They need replenishing only to the extent that they are accidentally
lost or degraded. We have lost what ability we once had to synthesize
nicotinic acid and riboflavin biologically, and are forced to obtain
the raw materials for NAD+ and FAD from our diet. Substances
such as these, which are needed only in minute quantities but nevertheless
are absolutely essential in these quantities, are termed vitamins.
Vitamin A, the precursor of retinal, is one example. Riboflavin
is vitamin B2, and nicotinic acid is niacin. Niacin deficiency
in humans causes penagra, a disease once common in the American
rural South but which now has been largely eradicated.
When NAD+ is reduced, one H binds to the ring, the electron
from the second H cancels the positive charge, and the proton goes
into solution, as shown above. When FAD is reduced, two hydrogen
atoms are attached to the flavin ring at two points, as at the left.
Energy is stored in both of these reduced molecules, to be released
again when the carrier molecule is reoxidized. Just as the amount
of energy obtained in an oxidation depends on what is used as the
oxidizing agent, so the energy that we can think of as stored in
reduced NADH or FADH2 varies with the substances used
to reoxidize them.
In normal 02 respiration, reoxidization of NADH takes place with
a liberation of 52.7 kcal mole-' of free energy: (next
NADH + H+ + ½O2 --> NAD+
+ H20 D` = 52.7 kcal mole-'
(The prime indicates a free energy change under the physiological
conditions of pH 7, or [H+] = 1(-7 mole litre-1, rather
than 1 mole litre-l.) Under these conditions we can think
of each mole of NADH as "carrying" 52.7 kcal of free energy
from the place where it was reduced to the place where it will be
reoxidized. A mole of FADH2 carries somewhat less energy:
FADH2 + ½02 --> FAD + H20
D` = -36.2 kcal mole-'
The dinucleotides NAD+ and FAD, and the nucleotide ATP,
cooperate as "big buckets" and "little buckets"
for energy in the energy extracting processes of living cells. When
foodstuffs are broken down, 53-kcal quantities of energy are stored
by reducing NAD+ to NADH, or smaller amounts by reducing
FAD to FADH2. These reduced dinucleotides, no matter
what their source, then can funnel into a common respiratory machinery
that reoxidizes them and transfers their energy in smaller packages
to ATP: three ATP per NADH molecule reoxidized, or two ATP per FADH2.
In the banking analogy for energy storage in Chapter 21, NADH molecules
are the nickels of the energy coinage and ATP molecules are the