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Chem 109 C
Fall 2014
Armen Zakarian
Office: Chemistry Bldn 2217
summary of previous sections
Catalysis (ch 23)
definition of catalyst, energy diagrams illustrating catalytic action
types of catalysis:
acid: specific and general
base: specific and general
nucleophilic: stronger Nu are better catalysts
metal-ion: types of activation
intramolecular reactions
why are they faster? effective molarity etc…
intramolecular catalysis: examples of each class (acid, base, Nu, metal)
overview of enzyme catalyzed reactions:
names of enzyme (“substrate” …..ase)
lock-and-key model
induced-fit model
examples of enzyme catalysis
carboxypeptidase A, chymotrypsin: what is going on in the active site
(what types of catalysis occur there?)
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Chapter 24: Coenzymes
Overview and Introduction:
•  many enzymes are inactive without cofactors
•  cofactors are 1) metal ions or 2) coenzymes
•  coenzymes - organic molecules, derived from vitamins
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Chapter 24: Coenzymes
Definitions:
!  holoenzyme
!  apoenzyme
Metabolism:
catabolism
anabolism
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Chapter 24: Coenzymes
page 1133
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Chapter 24: Coenzymes
factors characterizing a coenzyme:
•  structure
•  associated vitamin
•  type of reaction catalyzed
•  reaction mechanism
•  dietary source
•  associated disease
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NAD+-NADH, NADP+-NADPH
O
H H
NH2
O
O
-O
OH
HO
-O
NH2
P
O
N
O
HO
NAD+
OH
OH
HO
O
N
NH2
N
N
-O
O
N
NH2
O
N
vitamin:
O
P
N
N
O
O
O
O
-O
NH2
N+
O
P
O
P
O
N
O
nicotinamide
N
HO
OH
NADH
•  catalyze redox (oxidation-reduction) reactions
•  source of nicotinamide: meats, vegetables, peanuts etc. (not tobacco).
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•  deficiency disease: pellagra (skin lesions, sensitivity to light etc.)
NAD+-NADH, NADP+-NADPH
O
H H
NH2
O
O
-O
OH
HO
-O
NH2
P
O
N
O
HO
NAD+
OH
OH
HO
O
N
NH2
N
N
-O
O
N
NH2
O
N
vitamin:
O
P
N
N
O
O
O
O
-O
NH2
N+
O
P
O
P
O
N
O
nicotinamide
N
HO
OH
NADH
•  catalyze redox (oxidation-reduction) reactions
•  source of nicotinamide: meats, vegetables, peanuts etc. (not tobacco).
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•  deficiency disease: pellagra (skin lesions, sensitivity to light etc.)
NAD+-NADH, NADP+-NADPH
O
H H
NH2
O
-O
O
HO
OH
P
O
N
HO
HO
O
O
O P
O-
NADP+
-O
N
NH2
P
O
nicotinamide
N
N
HO
O-
O
OH
N
N
N
NH2
O
O
vitamin:
O
P
N
N
O
-O
NH2
O
-O
O
O
P
NH2
N+
O
O
O
N
O
O P
O-
O-
NADPH
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FAD-FADH2, FMN-FMNH2
NH2
N
N
N
N
O
O
O
P
P
O -O -O
O
O
OH
HO
OH
OH
OH
H
H
H
CH2
N
O
NH
N
O
FAD
N
N
N
N
O
O
O
P
P
O -O -O
O
O
OH
HO
OH
OH
OH
H
H
H
CH2
N
vitamin B2:
NH2
N
N
H
H
N
O
NH
OH
H
H
H
OH
OH
OH
CH2
N
N
N
O
NH
O
riboflavin
O
FADH2
•  catalyze redox (oxidation-reduction) reactions
•  source of riboflavin: milk, liver, mushrooms, etc.
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•  deficiency disease: skin inflammation, cracked lips, sensitivity to light…
FAD-FADH2, FMN-FMNH2
O
P
O - OO
OH
OH
OH
H
H
H
H
H
H
CH2
N
CH2
N
NH
N
O
FMN
O
vitamin B2:
O
P
O - OO
OH
OH
OH
N
N
H
FMNH2
H
N
OH
H
H
H
OH
OH
OH
CH2
O
N
N
NH
NH
N
O
O
O
riboflavin
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NAD+, NADP+
Oxidation with NAD+ (or NADP+):
OH
R
O
dehydrogenase
+ NAD+
R'
+ :B-
R
R'
+ NADH
+
H-B
General mechanism of oxidation:
:BH
R'
R
R'
O
oxidation of alcohol
H
H-B
R
R'
R
O-
H
O
O
H H O
O
NH2
NH2
NH2
N+
N
R
R
N+
R
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NAD+, NADP+
Oxidation with NAD+ (or NADP+), examples:
OH
-OOC
malate
COO-
+ NAD+
+ :B-
malate
dehydrogenase
O
-OOC
COO-
+ NADH
+
oxaloacetate
•  important reaction in the citric acid cycle
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H-B
NAD+, NADP+
Reduction with NADH (or NADPH), a reverse process:
O
R
OH
dehydrogenase
R'
+ NADH
+
H-B
R
R'
+ NAD+
+ :B-
General mechanism of reduction:
:BR'
H
H-B
R
R'
reduction of
carbonyl group
O
R
O
H
O
H H O
NH2
NH2
N
N+
R
R
•  NADH and NADPH are
H¯
donors
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NAD+, NADP+
Reduction with NADH (or NADPH), examples:
O
homoserine
dehydrogenase
NH3+
COO-
+ NADPH
β-aspartate semialdehyde
+
H-B
HO
NH3+
COO-
+ NADP+ + :B-
homoserine
•  important reaction in an anabolic pathway
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NAD+, NADP+
Oxidation - a more complex example:
glyceraldehyde-3-phosphate
dehydrogenase
O
O
OH
OPO32-
+
NAD+
+
O
-O P
-O OH
OPO32OH
+ NADH
+
OPO32-
D-glyceraldehyde-3-phosphate
D-1,3-diphosphoglycerate
R'
R
O-
H
O
NH2
N+
R
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H+
NAD+, NADP+
O
glyceraldehyde-3-phosphate
dehydrogenase
O
O
OH
+ NAD+
+
-O P
-O
OPO32-
OPO32OH
OH
+ NADH
H+
+
OPO32-
D-glyceraldehyde-3-phosphate
D-1,3-diphosphoglycerate
O
R
B-
H
substrate
H
GAP
S
H
R
R
O
H
B
S
ONAD+
H
NAD+
B-
H
H
R
NAD+
S
+
O
O
C
B
H
P OOproduct
H
R
S
O
O
-O
R
OP
O
O-
B
S
NAD+
S
O
NADH
NAD+
R
B
NADH
O
-O P
-O OH
O
NAD+
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NAD+, NADP+
Stereochemistry of enzymatic reactions
Ha
CH3
alcohol
dehydrogenase
Hb
+ NAD+
OH
Hb
CH3
+ NADHa +
O
H+
:BR'
H
H-B
R
R'
reduction of
carbonyl group
O
R
O
Ha
O
Ha Hb O
NH2
NH2
N
N+
R
R
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