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Main Menu. 14 .1 The Chemistry in Vitamins and Coenzymes. Nicotinamide Adenine Dinucleotide (NAD + ). Coenzyme (co-substrate) or cofactor in redox reactions. Niacinamide Nicotinamide. Niacin (Vitamin B 3 ) Nicotinic acid. - PowerPoint PPT Presentation
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14.1 The Chemistry in Vitamins and Coenzymes
1
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H
N
H
OH OH
H HO
OP
O
O
NH2
O
H
N
H
OH OH
H HO
OP
O
OO
N
N
N
H2N
H
N
H
OH OH
H HO
OP
OO
N
N
N
H2N
O
P
OO
O
N
H H
H OH
H OH
H OH
N
N
NH
O
O
H3C
H3C
H
N
H
OH OH
H HO
OP
OO
N
N
N
H2N
O
P
OO
O
CH2
CH3
CH3
OHO
HNH
NH
O
HS N
N NS
NH2
H3C
H
H3C
OH
OH
N
H H
H OH
H OH
H OH
N
N
NH
O
O
H3C
H3C
N
OH
OOHCH2
CH3
CH3
OHO
HNH
HO
O
N
OH
OHC
HO
H3C
Nicotinamide Adenine Dinucleotide (NAD+)
2
Coenzyme (co-substrate) or cofactor in redox reactions
H
N
H
OH OH
H HO
OPO
O
NH2
O
H
N
H
OH OH
H HO
OP
O
OO
N
N
N
H2N
N
OH
O
Niacin (Vitamin B3)Nicotinic acid
NAD+
N
NH2
O
NiacinamideNicotinamide
N
NHNH2O Isoniazid , also known as isonicotinylhydrazine (INH), is an organic compound that is the first-line medication in prevention and treatment of tuberculosis.
The Chemistry of NAD+
3
Coenzyme (co-substrate) or cofactor in redox reactions
N
NH2
O
N
NH2
OH H
HO O
H
+ H+
Electron-deficient aromatic ring
NAD+ NADH
The redox reactions can be reversible.
Loss of aromaticity
2 e- + H+
It is a 2-electron transfer process.
Often involved in
C=O processes
The Mechanism of NAD+
4
Coenzyme (co-substrate) or cofactor in redox reactions
NAD+
NADHN
NH2
OH H
OH
N
NH2
O
O
H
H
O+ H+
Flavin Adenine Dinucleotide (FAD)
5
Coenzyme (co-substrate) in redox reactions
Riboflavin (vitamin B2) H
N
H
OH OH
H HO
OP
OO
N
N
N
H2N
O
P
OO
O
N
H H
H OH
H OH
H OH
N
N
NH
O
O
H3C
H3C
OH
N
H H
H OH
H OH
H OH
N
N
NH
O
O
H3C
H3C
Ribitol from reduction of ribose.
A solution of riboflavin
Flavin mononucleotide (FMN)
O
N
H H
H OH
H OH
H OH
N
N
NH
O
O
H3C
H3C
PO
OO
NH
N
N
NH
O
O
H3C
H3C
Flavin (from Latin flavus, "yellow")
FAD
The Chemistry of FAD
6
Coenzyme (co-substrate) in redox reactions
N
N
N
NH
O
O
H3C
H3C
N
HN
N
NH
O
O
H3C
H3C
N
HN
NH
NH
O
O
H3C
H3CFAD
e- + H+ e- + H+
Often involved in
C=C processes
FADH.
FADH2
The redox reactions can be reversible.It can be a 2-electron or 1-electron transfer process.
The Mechanism of FAD
7
Coenzyme (co-substrate) in redox reactions
N
N
N
NH
O
O
H3C
H3C
HH
H H
FAD
N
HN
NH
NH
O
O
H3C
H3C
N
HN
N
NH
O
O
H3C
H3C
H
H H
FADH.
