CHAPTER 20

20.1 OxidativePhosphorylation in Eukaryotestakes 20.2 Oxidative Phosphorylation Depends

Place in Mitochondria on ElectronTransfer

Theflowofelectrons through the respiratory chain and

the NADH t FADHz that were generated in the
process ofATP synthesis takeplace in the

mitochondrial innermembrane citricAcid cycle are used intheelectrontransportchain

Mitochondria

arebound a double Membrane by In oxidative phosphorylation,

Twomembrane
systems outer and inner the inner electrons from NADH and Theelectrontransportchain is a

membrane is folded into a series of internal ridgescalled FADH2 are used to reduce seriesofcoupled Oxidation Reducti

molecular oxygen to water. The
crista

highly exergonic reduction of
Reactions

Therefore there is an intermembrane

space between molecular oxygen by NADH and

FADH2 is accomplished through a
eflowfromNADH to Ozis accomplish
the outer andinner The increase in surface intermediate
number of electron-transfer byAsaweseries of steps
area of the inner will see, NADH is oxidized by passing
reactions, which take place in a
mitochondrial membrane
electrons to flavin mononucleotide (FMN), an
provided by the cristae set of membrane proteins known
electron carrier similar to flavin adenine
creates more sites for as the electron-transport chain.
dinucleotide (FAD) but lacking the nucleotide
oxidative phosphorylation
than would be the case component (FIGURE 20.5). Reduced FMN is
with a simple, unfolded subsequently oxidized by the next electron carrier
in the chain, and the process repeats itself as the
membrane.
electrons flow down the electron-transport chain

Human beings contain an

estimated 14,000 m2 of
membrane
Outer
very permeable
Electrons are transferred from Appear tobe associatedin a
inner mitochondrial NADH to O2 through a chain of
membrane, which is the In contrast the inner membrane

three large protein complexes called
supramolecular complex whichfacilita

very IMPERMEABLE of
approximate equivalent to
the area of three football
is
NADH-Q oxidoreductase, Q- therapidtransfer substrate andprev
cytochrome c oxidoreductase, and
elds in the United States.
cytochrome c oxidase
thereleaseofreactionintermediates
Gmitochondrial porin, a 30-
to 35-kDa pore-forming
7 A large family of transporters protein also known as
shuttle metabolites such as ATP, VDAC, for voltage-
GA fourth large protein complex,
pyruvate, and citrate across the dependent anion channel. called succinate-Q reductase,

inner mitochondrial membrane. contains the succinate

dehydrogenase that generates

FADH2 in the citric acid cycle

20.2
Continued

h Electrons from this
FADH2 enter the electron-
Another key feature of the electron-transport chain is the prominence of
G
transport chain at Q-
coenzyme Q (Q) as an electron carrier. Coenzyme Q, also known as ubiquinone
cytochrome c
because it is a ubiquitous quinone in biological systems, is a quinone derivative
oxidoreductase. Electrons flow down an energy gradient from
with a long isoprenoid tail, which renders the molecule hydrophobic and allows it to
NADH to O2. The flow is catalyzed by four protein
diffuse rapidly within the inner mitochondrial membrane, where it shuttles protons
First, electrons from FADH2 feed into
complexes. Iron is a component of all of the
and electrons about.
the chain “downstream” of those from
complexes as well as cytochrome c, which links
NADH because the electrons of

complex III with complex IV.
GCoenzyme Q consists of more than one 5-carbon isoprene unit.

FADH2 have a lower reduction potential

. As a result, FADH2-derived electrons GSecond, note that iron is a prominent electron
hThe exact number depends on the species in which it is found. The most
pump fewer protons and thus yield carrier, appearing in several places. Iron in the
common form in mammals contains 10 isoprene units
fewer molecules of ATP. electron-transport chain appears in two
(coenzyme Q10).
fundamental forms: associated with sulfur as iron–
In both iron–sulfur proteins and

Gcytochromes, iron shuttles between its sulfur clusters located in iron–sulfur proteins (also

called nonheme-iron proteins; ) and as
Quinones can exist in several oxidation states (FIGURE 20.9). In the fully oxidized reduced ferrous (Fe2+) and oxidized

components of a heme-prosthetic group, which are
state (Q), coenzyme Q has two keto groups. The addition of one electron yields a ferric state (Fe3+)
embedded in a special class of proteins called

semiquinone radical anion (Q⋅−),whereas the addition of one electron and one cytochromes

The fact that iron is an electron
proton results in the semiquinone form (QH⋅). carrier in several places in the

electron-transport chain raises a

puzzling question.
The reduction of

G The addition of a second electron Gubiquinone (Q) to The answer to the puzzle is that the oxidation–reduction potential of

and proton generates ubiquinol iron ions can be altered by their environment. In regard to the electron-
(QH2), the fully reduced form of ubiquinol (QH2)

transport chain, the iron ion is not free; rather, it is embedded in

coenzyme Q. proceeds through a different proteins, enabling iron to have various reduction potentials and

semiquinone to play a role at several different locations in the chain.

intermediate (QH⋅).

 Thus, for quinones, electron-transfer

reactions are coupled to proton binding

TheRespiratoryChainConsistsof
20.3
and release, a property that is key to and aPhysicallinktotheCitric
ProtonPumps

transmembrane proton transport. A pool Acid

Cycle
of Q and QH2—the Q pool—is thought The

High

ofNADHEnterthe
PotentialElectrons
to exist in the inner mitochondrial

RespiratoryChainatNADH Q Oxidoreductase
membrane, although recent research

suggests that it is confined to the protein The electrons of NADH enter the chain at NADH-Q oxidoreductase

complexes of the electron transport chain. (also called Complex I and NADH dehydrogenase), an enormous

enzyme (>900 kDa) consisting of 45 polypeptide chains

organized into 14 core subunits that are conserved in all species

This proton pump is L-shaped, with a

hydrophobic horizontal arm lying in the and two types of prosthetic groups: FMN and iron–sulfur clusters.

membrane and a hydrophilic vertical arm

The electrons flow from NADH to FMN and What structural elements are required for proton pumping?

then through a series of seven iron–sulfur -The membrane-embedded part of the complex has four proton half-

clusters to Q. Note that all of the redox channels consisting, in part, of vertical helices. One set of half-

reactions take place in the extramembranous channels is exposed to the matrix; the other, to the intermembrane
space.

part of NADH-Q oxidoreductase.

-The vertical helices are linked on the matrix side by a long

horizontal helix (HL) that connects the matrix half-channels, while

the intermembrane space half-channels are joined by a series of

β-hairpin-helixconnecting elements (βH).

-An enclosed Q chamber, the site where Q accepts electrons from

NADH, exists near the junction of the hydrophilic portion and the
membrane-embedded portion.

-Finally, a hydrophilic funnel connects the Q chamber to a water-

lined channel, into which the half-channels open, that extends the

entire length of the membrane-embedded portion.