1. Digestion and Absorption Of Proteins and its Disorders
Dr Sara Amjad

2. Digestion Catabolism Mechanical and chemical breakdown of food
Mastication and mixing of food with water , bile and enzymes occur in stomach and intestine

3. Carbohydrates are converted into monosaccharide's
Proteins are converted into amino acids
Lipids are converted into fatty acids and glycerol

4. Protein Tissue building and maintenance Regulation of metabolism
Protein is required for …..
Tissue building and maintenance
e.g. hair, skin, organs, muscle,
antibodies, enzymes, hormones
Regulation of metabolism
e.g. Insulin
Energy

5. Contains right balance
Protein
Quality depends upon …..
digestibility
EAA profile
Highest quality
Contains right balance
of all EAA’s
Eggs & milk
Meat
(fish bird, mammal)
Vegetable / plant

6. two sources of proteins
1.Exogenous
2.Endogenos

7. 70-100 g dietary protein per day
g of endogenous protein secreted into the gut (enzymes) or shed from the epithelium as a result of cell turnover.

8. Amino Acid Pool – amino acids that are available throughout the body (tissues and fluids) for use when needed.
Protein Turnover – 300 grams of protein synthesized by the body each day, 200 grams are made from recycled amino acids.

10. 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.

11. Proteins are hydrolyzed by peptidases
Endopeptidases
Exopeptidases
Carboxypeptidases
Aminopeptidases

13. 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.

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

15. Digestion in stomach 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.

16. 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)

17. 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 carboxyl-side of aromatic amino acid residues-Phe, Trp and Tyr

18. Milk curdling action of pepsin
Gelatinase
End products of STOMACH digestion are Smaller Polypeptide and some AA

19. Digestion in small intestine
As the acidic stomach contents pass into the small intestine, the low pH triggers secretion of the hormone secretin and CCK into the blood.

20. 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.

21. 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)

22. 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.

23. 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

24. Carboxypeptidases remove successive carboxyl-terminal residues from peptides.
End products of PANCREATIC ENZYME digestion are Dipeptidases, Tripeptidases and some AA

25. Proteases of brush border of enterocytes
The final digestion of di- and oligopeptides is carried by small intestinal membrane-bound endopeptidases, dipeptidases and aminopeptidases.

26. 1.Amino peptidase..act on terminal peptide bond on side of protein having free amino group 2. Tripeptidases…hydrolyze tripeptides 3. Dipeptidases … hydrolyze dipeptides

27. Proteolytic enzyme with in enterocytes
Di-and tri-peptides are hydrolyzed to their constituent amino acids within the enterocyte by INTRACELLULAR PEPTIDASE

28. Final step is the transfer of amino acids out of the enterocyte into portal blood.
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

29. 2 to 4 percent of protein remains undigested
Unabsorbed protein enters in large intestine

32. ABSORPTION
Amino Acids are absorbed in the small intestine. The absorbed nutrients passes from the lumen of the small intestine into the bloodstream. Rapid absorption at duodenum and jejunum
lumen

33. Peptide Absorption  Energy required
More rapid than absorption of free amino acids
Active transport
 Energy required
Metabolized into free amino acids in enterocyte
Only free amino acids absorbed into blood

34. Free Amino Acid Absorption
Free amino acids
Na+ Na+

35. Basolateral Membrane
Groff & Gropper, 2000

38. The final transfer is; of free amino acids across the plasma membrane into the portal blood system through Na- independent transporters
Di- and tri peptides are transported by H ion dependent transport
Di- and tri peptides are further hydrolyzed to their constituent amino acids inside the enterocyte

39. After a protein-rich meal, protein digestion takes place
in the small intestine
The amino acids released are absorbed by intestinal epithelial cells
A large proportion of amino acids are transaminated to alanine, which is released into the portal vein and taken to the liver
Therefore, alanine is the major amino acid secreted by the gut and the principal carrier of nitrogen in the plasma

40. Absorption of Intact Proteins
Newborns
First 24 hours after birth
Immunoglobulins
Adults
Only amino acids

41. Absorption of intact proteins occurs
Paracellulary
Transcellulary
endocytosis
exocytosis

43. Disorders of Protein Digestion and Absorption
In individuals with a deficiency in pancreatic secretion ,for example due to
chronic pancreatitis
cystic fibrosis,
surgical removal of the pancreas,
the digestion and absorption of protein is incomplete
This results in undigested protein in the feces

44. Hartnup’s disease HARTNUP’S DISEASE
Inability of intestinal and epithelial cells to absorb amino acids.
Tryptophan absorption is severely effected
CYSTINUREA