Oxidative phosphorylation (or OXPHOS in short) (UK , US ) is a metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing the energy used to produce adenosine triphosphate (ATP). In most eukaryotes, this occurs within the mitochondria. Almost all aerobic organisms do oxidative phosphorylation. This pathway may be highly pervasive as it is a very efficient way to release energy, compared to alternative fermentation processes such as anaerobic glycolysis.
During oxidative phosphorylation, electrons are transferred from an electron donor to an electron acceptor such as oxygen, in a redox reaction. This redox reaction releases energy, which is used to form ATP. In eukaryotes, this redox reaction is performed by a series of protein complexes within the inner membrane of cell mitochondria, whereas in prokaryotes, this protein is located in the intermembrane membrane space. This collection of connected proteins is called the electron transport chain. In eukaryotes, five major protein complexes are involved, whereas in prokaryotes many different enzymes are present, using various electron donors and acceptor.
The energy released by the electrons flowing through the electron transport chain is used to transport the proton across the inner mitochondrial membrane, in a process called transport of electrons . This generates potential energy in the form of pH gradients and electrical potential across this membrane. This energy store is tapped when the proton flows back across the membrane and lowers the potential energy gradient, through a large enzyme called ATP synthase; this process is known as chemiosmosis. ATP synthase uses energy to convert adenosine diphosphate (ADP) into adenosine triphosphate, in phosphorylated reactions. The reaction is driven by the flow of protons, which forces the rotation of parts of the enzyme; ATP synthase is a rotary mechanical motor.
Although oxidative phosphorylation is an important part of metabolism, it produces reactive oxygen species such as superoxide and hydrogen peroxide, which cause the spread of free radicals, damaging cells and contributing to disease and, possibly, aging (aging). Enzymes that run these metabolic pathways are also the targets of many drugs and toxins that inhibit their activity.
This is the process of cell respiration terminals in eukaryotes and contributes to high ATP results.
Video Oxidative phosphorylation
Chemiosmosis
Oxidative phosphorylation works by using chemical reactions that release energy to induce a reaction that requires energy: Two sets of reactions are said to be combined. This means one can not happen without the other. The flow of electrons through the electron transport chain, from electron donors like NADH to electron acceptor such as oxygen, is an exergonic process - releasing energy, while ATP synthesis is an endergonic process, requiring energy input. Both the electron transport chain and the ATP synthase are embedded in the membrane, and energy is transferred from the electron transport chain to the synthesis of ATP by the movement of protons across this membrane, in a process called chemiosmosis . In practice, it's like a simple electrical circuit, with a proton current driven from a negative N-side membrane to the positive P side by a proton pumping enzyme from the electron transport chain. These enzymes are like batteries, because they work to drive current through the circuit. The movement of protons creates an electrochemical gradient across the membrane, often called the proton motive motif. It has two components: the difference of the proton concentration (a H gradient,? PH) and the difference in electrical potential, with the N-side having a negative charge.
ATP synthase releases this stored energy by completing the circuit and allowing the proton to flow beneath the electrochemical gradient, back to the N-side of the membrane. The electrochemical gradient induces the rotation of parts of the enzyme structure and attaches this movement to the ATP synthesis.
The two components of proton motive force have a thermodynamic similarity: In mitochondria, the bulk of energy is provided by its potential; in alkaliphil bacteria, the electrical energy must even compensate for the difference in pH upside down. Reversed, chloroplasts operate mainly on? PH. However, they also require a small membrane potential for the synthesis of ATP. In the case of fusobacterium Propionigenium modestum it encourages counter-rotation of subunits a and c of F O ATP motor synthase.
The amount of energy released by oxidative phosphorylation is high, compared with the amount produced by anaerobic fermentation. Glycolysis produces only two ATP molecules but somewhere between 30 and 36 ATP is produced by oxidative phosphorylation of 10 NADH and 2 molecules of succinate made by converting one molecule of glucose into carbon dioxide and water, while each beta oxidation cycle of the acidic fat around 14 ATP. The result of this ATP is the theoretical maximum value; in practice, some protons leak across the membrane, lowering the ATP results.
Maps Oxidative phosphorylation
Electrons and proton transfer molecules
The electron transport chain carries both protons and electrons, electrons passing from donor to acceptor, and transporting protons across the membrane. These processes use transfer molecules that are soluble and bound to proteins. In mitochondria, electrons are transferred in intermembrane space by electron transfer proteins dissolved in cytochrome water c. It carries only electrons, and this is transferred by the reduction and oxidation of the iron atoms that the protein holds in the heme group within its structure. Cytochrome c is also found in some bacteria, where it is located in the periplasmic space.
