Electron Transport Chain (ETC)- Components and Steps

Before we dive into the details of the electron transport chain (ETC), let us first review the main metabolic pathways that lead to the production of electrons and protons that fuel the ETC. These pathways are glycolysis, the tricarboxylic acid (TCA) cycle and oxidative phosphorylation.

Glycolysis is the process of breaking down glucose, a six-carbon sugar, into two molecules of pyruvate, a three-carbon compound. Glycolysis occurs in the cytoplasm of both prokaryotic and eukaryotic cells and does not require oxygen. It involves ten enzymatic reactions that can be divided into two phases: the preparatory phase and the payoff phase.

In the preparatory phase, two molecules of ATP are consumed to phosphorylate glucose and convert it into fructose-1,6-bisphosphate. This molecule is then cleaved into two three-carbon molecules: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). DHAP is then converted into another molecule of G3P by an isomerase enzyme.

In the payoff phase, each molecule of G3P undergoes a series of reactions that result in the formation of one molecule of pyruvate, two molecules of NADH and two molecules of ATP. Therefore, for each molecule of glucose that enters glycolysis, two molecules of pyruvate, four molecules of ATP and two molecules of NADH are produced. However, since two molecules of ATP were used in the preparatory phase, the net gain of ATP from glycolysis is only two molecules.

The fate of pyruvate depends on the availability of oxygen. In aerobic conditions, pyruvate is transported into the mitochondrial matrix where it is converted into acetyl-CoA by the pyruvate dehydrogenase complex. This reaction also produces one molecule of NADH and one molecule of CO2 for each molecule of pyruvate. Acetyl-CoA then enters the TCA cycle to generate more electrons and protons for the ETC.

In anaerobic conditions, pyruvate is reduced to lactate or ethanol by lactate dehydrogenase or alcohol dehydrogenase, respectively. These reactions regenerate NAD+ from NADH, allowing glycolysis to continue in the absence of oxygen.

The TCA cycle, also known as the Krebs cycle or the citric acid cycle, is a series of eight reactions that occur in the mitochondrial matrix of eukaryotic cells or in the cytoplasm of prokaryotic cells. The TCA cycle oxidizes acetyl-CoA, which is derived from pyruvate or fatty acids, into CO2 and generates high-energy electrons and protons that are transferred to NAD+ and FAD to form NADH and FADH2, respectively.

The TCA cycle begins with the condensation of acetyl-CoA with oxaloacetate, a four-carbon compound, to form citrate, a six-carbon compound. Citrate then undergoes a series of rearrangements and decarboxylations that regenerate oxaloacetate and release two molecules of CO2 for each molecule of acetyl-CoA. Along the way, three molecules of NADH, one molecule of FADH2 and one molecule of GTP (which can be converted to ATP) are produced for each molecule of acetyl-CoA.

The TCA cycle is an amphibolic pathway, meaning that it can function both catabolically and anabolically. Catabolically, it oxidizes acetyl-CoA to provide energy for cellular processes. Anabolically, it provides intermediates for biosynthetic pathways such as amino acid synthesis, fatty acid synthesis and nucleotide synthesis.

Oxidative phosphorylation is the process by which electrons from NADH and FADH2 are transferred to oxygen through a series of protein complexes embedded in the inner mitochondrial membrane (or the cytoplasmic membrane in bacteria). This process generates a proton gradient across the membrane that drives the synthesis of ATP by ATP synthase.

Oxidative phosphorylation consists of two components: the electron transport chain (ETC) and chemiosmosis. The ETC is composed of four complexes: complex I (NADH dehydrogenase), complex II (succinate dehydrogenase), complex III (cytochrome b-c1 complex) and complex IV (cytochrome c oxidase). These complexes are linked by two mobile electron carriers: coenzyme Q (also known as ubiquinone) and cytochrome c.

As electrons flow through the ETC from NADH or FADH2 to oxygen, they release energy that is used to pump protons from the mitochondrial matrix to the intermembrane space (or from the cytoplasm to the periplasm in bacteria). This creates an electrochemical gradient across the membrane that stores potential energy.

Chemiosmosis is the process by which protons flow back into the matrix (or cytoplasm) through ATP synthase, a rotary enzyme that uses the proton motive force to catalyze the formation of ATP from ADP and Pi. The coupling between electron transport and ATP synthesis is known as oxidative phosphorylation because oxygen is reduced at the end of the ETC and phosphorylation occurs at ATP synthase.

