ELECTRON TRANSPORT CHAIN (ETC)

Biochemistry assignment

Submitted to: Dr. Irum Gull

Submitted by: Syed Muhammad Zaki Haider (BSBT-025-F18)

Syed Muhammad Zaki Haider (BSBT025F18)

University of The Punjab (PU)
 ELECTRON TRANSPORT CHAIN (ETC) 09/24/2020

A
s we are already familiar with the fact that high
energy molecules like glucose is metabolized
(catabolism) in our cells by a series of oxidation
reactions as in glycolysis where we form pyruvate, the
pyruvate is oxidized to acetyl-COA which then further moves
on in TCA cycle. During all this process, the metabolic
intermediates of these reactions donate electrons to specific
coenzymes, nicotinamide adenine dinucleotide (NAD+) and
flavin adenine dinucleotide (FAD), to form the energy-rich
reduced forms, NADH and FADH2. These reduced coenzymes
can, in turn, each donate a pair of electrons to a specialized
set of electron carriers, collectively called the electron
transport chain (ETC), and this where we generate all the
energy used up in the previous processes in form of ATP (the
energy currency of cell of course). This is done when
electrons lose their energy while moving through ETC and
that energy is used to move protons (H+) across the inner
mitochondrial membrane (from matrix to intermembrane
space). A proton gradient is formed which is then used for ATP generation from ADP and
inorganic phosphate (Pi) when the protons are again moved across the inner mitochondrial
membrane through a carrier protein called ATP synthase. So here we see that 2 processes are
being coupled, energy obtained from one process is used to run the other process. This coupling
of electron transport with ATP synthesis is called as oxidative phosphorylation (OXPHOS). Here,
we will discuss the electron transportation aspect of OXPHOS.

LOCATION OF ETC:
ETC is the final common pathway where electrons derived from different energy fuels reduce
oxygen to water in the final step of the chain. ETC is located in the inner mitochondrial membrane
(except cytochrome c). We all know that mitochondria are double membranous organelle, with
outer membrane (which is permeable to most ions and small molecules due to presence of porin
protein) and the inner membrane (impermeable to most small ions, including H+, and small
molecules such as ATP, ADP, pyruvate, and other metabolites important to mitochondrial
function). In between both membranes there is the inter membrane space. Specialized carriers
or transport systems are required to move ions or molecules across inner membrane. The gel like
solution in the matrix is rich in proteins including the enzymes for pyruvate oxidation, amino

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 ELECTRON TRANSPORT CHAIN (ETC) 09/24/2020

acids, and fatty acids (by β-oxidation) as well as those of the tricarboxylic acid (TCA) cycle. The
synthesis of glucose, urea, and heme occurs partially in the matrix of mitochondria. Furthermore,
the matrix contains NAD+ and FAD (the oxidized forms of the two coenzymes that are required
as electron acceptors), and ADP and Pi, which are used to produce ATP.

COMPONENTS OF ETC:
ETC consists of 4 separate protein complexes (I, II, III, IV). These complexes accept or donate
electrons to the relatively mobile electron carrier coenzyme Q (CoQ) and cytochrome c. What
happens is that electrons are accepted at one carrier and then that carrier donates the electrons
to next carrier and so on, until electrons reach oxygen and water is formed by combination of O2
and H+. This requirement for O2 makes the electron transport process the respiratory chain,
which accounts for the greatest portion of the body’s use of O2.

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 ELECTRON TRANSPORT CHAIN (ETC) 09/24/2020

REACTIONS TAKING PLACE IN ETC:

Electrons to be moved arrive at ETC from NADH and FADH2, each one of these molecules donate
a pair of electrons to complex I and complex II respectively as shown in the figure above. With
the exception of CoQ, which is a lipid-soluble quinone, all members of the ETC are proteins. The
details of happenings at ETC are given below:

Complex I:
Complex I consist of NADH dehydrogenase, tightly bound molecule of FMN (flavin mono
nucleotide) and peptide subunits containing Fe-S centers (iron Sulphur). NADH + H+ formed by
reduction of NAD+ by dehydrogenases in previous reactions (as in TCA cycle) gets oxidized here
again to NAD+ and 2 electrons and 2H+ get accepted by FMN and it gets reduced to FMNH2. From
here electron move from FMN to Fe-S centers and then to CoQ. As electrons flow, they lose

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energy and that energy is used to pump four H+ across the inner mitochondrial membrane, from
the matrix to the intermembrane space.