Inside the inner mitochondrial membrane, fat-soluble electron carriers, coenzyme Q10 (Q) carry electrons and protons through the redox cycle. This small benzoquinone molecule is highly hydrophobic, so it diffuses freely within the membrane. When Q receives two electrons and two protons, it will be reduced to ubiquinol (QH 2 ); when QH 2 releases two electrons and two protons, it becomes oxidized back to the ubiquinone (Q) form. Consequently, if two enzymes are regulated so that Q decreases on one side of the membrane and QH 2 oxidizes on the other, ubiquinone will pair these reactions and shuttle the proton across the membrane. Some bacterial electron transport chains use different quinons, such as menaquinone, in addition to ubiquinone.
In proteins, electrons are transferred between the flavin cofactor, the iron-sulfur group, and the cytochrome. There are several types of iron-sulfur clusters. The simplest type found in the electron transfer chain consists of two iron atoms joining two inorganic sulfur atoms; this is called cluster [2Fe-2S]. The second type, called [4Fe-4S], contains a cube of four iron atoms and four sulfur atoms. Each iron atom in this group is coordinated by an additional amino acid, usually by a cysteine ​​sulfur atom. Cofactors of metal ions undergo redox reactions without binding or releasing protons, so in the electron transport chain they serve solely to transport electrons through proteins. The electrons move a considerable distance through the protein by jumping along this chain of cofactors. This happens with a quantum tunnel, which is rapidly above a distance of less than 1.4 ÃÆ' - 10 -9 m.
Eukaryotic electron transport chain
Many catabolic biochemical processes, such as glycolysis, citric acid cycle, and oxidation of beta, produce lessened NADH coenzymes. This coenzyme contains electrons that have high transfer potential; in other words, they will release large amounts of energy in oxidation. However, the cell does not release this energy at once, because it will be an uncontrollable reaction. Instead, electrons are removed from NADH and passed to oxygen through a series of enzymes each releasing a small amount of energy. A collection of enzymes, composed of complexes I to IV, are called electron transport chains and are found in the inner membranes of the mitochondria. The succinate is also oxidized by the electron transport chain, but enters the path at a different point.
In eukaryotes, enzymes in this electron transport system use energy released from NADH oxidation to pump protons across the inner membrane of mitochondria. This causes the proton to build up in the intermembrane space, and produces an electrochemical gradient across the membrane. The energy stored in this potential is then used by ATP synthase to generate ATP. Oxidative phosphorylation in eukaryotic mitochondria is the best example of this process. Mitochondrion is present in almost all eukaryotes, with the exception of anaerobic protozoa such as Trichomonas vaginalis which instead reduces the proton to hydrogen in the rest mitochondria called hydrogenosomes.
NADH-coenzyme_Q_oxidoreductase_.28complex_I.29 "> NADH-coenzyme Q oxidoreductase (complex I)
NADH-coenzyme Q oxidoreductase, also known as NADH dehydrogenase or complex I , is the first protein in the electron transport chain. Complex I is a giant enzyme with a mammalian complex that I have 46 subunits and a molecular mass of about 1,000 kilodaltons (kDa). This structure is known in detail only from bacteria; in most organisms, the complex resembles boots with large "balls" poking out of the membrane into the mitochondria. The genes that encode individual proteins are present in the cell nucleus and mitochondrial genome, as well as for many of the enzymes present in the mitochondria.
The reactions catalyzed by this enzyme are two oxidation NADH electrons by coenzyme Q10 or ubiquinone (represented as Q in the equation below), the fat-soluble quinine found in the mitochondrial membrane:
The initial reaction, and of course the entire electron chain, is the binding of the NADH molecule to complex I and the donation of two electrons. The electrons enter complex I through a prosthetic group attached to the complex, flavin mononucleotide (FMN). The addition of electrons to the FMN transforms it into a reduced form, FMNH 2 . The electrons are then transferred through a series of sulfur-iron groups: the second type of prosthetic group present in the complex. There are groups of iron-sulfur [2Fe-2S] and [4Fe-4S] in complex I.
When electrons pass through this complex, four protons are pumped from the matrix into intermembrane space. Exactly how this happens is unclear, but it seems to involve a conformational change in complex I that causes the protein to bind protons on the N-side of the membrane and release it on the P-side of the membrane. Finally, the electrons are transferred from the sulfur-iron chain to the ubiquinone molecule in the membrane. The reduction of ubiquinone also contributes to the formation of proton gradients, since two protons are taken from the matrix because they are reduced to ubiquinol (QH 2 ).
