Electron Transport Chains

An electron transport chain, or ETC, is the relationship ΔG = -nFΔE, where n =

composed of a group of protein the number of electrons transferred and
complexes in and around a membrane F = Faraday's constant. The larger a
that help energetically couple a series of positive ΔE, the more exergonic the
exergonic/spontaneous red/ox reactions red/ox reaction is.
to the endergonic pumping of protons
across the membrane to generate an
Step 3: If sufficient energy is
electrochemical gradient. This
transferred during an exergonic red/ox
electrochemical gradient creates a free
step, the electron carrier may couple
energy potential that is termed a proton
this negative change in free energy to
motive force whose energetically
the endergonic process of transporting a
"downhill" exergonic flow can later be
proton from one side of the membrane
coupled to a variety of cellular
to the other.
processes.

ETC overview
Step 4: After usually multiple red/ox
Step 1: Electrons enter the ETC from transfers, the electron is delivered to a
an electron donor, such as NADH or molecule known as the terminal electron
FADH2, which are generated during a acceptor. In the case of humans, the
variety of catabolic reactions, including terminal electron acceptor is oxygen.
those associated glucose oxidation. However, there are many, many, many,
Depending on the number and types of other possible electron acceptors in
electron carriers of the ETC being used nature; see below.
by an organism, electrons can enter at a
Note: Possible discussion
variety of places in the electron
transport chain. Entry of electrons at a Electrons entering the ETC do not have
specific "spot" in the ETC depends upon to come from NADH or FADH2. Many
the respective reduction potentials of other compounds can serve as electron
the electron donors and acceptors. donors; the only requirements are (1)
that there exists an enzyme that can
oxidize the electron donor and then
Step 2: After the first red/ox reaction,
reduce another compound, and (2) that
the initial electron donor will become
the ∆E0' is positive (e.g., ΔG<0). Even
oxidized and the electron acceptor will
small amounts of free energy transfers
become reduced. The difference in
can add up. For example, there are
red/ox potential between the electron
bacteria that use H2 as an electron
acceptor and donor is related to ΔG by
donor. This is not too difficult to believe
because the half reaction 2H+ + 2 complex itself. Once the complex is
e-/H2 has a reduction potential (E0') of reduced, the complex can serve as an
-0.42 V. If these electrons are electron donor for the next reaction.
eventually delivered to oxygen, then the
How do ETC complexes transfer
ΔE0' of the reaction is 1.24 V, which
electrons?
corresponds to a large negative ΔG (-
ΔG). Alternatively, there are some As previously mentioned, the ETC is
bacteria that can oxidize iron, Fe2+ at composed of a series of protein
pH 7 to Fe3+ with a reduction potential complexes that undergo a series of
(E0') of + 0.2 V. These bacteria use linked red/ox reactions. These
oxygen as their terminal electron complexes are in fact multi-protein
acceptor, and, in this case, the ΔE0' of enzyme complexes referred to
the reaction is approximately 0.62 V. as oxidoreductases or
This still produces a -ΔG. The bottom simply, reductases. The one exception
line is that, depending on the electron to this naming convention is the
donor and acceptor that the organism terminal complex in aerobic respiration
uses, a little or a lot of energy can be that uses molecular oxygen as the
transferred and used by the cell per terminal electron acceptor. That enzyme
electrons donated to the electron complex is referred to as an oxidase.
transport chain. Red/ox reactions in these complexes are
What are the complexes of the ETC?
typically carried out by a non-protein
moiety called a prosthetic group. The
ETCs are made up of a series (at least prosthetic groups are directly involved in
one) of membrane-associated red/ox the red/ox reactions being catalyzed by
proteins or (some are integral) protein their associated oxidoreductases. In
complexes (complex = more than one general, these prosthetic groups can be
protein arranged in a quaternary divided into two general types: those
structure) that move electrons from a that carry both electrons and protons
donor source, such as NADH, to a final and those that only carry electrons.
terminal electron acceptor, such as
oxygen. This particular donor/terminal Note!
acceptor pair is the primary one used in This use of prosthetic groups by
human mitochondria. Each electron members of ETC is true for all of the
transfer in the ETC requires a reduced electron carriers with the exception of
substrate as an electron donor and an quinones, which are a class of lipids that
oxidized substrate as the electron can directly be reduced or oxidized by
