1. Trypsin and Chymotrypsin
Protein digestion

2. Breaking down protein into absorbable amino acids and some di- and tri-peptides.

3. Parts of a polypeptide

4. Protein digestion starts in the starts in the stomach, and from there most of the chemical breakdown occurs in the first part of the small intestine, the duodenum. The pancreas secretes digestive enzymes, trypsin and chymotrypsin, among others.

5. Secreted as inactive precursor, zymogen, which have to be activated.
Trypsinogen is activated by enterokinase and then by other Trypsin
Chymotrypsinogens are activated by trypsin to form gamma chymotrypsins, and then are activated into alpha chymotrypsin.

6. The inactive chymotrypsinogen is activated into chymotrypsin, which has the desired conformation to produce the active site.

7. Serine proteases have a catalytic triad consisting of Ser195, His57, and Asp 102

8. The charge relay system:
Represented by chymotrypsin, same mechanism in trypsin
polypeptide is in the active site
an H+ ion moves from the serine amino acid to histidine amino acid
oxygen atom in serine forms a covalent bond to the carbon of one of the substrate’s peptide bonds, it acts as a nucleophile

9. Positive His-57 is stabilized by negative Asp-102
Bond between the carbon and the nitrogen in the peptide bond is broken
The nitrogen-containing group is stabilized by the formation of a bond to a hydrogen atom from His-57

10. The part of the polypeptide with nitrogen moves out of the active site (cleaved)

11. Water molecule moves into the active site
Oxygen in H2O loses an H+ ion to a nitrogen atom on His-57
The oxygen atom then forms a bond with the carbon atom in the remaining portion of the substrate

12. With double bond reformed, the bond between carbon and the oxygen of Ser-195 is broken
The –OH group on Ser-195 is restored with a transfer of an H+ ion from His-57
With this step, the Ser-195 and His-57 are both returned to their original forms

13. The remaining portion of the substrate moves out of the active site
Active site is back in its original form, ready to repeat the process

14. References
1-  Solomon, et al.  Biology 7th edition.  2005  Thomson Brooks/Cole.  CA 2-Trypsin., Wikipedia.  4/13/06
3-  Bishop, M. Chymotrypsin. mark_bishop/chymotrypsin.htm 4/18/06  Mark Bishop’s Chemistry Site 4-Berg, et al.  Biochemistry 5th edition W.H. Freeman Company. NY, NY.
5- Blow, D.M., The tortous story of Asp….His…Ser: structural analysis of α-chymotrypsin.  The PU Pancreatic Disease Center, Specialist in Pancreatitis and Pancreatic Cancer Center.  Visited 4/17/06 pancreas.htm
7- Serine Proteases Trypsin and Chymotrypsin., accessed 4/18/06 ~kelgalla/C483a2.html
8- Storch, Judy.  Human Digestive Tract., Anatomy, Physiology, and Biochemistry of the Gastrointestinal Tract.  2/27/06 (ppt)
9- Borgstrom, B., Studies of Intestinal Digestion and Absorption in the Human. May 23, 1957.
11- Garrett. Grisham, Biochemistry, Third Edition, Thomson Brooks/Cole.  CA
12- mb/goodsell/pdb/pdb46/ biology.kenyon.edu