FADH2
8
Coenzyme A (CoA, CoA-SH)
H
N
H
OH OH
H HO
OP
OO
N
N
N
H2N
O
P
OO
O
CH2
CH3
CH3
OHO
HNH
NH
O
HS
Transfer of acyl groups
OHCH2
CH3
CH3
OHO
HNH
HO
O
Pantothenic acid (vitamin B5) Coenzyme A
CoA SH
RCO2H H2O
CoA S
R
O Various metabolic pathways
Mechanisms are similar to Fischer esterification and transesterification.
pKa = 9-10
9
Thiamine or Vitamin B1
Cofactor for pyruvate dehydrogenase and a-ketoglutarate dehydrogenase
O
S CoAHS CoA+O-
O
NAD++
pyruvate
pyruvatedehydrogenase
O
+ CO2 + NADH
acetyl CoA
N
N NS
NH2
H3C
H
H3C
O PPi
N
N NS
NH2
H3C H3C
O PPi
+ H+
thiamine pyrophosphate (TPP)
The positive charge of thiazole makes the H more acidic.
10
Mechanism of Pyruvate Dehydrogenase Thiamine pyrophate (TPP), lipoamide and FAD are the catalytic cofactors.
OH
S S
O
Lipoic acid
NH
S S
O NH
O
lipoamide covalently attached to a Lys of the protein.
Mechanism:
NS
H3C
+OH3C
CO2-
+ H+ NS
H3C
H3COH
O
O
Electron deficient (electron sink)
Nucleophilic addition toward C=O
pyruvate
11
Mechanism of Pyruvate Dehydrogenase
S S
NS
H3C
H3CO
+
SH SH
H+
NS
H3C
H3COH
O
O
CO2
NS
H3C
H3COH
NS
H3C
H3COH
decarboxylation
CoA SH
SH SH
H3C O
SCoA
NS
H3C
H3C OH
SH S Similar to the formation of
hemiketal
NS
H3C
H3C O
SH S
H
Regenerate TPP
Acetyl CoA
Similar to the transesterification
12
Mechanism of Pyruvate Dehydrogenase
SH SHFAD
FADH2
S S
NAD+
NADH+H+
regeneratedFAD
regeneratedlipoamide (oxidized form)
R
O
CO2-
pyruvate (R = CH3)
CO2
TPP
E1
R
OH
TPPS
SR'
SHS
R'
OR
E2
HS CoA
SHSH
R'
S CoA
OR
FAD
FADH2
E3
NAD+
NADH
Consume NAD+
and generate NADH
Summary
13
Pyridoxal Phosphate (PLP) or Vitamin B6Common cofactor for aminotransferases
N
OH
C
HO
H3C
O H
CO2-R
NH3
CO2-
NH3O
-O
O
CO2-
+
alanine-ketoglutarate
alanineaminotransferase
CO2-
O
pyruvate
+
glutamate
O
-O
NH3
CO2-
N
OH
C
HO
H3C
N H
R CO2-
+ H2O
PLP
N
OHHO
H3C
N H
R CO2-
H
Formation of imine (Schiff base)
Isomerization of C=N
N
OHHO
H3C
H2N H
R CO2-
H
O
Pyridoxamine phosphate (PMP)
14
Learning Check1. NAD+ is a common co-enzyme involved in biological redox (reduction/oxidation) processes. Without specifying the R group, which nicotinamide (circled) group is aromatic?
N
O
NH2
OO
HO OH
R
NAD+
+ 2H+ + 2e-
N
O
NH2
OO
HO OH
R+ H+
NADH
(a) The one circled in NAD+ because there are 6 p electrons in the aromatic ring.(b) The one circled in NADH because there are 6 p electrons in the aromatic ring.(c) The one circled in NAD+ because there are 10 p electrons in the aromatic ring.(d) The one circled in NADH because there are 10 p electrons in the aromatic ring.(e) None of the above
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