Complex II:
Complex II contains succinate dehydrogenase that oxidizes succinate to fumarate (as happens in
TCA cycle), making FADH2. Electrons move from FADH2 to Fe-S centers, and then to COQ. No
hydrogen ions are pumped at this complex so no energy is lost at all.

Coenzyme Q (CoQ):
CoQ is a quinone derivative, also called ubiquinone because it is ubiquitous in biological systems.
CoQ is a mobile electron carrier and can accept electrons from NADH dehydrogenase (Complex
I), from succinate dehydrogenase (Complex II) and from other mitochondrial dehydrogenases.
CoQ then transfers electrons to Complex III. Thus, a function of CoQ is to link the flavoprotein
dehydrogenases to the cytochromes.

Complex III and complex IV are cytochromes proteins, containing a heme group (a porphyrin ring
plus iron),but unlike the heme groups of hemoglobin, the cytochrome iron is reversibly converted
from its ferric (Fe3+) to its ferrous (Fe2+) form as a normal part of its function as an acceptor and
donor of electrons.

Complex III:
Electrons from CoQ are accepted by Complex III that contains cytochrome bc1 and 4 protons (H+)
are pumped across the inner membrane.

Cytochrome C:
Electrons from complex III are accepted by cytochrome c, a mobile electron carrier situated on
the outer face of inner membrane (in the inter membrane space).

Complex IV:
Electrons from cytochrome c finally reach complex IV, which consists of Cu A, cytochrome a, CuB,
cytochrome a3 (and that is the exact sequence of movement of electrons in complex IV). Because
this cytochrome complex is the only electron carrier in which the heme iron has an available
coordination site that can react directly with O2, it also is called cytochrome c oxidase. At Complex
IV, the transported electrons, O2, and free H+ are brought together, and O2 is reduced to H2O. 2
protons are pumped at this complex as electrons move.

INHIBITORS AT DIFFFERENT SITES IN ETC:

Inhibitors may act at different sites in the respiratory chain, with the purpose of blocking the
passage of electron from one component of the chain to the other. Thus, we can understand
that in presence of these site-specific inhibitors, all electron carriers before the block are fully

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reduced (have electrons), whereas those located after the block are oxidized (did not receive
electrons). These inhibitors or blocks are given below:

➢ Amytal rotenone (block between FMN of complex I and CoQ)

➢ Antimycin A (block between cytochrome bc1 and cytochrome c)
➢ CN-, CO, H2S, NaN3 (block between cytochrome a+a3 and O2).

REDUCTION POTENTIAL AND ELECTRON TRANSPORT:

As electrons move through ETC from an electron donor (reductant or reducing agent) to an
electron acceptor (oxidant or oxidizing agent), the free energy released is used to pump hydrogen
ions across the inner membrane (at complexes I, II, III). This process happens in form of redox
pairs (loss of electrons on one end, gain of electrons at other). For instance, the oxidation of
NADH to NAD+ by NADH dehydrogenase at Complex I, accompanied by the reduction of FMN,
the prosthetic group, to FMNH2.

In a redox pair, the tendency of losing electrons is governed by the constant, E 0 (the standard
reduction potential), with units in volts. The more negative its value, the more will be the
tendency of the reductant of a redox pair to lose electrons. The more positive its value, the more
will be the tendency of the oxidant of a redox pair to accept electrons. The movement of
electrons through the electron carriers is because electrons move from more negative E0 to more
positive E0 as described in the table below:

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NADH AND FADH 2 IN ATP SYNTHESIS:

The standard free energy (free energy available for a reaction under standard conditions) of
phosphorylation of ADP to ATP is +7.3 kcal/mol. The transport of a pair of electrons from NADH
through the ETC releases 52.6 kcal. Therefore, more than sufficient energy is available to produce
three ATP from three ADP and three Pi (3 × 7.3 = 21.9 kcal/mol), the remaining calories are used
for auxiliary reactions in cell or released as heat.

We must keep in mind that one NADH pumps 10 H+ across the inner membrane when its electron
move in ETC to reduce one Oxygen atom (4 at complex I, 4 at complex III, 2 at complex III), while
FADH2 pumps 6 (because it is oxidized at complex II where no protons are pumped, thus energy
released in case of FADH2 is also lesser than NADH). And we need 4 protons for synthesis of 1
ATP (when they are entered again in the matrix of mitochondria via ATP synthase), thus P/O ratio
(ATP made per O atom reduced) is 3:1 for NADH and 2:1 for FADH2.

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