Biochemical Reaction
Mechanisms
1. Mechanism of action of a-chymotrypsin
2. Glycolysis: metabolism of glucose
3. Biosynthesis of steroids from squalene
Mechanism of action of
a-chymotrypsin
(An enzyme that hydrolyzes peptides
in the digestive system)
Catalytic triad: Asp102, His 57, Ser 195
O
H
O
C
His 57
His 57
CH2
CH2
N
Ser 195
N
CH2
CH2
H O
Asp 102
H
O
O
H
N
C
Ser 195
N
CH2
H
O
Asp 102
H
O
R
R'
O
N C
N C
1
CH2
R
2
R'
a-chymotrypsin mechanism…
O
O
H
C
His 57
His 57
CH2
CH2
N
Ser 195
N
CH2
CH2
O
H
Asp 102
O
O
R
3
N
CH2
free amine + acylated serine
C O
H
N
4
O
O
H
H
C O
CH2
H
Asp 102
R'
Ser 195
N
C
H
N
H
R'
R
amine replaced by water
a-chymotrypsin mechanism…
O
H
O
C
His 57
His 57
CH2
CH2
Ser 195
N
N
CH2
H
CH2
O
Asp 102
H
5
O
O
H
O
C
Ser 195
N
N
CH2
H
CH2
Asp 102
H
C O
R'
6
O
O
C O
R'
free acid
Glycolysis
Metabolism of glucose to form
pyruvate and ATP
Glycolysis converts glucose into
two pyruvate molecules

…with the production of 2 ATPs (high
energy storage in cells)
1.
2.
3.
4.
Isomerization of glucose to fructose
Formation of iminium ion; retro aldol to form
two 3-carbon sugars (as phosphates)
Isomerization of dihydroxyacetone to
glyceraldehyde (as phosphates)
Oxidation, isomerization, dehydration and
dephosphorylation to form pyruvate and ATP
Isomerization of glucose to
fructose
H
C
O
H
H C OH
HO C
C
OH
CH2OH
C OH
H
HO C
C O
H
HO C
H
H C OH
H C OH
H C OH
H C OH
H C OH
H C OH
-2
CH2OPO3
glucose-6-phosphate
-2
CH2OPO3
glucose-fructose enol
-2
CH2OPO3
fructose-6-phosphate
Iminium ion; retro aldol addition
-2
CH2OPO3
-2
CH2OPO3
C O
C NH Enz
H2N Enz
HO C H
H C OH
HO C H
H C O
H C OH
-2
fructose-1,6-bisphosphate
C NH Enz
HO C H
(enol form)
+
H
H C O
H C OH
CH2OPO3
-2
CH2OPO3
-2
CH2OPO3
H C OH
-2
CH2OPO3
glyceraldehyde-3-phosphate
Isomerization to glyceraldehyde
-2
CH2OPO3
C NH Enz
-2
CH2OPO3
H2O
C O
HO C H
H2N Enz
+
CH2OH
(enol form)
dihydroxyacetone-phosphate
H
CH2OH
C O
C
OH
H
C OH
-2
CH2OPO3
dihydroxyacetone-phosphate
(turned upsidedown)
H C OH
-2
CH2OPO3
(enol form)
C
O
-2
CH2OPO3
glyceraldehyde-3-phosphate
Oxidation, isomerization and
dephosphorylation (ATP forming)
H
C
O
O
[O]
H C OH
CH2OPO3
-2
(sev. steps)
C
O
H C OPO3
O
-H2O
-2
CH2OH
C
-2
C OPO3
CH2
glyceraldehyde-3-phosphate
O
C
O
phosphoenolpyruvate
O
ADP
-2
ATP
O
C
O
C OPO3
C O
CH2
CH3
phosphoenolpyruvate
pyruvate
Biosynthesis of Steroids
from Squalene
Squalene (a shark oil terpene)
squalene
Epoxidation of Squalene
squalene oxidase
O
Acid-Catalyzed Epoxide
Ring Opening; A Ring Formation
+
H O
A
H O
+
Reaction of Alkene
with Carbocation; B Ring
A
+
H O
A
H O
B
+
Cyclization to form C Ring
A
B
+
H O
H
C
A
H O
B
+
Cyclization to form D Ring
H
+
H O
H
+
C
A
H O
B
D
Hydride and Methyl Shifts
H
+
H
H O
+
H O
Eventually...Cholesterol !
+
(several steps)
H O
CH3
CH3
H
HO
H
H
H
Grading / Final Exam
Example:
You may replace any of the 5
tests by an improved grade
on that section of the Exam.
Only the higher grade counts.
You need not retake a section if
you are happy with your
grade on that test.
Everyone must take Section 6
(Ch 25, 26, 27 & 29) plus
Section 7 (comprehensive;
mostly synthesis)
1
2
3
4
5
Hour test
42
30
28
41
37
Ch. 25-29
compreh.
---
Exam
-38
42
-36
38
32
Your (best) score on these seven sections plus
the sum of your gla scores determines your grade.