Human Physiology, 14th edition (2016)

Enzymes and Energy 101

therefore indicated by NADH  1  H^1 (the H^1 represents a free

proton). When the reduced forms of these two coenzymes par-

ticipate in an oxidation-reduction reaction, they transfer two

hydrogen atoms to the oxidizing agent ( fig. 4.18 ). The ability

of FAD and NAD to transfer protons and electrons in this way

is particularly important in metabolic reactions that provide

energy (ATP) for the cells, as described in chapter 5.

Each FAD can accept two electrons and can bind two pro-
tons. Therefore, the reduced form of FAD is combined with
the equivalent of two hydrogen atoms and may be written as
FADH 2. Each NAD can also accept two electrons but can bind
only one proton (see fig.  4.17 ). The reduced form of NAD is

Figure 4.18 The action of NAD. NAD is a coenzyme
that transfers pairs of hydrogen atoms from one molecule to
another. In the first reaction, NAD is reduced (acts as an oxidizing
agent); in the second reaction, NADH is oxidized (acts as a
reducing agent). Oxidation reactions are shown by red arrows,
reduction reactions by blue arrows.

X–H 2 NAD

X NADH + H+ NADH + H+

NAD is oxidizing agent

(it becomes reduced)

NADH is reducing agent

(it becomes oxidized)

Y

NAD Y–H 2

Figure 4.17 Structural formulas for NAD^1 , NADH, FAD, and FADH 2. ( a ) When NAD^1 reacts with two hydrogen atoms,
it binds to one of them and accepts the electron from the other. This is shown by two dots above the nitrogen ( N ) in the formula ̈
for NADH. ( b ) When FAD reacts with two hydrogen atoms to form FADH 2 , it binds each of them to a nitrogen atom at the reaction
sites.

CNH 2

O

N

+

Reaction

site

(a)

(b)

Oxidized state

N

HH

..

Reduced state

+ 2 +

NAD+ NADH

Rest of the molecule

Two electrons added

Rest of the molecule

NN

NH

H N

3 C

H 3 C

FAD

Oxidized state

FADH 2

Reduced state

OO

OO

Reaction

site

Reaction

site

NN

NH

H N

3 C

H 3 C

H

H

+ 2

Rest of the molecule Rest of the molecule

H

H

H+

CLINICAL APPLICATION

We need niacin because it is converted into nicotinamide,

which forms nicotinamide adenine dinucleotide (NAD) and

nicotinamide adenine dinucleotide phosphate (NADP). These

function as coenzymes for the transfer of electrons in oxida-

tion-reduction reactions within mitochondria, which are the

processes by which our cells obtain energy for ATP produc-

tion from the breakdown of food. Similarly, we need riboflavin

to form flavin adenine dinucleotide (FAD) for the same mito-

chondrial processes that yield ATP. Niacin and riboflavin do

not directly provide the cells with energy, and eating exces-

sive amounts of these vitamins will not increase the food

energy available to the body.