Organic Chemistry

Section 25.2 Niacin: The Vitamin Needed for Many Redox Reactions 1043

recognized by the enzyme. Molecular recognitionallows the enzyme to bind the
substrate and the coenzyme in the proper orientation for reaction.
In addition, a redox reagent found in a biological system must be less reactive than a
laboratory redox reagent because it must be selective. For example, a biological reduc-
ing agent cannot reduce just any reducible compound with which it comes into contact.
Biological reactions are much more carefully controlled than that. Because the coen-
zymes are relatively unreactive compared with nonbiological redox agents, the reaction
between the substrate and the coenzyme does not occur at all or takes place very slowly
without the enzyme. For example, NADH will reduce an aldehyde or a ketone only in
the presence of an enzyme. and are more reactive hydride donors—
much too reactive to exist in the aqueous environment of the cell. Similarly, is a
much more selective oxidizing agent than the typical oxidizing agents used in the labo-
ratory; for example, will oxidize an alcohol only in the presence of an enzyme.
Because a biological reducing agent must be recycled (rather than having its oxi-
dized form thrown away as would be the case for a reducing agent used in a laboratory),
the equilibrium constant between the oxidized and reduced forms is generally close to
unity. Therefore, biological redox reactions are not highly exergonic; rather, they are
equilibrium reactions that are driven in the appropriate direction by the removal of
reaction products as a result of participation in subsequent reactions.
As you study the coenzymes in this chapter, don’t let the complexity of their struc-
tures deter you. Notice that only a small part of the coenzyme is actually involved in
the chemical reaction. Notice also that the coenzymes follow the same rules of organ-
ic chemistry as do the simple organic molecules with which you are familiar.
We saw in Section 5.16 that an oxidizing enzyme can distinguish between the two
hydrogens on the carbon from which it catalyzes the removal of a hydride ion. For
example, alcohol dehydrogenase removes only the pro-Rhydrogen, of ethanol.
( is the pro-Shydrogen.)

Similarly, a reducing enzyme can distinguish between the two hydrogens at the
4-position of the nicotinamide ring of NADH. An enzyme has a specific binding site for
the coenzyme, and when it binds the coenzyme, it blocks one of its sides. If the enzyme
blocks the B-side of NADH, the substrate will bind to the A-side and the hydride ion
will be transferred to the substrate. If the enzyme blocks the A-side of the coenzyme, the
substrate will have to bind to the B-side and the hydride ion will be transferred. Cur-
rently, 156 dehydrogenases are known to transfer Ha,and 121 are known to transfer Hb.

Hb

Ha

CH 3 OH + NAD+

alcohol

dehydrogenase

Hb

Ha

CH 3 CO+ NADHa + H+

Hb

ethanol acetaldehyde

Hb

Ha,

NAD+

NAD+

NaBH 4 LiAlH 4

R N

C

O

Hb

Ha H

substrate

A-side

B-side

R N

C

C

H 2 N

O

O

Hb

Ha

H

The enzyme blocks the B-side of the coenzyme,

so the substrate binds to the A-side.

The enzyme blocks the A-side of the coenzyme,

so the substrate binds to the B-side.

enzyme

C

H 2 N

O