Biochemical

Biochemical Reaction
Reaction
Mechanisms
Mechanisms
1. Mechanism of action of -chymotrypsin
2. Glycolysis: metabolism of glucose
3. Biosynthesis of steroids from squalene
Mechanism
Mechanism of
of action
action of
of
-chymotrypsin
-chymotrypsin
(An enzyme that hydrolyzes peptides
in the digestive system)
 Catalytic
Catalytic triad:
triad: Asp
Asp102
102
,, His
His , Ser
57 Ser 195
57 , 195

His 57 His 57
CH2 CH2

H H
O O O O N Ser 195
N Ser 195
C C
N N
CH2 CH2
CH2 CH2 H
H O
Asp 102 O
Asp 102 H O
H O
N C N C
1 R R' R R'
2
 -chymotrypsin
-chymotrypsin mechanism…
mechanism…

His 57 His 57
CH2 CH2

H H
O N O O N Ser 195
O Ser 195 C
C N
N CH2
CH2 CH2
CH2
H O
Asp 102 H O Asp 102
H O
H H C O
N C O H
R N R'
R' R
3 4

free amine + acylated serine amine replaced by water

 -chymotrypsin
-chymotrypsin mechanism…
mechanism…

His 57 His 57
CH2 CH2

H H
O N Ser 195 O O N Ser 195
O
C C N
N CH2 CH2
CH2 H CH2 H
O
O
Asp 102 Asp 102
O O
H C O H C O

5 R' 6 R'
free acid
Glycolysis
Glycolysis
Metabolism of glucose to form
pyruvate and ATP
 Glycolysis
Glycolysis converts
converts glucose
glucose into
into
two
two pyruvate
pyruvate molecules
molecules
 …with the production of 2 ATPs (high
energy storage in cells)
1. Isomerization of glucose to fructose
2. Formation of iminium ion; retro aldol to form
two 3-carbon sugars (as phosphates)
3. Isomerization of dihydroxyacetone to
glyceraldehyde (as phosphates)
4. Oxidation, isomerization, dehydration and
dephosphorylation to form pyruvate and ATP
 Isomerization
Isomerization of
of glucose
glucose to
to
fructose
fructose

H O H OH
C C CH2OH
H C OH C OH C O
HO C H HO C H HO C H
H C OH H C OH H C OH
H C OH H C OH H C OH
-2 -2 -2
CH2OPO3 CH2OPO3 CH2OPO3

glucose-6-phosphate glucose-fructose enol fructose-6-phosphate

 Iminium
Iminium ion;
ion; retro
retro aldol
aldol addition
addition

-2
CH2OPO3
-2
CH2OPO3
-2 CH2OPO3

C O C NH Enz C NH Enz
H2N Enz HO C H
HO C H HO C H
H (enol form)
+
H C OH H C O
H C O
H C OH H C OH
-2 -2 H C OH
CH2OPO3 CH2OPO3 -2
CH2OPO3
fructose-1,6-bisphosphate
glyceraldehyde-3-phosphate
 Isomerization
Isomerization to
to glyceraldehyde
glyceraldehyde
-2 -2
CH2OPO3 CH2OPO3
H2O
C NH Enz C O + H2N Enz
HO C H CH2OH

(enol form) dihydroxyacetone-phosphate

H OH H O
CH2OH C C
C O C OH H C OH
-2 -2 -2
CH2OPO3 CH2OPO3 CH2OPO3
dihydroxyacetone-phosphate (enol form) glyceraldehyde-3-phosphate
(turned upsidedown)
 Oxidation,
Oxidation, isomerization
isomerization and
and
dephosphorylation
dephosphorylation (ATP
(ATP forming)
forming)
H O O O O O
C C
[O] -H2O C
H C OH H C OPO3
-2 -2
(sev. steps) C OPO3
-2
CH2OPO3 CH2OH CH2
glyceraldehyde-3-phosphate phosphoenolpyruvate

O O ADP ATP O O
C C
-2
C OPO3 C O
CH2 CH3

phosphoenolpyruvate pyruvate
Biosynthesis
Biosynthesis of
of Steroids
from
from Squalene
Squalene
Squalene
Squalene (a
(a shark
shark oil
oil terpene)
terpene)

squalene
Epoxidation
Epoxidation of
of Squalene
Squalene

squalene oxidase

O
Acid-Catalyzed
Acid-Catalyzed Epoxide
Epoxide
Ring
Ring Opening;
Opening; AA Ring
Ring Formation
Formation

H O
+

+
A

H O
Reaction
Reaction of
of Alkene
Alkene
with
with Carbocation;
Carbocation; B
B Ring
Ring

+
A

H O

+
A B

H O
Cyclization
Cyclization to
to form
form C
C Ring
Ring

+
A B

H O

H
+
C

A B

H O
Cyclization
Cyclization to
to form
form D
D Ring
Ring
H
+

H O

H
+
C D
A B

H O
Hydride
Hydride and
and Methyl
Methyl Shifts
Shifts
H +

H O

H O
Eventually...Cholesterol
Eventually...Cholesterol !!

(several steps)
H O

CH3

CH3 H H

H H
HO
 Grading
Grading // Final
Final Exam
Exam
You may replace any of the 5 Example:
tests by an improved grade
on that section of the Exam. Hour test Exam
1 42 --
Only the higher grade counts.
2 30 38
You need not retake a section if 3 28 42
you are happy with your 4 41 --
grade on that test.
5 37 36
Everyone must take Section 6
(Ch 25, 26, 27 & 29) plus Ch. 25-29 -- 38
Section 7 (comprehensive; compreh. -- 32
mostly synthesis)
Your (best) score on these seven sections plus
the sum of your gla scores determines your grade.