Electron Transport Chain

 Electron Transport Chain

Definition-The electron transport chain (ETC or respiratory chain) is a series of protein complexes that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples this electron transfer with the transfer of protons (H⁺ ions) across a membrane. The electron transport chain is built up of peptides, enzymes, and other molecules.

Introduction- The flow of electrons through the electron transport chain is an exergonic process. The energy from the redox reactions creates an electrochemical proton gradient that drives the synthesis of adenosine triphosphate (ATP). In aerobic respiration, the flow of electrons terminates with molecular oxygen being the final electron acceptor. In anaerobic respiration, other electron acceptors are used, such as sulfate.

In the electron transport chain, the redox reactions are driven by the Gibbs free energy state of the components. Gibbs free energy is related to a quantity called the redox potential. The complexes in the electron transport chain harvest the energy of the redox reactions that occur when transferring electrons from a low redox potential to a higher redox potential, creating an electrochemical gradient. It is the electrochemical gradient created that drives the synthesis of ATP via coupling with oxidative Phosphorylation with ATP synthase.

In eukaryotic organisms the electron transport chain, and site of oxidative Phosphorylation, is found on the inner mitochondrial membrane. The energy stored from the process of respiration in reduced compounds (such as NADH and FADH) is used by the electron transport chain to pump protons into the inter membrane space, generating the electrochemical gradient over the inner mitochondrial membrane.

Most eukaryotic cells have mitochondria, which produce ATP from products of the citric acid cycle, fatty acid oxidation, and amino acid oxidation. At the inner mitochondrial membrane, electrons from NADH and FADH₂ pass through the electron transport chain to oxygen, which is reduced to water. 

The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor will pass electrons to a more  electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain.

Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by "pumping" protons into the inter membrane space, producing a thermodynamic state that has the potential to do work. This entire process is called oxidative Phosphorylation since ADP is phosphorylated to ATP by using the electrochemical gradient established by the redox reactions of the electron transport chain.

Mitochondrial redox carriers

Energy obtained through the transfer of electrons down the electron transport chain is used to pump protons from the mitochondrial matrix into the inter membrane space, creating an electrochemical proton gradient (ΔpH) across the inner mitochondrial membrane. This proton gradient is largely but not exclusively responsible for the mitochondrial membrane potential (ΔΨ_M). It allows ATP synthase to use the flow of H⁺ through the enzyme back into the matrix to generate ATP from adenosine diphosphate (ADP) and inorganic phosphate.

Complex I (NADH coenzyme Q reductase; labeled I) accepts electrons from the Krebs cycle electron carrier nicotinamide adenine dinucleotide (NADH), and passes them to coenzyme Q (ubiquinone; labeled Q), which also receives electrons from complex II (succinate dehydrogenase; labeled II). Q passes electrons to complex III (cytochrome bc₁ complex; labeled III), which passes them to cytochrome C. cytochrome C passes electrons to complex IV (cytochrome coxidase; labeled IV), which uses the electrons and hydrogen ions to reduce molecular oxygen to water.

Four membrane-bound complexes have been identified in mitochondria. Each is an extremely complex transmembrane structure that is embedded in the inner membrane. Three of them are proton pumps. The structures are electrically connected by lipid-soluble electron carriers and water-soluble electron carriers.

The overall electron transport chain:

Complex I

In complex I (NADH ubiquinone oxireductase, Type I NADH dehydrogenase, or mitochondrial complex I; EC 1.6.5.3), two electrons are removed from NADH and transferred to a lipid-soluble carrier, ubiquinone (Q). The reduced product, ubiquinol (QH₂), freely diffuses within the membrane, and Complex I translocates four protons (H⁺) across the membrane, thus producing a proton gradient. Complex I is one of the main sites at which premature electron leakage to oxygen occurs, thus being one of the main sites of production of superoxide.

