Electron transport chain
An electron transport chain is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions and couples this electron transfer with the transfer of protons across a membrane. Many of the enzymes in the electron transport chain are embedded within the membrane.
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. In aerobic respiration, the flow of electrons terminates with molecular oxygen as the final electron acceptor. In anaerobic respiration, other electron acceptors are used, such as sulfate.
In an electron transport chain, the redox reactions are driven by the difference in the Gibbs free energy of reactants and products. The free energy released when a higher-energy electron donor and acceptor convert to lower-energy products, while electrons are transferred from a lower to a higher redox potential, is used by the complexes in the electron transport chain to create an electrochemical gradient of ions. It is this electrochemical gradient that drives the synthesis of ATP via coupling with oxidative phosphorylation through ATP synthase.
In eukaryotic organisms, the electron transport chain, and site of oxidative phosphorylation, is found on the inner mitochondrial membrane. The energy released by reactions of oxygen and reduced compounds such as cytochrome c and NADH and FADH is used by the electron transport chain to pump protons into the intermembrane space, generating the electrochemical gradient over the inner mitochondrial membrane. In photosynthetic eukaryotes, the electron transport chain is found on the thylakoid membrane. Here, light energy drives electron transport through a proton pump and the resulting proton gradient causes subsequent synthesis of ATP. In bacteria, the electron transport chain can vary between species but it always constitutes a set of redox reactions that are coupled to the synthesis of ATP through the generation of an electrochemical gradient and oxidative phosphorylation through ATP synthase.
Mitochondrial electron transport chains
Most eukaryotic cells have mitochondria, which produce ATP from reactions of oxygen with products of the citric acid cycle, fatty acid metabolism, and amino acid metabolism. At the inner mitochondrial membrane, electrons from NADH and FADH pass through the electron transport chain to oxygen, which provides the energy driving the process as it is reduced to water. The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor will pass electrons to an acceptor of higher redox potential, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the terminal electron acceptor in the chain. Each reaction releases energy because a higher-energy donor and acceptor convert to lower-energy products. Via the transferred electrons, this energy is used to generate a proton gradient across the mitochondrial membrane by "pumping" protons into the intermembrane space, producing a state of higher free energy 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 that the redox reactions of the electron transport chain have established driven by energy-releasing reactions of oxygen.Mitochondrial redox carriers
Energy associated with the transfer of electrons down the electron transport chain is used to pump protons from the mitochondrial matrix into the intermembrane space, creating an electrochemical proton gradient across the inner mitochondrial membrane. This proton gradient is largely but not exclusively responsible for the mitochondrial membrane potential. It allows ATP synthase to use the flow of H+ through the enzyme back into the matrix to generate ATP from adenosine diphosphate and inorganic phosphate. Complex I accepts electrons from the Krebs cycle electron carrier nicotinamide adenine dinucleotide, and passes them to coenzyme Q, which also receives electrons from Complex II. Q passes electrons to Complex III, which passes them to cytochrome c. Cyt c passes electrons to Complex IV.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 can be summarized as follows:
Complex I
In Complex I, two electrons are removed from NADH and transferred to a lipid-soluble carrier, ubiquinone. The reduced product, ubiquinol, freely diffuses within the membrane, and Complex I translocates four protons 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 to FMNH in one two-electron step. FMNH is then oxidized in two one-electron steps, through a semiquinone intermediate. Each electron thus transfers from the FMNH to an Fe–S cluster, from the Fe-S cluster to ubiquinone. Transfer of the first electron results in the free-radical form of Q, and transfer of the second electron reduces the semiquinone form to the ubiquinol form, QH. During this process, four protons are translocated from the mitochondrial matrix to the intermembrane space. As the electrons move through 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 intermembrane space per two electrons from NADH.
Complex II
In Complex II additional electrons are delivered into the quinone pool originating from succinate and transferred to Q. Complex II consists of four protein subunits: succinate dehydrogenase ; succinate dehydrogenase iron–sulfur subunit mitochondrial ; succinate dehydrogenase complex subunit C ; and succinate dehydrogenase complex subunit D. Other electron donors also direct electrons into Q. Complex II is a parallel electron transport pathway to Complex I, but unlike Complex I, no protons are transported to the intermembrane 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, the Q-cycle contributes to the proton gradient by an asymmetric absorption/release of protons. Two electrons are removed from QH at the QO site and sequentially transferred to two molecules of cytochrome c, a water-soluble electron carrier located within the intermembrane space. The two other electrons sequentially pass across the protein to the Qi site where the quinone part of ubiquinone is reduced to quinol. A proton gradient is formed by one quinol oxidations at the Qo site to form one quinone at the Qi site.When electron transfer is reduced, Complex III may leak electrons to molecular oxygen, resulting in superoxide formation.
This complex is inhibited by dimercaprol, naphthoquinone and antimycin.
Complex IV
In Complex IV, sometimes called cytochrome AA3, four electrons are removed from four molecules of cytochrome c and transferred to molecular oxygen and four protons, 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, contributing to the proton gradient. The exact details of proton pumping in Complex IV are still under study. Cyanide is an inhibitor of Complex IV.Coupling with oxidative phosphorylation
According to the chemiosmotic coupling hypothesis, proposed by Nobel Prize in Chemistry winner Peter D. Mitchell, the electron transport chain and oxidative phosphorylation are coupled by a proton gradient across the inner mitochondrial membrane. The efflux of protons from the mitochondrial matrix creates an electrochemical gradient. This gradient is used by the FF ATP-synthase complex to make ATP via oxidative phosphorylation. ATP-synthase is sometimes described as Complex V of the electron transport chain.The F component acts as a channel that harnesses the proton flow to drive rotation. It is composed of a, b and c subunits. Protons in the inter-membrane space of mitochondria first enter the ATP-synthase complex through an a subunit channel. Then protons bind to the c subunits, which are oriented in a ring, where the number of c subunits determines how many protons are required to make the c-ring and the attached γ-rotor turn one full revolution. There are 8 c subunits in humans, thus 8 protons are required. Protons are released as a result of the rotation of the c-ring, being directed into the mitochondrial matrix along the a subunit channels. This proton reflux drives the mechanical rotation of the c-ring and the γ-axle. The rotation of the γ-rotor causes the sequential alternation of conformational states in the catalytic β-subunits in F.
There are three different conformational states, which are:
- Open, in this state the β-subunit has low affinity to ligands, releasing the previously synthesized ATP molecule.
- Loose, Binds ADP and Pi together loosely.
- Tight, Binds ADP and Pi so tightly that it catalyzes the condensation reaction to form ATP.
Coupling with oxidative phosphorylation is a key step for ATP production. However, in specific cases, uncoupling the two processes may be biologically useful. The uncoupling protein, thermogenin—present in the inner mitochondrial membrane of brown adipose tissue—provides for an alternative flow of protons back to the inner mitochondrial matrix. Thyroxine is also a natural uncoupler. This alternative flow results in thermogenesis rather than ATP production.