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

THE PROTON PUMPS OF THE ELECTRON-TRANSPORT CHAIN
771
(A) STEP 1 (B) STEP 2
cytochrome c
2 H +
2
c
cristae space
c 1
QH
e –
2 QH 2
QH 2
Q
e –
QH
Q
Q
Q
H +
b L
b H
cytochrome
c reductase
matrix
c
c 1
b L
b H
H +
Because oxygen has a high affinity for electrons, it can release a large amount
of free energy when it is reduced to form water. Thus, the evolution of cellular respiration,
in which O 2 is converted to water, enabled organisms to harness much
more energy than can be derived from anaerobic metabolism. As we discuss later,
the availability of the large amount of energy released by the reduction of molecular
oxygen to form water is thought to have been essential to the emergence of
multicellular life: this would explain why all large organisms respire. The ability
of biological systems to use O 2 in this way, however, requires sophisticated chemistry.
Once a molecule of O 2 has picked up one electron, it forms a superoxide
radical anion (O 2 •– ) that is dangerously reactive and rapidly takes up an additional
three electrons wherever it can get them, with destructive effects on its immediate
environment. We can tolerate oxygen in the air we breathe only because
the uptake of the first electron by the O 2 molecule is slow, allowing cells to use
enzymes to control electron uptake by oxygen. Thus, cytochrome c oxidase holds
QH 2
QH •
H +
e – e –
Figure 14–23 The two-step mechanism
of the cytochrome c reductase Q-cycle.
(A) In step 1, ubiquinol reduced by NADH
dehydrogenase docks to the cytochrome c
reductase complex. Oxidation of the quinol
produces two protons and two electrons.
The protons are released into the cristae
space. One electron passes via an iron-sulfur
cluster to heme c 1 , and then to the soluble
electron carrier protein cytochrome c on the
membrane surface. The second electron
passes via hemes b L and b H to a ubiquinone
(red Q) bound at a separate site near the
matrix side of the protein. Uptake of a proton
from the matrix produces an ubisemiquinone
radical (see Figure 14–17), which remains
bound to this site (red QH • in B).
(B) In step 2, a second ubiquinol (blue
QH 2 ) docks and releases two protons and
two electrons, as described for step 1. One
electron is passed to a second cytochrome
c, whereas the other electron is accepted
by the ubisemiquinone. The ubisemiquinone
takes up a proton from the matrix and is
released into the lipid bilayer as fully reduced
ubiquinol (red QH 2 ).
On balance, the oxidation of one ubiquinol
in the Q cycle pumps two protons through
the membrane by a directional release
and uptake of protons (see Figure 14–21),
while releasing another two into the cristae
space. In addition, in each of the two steps
(A) and (B), one electron is transferred to a
cytochrome c carrier (Movie 14.4).
MBoC6 n14.319/14.23
electrons in from
cytochrome c
subunit II
CRISTA
SPACE
Cu
e –
MATRIX
heme a
Cu
(A)
subunit I
heme a 3
(C)
(B)
Figure 14–24 The structure of cytochrome c oxidase. The final complex in the mitochondrial electron-transfer chain consists of 13 different
protein subunits, with a total mass of 204,000 daltons. (A) The entire dimeric complex is shown, positioned in the crista membrane. The highly
conserved subunits I (green), II (purple), and III (blue) are encoded by the mitochondrial genome, and they form the functional core of the enzyme.
(B) The functional core of the complex. Electrons pass through this structure from cytochrome c via bound copper ions (blue spheres) and hemes
(red) to an O 2 molecule bound between heme a 3 and a copper ion. The four protons needed to reduce O 2 to water are taken up from the matrix; see
also Figure 14–25. (C) This shows the symbol for cytochrome c oxidase used throughout this chapter. (PDB code: 2OCC.)