Oxidative phosphorylation is the major source of ATP in aerobic organisms. It can produce up to 34 molecules of ATP per molecule of glucose oxidized, depending on the efficiency of electron transfer and proton pumping. Oxidative phosphorylation also generates water as a by-product, which helps maintain cellular hydration and pH balance.

The electron transport chain (ETC) is a series of protein complexes that transfer electrons from electron donors to electron acceptors and use the energy released to create a proton gradient across a membrane. The proton gradient is then used to drive the synthesis of ATP by a process called chemiosmosis.

The location of the ETC depends on the type of organism and the cellular compartment where the ETC takes place. In bacteria, the ETC is located in the cytoplasmic membrane, which is the innermost layer of the cell envelope that separates the cytoplasm from the external environment. The cytoplasmic membrane is composed of a phospholipid bilayer with embedded proteins that function as electron carriers and proton pumps. The ETC in bacteria can be branched, cyclic or linear, depending on the type of electron donors and acceptors available. Some bacteria can also use alternative electron acceptors, such as nitrate, sulfate or fumarate, instead of oxygen, depending on the environmental conditions.

In eukaryotic cells, the ETC is located on the inner membrane of the mitochondria, which are organelles that produce most of the ATP in the cell. The inner membrane of the mitochondria is also composed of a phospholipid bilayer with embedded proteins that function as electron carriers and proton pumps. The ETC in eukaryotes is linear and consists of four main complexes: complex I (NADH dehydrogenase), complex II (succinate dehydrogenase), complex III (cytochrome bc1 complex) and complex IV (cytochrome c oxidase). The ETC in eukaryotes uses NADH and FADH2 as electron donors and oxygen as the final electron acceptor.

The location of the ETC in bacteria and eukaryotes determines the direction of the proton gradient and the ATP synthesis. In bacteria, the ETC pumps protons out of the cytoplasm to the periplasmic space or the external environment, creating a proton gradient across the cytoplasmic membrane. The protons then flow back into the cytoplasm through ATP synthase, which is a protein complex that catalyzes the formation of ATP from ADP and inorganic phosphate. In eukaryotes, the ETC pumps protons from the mitochondrial matrix to the intermembrane space, creating a proton gradient across the inner mitochondrial membrane. The protons then flow back into the matrix through ATP synthase, which is also located on the inner mitochondrial membrane.

The location of the ETC also affects its regulation and efficiency. In bacteria, the ETC can be regulated by changing the type and availability of electron donors and acceptors, as well as by modifying the expression and activity of some ETC components. The ETC in bacteria can also have different efficiencies depending on the redox potential of the electron donors and acceptors. In eukaryotes, the ETC is mainly regulated by the availability of oxygen and substrates (NADH and FADH2), as well as by feedback inhibition from ATP and reactive oxygen species (ROS). The ETC in eukaryotes has a relatively high efficiency, as it can produce up to 2.5 ATP per NADH and 1.5 ATP per FADH2.

The location of the ETC in bacteria and eukaryotes reflects their evolutionary history and adaptation to different environments. Bacteria are prokaryotes that lack membrane-bound organelles and have a simple cell structure. They can live in diverse habitats and use various sources of energy for their metabolism. Eukaryotes are more complex organisms that have membrane-bound organelles and a nucleus. They are thought to have evolved from an endosymbiotic event between an ancestral prokaryote and an aerobic bacterium that became the mitochondrion. The mitochondrion retained its own DNA and some of its metabolic functions, including the ETC.

The electron transport chain consists of a series of protein complexes and small molecules that transfer electrons from electron donors (such as NADH and FADH2) to electron acceptors (such as oxygen) in a redox reaction. The energy released by these electron transfers is used to pump protons across the inner mitochondrial membrane, creating a proton gradient that drives the synthesis of ATP by ATP synthase. The main components of the electron transport chain are:

