1. Digestion and Absorption Of Proteins Prof. Dr. Arzu SEVEN

2. Total protein load received by the gut is derived from 2 sources: 70-100 g dietary protein per day 35-200 g of endogenous protein secreted into the gut (enzymes) or shed from the epithelium as a result of cell turnover.

3. The digestion and absorption of protein is extremely efficient: only 1-2 g of nitrogen=equivalent to 6-12 of protein is lost into the feces daily. Proteins are hydrolyzed by peptidases

4. Endopeptidases (cleave internal peptide bonds) Exopeptidases Carboxypeptidases Aminopeptidases

5. Endopeptidases break down large polypeptides to smaller oligopeptides which can be acted upon by exopeptidases to produce amino acids and di- and tripeptides which are absorbed by enterocytes.

6. Depending on the source of peptidases, the protein digestive process can be divided into 3 phases: 1-Gastric 2-Pancreatic 3-Intestinal

7. Protein digestion begins in the stomach. Entry of dietary protein into the stomach stimulates the gastric mucosa to secrete gastrin. HCI secreted by the parietal cells reduces the pH of stomach to 1-2 The acidic gastric juice is both an antiseptic agent, killing most bacteria and other foreign cells, and a denaturating agent, unfolding globular proteins.

8. Denaturation unfolds polypeptide chains, making proteins more accesible to protease activity. Pepsins are secreted by the chief cells of the gastric mucosa, as inactive precursors, pepsinogen I and II, and are activated either by autoactivation at ph<5 or by autocatalysis. (a cleavage mediated by pepsinogen itself)

9. At ph>2.0, the liberated peptide remains bound to pepsin and acts as an inhibitor of pepsin activity. This inhibition is removed either by a drop in pH below 2.0 or by further pepsin action. Pepsin hydrolyzes ingested proteins at peptide bonds on the amino-terminal side of aromatic amino acid residues-Phe, Trp and Tyr

10. The end product of protein digestion in the stomach is peptide. As the acidic stomach contents pass into the small intestine, the low pH triggers secretion of the hormone secretin into the blood.

11. Secretin stimulates the pancreas to secrete bicarbonate into the small intestine to neutralize gastric HCI, abruptly increasing pH to about 7. Gastric protein digests stimulate cholecytokinin release in the duodenum, triggering the release of main digestive enzymes by the pancreas.

12. Proteolytic enzymes,released from the pancreas,are inactive zymogens. Duodenal enteropeptidase converts trypsinogen to active trypsin. This enzyme is capable of autoactivation and activation of all other pancreatic zymogens - chymo-trypsinogen, proelastase, procarboxy- peptidases (A and B)

13. Because of this prime role of trypsin in activating other pancreatic enzymes, its activity is controlled within the pancreas and pancreatic ducts by a small molecular weight inhibitory peptide.(pancreatic trypsin inhibitor) Synthesis of enzymes as inactive precursors protects the exocrine cells from destructive proteolytic attack.

14. Pancreatic proteases have different substrate specificity with respect to peptide bond cleavage. Trypsin arginine and Iysine residues Chymotrypsin aromatic amino acids Elastase hydrophobic amino acids

15. Carboxypeptidases are zinc containing enzymes that remove successive carboxyl-terminal residues from peptides. The combined effect of these pancreatic enzymes produces free amino acids and peptides of 2-8 residues.

16. .Sodium bicarbonate, produced by the pancreas, neutralizes the acid contents of the stomach as they pass into duodenum, thus promoting pancreatic protease activity. The final digestion of di- and oligopeptides is carried by small intestinal membrane- bound endopeptidases, dipeptidases and aminopeptidases.

17. The end products of this surface enzyme activity are free amino acids, and di-and tripeptides which are absorbed across the enterocyte membrane by specific carrier-mediated transport. Di-and tri-peptides are further hydrolyzed to their constituent amino acids within the enterocyte. Final step is the transfer of amino acids out of the enterocyte into portal blood.

18. In humans, most globular proteins from animal sources are almost completely hydrolyzed to amino acids in the GI tract, some fibrous proteins, such as keratin, are only partly digested.

19. Acute pancreatitis is a disease caused by obstruction of the normal pathway by which pancreatic enzymes enter the intestine. The zymogens of the proteolytic enzymes are converted to their catalytically active forms,prematurely, inside the pancreatic cells and attact the pancreatic tissue itself.