Electron transport chain (ETC) is a system that comprises a sequence of electron carriers which work cooperatively to transfer electrons from electron donors to electron acceptors within the cell of a living organism. It shows a series of oxidation reduction reactions or redox reactions in which electrons in the form of energy or ATP can be translocated within the cell or from one part of the cell to another as electrons flow within the energized membrane. Energy produced by the ETC is used for the formation of ATP via the process of oxidative phosphorylation as shall be seen later in this section. In the electron transport chain, electrons flow from molecules or electron carriers with more negative reduction potentials to molecules with more positive potentials; and this is exemplified in the redox reaction which shows how water is formed from hydrogen (a more negative reduction potential molecule) and oxygen, a more positive oxidation molecule. The electrons in the electron transport chain (ETC) move in steps from carrier to carrier downhill the ETC (Figure 1); and as one molecule is oxidized, the next becomes reduced and gains electrons in the process, and this process continues with the sole aim of generating energy (ATP) for the cell. As one substance is enzymatically oxidized, another becomes enzymatically reduced. This process continues until the electrons are found in their final state in which oxygen is reduced to water. The activities of the electron transport chain (which is vital for energy generation for the cell) occurs in virtually all living cells (inclusive of prokaryotic and eukaryotic cells). Plant cells, bacterial cells and mammalian cells all carry out electron transport in their inner mitochondrial membrane and cytoplasmic membranes as the case may be even though some variations may exist among the different cells.
Oxygen is usually the final electron acceptor of the ETC while NADH and FADH2 are the electron donors or reducing agents of the electron transport chain. Ubiquinone, quinines, riboflavin and cytochromes and other flavoproteins and iron-containing molecules such as iron-sulphur proteins are other examples of electron-carrying molecules of the ETC or respiratory chain. The electron transport chain occurs in the periplasmic space or cytoplasmic membrane of prokaryotic cells. In eukaryotic cells, the electron transport chain is located in the inner mitochondrial membrane of the mitochondrion, a membrane-bound organelle that is lacking in bacterial cells. The electron transport chain shows how electrons flow from electron carriers or donors to electron acceptors in a coordinated manner that is enzymatically stimulated (Figure 1). The activities going on in the ETC results in the formation of proton motive force (PMF) which is vital for carrying out work in the cell. Generally, the electron transport chain operates more like a proton pumping machine or proton pump – in which the energy produced during the movement of electrons across the energized membrane, is utilized in bringing out or extruding protons across the membrane. A transmembrane proton gradient is formed during this process; and it is used as a source of vital energy or ATP for the cell’s work. Proton motive force (PMF) is defined as the energized state of a membrane that is created by a protein gradient.
Figure 1: Schematic illustration of the flow of electrons in the electron transport chain (ETC).
Figure 2: Schematic illustration of the four (4) complexes of the ETC in mammalian cells.
It is usually formed through the action of the electron transport chain; and PMF causes the membrane to be in an energized state in which energy could be generated or utilized for several chemical and mechanical works in the cell. The cytoplasmic or plasma membrane and the inner mitochondrial membrane are typical examples of places where the PMF could be generated. As electrons are translocated or transported within the inner mitochondrial membrane, protons are separated from the electron carriers or electrons in the process and this puts the membrane in an energized state or condition critical for work in the cell. Proton motive force is generated in several ways in the cell, and the activity of the ETC is one sure way of generating PMF in the cell for chemical and mechanical work.
The proton motive force is of immense biological significance to the cell (inclusive of prokaryotic and eukaryotic cells) because of the roles it plays in electron transport as well as in energy generation since the cytoplasmic membranes (as is obtainable in prokaryotic cell) and the inner mitochondrial membrane (as is obtainable in eukaryotic cells) must be in an energized state for ATP or energy to be generated for the cell. And the energy so generated is what the cell eventually utilizes for its normal or daily cellular and metabolic activities. The synthesis or breakdown of ATP always puts the membranes of the cell at an energized state in which the PMF can be generated. The mammalian electron transport chain is the most studied type of ETCs; and it is mainly made up of four complexes which are designated as Complex I – IV (Figure 2.
