Essential Cell Biology 5th edition

Molecular Mechanisms of Electron Transport and Proton Pumping
475
electrons
donated by
cytochrome c
subunit II
e –
Cu
INTERMEMBRANE
SPACE
MATRIX
heme a
Cu
heme
oxygenbinding
site
subunit I
(A)
(B)
Figure 14–24 Cytochrome c oxidase is a finely tuned protein machine. The protein is a dimer formed from a
monomer with 13 different protein subunits. (A) The entire protein is shown positioned in the inner mitochondrial
membrane. The three colored subunits that form the functional core of the complex are encoded by the
mitochondrial genome; the remaining subunits are encoded by the nuclear genome. (B) As electrons pass through
this protein on the way to its bound O 2 molecule, they cause the protein to pump protons across the membrane.
As indicated, a heme and a copper atom (Cu) form the site where a tightly bound O 2 molecule will receive four
electrons to produce H 2 O. Only two of the 13 subunits are shown.
ECB5 e14.26/14.26
The active site of cytochrome c oxidase therefore holds on tightly to
an oxygen molecule until it receives all four of the electrons needed to
convert it to two molecules of H 2 O. This retention is critical, because it
prevents superoxide radicals from attacking macromolecules throughout
the cell—a type of damage that has been postulated to contribute to
human aging.
The evolution of cytochrome c oxidase allowed cells to use O 2 as an electron
acceptor, and this protein complex is essential for all aerobic life.
Poisons such as cyanide are extremely toxic because they bind tightly to
cytochrome c oxidase complexes, thereby halting electron transport and
the production of ATP.
INTERMEMBRANE
SPACE
HIGH
H + affinity
H + LOW
H + affinity
H +
MATRIX
H +
energy from
electron transport
Figure 14–25 Proton pumping is coupled to electron transport. This type of mechanism is thought to be used by the NADH
dehydrogenase complex and by cytochrome c oxidase, as well as by many other proton pumps. The protein is driven through a cycle
of three conformations. In one of these conformations, the protein has a high affinity for H + , causing it to pick up an H + on the matrix
side of the membrane. In another conformation, the protein has a low affinity for H + , causing it to release an H + on the other side of the
membrane. As indicated, the cycle goes only in one direction—releasing the proton into the intermembrane space—because one of
the steps is driven by allosteric change in conformation driven by the energetically favorable transport of electrons.
ECB5 m14.28-14.27