Download Chymotrypsin and Trypsin

Trypsin and Chymotrypsin
Protein digestion
Breaking down protein into absorbable
amino acids and some di- and tripeptides.
Parts of a polypeptide
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.
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.
The inactive
chymotrypsinogen is
activated into
chymotrypsin, which has
the desired conformation
to produce the active
site.
Serine proteases have a catalytic triad
consisting of Ser195, His57, and Asp 102
Ser195
His57
Gly193
N
Asp102
N
H
O
H
O
N
O
H
N
H
O
HO
R1
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
•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
•The part of the polypeptide
with nitrogen moves out of the
active site (cleaved)
•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
•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
•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
References
1- Solomon, et al. Biology 7th edition. 2005 Thomson Brooks/Cole. CA
2-Trypsin., Wikipedia. 4/13/06 http://en.wikipedia.org/wiki/Trypsin
3- Bishop, M. Chymotrypsin. www.mpcfaculty.net/ mark_bishop/chymotrypsin.htm
4/18/06 Mark Bishop’s Chemistry Site
4-Berg, et al. Biochemistry 5th edition. 2002 W.H. Freeman Company. NY, NY.
5- Blow, D.M., The tortous story of Asp….His…Ser: structural analysis of αchymotrypsin. 1997.
6-The PU Pancreatic Disease Center, Specialist in Pancreatitis and Pancreatic Cancer
Center. Visited 4/17/06 www.ucpancreas.org/ pancreas.htm
7- Serine Proteases Trypsin and Chymotrypsin., accessed 4/18/06
www.cs.indiana.edu/ ~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, 2005. Biochemistry, Third Edition, Thomson Brooks/Cole. CA
12- www.scripps.edu/ mb/goodsell/pdb/pdb46/ biology.kenyon.edu