Electron Transport Chain (ETC): An Introduction

• The NADH and FADH₂ formed in glycolysis, TCA cycle and fatty acid oxidation are energy-rich molecules because they contain a pair of electrons that have high transfer potential.
• ATP is generated as a result of the energy produced when electrons from NADH and FADH₂ are passed to molecular oxygen by a series of electron carriers, collectively known as the electron transport chain (ETC).
• The electron transport chain is also called the Cytochrome oxidase system or as the Respiratory chain.
• The components of the chain include FMN, Fe–S centers, coenzyme Q, and a series of cytochromes (b, c1, c, and aa3).
• The energy derived from the transfer of electrons through the electron transport chain is used to pump protons across the inner mitochondrial membrane from the matrix to the cytosolic side.
• As a result, an electrochemical gradient is generated, consisting of a proton gradient and a membrane potential.
• The energy created by the formation of this gradient is then harnessed to form ATP as the protons travel down their gradient into the matrix through the ATP synthase channel.
• The oxidation of 1 mole of NADH generates approximately 2.5 moles of ATP, whereas the oxidation of 1 mole of FADH₂ generates approximately 1.5 moles of ATP.
• Because energy generated by the transfer of electrons through the electron transport chain to O₂ is used in the production of ATP, the overall process is known as oxidative phosphorylation.
• Thus, the electron transport and ATP production occur simultaneously and are tightly coupled.

Location of ETC

The respiratory chain is located in the cytoplasmic membrane of bacteria but in case of eukaryotic cells it is located on the membrane of mitochondria.

Components of the Electron Transport Chain

1. Complex I (NADH dehydrogenase)

• It contains FMN, which accepts 2 electrons and H + from 2 NADH to become the reduced form of FMNH₂; also contains iron atoms, which assist in the transfer of the e − and H + to coenzyme Q.

2. Complex II (Succinate dehydrogenase)

• Contains iron and succinate, which oxidizes FAD to form FADH₂

3. Coenzyme Q

• Accepts electrons from FMNH₂ (complex I) and FADH₂ (complex II) and transfers electrons to complex III.

4. Complex III (cytochrome b)

• It contains heme group, in which the Fe 3+ accepts the electrons from coenzyme Q to become Fe 2+. Transfers electrons to cytochrome c.

5. Cytochrome c

• It contains the heme group, in which the Fe 3+ accepts the electrons from complex III to become Fe 2+. Transfers electrons to complex IV.

6. Complex IV (cytochrome a)

•  It contains the heme group, in which the Fe 3+ accepts electrons from cytochrome c to become Fe 2+. Transfers electrons to O₂, which is combined with hydrogen to form H₂O.

7. Complex V (ATP synthase)

• It contains a proton channel that allows for protons to cross into the matrix, using the proton gradient energy to form ATP.

Major Steps in Electron Transport Chain

1. Transfer of electrons from NADH to coenzyme Q

• NADH passes electrons via the NADH dehydrogenase complex (complex I) to FMN. The complex is also known as the NADH:CoQ oxidoreductase.
• NADH is produced 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.
• NADH produced in the mitochondrial matrix diffuses to the inner mitochondrial membrane where it passes electrons to FMN, which is tightly bound to a protein.
• FMN passes the electrons through a series of iron–sulfur (Fe–S) complexes to coenzyme Q, which accepts electrons one at a time, forming first the semiquinone and then ubiquinol.
• The energy produced by these electron transfers is used to pump protons to the cytosolic side of the inner mitochondrial membrane.
• As the protons flow back into the matrix through the pores in the ATP synthase complex, ATP is generated.

2. Transfer of electrons from coenzyme Q to cytochrome c

• Coenzyme Q passes electrons through Fe–S centers to cytochromes b and c1, which transfer the electrons to cytochrome c.
• The protein complex involved in these transfers is called complex III, or the cytochrome b-c1 complex. The complex is also known as CoQ:C1 oxidoreductase.
• These cytochromes each contain heme as a prosthetic group but have different apoproteins.
• In the ferric (Fe3+) state, the heme iron can accept one electron and be reduced to the ferrous (Fe2+) state.
• Because the cytochromes can only carry one electron at a time, two molecules in each cytochrome complex must be reduced for every molecule of NADH that is oxidized.
• The energy produced by the transfer of electrons from coenzyme Q to cytochrome c is used pump protons across the inner mitochondrial membrane.
• As the protons flow back into the matrix through the pores in the ATP synthase complex, ATP is generated.
• Electrons from FADH₂, produced by reactions such as the oxidation of succinate to fumarate, enter the electron transport chain at complex II, which contains succinate dehydrogenase.
• Complex II will transfer electrons to coenzyme Q, without the associated proton pumping across the inner mitochondrial membrane.

3. Transfer of electrons from cytochrome c to oxygen

• Cytochrome c transfers electrons to the cytochrome aa3 complex, which transfers the electrons to molecular oxygen, reducing it to water.
• Cytochrome oxidase (complex IV) catalyzes this transfer of electrons.
• Cytochromes a and a3 each contain a heme and two different proteins that each contain copper.
• Two electrons are required to reduce one atom of oxygen; therefore, for each NADH that is oxidized, one-half of O2 is converted to H2O.
• The energy produced by the transfer of electrons from cytochrome c to oxygen is used to pump protons across the inner mitochondrial membrane.
• As the protons flow back into the matrix, ATP is generated.

ATP Generation in ETC

The production of ATP is coupled to the transfer of electrons through the electron transport chain to O₂. The overall process is known as oxidative phosphorylation. Protons flow down their electrochemical gradient through the membrane-bound ATP synthase. The flow of protons through the ATPase allows the enzyme to synthesize ATP.

• The exact amount of ATP that is generated by this process has not been clearly established, but current thought indicates that for each pair of electrons that enters the chain from NADH, 10 protons are pumped out of the mitochondria. As it takes four protons to flow through the ATPase to synthesize one ATP, 2.5 moles (10 divided by 4) of ATP can be generated from 1 mole of NADH.
• For every mole of FADH₂ that is oxidized, approximately 1.5 moles of ATP are generated because the electrons from FADH₂ enter the chain via coenzyme Q, bypassing the NADH dehydrogenase step (lead to the extrusion of 6 protons per pair of electrons, instead of the 10 protons per pair of electrons).

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Significance of Electron Transport Chain

• The electron transport chain is the final and most important step of cellular respiration.
• While Glycolysis and the Citric Acid Cycle make the necessary precursors, the electron transport chain is where a majority of the ATP is created.
• It has an important role in both photosynthesis and cellular respiration.

References

1. Smith, C. M., Marks, A. D., Lieberman, M. A., Marks, D. B., & Marks, D. B. (2005). Marks’ basic medical biochemistry: A clinical approach. Philadelphia: Lippincott Williams & Wilkins.
2. Rodwell, V. W., Botham, K. M., Kennelly, P. J., Weil, P. A., & Bender, D. A. (2015). Harper’s illustrated biochemistry (30th ed.). New York, N.Y.: McGraw-Hill Education LLC.
3. Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2000). Lehninger principles of biochemistry. New York: Worth Publishers.
4. Voet, D., & Voet, J. G. (1995). Biochemistry. New York: J. Wiley & Sons.