The pathway of electrons is as follows-

NADH is oxidized to NAD⁺, by reducing Flavin mononucleotide  FMN to FMNH₂ in one two-electron step. FMNH₂ is then oxidized in two one-electron steps, through a semiquinone intermediate. Each electron thus transfers from the FMNH₂ to a Fe-S cluster, from the Fe-S cluster to ubiquinone (Q). Transfer of the first electron results in the free-radical (semiquinone) form of Q, and transfer of the second electron reduces the semiquinone form to the ubiquinol form, QH₂. During this process, four protons are translocated from the mitochondrial matrix to the inter membrane space.  As the electrons become continuously oxidized and reduced throughout the complex an electron current is produced along the 180 Angstrom width of the complex within the membrane. This current powers the active transport of four protons to the inter membrane space per two electrons from NADH.

Complex II

In complex II (succinate dehydrogenase or succinate-CoQ reductase) additional electrons are delivered into the quinone pool (Q) originating from succinate and transferred (via flavin adenine dinucleotide (FAD)) to Q. Complex II consists of four protein subunits: succinate dehydrogenase, (SDHA); succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial, (SDHB); succinate dehydrogenase complex subunit C,(SDHC) and succinate dehydrogenase complex, subunit D,(SDHD). Other electron donors (e.g., fatty acids and glycerol 3-phosphate)also direct electrons into Q (via FAD). Complex II is a parallel electron transport pathway to complex 1, but unlike complex 1, no protons are transported to the inter membrane space in this pathway. Therefore, the pathway through complex II contributes less energy to the overall electron transport chain process.

Complex III

In complex III (cytochrome bc₁ complex or CoQH₂-cytochrome c reductase)the Q-cycle contributes to the proton gradient by an asymmetric absorption/release of protons. Two electrons are removed from QH₂ at the Q_O site and sequentially transferred to two molecules of cytochrome c, a water-soluble electron carrier located within the inter membrane space. The two other electrons sequentially pass across the protein to the Q_i site where the quinone part of ubiquinone is reduced to quinol. A proton gradient is formed by one quinol {\displaystyle {\ce {2H+2e-}}}oxidations at the Q_o site to form one quinone {\displaystyle {\ce {2H+2e-}}}at the Q_i site. (In total, four protons are translocated: two protons reduce quinone to quinol and two protons are released from two ubiquinol molecules.)

When electron transfer is reduced, by a high membrane potential or respiratory inhibitors such as antimycin A, Complex III may leak electrons to molecular oxygen which results in superoxide formation. This complex is inhibited by dimercaprol (British Antilewisite, BAL), Napthoquinone and Antimycin.

Complex IV

In complex IV (cytochrome c oxidase), sometimes called cytochrome AA3, four electrons are removed from four molecules of cytochrome c and transferred to molecular oxygen (O₂), producing two molecules of water. The complex contains coordinated copper ions and several heme groups. At the same time, eight protons are removed from the mitochondrial matrix (although only four are translocated across the membrane), contributing to the proton gradient. The exact details of proton pumping in complex IV are still under study. Cyanide is an inhibitor of complex 4.

Electron Donors

In the current biosphere, the most common electron donors are organic molecules. Organisms that use organic molecules as an electron source are called organotrophs. Chemo organotrophs (animals, fungi, protists) and photolithographs (plants and algae) constitute the vast majority of all familiar life forms. Some prokaryotes can use inorganic matter as an electron source. Such an organism is called a (chemo) lithotrophs ("rock-eater"). Inorganic electron donors include hydrogen, carbon monoxide, ammonia, nitrite, sulfur, sulfide, manganese oxide, and ferrous iron. Lithotrophs have been found growing in rock formations thousands of meters below the surface of Earth. Because of their volume of distribution, lithotrophs may actually outnumber organotrophs and phototrophs in our biosphere.

Electron Acceptors

Just as there are a number of different electron donors (organic matter in organotrophs, inorganic matter in lithotrophs), there are a number of different electron acceptors, both organic and inorganic. If oxygen is available, it is most often used as the terminal electron acceptor in aerobic bacteria and facultative anaerobes. Mostly in anaerobic environments different electron acceptors are used, including nitrate, nitrite, ferric iron, sulfate, carbon dioxide, and small organic molecules such as fumarate.