The four complexes of the ETC are linked by cytochrome c and coenzyme Q (CoQ); and these four complexes of the ETC (i.e. Complexes I – IV) summarizes how electrons flow from NADH (an electron donor) and succinate to oxygen (an electron acceptor) within the inner mitochondrial membrane. Looking closely to the redox reactions going on in the electron transport chain in the inner mitochondrial membrane, it would be observed that electrons flow in a particular pattern especially form electron donors or reducing agents to electron acceptors or oxidizing agents. Electrons move from NADH, FADH2, succinate and other electron donors through flavoproteins, cytochromes, ubiquinone and iron-sulphur proteins and then finally to oxygen (the final electron acceptor of the ETC); and as oxidation-reduction reaction occurs in the ETC, energy is generated in the form of ATP for the cell. The four complexes that make up the mammalian ETC are highlighted in this section. It is noteworthy that the activities or chemical reactions going in among the four complexes of the ETC (i.e., Complexes I – IV) are critical for the formation of proton motive force (PMF) required for the formation of energy or ATP in the cell.
- Complex I is made up of NADH and ubiquinone. It basically contains flavoprotein molecules that transfer electrons from NADH to the iron-sulphur (Fe-S) center of the ETC. In complex I of the ETC, electrons can also flow from NADH to ubiquinones. The activities of complex I can be inhibited by inhibitors of the electron transport chain (e.g., rotenone).
- Complex II is mainly made up of succinate, cytochrome (cyt) and Fe-S. Electrons are transported from succinate to ubiquinone in Complex II; and it is also subject to inhibition by inhibitors of the electron transport chain reaction.
- Complex III consists of cytochromes (e.g., cyt b and cyt c) and Fe-S molecules. Unlike in Complex I and Complex II where electrons flow from the NADH and succinate respectively to ubiquinone; electrons flow from ubiquinone to cytochromes (especially cyt c) in the Complex III of the ETC. Complex III can also be inhibited by inhibitors of the ETC. Antimycin, an antibiotic is a typical inhibitor of the Complex III of the ETC.
- Complex IV is the last phase of the ETC complexes. It is made up of cytochrome oxidase, cyt c and cyt a3 as well as other protein-bound molecules and cytochromes. Complex IV is responsible for the reduction of oxygen (the final electron acceptor) to water. This reduction of O2 to H2O is an irreversible reaction; and it is catalyzed by the enzyme cytochrome oxidase. Complex IV like the other Complexes of the ETC (i.e. Complexes I, II and III) can be inhibited by inhibitors of the ETC. Cyanide, carbon monoxide (CO) and azide are typical examples of chemicals or substances that can inhibit the Complex IV of the ETC. The inhibitors of the ETC stop the flow of electrons from electron donors to electron acceptors within the inner mitochondrial membrane; and once electron flow in this system is blocked, energy in the form of ATP will not be generated because PMF will not be generated in the energy transducing-membranes of the mitochondria. And since PMF is vital to the biosynthesis of ATP for cellular work, the cell dies from lack of energy to carry out its normal metabolic and cellular activities. Uncouplers are other examples of chemicals that block ATP synthesis; but unlike the usual inhibitors of the activities of the ETC, uncouplers (e.g., Dinitrophenol) only inhibit ATP synthesis without affecting the flow of electrons from electron donors to electron acceptors in the ETC.
Alberts B, Bray D, Lewis J, Raff M, Roberts K and Watson J.D (2002). The molecular Biology of the Cell. Fourth edition. New York, Garland, USA.
Bains W (1998). Biotechnology: From A to Z. 2nd ed. Oxford University Press, New York, USA.
Berg JM, Tymoczko JL, Stryer L (2002). Biochemistry (5th ed.). New York, NY: W. H. Freeman.
Bourgaize D, Jewell T.R and Buiser R.G (1999). Biotechnology: Demystifying the Concepts. Pearson Education, San Francisco, CA.
Brooks G.F., Butel J.S and Morse S.A (2004). Medical Microbiology, 23rd edition. McGraw Hill Publishers. USA.
Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston, Massachusetts: Pearson Prentice Hall.
Cooper G.M and Hausman R.E (2004). The cell: A Molecular Approach. Third edition. ASM Press.
Dale J (2003). Molecular genetics of bacteria. Jeremy W. Dale and Simon Park (4th eds.). John Wiley & Sons Ltd, West Sussex, UK.
David L. Rimon (2002). Emery and Rimoin’s Principles and Practice of Medical Genetics. London; New York. Churchill Livingstone Publishers, 2002.
Dictionary of Microbiology and Molecular Biology, 3rd Edition. Paul Singleton and Diana Sainsbury. 2006, John Wiley & Sons Ltd. Canada.
Karp, Gerald (2009). Cell and Molecular Biology: Concepts and Experiments. John Wiley & Sons. Maton, Anthea (1997). Cells Building Blocks of Life. New Jersey: Prentice Hall.
Nelson, David L.; Cox, Michael M. (2005). Lehninger Principles of Biochemistry (4th ed.). New York: W.H. Freeman.