Succinate-Q oxidoreductase (complex II)
Succinate-Q oxidoreductase, also known as complex I/II or succinate dehydrogenase, is the second entry point to the electron transport chain. This is unusual because it is the only enzyme that is part of the citric acid cycle and the electron transport chain. Complex II comprises four protein subunits and contains flavin adenine (FAD) flavin dinucleotide catalysts, iron-sulfur groups, and heme groups that do not participate in the transfer of electrons to coenzyme Q, but are believed to be important in lowering reactive production. oxygen species. It oxidizes succinate into fumarate and reduces ubiquinone. Because this reaction releases less energy than the oxidation of NADH, complex II does not transport protons across the membrane and does not contribute to the proton gradient.
In some eukaryotes, such as the parasitic worm Ascaris suum , enzymes similar to complex II, fumarate reductase (menaquinol: fumarate oxidoreductase, or QFR), operate in reverse to oxidize ubiquinol and reduce fumarate. This allows the worms to survive in the anaerobic environment of the colon, performing anaerobic oxidative phosphorylation with the fumarate as an electron acceptor. Another unconventional function of complex II is seen in the malaria parasite Plasmodium falciparum . Here, the action of inverse II complexes as an important oxidase in ubiquinol regeneration, which parasites use in the form of unusual pyrimidine biosynthesis.
Transfer electron flavoprotein-Q oxidoreductase
Electron transfer of flavoprotein-ubiquinone oxidoreductase (ETF-Q oxidoreductase), also known as electron transfer-flavoprotein dehydrogenase , is the third entry point into the electron transport chain. This is an enzyme that accepts electrons from flavoproteins transferring electrons in a mitochondrial matrix, and using these electrons to reduce ubiquinone. This enzyme contains flavin and the group [4Fe-4S], but, unlike other respiratory complexes, this enzyme attaches to the membrane surface and does not cross the lipid bilayer.
In mammals, this metabolic pathway is important in the oxidation of beta fatty acids and the catabolism of amino acids and choline, as it receives electrons from various acetyl-CoA dehydrogenases. In plants, ETF-Q oxidoreductase is also important in metabolic responses that allow survival in long periods of darkness.
Q-cytochrome c oxidoreductase (complex III)
Q-cytochrome c oxidoreductase is also known as cytochrome c reductase , cytochrome bc 1 complex , or only complex III . In mammals, this enzyme is a dimer, with each subunit complex containing 11 protein subunits, an iron-sulfur group [2Fe-2S] and three cytochromes: one cytochrome c 1 and two b cytochromes. Cytochrome is a kind of electron transfer protein that contains at least one heme group. Iron atoms in complex heme III groups alternate between reduced iron (2) and oxidized iron (3) as electrons are transferred through proteins.
The reaction catalyzed by complex III is the oxidation of one molecule of ubiquinol and the reduction of two cytochrome c molecules, a heme protein loosely associated with the mitochondria. Unlike coenzyme Q, which carries two electrons, cytochrome c carries only one electron.
Since only one electron can be transferred from the donor QH 2 to the cytochrome c acceptor at a time, the reaction mechanism of complex III is more complicated than the other respiratory complexes, and occurs in two steps called cycle Q. In the first step , the enzyme binds to three substrates, first, QH 2 , which is then oxidized, with one electron passed to the second substrate, cytochrome c. Two protons removed from QH 2 enter the intermembrane space. The third substrate is Q, which receives the second electron of QH 2 and is reduced to Q .- , which is free radical ubisemiquinone. The first two substrates are released, but the ubisemiquinone intermediates remain attached. In the second step, the second molecule QH 2 is bound and re-passes the first electron to the cytochrome acceptor c. The second electron is passed to the bound ubisemiquinone, reducing it to QH 2 because it obtains two protons from the mitochondrial matrix. This QH 2 is then released from the enzyme.
Since the coenzyme Q is reduced to ubiquinol on the inner side of the membrane and oxidized to ubiquinone on the other side, the transfer of protons across the membrane occurs, adding to the proton gradient. A rather complicated two-step mechanism by which this happens is important, as it increases the efficiency of proton transfer. If, instead of the Q cycle, one molecule QH 2 is used to directly reduce two cytochrome c molecules, the efficiency will be halved, with only one proton being transferred per cytochrome c reduced.
Cytochrome c oxidase (complex IV)
Cytochrome c oxidase, also known as complex IV , is the last protein complex in the electron transport chain. The mammalian enzyme has a very complex structure and contains 13 subunits, two heme groups, as well as some metal ion cofactors - all three copper atoms, one from magnesium and one from zinc.
