Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

68 Chapter 2: Cell Chemistry and Bioenergetics
regenerates NADP + , it is the NADPH that is oxidized and the substrate that is
reduced. The NADPH is an effective donor of its hydride ion to other molecules for
the same reason that ATP readily transfers a phosphate: in both cases the transfer
is accompanied by a large negative free-energy change. One example of the use of
NADPH in biosynthesis is shown in Figure 2–37.
The extra phosphate group on NADPH has no effect on the electron-transfer
properties of NADPH compared with NADH, being far away from the region
involved in electron transfer (see Figure 2–36C). It does, however, give a molecule
of NADPH a slightly different shape from that of NADH, making it possible for
NADPH and NADH to bind as substrates to completely different sets of enzymes.
Thus, the two types of carriers are used to transfer electrons (or hydride ions)
between two different sets of molecules.
Why should there be this division of labor? The answer lies in the need to
regulate two sets of electron-transfer reactions independently. NADPH operates
chiefly with enzymes that catalyze anabolic reactions, supplying the high-energy
electrons needed to synthesize energy-rich biological molecules. NADH, by contrast,
has a special role as an intermediate in the catabolic system of reactions that
generate ATP through the oxidation of food molecules, as we will discuss shortly.
The genesis of NADH from NAD + , and of NADPH from NADP + , occur by different
pathways and are independently regulated, so that the cell can adjust the supply
of electrons for these two contrasting purposes. Inside the cell the ratio of NAD +
to NADH is kept high, whereas the ratio of NADP + to NADPH is kept low. This provides
plenty of NAD + to act as an oxidizing agent and plenty of NADPH to act as
a reducing agent (Figure 2–37B)—as required for their special roles in catabolism
and anabolism, respectively.
There Are Many Other Activated Carrier Molecules in Cells
Other activated carriers also pick up and carry a chemical group in an easily transferred,
high-energy linkage. For example, coenzyme A carries a readily transferable
HO
NADPH
7-dehydrocholesterol
C
C
H
+ H +
(B)
oxidizing agent
for catabolism
NADP
NAD + +
NADH
NADPH
reducing agent
for anabolism
NADP +
(A)
HO
C
C
H
H
H
cholesterol
Figure 2–37 NADPH as a reducing agent. (A) The final stage in the biosynthetic route leading to
cholesterol. As in many other biosynthetic reactions, the reduction of the C=C bond is achieved by
the transfer of a hydride ion from the carrier molecule NADPH, plus a proton (H + ) from the solution.
(B) Keeping NADPH levels high and NADH levels low alters their affinities for electrons (see
Panel 14–1, p. 765). This causes NADPH to be a much stronger electron donor (reducing
agent) than NADH, and NAD + therefore to be a much better electron acceptor (oxidizing
agent) than NADP + , as indicated ṀBoC6 m2.61/2.37