the stomach.
- Enterokinase — brush border enzyme that activates trypsinogen.
- Proteases — enzymes that break down proteins (e.g., trypsin, chymotrypsin).
- Brush border — microvilli surface of enterocytes containing digestive enzymes.
- Enterocyte — absorptive cell in the intestinal lining.
- Cholecystokinin (CCK) — hormone stimulating pancreatic enzyme release.
- Dipeptidase/Aminopeptidase — brush border enzymes breaking down dipeptides and peptides.
- Hepatic portal vein — blood vessel transporting absorbed nutrients to the liver.
Action Items / Next Steps
- Review supporting videos on carbohydrate and lipid digestion for comparison.
- Study the roles and specific targets of digestive enzymes.
- Prepare for potential exam questions on enzyme activation, sites of digestion, and absorption mechanisms.