Electron Transport Chain and oxidative phosphorylation

Submitted by

Dr. Sakshi Verma

Assistant Professor

Zoology Department

HMV, Jalandhar

Electron Transport Chain System and oxidative phosphorylation

• The Electron Transport System also called the Electron Transport Chain, is a chain of reactions that converts redox energy available from oxidation of NADH and FADH₂, into proton-motive force which is used to synthesize ATP through conformational changes in the ATP synthase complex through a process called oxidative phosphorylation.
• Oxidative phosphorylation is the last step of cellular respiration.
• This stage consists of a series of electron transfer from organic compounds to oxygen while simultaneously releasing energy during the process.
• In aerobic respiration, the final electron acceptor is the molecular oxygen while in anaerobic respiration there are other acceptors like sulfate.

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Electron Transport Chain System and oxidative phosphorylation

• This chain of reactions is important as it involves breaking down of ATP into ADP and resynthesizing it in the process to ATP, thus utilizing the limited ATPs in the body about 300 times in a day.
• The electron flow takes place in four large protein complexes that are embedded in the inner mitochondrial membrane, together called the respiratory chain or the electron-transport chain.
• This stage is crucial in energy synthesis as all oxidative steps in the degradation of carbohydrates, fats, and amino acids converge at this final stage of cellular respiration, in which the energy of oxidation drives the synthesis of ATP.

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Electron Transport Chain System and oxidative phosphorylation

• The number of electron transport chains in the mitochondria depends on the location and function of the cell. In the liver mitochondria, there are 10, 000 sets of electron transport chains while the heart mitochondria have three times the number of electron transport chain as in the liver mitochondria.

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Electron Transport Chain System and oxidative phosphorylation

• Electron Transport Chain Components/ Electron carriers:
• Electrons in the chain are transferred from substrate to oxygen through a series of electron carriers.
• The following are the components of electron transport chain:
• FMN (Flavin Mononucleotide)
• At the beginning of the electron transfer chain, the electrons from NADH are transferred to the flavin Mononucleotide (FMN) reducing it to FMNH₂.
• NAD⁺ + H⁺ + FMN  →  NAD + FMNH₂
• The transfer of electrons is catalyzed by the action of NADH dehydrogenase.
• The electrons are further transferred to a series of iron-sulfur complexes (Fe-S) which have a higher relative affinity towards the electrons.

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Electron Transport Chain System and oxidative phosphorylation

• b. Ubiquinone (Co-enzyme-Q)
• Between the flavoproteins and cytochromes are other electron carriers termed ubiquinone (UQ).
• Ubiquinone is the only electron carrier in the respiratory chain that is not bound attached to a protein. This allows the molecule to move between the flavoproteins and the cytochromes.
• Once the electrons are transferred from FMNH₂ via the Fe-S centers to the ubiquinone, it becomes UQH2 and the oxidized form of flavoprotein (FMN) is released.
• FMNH₂ + UQ  →  FMN + UQH₂

Electron Transport Chain System and oxidative phosphorylation

• c. Cytochromes
• The next electron carriers are cytochromes that are red or brown colored proteins containing a heme group that carries the electrons in a sequence from ubiquinone to the molecular oxygen.
• However, each cytochrome, like Fe-S centers, only transfers a single electron whereas other electron carriers like FMN and ubiquinone transfer two electrons.

Electron Transport Chain System and oxidative phosphorylation

• c. Cytochromes
• There are five types of cytochromes between ubiquinone and the molecular oxygen, each designated as a, b, c, and so on.
• These are named on the basis of their ability to absorb light of different wavelengths (cytochrome a absorbs the longest wavelength, b absorbs the next longest wavelength and so on).