This enzyme mediates the final reaction in the electron transport chain and transfers the electrons to oxygen, while pumping the protons across the membrane. The last electron receiving oxygen, also called the electron acceptor terminal , is reduced to water in this step. Both the direct pumping of protons and the consumption of proton matrices in oxygen reduction contribute to the proton gradient. The catalyzed reaction is oxidation of cytochrome c and oxygen reduction:
Alternative reductase and oxidase
Many eukaryotic organisms have different electron transport chains of the much studied mammalian enzyme described above. For example, plants have an alternative NADH oxidase, which oxidizes NADH in the cytosol rather than in the mitochondrial matrix, and passes these electrons to the ubiquinone pool. These enzymes do not transport protons, and, therefore, reduce ubiquinone without altering the electrochemical gradient across the inner membrane.
Another example of the divergent electron transport chain is the alternative oxidase , found in plants, as well as some fungi, protists, and possibly some animals. This enzyme transfers direct electrons from ubiquinol to oxygen.
The electron transport lines generated by alternative NADH and ubiquinone oxidase have lower ATP results than the full line. The gains generated by the shortened path are not entirely clear. However, alternative oxidase is produced in response to pressures such as cold, reactive oxygen species, and infection by pathogens, as well as other factors that inhibit the complete electron transport chain. Alternative pathways may, therefore, increase organism resistance to injury, by reducing oxidative stress.
Complex organization
The original model for how complex the respiratory chain is organized is that they diffuse freely and independently in the mitochondrial membranes. However, recent data suggest that complexes may form high order structures called supercomplexes or "respirasomes". In this model, various complexes exist as collections of enzymes interacting with each other. This association may allow channeling of substrates between various enzyme complexes, increasing the rate and efficiency of electron transfer. In such supercomplex mammals, some components will be present in higher quantities than others, with some data showing the ratio between complex I/II/III/IV and ATP synthase about 1: 1: 3: 7: 4. However, the debate over this supercomplex hypothesis is not fully resolved, as some data do not seem to fit this model.
The prokaryotic electron transport chain
In contrast to the general similarities in the structure and function of electron transport chains in eukaryotes, bacteria and archaea have many electron transfer enzymes. It uses a set of chemicals that are as large as a substrate. Generally with eukaryotes, prokaryotic electron transport uses energy released from substrate oxidation to pump ions across the membrane and produce electrochemical gradients. In bacteria, oxidative phosphorylation in Escherichia coli is understood in the most detail, while archaea systems are currently poorly understood.
The main difference between eukaryotic and prokaryotic oxidative phosphorylation is that bacteria and archaea use many different substances to donate or receive electrons. This allows prokaryotes to grow under various environmental conditions. In E. coli , for example, oxidative phosphorylation may be driven by a large number of reducing agents and oxidizers, listed below. The midpoint potential of the chemicals measures how much energy is released when oxidized or decreases, with reducing agents having positive potential and positive oxidation potential of agents.
As indicated above, E. coli can grow by reducing agents such as formatting, hydrogen, or lactate as electron donors, and nitrate, DMSO, or oxygen as acceptors. The greater the potential difference between the midpoint of the oxidizer and the reducing agent, the more energy is released when reacting. Of these compounds, the succinate/fumarate pair is unusual, because the midpoint potential is near zero. Succinate can be oxidized to fumarate if a strong oxidizing agent such as oxygen is available, or the fumarate can be reduced to succinate using a strong reducing agent such as the formation. These alternative reactions are catalyzed by succinic dehydrogenase and fumarate reductase, respectively.
Some prokaryotes use redox couples which have only a small difference in potential midpoints. For example, nitrifying bacteria such as Nitrobacter oxidize nitrite to nitrate, donating electrons to oxygen. The small amount of energy released in this reaction is sufficient to pump protons and produce ATP, but not enough to produce NADH or NADPH directly for use in anabolism. This problem is solved by using nitric oxidoreductase to produce sufficient proton motion force to run part of the electron transport chain in reverse, causing complex I to produce NADH.
Prokaryotes control the use of these electron donors and acceptors by varying which enzymes are produced, in response to environmental conditions. This flexibility is possible because different oxidases and reductases use the same ubiquinone pool. This allows many combinations of enzymes to work together, linked by common ubiquinol intermediates. Therefore, this breathing chain has a modular design, with a collection of interchangeable enzyme systems.
In addition to this metabolic diversity, prokaryotes also have different isozymes that catalyze the same reaction. For example, in E. coli , there are two types of ubiquinol oxidase that use oxygen as an electron acceptor. In very aerobic conditions, cells use low affinity oxidase for oxygen which can carry two protons per electron. However, if oxygen levels go down, they switch to oxidase that only transfers one proton per electron, but has a high affinity for oxygen.