• Complex I (NADH dehydrogenase): This is the first and largest complex in the chain, composed of about 45 subunits. It catalyzes the oxidation of NADH to NAD+ and the reduction of coenzyme Q (also known as ubiquinone or Q) to ubiquinol (QH2). It also pumps four protons from the mitochondrial matrix to the intermembrane space, contributing to the proton gradient. Complex I contains flavin mononucleotide (FMN) and several iron-sulfur (Fe-S) clusters as prosthetic groups that facilitate the electron transfer.
• Complex II (succinate dehydrogenase): This is the second complex in the chain, composed of four subunits. It catalyzes the oxidation of succinate to fumarate in the citric acid cycle and the reduction of Q to QH2. It does not pump protons across the membrane, so it does not contribute to the proton gradient. Complex II contains flavin adenine dinucleotide (FAD) and several Fe-S clusters as prosthetic groups that facilitate the electron transfer.
• Coenzyme Q (ubiquinone): This is a small, lipid-soluble molecule that acts as a mobile electron carrier in the chain. It can accept one or two electrons from complex I or complex II and transfer them to complex III. It can also diffuse freely in the lipid bilayer of the inner mitochondrial membrane, allowing it to shuttle electrons between different complexes.
• Complex III (cytochrome bc1 complex): This is the third complex in the chain, composed of 11 subunits. It catalyzes the oxidation of QH2 to Q and the reduction of cytochrome c, a small protein that carries one electron at a time. It also pumps four protons from the matrix to the intermembrane space, contributing to the proton gradient. Complex III contains several heme groups and one Fe-S cluster as prosthetic groups that facilitate the electron transfer.
• Cytochrome c: This is a small, water-soluble protein that acts as a mobile electron carrier in the chain. It can accept one electron from complex III and transfer it to complex IV. It can also diffuse freely in the intermembrane space, allowing it to shuttle electrons between different complexes.
• Complex IV (cytochrome c oxidase): This is the fourth and final complex in the chain, composed of 13 subunits. It catalyzes the oxidation of cytochrome c and the reduction of molecular oxygen to water. It also pumps two protons from the matrix to the intermembrane space, contributing to the proton gradient. Complex IV contains several heme groups and two copper ions as prosthetic groups that facilitate the electron transfer.
• ATP synthase (complex V): This is not part of the electron transport chain, but it is essential for ATP production. It is composed of two subunits: F0 and F1. F0 is embedded in the inner mitochondrial membrane and forms a channel for protons to flow back into the matrix. F1 is attached to F0 and protrudes into the matrix. It contains a rotating part that uses the energy from proton flow to synthesize ATP from ADP and phosphate. ATP synthase can produce up to three ATP molecules for every two electrons that pass through the electron transport chain.

The electron transport chain consists of a series of redox reactions that transfer electrons from electron donors (such as NADH and FADH2) to electron acceptors (such as coenzyme Q and cytochrome c) and ultimately to oxygen. The energy released by these electron transfers is used to pump protons across the inner mitochondrial membrane, creating a proton gradient that drives the synthesis of ATP by ATP synthase. The major steps in the electron transport chain are:

• 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.
• 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.
• 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.

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).

The total number of ATP molecules produced by one glucose molecule depends on several factors, such as the shuttle system used to transport electrons from NADH in the cytosol to the mitochondria, and the use of proton gradient for other purposes besides ATP synthesis. However, a common estimate is that one glucose molecule can yield about 30-32 ATP molecules under aerobic conditions.

ATP is the main energy currency of the cell and is essential for many biochemical reactions and cellular processes. The electron transport chain is therefore a vital component of cellular respiration and energy metabolism.

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. ATP is the universal energy currency for living organisms, as it provides the energy needed for various metabolic processes and cellular functions. The electron transport chain is also the only part of glucose metabolism that uses atmospheric oxygen, which is essential for aerobic life forms.

The electron transport chain also has an important role in photosynthesis, the process by which plants and some other organisms convert light energy into chemical energy. In photosynthesis, the electron transport chain is part of the light-dependent reactions that take place in the thylakoid membrane of chloroplasts. The electron transport chain uses light energy to create a proton gradient that drives the synthesis of ATP and NADPH, which are then used in the light-independent reactions to produce glucose and other organic molecules. Thus, the significance of the electron transport chain in photosynthesis is the formation of ATP molecules that chemically store the energy needed in food production. The production of the ATP molecules happens in the mitochondria cells of the plant, as well as the chloroplasts.

The electron transport chain is therefore a vital component of both cellular respiration and photosynthesis, as it enables the efficient transfer of electrons and protons from donors to acceptors, generating a proton gradient that powers ATP synthesis. The electron transport chain is also responsible for maintaining the balance of oxygen and carbon dioxide in the atmosphere, as it consumes oxygen and produces water in cellular respiration, and produces oxygen and consumes water in photosynthesis. Without the electron transport chain, life as we know it would not be possible.

We are Compiling this Section. Thanks for your understanding.