Electron Transport Chain System and oxidative phosphorylation

• Electron Transport Chain Equation:
• The electron transport chain consists of a series of oxidation-reduction reactions that lead to the release of energy. A summary of the reactions in the electron transport chain is:
• NADH + 1/2O₂ + H⁺ + ADP + Pi  →  NAD⁺ + ATP + H₂O

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Electron Transport Chain System and oxidative phosphorylation

• Electron Transport Chain Complexes:
• A chain of four enzyme complexes is present in the electron transport chain that catalyzes the transfer of electrons through different electron carriers to the molecular oxygen.

a) Complex I (Mitochondrial complex I/ NADH-CoQ oxidoreductase)

• Complex I in the electron transport chain is formed of NADH dehydrogenases and the Fe-S centers that catalyzes the transfer of two electrons from NADH to ubiquinone (UQ).
• At the same time, the complex translocates four H⁺ ions through the membrane, creating a proton gradient.
• NADH + H⁺ + CoQ  →  NAD⁺ + CoQH₂
• NADH is first oxidized to NAD⁺ by reducing FMN to FMNH2 in a two-step electron transfer.
• FMNH₂ is then oxidized to FMN where the two electrons are first transferred to Fe-S centers and then to ubiquinone.

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Electron Transport Chain System and oxidative phosphorylation

b) Complex II (Mitochondrial complex II/ Succinate-CoQ oxidoreductase)

• Complex II consists of succinic dehydrogenase, FAD, and Fe-S centers.
• The enzyme complex catalyzes the transfer of electrons from other donors like fatty acids and glycerol-3 phosphate to ubiquinone through FAD and Fe-S centers.
• This complex runs parallel to the Complex II, but Complex II doesn’t translocate H+ across the membrane, as in Complex I.
• Succinate + FADH₂ + CoQ  →  Fumarate + FAD⁺ + CoQH₂

Electron Transport Chain System and oxidative phosphorylation

c) Complex III (Mitochondrial complex III/ CoQH₂ –cytochrome c oxidoreductase)

• Complex III consists of cytochrome b, c, and a specific Fe-S center.
• The enzyme complex, cytochrome reductase, catalyzes the transfer of two electrons from reduced CoQH₂ to two molecules of cytochrome c.
• Meanwhile, the protons (H⁺) from the ubiquinone are release across the membrane aiding to the proton gradient.
• The CoQH₂ is oxidized back to CoQ while the iron center (Fe³⁺) in the cytochrome c is reduced to Fe²⁺.
• CoQH₂ + 2 cytc c (Fe³⁺)  →  CoQ + 2 cytc c (Fe²⁺) + 4H⁺

Electron Transport Chain System and oxidative phosphorylation

d) Complex IV (Mitochondrial complex IV)

• Complex IV consists of cytochrome a and a3, which is also termed cytochrome oxidase.
• This is the last complex of the chain and is involved in the transfer of two electrons from cytochrome c to molecular oxygen (O2) forming water.
• In the meantime, four protons are translocated across the membrane aiding the proton gradient.
• 4 cytc c (Fe ²⁺) + O₂   →  4cytc c (Fe³⁺) + H₂O

Fig.: Electron Transport System of Mitochondria

Electron Transport Chain System and oxidative phosphorylation

• Electron Transport Chain Steps:
• The following steps are involved in electron transfer chains which involve the movement of electrons from NADH to molecular oxygen:

1. Transfer of electrons from NADH to Ubiquinone (UQ)

• NADH is produced in different other cycles by the α-ketoglutarate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase reactions of the TCA cycle, by the pyruvate dehydrogenase reaction that converts pyruvate to acetyl-CoA, by β-oxidation of fatty acids, and by other oxidation reactions.

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Electron Transport Chain System and oxidative phosphorylation

1. Transfer of electrons from NADH to Ubiquinone (UQ)

• NADH produced in the mitochondrial matrix is transferred into the intermembrane space.
• The NADH then transfers the electrons to FMN present in the intermembrane space via the complex I (NADH dehydrogenase).
• FMN then passes the electrons to the Fe-S center (one electron to one Fe-S center) which then transfers the electrons, one at a time to CoQ forming semiquinone and then ubiquinol.

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Electron Transport Chain System and oxidative phosphorylation

1. Transfer of electrons from NADH to Ubiquinone (UQ)

The electron transfer creates energy which is used to pump two protons across the membrane creating a potential gradient.

• 2. Transfer of electrons from FADH₂ to CoQ
• The oxidation of succinate to fumarate results in the reduction of FAD to FADH₂.
• The electrons from FADH₂ enter the electron transport chain catalyzed by complex II, succinic dehydrogenase.
• Like in complex I, the electrons reach CoQ through a series of Fe-S centers.
• However, complex II doesn’t pump any protons across the membrane.

