The Electron Transport System
of Mitochondria
Embedded in the inner membrane are
proteins and complexes of molecules that
are involved in the process called electron transport.
The electron transport system (ETS), as it is
called, accepts energy from carriers
in the matrix and stores it to a form that can
be used to phosphorylate ADP. Two energy carriers
are known to donate energy to the ETS, namely nicotine
adenine dinucleotide (NAD) and flavin adenine dinucleotide
(FAD). Reduced NAD carries energy to complex I
(NADH-Coenzyme Q Reductase) of the electron transport
chain. FAD is a bound part of the succinate dehydrogenase
complex (complex II).
It is reduced when the substrate succinate binds the complex.
What happens when NADH binds to
complex I? It binds to a prosthetic group called
flavin mononucleotide (FMN), and is immediately
re-oxidized to NAD. NAD is"recycled," acting as
an energy shuttle.
What happens to the hydrogen
atom that comes off the NADH? FMN receives the
hydrogen from the NADH and two electrons. It also
picks up a proton from the matrix. In this reduced
form, it passes the electrons to iron-sulfur clusters
that are part of the complex, and forces two protons
into the intermembrane space.
The obligatory forcing of protons
into the intermembrane space is a key concept.
Electrons cannot pass through complex I without
accomplishing proton translocation. If you prevent
the proton translocation, you prevent electron
transport. If you prevent electron transport, you
prevent proton translocation. The events must happen
together or not at all.
Electron transport carriers
are specific, in that each carrier accepts electrons
(and associated free energy) from a specific type
of preceeding carrier. Electrons pass from complex
I to a carrier (Coenzyme Q) embedded by itself
in the membrane. From Coenzyme Q electrons are
passed to a complex III which is associated with
another proton translocation event. Note that the
path of electrons is from Complex I to Coenzyme
Q to Complex III. Complex II, the succinate dehydrogenase
complex, is a separate starting point, and is not a
part of the NADH pathway.
From Complex III the pathway is to
cytochrome c then to a Complex IV (cytochrome
oxidase complex). More protons are translocated
by Complex IV, and it is at this site that oxygen
binds, along with protons, and using the electron
pair and remaining free energy, oxygen is reduced
to water. Since molecular oxygen is diatomic, it
actually takes two electron pairs and two cytochrome
oxidase complexes to complete the reaction sequence
for the reduction of oxygen.
This last step in electron transport serves the critical function
of removing electrons from the system so that electron
transport can operate continuously.
The reduction of oxygen is not an
end in itself. Oxygen serves as an electron acceptor,
clearing the way for carriers in the sequence to
be reoxidized so that electron transport can continue.
In your mitochondria, in the absence of oxygen,
or in the presence of a poison such as cyanide,
there is no outlet for electrons. All carriers
remain reduced and Krebs products become out of
balance because some Krebs reactions require NAD
or FAD and some do not. However, you don't really
care about that because you are already dead. The
purpose of electron transport is to conserve energy
in the form of a chemiosmotic gradient. The gradient,
in turn, can be exploited for the phosphorylation
of ADP as well as for other purposes. With the
cessation of aerobic metabolism cell damage is
immediate and irreversible.
From succinate, the sequence
is Complex II to Coenzyme Q to Complex III to cytochrome
c to Complex IV. Thus there is a common electron
transport pathway beyond the entry point, either
Complex I or Complex II. Protons are
not translocated at Complex II. There isn't sufficient
free energy available from the succinate dehydrogenase
reaction to reduce NAD or to pump protons at more
than two sites.
Is the ETS
a sequence?
Before the development of the fluid mosaic model
of membranes, the ETS was pictured as a chain,
in which each complex was fixed in position relative
to the next. Now it is accepted that while the
complexes form 'islands' in the fluid membrane,
they move independently of one another, and exchange
electrons when they are in mutual proximity.
Textbooks necessarily show the ETS as a physical
sequence of complexes and carriers. This has
the unintentional effect of implying that they
are all locked in place. The fluid nature of
membranes allows electron exchange to take place
in a test tube containing membrane fragments.
The location of ETS complexes on
the inner membrane has two major consequences.
By floating in two-dimensional space,
the likelihood of carriers making an exchange
is much higher than if they were in solution
in the three dimensional space of the matrix.
They are exposed to the matrix side of the membrane,
of course, for access to succinate and NADH,
but have limited mobility. Second, the location
of the ETS on the inner membrane enables them
to establish a chemiosmotic gradient.
Electron pathways and inhibition
Electron transport
inhibitors act by binding one or more electron
carriers, preventing electron transport directly.
Changes
in the rate of dissipation of the chemiosmotic
gradient have no effect on the rate of electron
transport with such inhibition. In fact, if electron
transport is blocked the chemiosmotic gradient
cannot be maintained. No matter what substrate
is used to fuel electron transport, only two
entry points into the electron transport system
are known to be used by mitochondria. A consequence
of having separate pathways for entry of electrons
is that an ETS inhibitor can affect one part
of a pathway without interfering with another
part. Respiration can still occur depending on
choice of substrate.
An inhibitor may competely block
electron transport by irreversibly binding to a
binding site. For example, cyanide binds cytochrome
oxidase so as to prevent the binding of oxygen.
Electron transport is reduced to zero. Breathe
all you want - you can't use any of the oxygen
you take in. Rotenone, on the other hand, binds
competitively, so that a trickle of electron flow
is permitted. However, the rate of electron transport
is too slow for maintenance of a gradient.
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