The electron transport chain (ETC) transfers electrons from nutrients to oxygen to generate energy in the form of ATP. It is located in the inner mitochondrial membrane and consists of five protein complexes linked by electron carriers. As electrons move through the complexes, protons are pumped from the mitochondrial matrix to the intermembrane space, creating a proton gradient used by ATP synthase to phosphorylate ADP to ATP. The overall reaction produces approximately 30-32 molecules of ATP per glucose molecule depending on the electron shuttle used. Key components of the ETC include NADH dehydrogenase, succinate dehydrogenase, cytochrome reductase, cytochrome oxidase, and ATP synthase.

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ELECTRON TRANSPORT CHAIN
SUBHASMITH PRADHAN
B.PHARMACY(2016-20)
ADITYA PHARMACY COLLEGE
Electron transport chain :-
ETC is the transfer of electrons from NADH and FADH2 to
oxygen via multiple carriers. • The electrons derieved from
NADH and FADH2 combine with O2, and the energy
released from these oxidation/reduction reactions is used to
derieve the synthesis of ATP from ADP. • This transfer of
electrons is done by multiple carriers which constitute the
ELECTRON TRASPORT CHAIN.
LOCATION-
 ETC is localized in Mitochondria.
 MC are the centres for metabolic oxidative reactions to
generate reduced coenzymes (NADH and FADH2)
which in turn, are utilized in ETC to liberate E in the
form of ATP.

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 Hence, MC is regarded as Power House of the Cell.
MYTOCHONDRIAL ORGANIGATION-
5 distinct parts.
1. the outer membrane
2. the inner membrane

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3. the inter membrane space
4. the cristae
5. the matrix.
INNER MITO CHONDRIAL MEMBRAIN:-
 ETC and ATP synthesizing system are located on
IMM.
 IMM is rich in proteins.
 It is impermeable to ions(H+ ,K+ ,Na+ ) and small
molecules (ADP, ATP).
 IMM is highly folded to form Cristae.
 The surface area of the IMM is greatly increased
due to Cristae.
 The IMM Possesses specialized particles ( that look
like lollipops ), the phosphorylating subunits which
are the centres for ATP production.
MIROCHONDRIAL MATRIX-
 The interior ground substance.
 Rich in enzymes responsible for TCA Cycle,
oxidation of FA and the oxidation of amino
acids.

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COMPONENTS OF ETC
COMPLEX NAME NO.OF
PROTINE
PROSTHETIC
GROUP
Complex-I NADH
Dehydrogenase
46 FMN,9 Fe-S
cntrs
Complex-II Succinate-CoQ
Reductase
5 FAD, cyt b560,
3Fe-S cntrs

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Complex-III CoQ-cyt C
Reductase
11 cyt bH, cyt bL,
cyt c1, Fe-SRieske
Complex-IV Cytochrome
oxidase
13 cyt a, cyt
a3,Cua, Cub
COMPLEX-1 NADH Dehydrogenase
Complex I catalyses oxidation of NADH, with reduction of
coenzyme Q.
NADH + H+
+ Q → NAD+
+ QH2
It includes at least 46 proteins, along with prosthetic groups
FMN & several Fe-S centers.
Pumps 4 protons across the mitochondrial membrane.
The initial electron transfers are:
NADH + H+
+ FMN → NAD+
+ FMNH2
FMNH2 + (Fe-S)ox → FMNH· + (Fe-S)red+ H+
After Fe-S is reoxidized by transfer of the electron to the next
iron-sulphur center in the pathway:
FMNH· + (Fe-S)ox → FMN + (Fe-S)red + H+
Iron-sulphur centers are arranged as a wire, providing a
pathway for e- transfer from FMN through the protein

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N2, the last Fe-S center in the chain, passes e-
one at a time to
the mobile lipid redox carrier coenzyme Q. A proposed
binding site for CoQ is close to N2 at the interface of
peripheral & membrane domains. Coenzyme Q accepts 2e-
and picks up 2H+
to yield the fully reduced QH2.
NADH
NAD+
COMPLEX-1
Co-enzymeQ(Ubiquinone)
It is a benzoquinone linked to a number of isoprene units. •
Coenzyme Q (CoQ, Ubiquinone) is very hydrophobic. It
dissolves in the hydrocarbon core of a membrane. • 3 redox
states- 1. Fully oxidised- UbiquinoneQ 2. Partially oxidised-
Semiquinone 3. Fully reduced- Ubiquione
• Only electron carrier that is not a protein bound prosthetic
group.
Complex-2 succinate dehydrogenase
• Succinate Dehydrogenase of the Krebs Cycle is also called
complex II or Succinate-CoQ Reductase.
• Inner mitochondrial membrane bound protein.
MEMBRAIN
DOMAIN
FMN
INNER MITOCHONDRIAL MEMBRAIN
PERIPHERAL DOMAIN
MATRIX

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• FAD is the initial e- acceptor.
•FAD is reduced to FADH2 during oxidation of succinate to
fumarate.
•FADH2 is then reoxidized by transfer of electrons through a
series of 3 iron- sulphur centers to CoQ, yielding QH2.
•It does not pump any proton during transport of electron
across the inner mitochondrial membrane.