1 and back to the membrane is a long trunk subunit like an anchor? and? subunit to the base of the enzyme.As the protons cross the membrane through the channel at the base of the ATP synthase, the propulsion Moton-F O rotates. Rotation may be caused by a change in ionization of amino acids in the c subunit ring that causes electrostatic interactions that push the c subunit ring across the proton channel. This rotating ring in turn drives the rotation of the central axle (the subunit shaft) inside? and? subunit. That? and? The subunit is prevented from spinning itself by the side arm, which acts as a stator. This movement from the tip? subunit in ball? and? subunit provides energy for active sites within? subunit to undergo a cycle of motion that produces and then releases ATP.
This ATP synthesis reaction is called the binding change mechanism and involves the active site of a? subunit cycling between the three states. In the "open" state, ADP and phosphate enter the active site (shown in brown on the diagram). The protein then closes around the molecule and ties it loosely - the state of "loose" (shown in red). The enzyme then changes its shape again and forces these molecules together, with the active site in a "tight" state (shown in pink) that binds the newly produced ATP molecule with a very high affinity. Finally, the active site cycle returns to open state, releases ATP and binds more ADP and phosphate, ready for the next cycle.
In some bacteria and archaea, the synthesis of ATP is driven by the movement of sodium ions through the cell membrane, rather than the movement of protons. Archaea such as Methanococcus also contain A 1 synthesis A o , an enzyme form containing additional proteins with some similarities in sequence to the other. synthetic subunits of bacterial and eukaryotic ATP synthase. It is possible that, in some species, the enzyme form A 1 A o is a special sodium-driven ATP synthase, but this may not be true in all cases..
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Reactive oxygen species
The oxygen molecule is the ideal terminal electron acceptor because it is a powerful oxidizer. Oxygen reduction does involve potentially dangerous intermediates. Although the transfer of four electrons and four protons reduces oxygen to water, which is harmless, the transfer of one or two electrons produces superoxide anions or peroxides, which are highly reactive.
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These reactive oxygen species and their reaction products, such as hydroxyl radicals, are very harmful to cells, because they oxidize proteins and cause mutations in DNA. This cell damage may contribute to the disease and is proposed as one of the causes of aging.
The cytochrome c oxidase complex is highly efficient in reducing oxygen to water, and releases very little partially reduced intermediate; However, a small number of superoxide anions and peroxides are produced by the electron transport chain. Most important is the reduction of coenzyme Q in complex III, as a highly reactive free radical formed from reactive reactive. This unstable species can cause "leakage" of electrons when electrons transfer directly to oxygen, forming superoxide. Because the production of reactive oxygen species by the proton pumping complex is greatest at high membrane potentials, it has been proposed that mitochondria regulate their activity to maintain membrane potential in a narrow range that balances ATP production against oxidant formation. For example, oxidants can activate proteins that release proteins that reduce membrane potential.
To counteract this reactive oxygen species, cells contain many antioxidant systems, including antioxidant vitamins such as vitamin C and vitamin E, and antioxidant enzymes such as superoxide dismutase, catalase, and peroxidase, which detoxifies reactive species, limiting damage to cells.
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Inhibitors
There are several well known drugs and toxins that inhibit oxidative phosphorylation. Although one of these toxins only inhibits one enzyme in the electron transport chain, the inhibition of any step in this process will stop the rest of the process. For example, if oligomycin inhibits ATP synthase, protons can not return to the mitochondria. As a result, the proton pump can not operate, because the gradient becomes too strong to overcome. NADH is then no longer oxidized and the citric acid cycle stops operating because the concentration of NAD falls below the concentrations that these enzymes can use.
Not all oxidative phosphorylation inhibitors are toxic. In a brown adipose tissue, a regulated proton channel called a release protein can separate respiration from ATP synthesis. This rapid respiration generates heat, and is very important as a way of maintaining body temperature to hibernate animals, although this protein also has a more general function in the response of cells to stress.
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History
The field of oxidative phosphorylation began with a report in 1906 by Arthur Harden of an important role for phosphate in cellular fermentation, but initially only sugar phosphate was known to be involved. However, in the early 1940s, the relationship between sugar oxidation and the generation of ATP was determined by Herman Kalckar, who asserted the central role of ATP in the energy transfer proposed by Fritz Albert Lipmann in 1941. Then, in 1949, Morris Friedkin and Albert L. Lehninger proves that NADH coenzymes connect metabolic pathways such as citric acid cycle and ATP synthesis. The term oxidative phosphorylation was created by Volodymyr Belitser in 1939.
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