acceptor. In most cases, the electron the oxidoreductases. Both the
acceptor is a member of the enzyme Quinone(red) and the
Quinone(ox) forms of these lipids are and transport it into the mitochondria
soluble within the membrane and can where it is used as the final acceptor of
move from complex to complex to electrons from our electron transport
shuttle electrons. chains. That process - because oxygen
is used as the terminal electron acceptor
The electron and proton carriers
- is called aerobic respiration.
Flavoproteins (Fp), these proteins
While we may use oxygen as the
contain an organic prosthetic group
terminal electron acceptor for our
called a flavin, which is the actual
respiratory chains, this is not the only
moiety that undergoes the
mode of respiration on the planet.
oxidation/reduction reaction. FADH2 is
Indeed, the more general processes of
an example of an Fp.
respiration evolved at a time when
Quinones are a family of lipids, which oxygen was not a major component of
means they are soluble within the the atmosphere. As a consequence,
membrane. many organisms can use a variety of
compounds including nitrate (NO3-),
It should also be noted that NADH and nitrite (NO2-), even iron (Fe3+) as
NADPH are considered electron (2e-) terminal electron acceptors. When
and proton (2 H+) carriers. oxygen is NOT the terminal electron
acceptor, the process is referred to
Electron carriers
as anaerobic respiration. Therefore,
Cytochromes are proteins that contain respiration or oxidative
a heme prosthetic group. The heme is phosphorylation does not require
capable of carrying a single electron. oxygen at all; it simply requires a
compound with a high enough reduction
Iron-Sulfur proteins contain a nonheme
potential to act as a terminal electron
iron-sulfur cluster that can carry an
acceptor, accepting electrons from one
electron. The prosthetic group is often
of the complexes within the ETC.
abbreviated as Fe-S
The ability of some organisms to vary
Aerobic versus anaerobic respiration
their terminal electron acceptor provides
We humans use oxygen as the terminal metabolic flexibility and can ensure
electron acceptor for the ETCs in our better survival if any given terminal
cells. This is also the case for many of acceptor is in limited supply. Think
the organisms we intentionally and about this: in the absence of oxygen,
frequently interact with (e.g. our we die; but other organisms can use a
classmates, pets, food animals, etc). We different terminal electron acceptor
breath in oxygen; our cells take it up
when conditions change in order to regenerate Complex II(ox) and create
survive. the reduced form of the terminal
electron acceptor, AH. In this specific
A generic example: A simple, two-
example, Complex II can also
complex ETC
translocate a proton during the process.
The figure below depicts a generic If A is molecular oxygen, AH represents
electron transport chain, composed of water and the process would be
two integral membrane complexes; considered to be a model of an aerobic
Complex I(ox) and Complex II(ox). A ETC. By contrast, if A is nitrate, NO3-,
reduced electron donor, designated DH then AH represents NO2-(nitrite) and
(such as NADH or FADH2) reduces this would be an example of an
Complex I(ox), giving rise to the anaerobic ETC.
oxidized form D (such as NAD+ or
FAD+). Simultaneously, a prosthetic
group within Complex I is now reduced
(accepts the electrons). In this example,
the red/ox reaction is exergonic and the
free energy difference is coupled by the
enzymes in Complex I to the endergonic
translocation of a proton from one side
of the membrane to the other. The net
result is that one surface of the
membrane becomes more negatively
charged, due to an excess of hydroxyl
ions (OH-), and the other side becomes
positively charged due to an increase in
protons on the other side. Complex Figure 1. Generic 2 complex electron
I(red) can now reduce a mobile electron transport chain. In the figure, DH is the
carrier Q, which will then move through electron donor (donor reduced), and D
the membrane and transfer the is the donor oxidized. A is the oxidized
electron(s) to the prosthetic group of terminal electron acceptor, and AH is
Complex II(red). Electrons pass from the final product, the reduced form of
Complex I to Q then from Q to Complex the acceptor. As DH is oxidized to D,
II via thermodynamically spontaneous protons are translocated across the
red/ox reactions, regenerating Complex membrane, leaving an excess of
I(ox), which can repeat the previous hydroxyl ions (negatively charged) on
process. Complex II(red) then reduces one side of the membrane and protons
A, the terminal electron acceptor to (positively charged) on the other side of
the membrane. The same reaction
occurs in Complex II as the terminal
electron acceptor is reduced to AH.