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Electron Transport Chain System and oxidative phosphorylation

3. Transfer of electrons from CoQH₂ to cytochrome c

• The reduced CoQH₂ transfer electrons through cytochrome b and c1 which finally reaches cytochrome c.
• Complex II (cytochrome reductase) catalyzes this process where the Fe³⁺ present in the cytochrome is reduced to Fe²⁺.
• Each cytochrome transfers one electron each and thus two molecules of cytochrome are reduced for the transfer of electrons for every NADH oxidized.
• Energy is produced during the transfer of electrons which is utilized to pump protons across the membrane aiding to the potential gradient.

Electron Transport Chain System and oxidative phosphorylation

• 4. Transfer of electrons from cytochrome c to molecular oxygen
• The final step in the electron transfer chain is catalyzed by complex IV (cytochrome oxidase) where electrons are transferred from cytochrome c to molecular oxygen. Firstly, the electrons are transferred from cytochrome c to cytochrome a moiety of the complex, and then to cytochrome a₃ which contains copper. This copper atom alternates between oxidized (2⁺) form and reduced (1⁺) form as it transfers electrons from cytochrome a₃ to molecular oxygen.

Electron Transport Chain System and oxidative phosphorylation

• 4. Transfer of electrons from cytochrome c to molecular oxygen
• Since two electrons are required to reduce one molecule of oxygen to water, for each NADH oxidized half of oxygen is reduced to water.
• Similarly, the Fe²⁺ of the cytochrome c is oxidized to Fe³⁺. The energy released during this process is used to pump protons across the membrane.
• The transfer of protons back to the matrix results in the formation of ATP.

Significance of Electron transport Chain

• Its significance lies in its role in energy production, specifically in synthesizing ATP, the main energy currency of the cell. The following are the key points of its significance:

1) ATP Production:

• The ETC generates the majority of ATP during cellular respiration through a process called oxidative phosphorylation. Electrons, transferred from NADH and FADH₂ produced in earlier stages (glycolysis, citric acid cycle), flow through a series of protein complexes in the membrane. This flow powers the movement of protons across the membrane, creating a proton gradient that drives ATP synthase, ultimately producing ATP.

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Significance of Electron transport Chain

2) Oxidation of NADH and FADH₂:

• The ETC helps oxidize NADH and FADH₂ back into NAD⁺ and FAD, making them available for use in glycolysis and the citric acid cycle. This oxidation is essential for continuing these processes, which provide the cell with a steady supply of energy.

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Significance of Electron transport Chain

3) Creation of a Proton Gradient:

• As electrons move through the ETC, protons (H⁺) are pumped from the mitochondrial matrix into the intermembrane space, establishing a proton gradient. This gradient, also known as the electrochemical gradient, is a form of stored energy. When protons flow back into the matrix via ATP synthase, it facilitates ATP production.

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Significance of Electron transport Chain

4. Oxygen as the Final Electron Acceptor:

• Oxygen plays a vital role in the ETC as the final electron acceptor. At the end of the chain, electrons combine with protons and oxygen to form water. This step is essential for maintaining the flow of electrons through the chain, and without oxygen, the entire process would back up, halting ATP production.

5. Heat Production:

• Besides ATP generation, the ETC also releases some energy as heat, contributing to thermoregulation in organisms like mammals. In some specialized tissues, like brown fat, the ETC uncouples ATP production, leading to more heat generation rather than ATP.

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Significance of Electron transport Chain

In summary, the electron transport chain is vital for efficient ATP production, regenerating essential coenzymes, maintaining cellular energy balance, and even regulating heat production in organisms. It is a central process in aerobic metabolism.

REFERENCES:

• Lehninger, A.L., Nelson, D.L. and Cox, M.M., 2005. Lehninger principles of biochemistry. Macmillan.
• Jain, J.L., 2004. Fundamentals of biochemistry. S. Chand Publishing.
• Satyanarayana, U., 2013. Biochemistry. Elsevier Health Sciences.