1. Lecture 51 : Digestion and absorption of protein Digestion and absorption of protein ط Peptidases : Gastric and Intestinal ط Pancreatic peptidases ط Amino acid transport across intestinal cells D4 1070-3

2. Introduction · Digestion & absorption of proteins are very efficient processes (low N2 lost with stool) because of mixture of peptidases · Proteins are broken down by hydrolases (peptidases): 1. Endopeptidases (proteases): initial attack of internal bonds of long polypeptides & liberate peptides fragments (oligopeptides, 4-8 residues) 2. Exopeptidases: cleave off small peptides to tri/dipeptides (3/2 residues) and free AA from either the: a) COOH-terminus (carboxypeptidases) b) NH2-terminus (aminopeptidases)

3. Introduction · fig26.21, Digestion & absorption of proteins are divided into 3 phases depending on peptidases source (Gastric, Pancreatic & Intestinal phases) · Seven brush border specific transport systems are identified for uptake of AA & small peptides: 1. neutral AA with short / polar side chain (ser, thr, ala) 2. neutral AA with aromatic / hydrophobic side chain (phe, tyr, met, val, leu, ile) 3. basic AA and cystine (lys, arg, cys-cys) 4. Acidic AA (asp, glu) 5. β-AA (β-ala, taurine) 6. imino acids (pro, hyp) 7. dipeptides (gly-sacrosine)

4. Digestion of Proteins 1. fig26.20, Gastric Phase 2. Pancreatic Phase 3. Intestinal Phase

5. Digestion of Proteins 1. fig26.20, Gastric Phase a) HCl denatures protein and release fragments of large peptides (polypeptides) b) Protein  Pepsin (protease) “proenzyme pepsinogen”  Oligopeptides + some AA · fig26.22, Peptides & AA activate (+) cholecystokinin (CCK) that is released into the duodenum to initialize next phase (pancreatic phase)

6. Digestion of Proteins 2. Pancreatic Phase * Enteropepitase (protease) activates (+) trypsinogen (proenzyme) to trypsin (protease) * Table26.6, Trypsin activates (+) further proenzymes to enzymes a) Protein  Trypsin (protease) “trypsinogen”  oligopeptides b) Protein  Chymotrypsin (protease) “chymotyrpsinogen”  oligopeptides c) Protein  Elastase (protease) “proelastase”  oligopeptides d) Poly/oligopeptide  Carboxypeptidase A (carboxypeptidase) “procarboxypeptidase A”  tri/dipeptides + AA e) Poly/oligopeptides  Carboxypeptidase B (carboxypeptidase) “procarboxypeptidase B”  tri/dipeptides + AA * at this point, peptides account for 60% of N2

7. Digestion of Proteins 3. Intestinal Phase a) Intestinal Lumen (brush border) · Protein  Enteropeptidase (endopeotidase)  Poly/oligopeptides · Poly/oligopeptide  Aminopeptidase  tri/dipeptides + AA b) Intestinal Epithelial Cell (cytoplasmic) · Table26.2, Tri/dipeptides  Dipeptidase  AA * AA & small peptides (tri/di) are absorbed into the cell by specific carrier- mediated transport system * Hydroproline & praline containing tri/dipeptidases are not hydrolyzed in the cytoplasm

8. Absorption of Small Peptides & AAs fig26.21 1. Na+-dependent transport AA cotransport with 2 Na+ (1 at luminal “brush border” membrane / 1 at contraluminal plasma membrane) … and counter transport with 1 K+ (at contraluminal plasma membrane) 2. Na+-independent transport Tri/dipeptides cotransport with 1 H+ (at luminal “brush border” membrane) … and counter transport with 1 K+ (at contraluminal plasma membrane) * The foetus & neonate can absorb intact proteins by endocytosis (or penocytosis) to transport maternal antibodies (γ-globulins) not for nutrition