Attribution: Marc T. Facciotti (original

work)

Exercise 1

Thought question

Based on figure 1, use an electron tower

to figure out the difference in the
electrical potential if (a) DH is NADH
and A is O2, and (b) DH is NADH and A Figure 2. The electron transport chain
is NO3-. Which pairs of electron donor is a series of electron transporters
and terminal electron acceptor (a) or (b) embedded in the inner mitochondrial
"extract" the greatest amount of free membrane that shuttles electrons from
energy? NADH and FADH2 to molecular oxygen.
In the process, protons are pumped
Detailed look at aerobic respiration
from the mitochondrial matrix to the
The eukaryotic mitochondria have intermembrane space, and oxygen is
evolved a very efficient ETC. There are reduced to form water.
four complexes composed of proteins,
Complex I
labeled I through IV depicted in the
figure below. The aggregation of these To start, two electrons are carried to the
four complexes, together with first protein complex aboard NADH. This
associated mobile, accessory electron complex, labeled I in Figure 2, includes
carriers, is called also called an electron flavin mononucleotide (FMN) and iron-
transport chain. This type of electron sulfur (Fe-S)-containing proteins. FMN,
transport chain is present in multiple which is derived from vitamin B2, also
copies in the inner mitochondrial called riboflavin, is one of several
membrane of eukaryotes. prosthetic groups or cofactors in the
electron transport chain. Prosthetic
groups are organic or inorganic,
nonpeptide molecules bound to a
protein that facilitate its function;
prosthetic groups include coenzymes,
which are the prosthetic groups of
enzymes. The enzyme in Complex I is
also called NADH dehydrogenase and is Complex III
a very large protein containing 45
The third complex is composed of
individual polypeptide chains. Complex I
cytochrome b, another Fe-S protein,
can pump four hydrogen ions across the
Rieske center (2Fe-2S center), and
membrane from the matrix into the
cytochrome c proteins; this complex is
intermembrane space thereby helping to
also called cytochrome oxidoreductase.
generate and maintain a hydrogen ion
Cytochrome proteins have a prosthetic
gradient between the two
group of heme. The heme molecule is
compartments separated by the inner
similar to the heme in hemoglobin, but
mitochondrial membrane.
it carries electrons, not oxygen. As a
Q and Complex II result, the iron ion at its core is reduced
and oxidized as it passes the electrons,
Complex II directly receives FADH2,
fluctuating between different oxidation
which does not pass through Complex I.
states: Fe2+ (reduced) and
The compound connecting the first and
Fe3+ (oxidized). The heme molecules in
second complexes to the third is
the cytochromes have slightly different
ubiquinone (Q). The Q molecule is lipid
characteristics due to the effects of the
soluble and freely moves through the
different proteins binding them, giving
hydrophobic core of the membrane.
slightly different characteristics to each
Once it is reduced, (QH2), ubiquinone
complex. Complex III pumps protons
delivers its electrons to the next
through the membrane and passes its
complex in the electron transport chain.
electrons to cytochrome c for transport
Q receives the electrons derived from
to the fourth complex of proteins and
NADH from Complex I and the electrons
enzymes (cytochrome c is the acceptor
derived from FADH2 from Complex II,
of electrons from Q; however, whereas
succinate dehydrogenase. Since these
Q carries pairs of electrons, cytochrome
electrons bypass and thus do not
c can accept only one at a time).
energize the proton pump in the first
complex, fewer ATP molecules are made Complex IV
from the FADH2 electrons. As we will
The fourth complex is composed of
see in the following section, the number
cytochrome proteins c, a, and a3. This
of ATP molecules ultimately obtained is
complex contains two heme groups (one
directly proportional to the number of
in each of the two Cytochromes, a, and
protons pumped across the inner
a3) and three copper ions (a pair of CuA
mitochondrial membrane.
and one CuB in Cytochrome a3). The
cytochromes hold an oxygen molecule
very tightly between the iron and copper
ions until the oxygen is completely
reduced. The reduced oxygen then picks energy of reaction and couples the
up two hydrogen ions from the exergonic transfer of energy associated
surrounding medium to make water with the movement of protons down
(H2O). The removal of the hydrogen their electrochemical gradient to the
ions from the system contributes to the endergonic addition of a phosphate to
ion gradient used in the process of ADP, forming ATP.
chemiosmosis.

Chemiosmosis

In chemiosmosis, the free energy from

the series of red/ox reactions just
described is used to pump protons
across the membrane. The uneven
distribution of H+ ions across the
membrane establishes both
concentration and electrical gradients
(thus, an electrochemical gradient),
owing to the proton's positive charge
and their aggregation on one side of the
membrane.

If the membrane were open to diffusion

by protons, the ions would tend to
diffuse back across into the matrix, Figure 3. ATP synthase is a complex,
driven by their electrochemical gradient. molecular machine that uses a proton
Ions, however, cannot diffuse through (H+) gradient to form ATP from ADP
the nonpolar regions of phospholipid and inorganic phosphate (Pi).
membranes without the aid of ion
channels. Similarly, protons in the Credit: modification of work by Klaus
intermembrane space can only traverse Hoffmeier
the inner mitochondrial membrane Note: possible discussion
through an integral membrane protein
called ATP synthase (depicted below). Dinitrophenol (DNP) is a small chemical
This complex protein acts as a tiny that serves to uncouple the flow of
generator, turned by transfer of energy protons across the inner mitochondrial
mediated by protons moving down their membrane to the ATP synthase, and
electrochemical gradient. The thus the synthesis of ATP. DNP makes
movement of this molecular machine the membrane leaky to protons. It was
(enzyme) serves to lower the activation used until 1938 as a weight-loss drug.
Why might it be dangerous? Cyanide inhibits cytochrome c oxidase, a
component of the electron transport
In healthy cells, chemiosmosis (depicted
chain. If cyanide poisoning occurs,
below) is used to generate 90 percent of
would you expect the pH of the
the ATP made during aerobic glucose
intermembrane space to increase or
catabolism; it is also the method used in
decrease? What effect would cyanide
the light reactions of photosynthesis to
have on ATP synthesis?
harness the energy of sunlight in the
process of photophosphorylation. Recall
that the production of ATP using the
process of chemiosmosis in
mitochondria is called oxidative
phosphorylation and that a similar
process can occur in the membranes of
bacterial and archaeal cells. The overall
result of these reactions is the
production of ATP from the energy of

Note: Possible Discussion

Electrons removed originally from a

reduced organic molecule like glucose.

In the aerobic example, these electrons transport chain is used by ATP synthase
to form ATP in a Gram-bacteria.
Ultimately reduce oxygen and thereby
create water.

Figure 4. In oxidative phosphorylation,

the pH gradient formed by the electron