this chapter looked at the digestion, absorption, and transport of proteins. digestion of proteins begins in the stomach, when the zymogen pepsinogen (recall that this is secreted by the parietal cells in the gastric pits) is autocatalytically cleaved to pepsin. pepsin works as an endopeptidase, randomly cleaving peptide bonds within the protein.
in the intestine, protein digestion continues with enzymes secreted from the pancreas, in zymogenic (inactive) form: trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase. trypsinogen is cleaved first by enteropeptidase into trypsin. trypsin both works to digest proteins directly by cleaving peptide bonds adjacent to carboxyl groups contained by arginine or lysine, and more importantly, it activates the other digestive enzymes.
it converts chymotrypsinogen to chymotrypsin, which then cleaves peptide bonds adjacent to carboxyl groups from acidic or hydrophobic amino acids. it converts proelastase to elastase, which then cleaves peptide bonds in elastin as well as those next to carboxyl groups contained by small chain amino acids such as alanine, glycine, and serine. finally, it activates carboxypeptidase from procarboxypeptidase, which acts an exopeptidase; cleaving amino acids one at a time from the outside edges of the protein fragments created by digestion via the other pancreatic enzymes.
in addition to pancreatic enzymes, the intestinal epithelial cells also contain protein digesting enzymes; these include aminopeptidases, which also act as exopeptidases, and intracellular peptidases, which break down protein fragments that have been absorbed by the enterocytes.
the amino acids produced from degradation of proteins are transported into enterocytes via Na+ cotransporters, similar to the glucose / Na+ cotransporters seen in carbohydrate digestion. these transporters are powered by the low Na+ concentration in the cells which is manufactured by the Na+/K+ pumps. thus amino acids are absorbed via secondary active transport- and then they diffuse out of the serosal side via facilitated transport proteins.
the "intracellular amino acid pool" is a measure of how much amino acid there is at any given moment within a cell. this is a dynamic balance between proteins acquired from the diet vs. the degradation of proteins. the "half life" of a protein refers to the point at which 50% of the protein has been degraded; proteins in muscle cells, digestive enzymes, or hemoglobin, are all examples of proteins which have a short half life and therefore a high "turnover" rate.
a few notes about intracellular protein digestion: cells can digest proteins by the process of "autophagy", in which proteins in extracellular vesicles fuse with lysosomes, which contain proteases which degrade the proteins into amino acids, which then are absorbed into the cytoplasm. another method of protein digestion is through the ubiquitin / proteasome pathway, in which ubiquitin is attached to proteins, "tagging" them for digestion via proteasomes, which are large barrel shaped proteins with multiple internal proteolytic sites.
questions
1. what form are the protein digesting enzymes secreted in?
2. where are parietal and chief cells located and what do they secrete?
3. how is pepsinogen activated?
4. describe the action of pepsin on proteins.
5. what are the zymogens that are secreted by the pancreas into the intestine?
6. describe trypsinogen's role in protein digestion in the intestine.
7. how is trypsinogen activated?
8. how does trypsin directly digest proteins?
9. describe the digestive action of chymotrypsin on proteins.
10. describe the digestive action of elastase on proteins.
11. describe the action of carboxypeptidase on proteins.
12. what is the difference between carboxypeptidase A and B?
13. where are aminopeptidases located and what do they do?
14. what are intracellular peptidases?
15. describe the transport of amino acids from the intestinal lumen into enterocytes.
16. describe the transport of amino acids from the enterocyte to the portal vein.
17. describe the diversity of amino acid transport proteins on the apical side of enterocytes.
18. how do amino acids get transported into cells of peripheral tissues?
19. in what way does transport and absorption of amino acids into peripheral tissues differ from that of carbohydrates?
20. what is the half life of a protein?
21. what are some examples of proteins that undergo extensive synthesis and degradation in the body?
22. how much of the cells lining the intestinal wall are replaced each day?
23. what percentage of proteins that are absorbed from the intestines are excreted?
24. what is autophagy?
25. which enzymes in lysosomes aid in protein digestion?
26. what is the ubiquitin-proteasoms pathway?
27. how does ubiquitin "tag" proteins?
28. what is a proteasome?
answers
1. zymogenic: an inactive, larger form of the enzyme that is activated by proteolytic cleavage once in the digestive tract.
2. in the gastric pits / epithelium of the stomach. parietal cells secrete HCl and chief cells secrete pepsinogen.
3. the acidity in the stomach allows pepsinogen to be cleaved to its active form, pepsin.
4. pepsin acts as an endopeptidase, cleaving peptide bonds at random intervals within the denatured protein.
5. trypsinogen, pepsinogen, proelastase, procarboxypeptidase.
6. trypsin (the activated form of trypsinogen) catalyzes the activation of the other pancreatic enzymes to their active forms, as well as directly aiding in the digestion of proteins.
7. through enteropeptidase.
8. trypsin cleaves peptide bonds adjacent to carboxyl groups that are provided by lysine or arginine.
9. chymotrypsin cleaves peptide bonds next to residues that contain hydrophobic or acidic amino acids.
10. elastase cleaves peptide bonds within elastase as well as bonds next to residues with small side chains (alanine, glycine, serine)
11. carboxypeptidase acts an exopeptidase, removing amino acids one at a time from the carboxyl end, from the smaller peptides resulting from breakdown of the other pancreatic enzymes mentioned above.
12. A preferentially cleaves hydrophobic amino acids while B preferentially cleaves basic amino acids.
13. they are located on the epithelial wall of the intestine and act as exopeptidases, removing one amino acid at a time.
14. the enzymes within cells that break down peptides which are absorbed.
15. a Na+/K+ pump in the enterocyte creates a low concentration of Na+ in the enterocyte. The resulting influx of Na+ is coupled with amino acid transport, this is called secondary active transport.
16. the amino acids in the enterocytes are transported into the portal vein via "facilitated transporters"
17. there are at least 6 such transport proteins which have overlapping specificities for different types of amino acids.
18. mainly through Na+ cotransporters.
19. amino acids are transported into cells mainly by Na+ cotransporters wheras in peripheral tissues carbohydrates are transported by facilitated transporters (recall the GLUT transporters). in the intestine and renal cells the absorption of both amino acids and carbohydrates are Na+ coupled.
20. the point at which 50% of the protein in a cell has been degraded.
21. hemoglobin, muscle proteins, digestive enzymes.
22. roughly 1/4th.
23. roughly 6%.
24. the process by which cells digest proteins using lysosomal enzymes.
25. the cathepin family of proteases.
26. a method of intracellular protein digestion using ubiquitin tagging and degradation via proteosomes.
27. by covalently binding to the epsilon-amino group of lysine residues.
28. a cylindrical 20S protein complex with multiple internal proteolytic sites.
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