Organic Chemistry

Section 25.2 Niacin: The Vitamin Needed for Many Redox Reactions 1041

The differentiation between the coenzymes used in catabolism and anabolism is
maintained because the enzymes that catalyze these oxidation–reduction reactions
exhibit strong specificity for a particular coenzyme. For example, an enzyme that
catalyzes an oxidation reaction can readily tell the difference between and
if the enzyme is in a catabolic pathway, it will bind but not
In addition, the relative concentrations of the coenzymes in the cell encourage binding
of the appropriate coenzyme. For example, because and NADH are catabolic
coenzymes and catabolic reactions are most often oxidation reactions, the
concentration in the cell is much greater than the NADH concentration. (The cell
maintains its ratio near 1000.) Because and NADPH are
anabolic coenzymes and anabolic pathways are predominantly reduction reactions, the
concentration of NADPH in the cell is greater than the concentration of
(The ratio of is maintained at about 0.01.)

Mechanisms for Pyridine Nucleotide Coenzymes
How do these oxidation–reduction reactions take place? All the chemistry of the
pyridine nucleotide coenzymes ( NADH, and NADPH) takes place at
the 4-position of the pyridine ring. The rest of the molecule is important for binding the
coenzyme to the proper site on the enzyme. If a substrate is being oxidized, it donates a
hydride ion to the 4-position of the pyridine ring. In the following reaction, the
primary alcohol is oxidized to an aldehyde. A basic amino acid side chain of the en-
zyme can help the reaction by removing a proton from the oxygen in the substrate.

Glyceraldehyde-3-phosphate dehydrogenase is an example of an enzyme that uses
as an oxidizing coenzyme. The enzyme catalyzes the oxidation of the aldehyde
group of glyceraldehyde-3-phosphate (GAP) to an anhydride of a carboxylic acid and
phosphoric acid. This is a reaction that occurs in glycolysis (Figure 25.3).

In the first step of the mechanism for this reaction, an SH group of a cysteine side
chain at the active site of the enzyme reacts with glyceraldehyde-3-phosphate to form a
tetrahedral intermediate. A side chain of the enzyme increases cysteine’s nucleophilici-
ty by acting as a general-base catalyst. The tetrahedral intermediate expels a hydride
ion, transferring it to the 4-position of the pyridine ring of an that is bonded to
the enzyme at an adjacent site. NADH dissociates from the enzyme, and the enzyme
binds a new NAD+.Phosphate reacts with the thioester, forming the anhydride product

NAD+

NAD+

O

N+

oxidation of substrate

reduction of coenzyme

CNH 2

O

OHB

N

CNH 2

R R

HH

H

OH B– C

H

H

4

3

6 2

5

1

C

(H-)

NAD+, NADP+,

[NADP+]>[NADPH]

NADP+.

[NAD+]>[NADH] NADP+

NAD+

NAD+

NADP+; NAD+, NADP+.

NAD+

O O

+

-aspartate-semialdehyde

HCCH 2 CHCO− NADPH + H+

O

+

homoserine

HOCH 2 CH 2 CHCO− NADP+

+NH

3

homoserine

dehydrogenase

+NH

3

D-glyceraldehyde-3-phosphate

CH

CH 2 OPO 32 −

O

H OH ++NAD+ ++NADH H+

D-1,3-diphosphoglycerate

COPO 32 −

CH 2 OPO 32 −

O

− H OH

O OH

O

−O

P

glyceraldehyde-

3-phosphate

dehydrogenase

Tutorial:

Mechanisms of - and

NADH-dependent reactions

NAD+