14.1 The Chemistry in
Vitamins and Coenzymes
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Nicotinamide Adenine Dinucleotide
(NAD+)
Coenzyme (co-substrate) or cofactor in redox reactions
Niacin (Vitamin B3)
Nicotinic acid
NAD+
Niacinamide
Nicotinamide
Isoniazid , also known as
isonicotinylhydrazine (INH), is an
organic compound that is the firstline medication in prevention and
treatment of tuberculosis.
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The Chemistry of NAD+
Coenzyme (co-substrate) or cofactor in redox reactions
NAD+
NADH
2 e- + H+
Electron-deficient
aromatic ring
Loss of aromaticity
Often
involved in
C=O
processes
The redox reactions can be reversible.
It is a 2-electron transfer process.
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The Mechanism of NAD+
Coenzyme (co-substrate) or cofactor in redox reactions
NAD+
NADH
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Flavin Adenine Dinucleotide (FAD)
Coenzyme (co-substrate) in redox reactions
Ribitol from
reduction of
ribose.
FAD
Riboflavin (vitamin B2)
Flavin
mononucleotide
(FMN)
A solution of
riboflavin
Flavin (from Latin
flavus, "yellow")
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The Chemistry of FAD
Coenzyme (co-substrate) in redox reactions
FADH.
FAD
e- + H+
e- + H+
FADH2
Often
involved in
C=C
processes
The redox reactions can be reversible.
It can be a 2-electron or 1-electron transfer process.
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The Mechanism of FAD
Coenzyme (co-substrate) in redox reactions
FADH.
FAD
FADH2
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Coenzyme A (CoA, CoA-SH)
Transfer of acyl groups
Coenzyme A
pKa = 9-10
Pantothenic acid (vitamin B5)
Various
metabolic
pathways
Mechanisms are similar to
Fischer esterification and
transesterification.
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Thiamine or Vitamin B1
Cofactor for pyruvate dehydrogenase and a-ketoglutarate
dehydrogenase
thiamine pyrophosphate
(TPP)
The positive charge of thiazole
makes the H more acidic.
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Mechanism of Pyruvate Dehydrogenase
Thiamine pyrophate (TPP), lipoamide and FAD are the catalytic cofactors.
Lipoic acid
lipoamide covalently attached to a Lys of the protein.
Mechanism:
pyruvate
Nucleophilic addition
toward C=O
Electron deficient
(electron sink)
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Mechanism of Pyruvate Dehydrogenase
decarboxylation
Similar to the
transesterification
Acetyl CoA
Regenerate TPP
Similar to the
formation of
hemiketal
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Mechanism of Pyruvate Dehydrogenase
regenerated
lipoamide
(oxidized form)
Consume NAD+
and generate
NADH
Summary
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Pyridoxal Phosphate (PLP) or Vitamin B6
Common cofactor for aminotransferases
PLP
Formation of imine
(Schiff base)
Isomerization of
C=N
Pyridoxamine
phosphate (PMP)
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Learning Check
1. NAD+ is a common co-enzyme involved in biological redox
(reduction/oxidation) processes. Without specifying the R group, which
nicotinamide (circled) group is aromatic?
O
O
NH2
NH2
N
O
O
R
HO
+ 2H+ + 2e-
OH
NAD
+
N
O
O
R
HO
+ H+
OH
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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