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Protein Digestion

&
Amino Acids Absorption
Learning objectives

Sites of protein digestion in G.I tract
List the proteolytic enzymes of G.I tract
Proenzyme (zymogen) forms of the proteolytic enzymes and
their activation
Digestion of proteins by proteolytic enzymes with their
specificities
Absorption of amino acids from intestine

Gastro intestinal tract
(GIT)
Dietary proteins
Peptides
Amino acids
Intestinal cells Portal blood
Amino acids
Peptidases
Peptidases
- Proteases (proteolytic enzymes)
- Exopeptidases
- Cleave external (terminal) peptide bonds
- egs: - Amino peptidase
- Carboxy peptidase
- Endopeptidase
- Cleave internal peptide bonds
- egs: Pepsin, trypsin, chymotrypsin, enteropeptidase, elastase
- In stomach, pancreas and intestine
- Synthesized as inactive zymogens (proenzymes)
- Secretion and activation mediated by cholecystokinin & secretin
- Significance (eg: Acute pancreatitis)
- Cleaved to their active protease form in the GI tract
(proteolytic activation/post translational modification)
- Have specificity for the substrates
Protein Digestion & Amino Acids Absorption
Protein Digestion
- Stomach:
- HCl
- From ------------ Cells
- Denatures the proteins
- Purpose??
- Pepsin
- From ------------ Cells
- Proteins to smaller polypeptides
- Pancreas:
- Exocrine pancreatic enzymes
e.g. Trypsin, chymotrypsin, elastase, carboxypeptidases act in
the small intestine on proteins and smaller peptides
oligopeptides and AAs
-Intestine:
- Brush border enzymes
- Enteropeptidase (Enterokinase)
- Aminopeptidase
Protein Digestion (contd..)
Activation of the Digestive Proteases
Autocatalytic
cleavage
Protein Digestion (contd..)
Specificity of the Digestive Proteases:
Protein Digestion (contd..)
The Products are amino acids, dipeptides and tri peptides
Abnormalities in protein digestion
Seen in individuals with a deficiency in pancreatic secretion
- Chronic pancreatitis
- Cystic fibrosis
- Surgical removal of pancreas
- Steatorrhea
- Undigested protein





Protein Digestion (contd..)
Clinical Correlations: Cystic Fibrosis
Thick exocrine pancreatic secretions, due to reduced Cl
-
permeability,
leads to luminal dehydration
- Inspissation: - Drying/thickening of pancreatic secretions
- Obstruction of pancreatic ducts
- Pancreatic enzymes cannot enter the intestine
in adequate amounts
- Steatorrhea
- These enzymes can be replaced orally
- Patients can take them as supplements with meals






Protein Digestion (contd..)
- Deficiency of protein in diet that is adequate in calories
- Children suffer from:
- Muscle wasting
- Decreased concentration of plasma proteins,
(albumin) edema, a distended abdomen (children
appear plump)
- Decreased availability of amino acids for synthesis of
new proteins may lead to:
- Decreased ability to produce digestive
enzymes & new intestinal epithelial cells
Clinical Correlations: PEM- Kwashiorkor
Protein Digestion (contd..)
- From intestinal brush border through:
- Na
+
- dependent secondary active transport system
(free amino acids)
-Transport linked to the -glutamyl cycle
- Di and tri-peptides are taken up by proton-linked
transport system
- Facilitated diffusion





Protein Digestion & Amino Acids Absorption
Amino Acids Absorption
- Na
+
- dependent secondary
active transport systems
- Co-transport of Na
+
and the
amino acid on apical membrane
driven by Na
+,
K
+
-ATPase
on the serosal membrane
- Facilitated transporters on
serosal membrane
(Similar to glucose absorption)




Protein Digestion & Amino Acids Absorption
Amino Acids Absorption
Amino Acids Absorption (contd..)
- 7 different Na
+
-dependent transporters on the
apical brush border as well in the PCT of kidney with
overlapping specificity for AAs
- Neutral AAs (trypotophan.)
- Proline and hydroxyproline
- Acidic AAs
- Basic AAs (Arg, Lys), ornithine (urea
cycle intermediate) and cysteine (COAL)
-These transporters are proteins


-glutamyl cycle:
-GGT (Gamma-glutamyl transferase)

catalyzes the
transfer of the gamma-glutamyl moiety of glutathione to an
amino acid
- Defect in the transport of cystine and basic amino acids
(lysine, arginine, ornithine) COAL
- In the epithelial brush border membranes of cells in small
intestine and renal tubules
- Precipitation of cystine kidney stones (calculi)
severe pain and bleeding
- Oral hydration

Clinical Correlations: Cystinuria
Amino Acids Absorption (contd..)
- Defect in transport of neutral amino acids across both
intestinal and renal epithelial cells (essential AAs; Ile, leu,
Phe, Thr, Trp, Val; non-essential AAs; ala, ser, tyr)
- Signs and symptoms due to deficiency of essential amino
acids (tryptophan) and the vitamin niacin (pellagra-like
manifestations)
- Photosensitivity rash, ataxia, neuropsychiatric problems
- Treatment with:
- Dietary niacin
High protein diet
Clinical Correlations: Hartnup Disease
Amino Acids Absorption (contd..)
- Disease of malabsorption
- Immune-mediated
- Gluten
- Protein in wheat, barley and rye
- Gluten allergy
- Antibody production
- Damage to the small intestine


Clinical Correlations: Celiac sprue
Amino Acids Absorption (contd..)