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• X-ray crystallographic analysis of E. coli complex II
indicates a linear arrangement of electron carriers within
complex II, consistent with the predicted sequence of electron
transfers:
FAD → FeScenter 1 → FeScenter 2 → FeScenter 3 → CoQ
Complex-3 CoQ- Cyt Reductase
Complex III accepts electrons from coenzyme QH2 that is
generated by electron transfer in complexes I & II.
• Concominantly, it releases two protons into trans membrane
space.
• Within complex 3,the released electrons are transferred to an
iron sulfur center and then to two b-type cytochromes or
cytochrome c1.
• Finally the two electrons are transferred to two molecules of
the oxidised form of cytochrome c. two additional protons are
translocated from mitochondrial matrix across the
intermembrane space. This transfer of protons involves the
proton motive Q cycle.

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Cytochromes
Cytochromes are proteins with heme prosthetic groups. They
absorb light at characteristic wavelengths.
• It carries electron one at a time to complex 4.
• Major respiratory Cytochromes- b, c or a.
• In ETC-
Two a type cyt i.e. cyt a and a3.

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Two b type cyt i.e. cyt b1 and b2.
Two c type cyt i.e. cyt c and c1.
• Cytochrome c is a key regulator of programme cell death in
mammalian cells.
Complex-4 Cytochrome Oxidase
It catalyses the transfer of electrons from reduced cyt c to
molecular oxygen.
• Contains 13 subunits
• 2 heme groups i.e. heme a & heme a3
• 3 copper ions arranged as 2 copper centers designated as
Cua & Cub.
• Cua contain 2 copper ions linked by 2 bridging disulfide
residues.
• Cub is coordinated by 3 histidine residues.
• Two protons per pair of electron are pumped across the
membrane and another two protons are transferred to
molecular oxygen to form water.

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• Metal centers of cytochrome oxidase (complex IV):
• heme a & heme a3,
• CuA (2 adjacent Cu atoms) & CuB.
• O2 reacts at a binuclear center consisting of heme a3 and
CuB.
•Electrons enter complex IV one at a time from cyt c to CuA.
•They then pass via cyt a to the binuclear center where the
chemical reaction takes place.
e- transfer:
cyt c → CuA → cyt a → heme a3/CuB → O2

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CYTOCHROME-C OXIDASE

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Complex-5 ATP Synthase
• Mitochondrial ATP synthase consist of two multisubunit
components F0 and F1 which are linked by a slender stalk.

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• F0 is a electrically driven motor that spans the lipid bilayer
forming a channel through which protons can cross the
membrane.
• F0 provides channel for protons.
• F1 harvest the free energy derived from proton movement
down the electrochemical gradient by catalyzing the synthesis
of ATP.
• F1 Phosphorylates ADP to ATP.

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SUMMARY OF ATP SYNTHESIS
PATHWAY NADH FADH2 ATP
GLYCOLYSIS 2 0 2
KREBS
CYCLE
8 2 2
TOTAL 10 2 4
TOTAL ATP 25 3 4
1 NADH
10H+
× 𝟏𝑨𝑻𝑷
𝟒𝐇+
1FADH2
6H+
×
𝟏𝑨𝑻𝑷
𝟒𝑯+
TOTAL ATP FROM MITOCONDRIAL MATRIX
Pyruvate dehydrogenase
NADH………………… 2.5 ATP
Krebs cycle
3NADH ×2.5ATP̸ NADH………… 7.5ATP
FADH2×1.5 ATP̸ FADH2………… 1.5ATP

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GTP×1ATP̸ GTP ……………… 1.0 ATP
(from a separate reaction)
total
........ 12.5 ATP
WHAT ABOUT NADH FROM GLYCOLYSIS-
 NADH made in cytosol
 can´t get into matrix of mitochondrion
 2 mechanism
1. In muscle and brain
(Glycerol Phosphate Shuttle)
2. In Liver and Heart
(Malate/Aspartate Shuttle)
GLYCEROL PHOSPHATE SHUTTLE
 In Muscle and Brain
 Each NADH converted to FADH2
 FADH2 enters later in electron
transport chain
 Produces 1.5 ATP
GLYCEROLPHOSPHATE SHUTTLE-
 2 NADH per glucose→2FADH2
 2FADH2×1.5 ATP/ FADH2……… 3.0 ATP

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 2 ATP in glycolysis…………. 2.0ATP
 From pyruvate and krebs
12.5 ATP × 2 per glucose………. 25.0 ATP
TOTAL= 30.0 ATP / Glucose

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MALTATE ASPERTATE SHUTTLE
In Liver and Heart
NADH oxidized while reducing oxaloacetate to
malate

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→ Malate Dehydrogenase
Malate crosses membrane
TOTAL ATP PER GLUCOSE IN LIVER AND HEART:-
Malate – Aspertate Shuttle
 2 NADH Per Glucose→2 NADH
2NADH× 2ATP/ NADH………. 5.0 ATP
2ATP from glycolysis…………. 2.0 ATP
From pyruvate and krebs,
12.5 ATP× 2per glucose……. 25.0 ATP
TOTAL= 32.0 ATP/ Glucose

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32.0 ATP/ glucose

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Inhibitors of ETC
ROTENONE-Complex-1
AMYTAL-Complex-1
Piericidine- Competes with CoQ
AntimicinA-Complex3
Cyanide, Azide, Carbon monoxide- Binds with
complex 4 and inhibits transfer of electron to oxygen.
UNCOUPLERS OF ETC
 2,4 Dinitrophenol
 dicoumarol
 carbonyl cyanide p-
Fluoromethoxyphenylhydrazone(FCCP)
The main key points:-

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 what is the chain
 location
 structuralfeatures
 components and the types
 cytochromes
 ATP calculations
 malate aspartate shuttle
 glucose phosphate shuttle
 inhibitiors of ETC
 Uncoupler of ETC

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