Oxidative phóphorylation

Nguyen Le Quyen
bt060138
Oxidative Phosphorylation
Brief content
1.What is Oxidative Phosphorylation
2.Overview of energy transfer by chemiosmosis
3.Electron and proton transfer molecules
4.Eukaryotic electron transport chains
a.NADH-coenzyme Q oxidoreductase (complex I)…
5.Prokaryotic electron transport chains
6.Reactive oxygen species
7.Inhibitors






1.What is Oxidative Phosphorylation
-Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate (ATP).
-In other words, it is the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH2 to O2 by a series of electron carriers
-This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms.


2.Overview of energy transfer by chemiosmosis
-Oxidative phosphorylation works by using energy-releasing chemical reactions to drive energy-requiring reactions: The two sets of reactions are said to be coupled.
-This means one cannot occur without the other.
- The flow of electrons through the electron transport chain, from electron donors such as NADH to electron acceptors such as oxygen, is an exergonic process – it releases energy, whereas the synthesis of ATP is an endergonic (recieving the energy process, which requires an input of energy)
-Both the electron transport chain and the ATP synthase are embedded in a membrane, and energy is transferred from electron transport chain to the ATP synthase by movements of protons across this membrane, in a process called chemiosmosis
-The amount of energy released by oxidative phosphorylation is high, compared with the amount produced by anaerobic fermentation.
- Glycolysis produces only 2 ATP molecules, but somewhere between 30 and 36 ATPs are produced by the oxidative phosphorylation of the 10 NADH and 2 succinate molecules made by converting one molecule of glucose to carbon dioxide and water.
-Actually, some protons leak across the membrane, lowering the yield of ATP
3.Electron and proton transfer molecules
-The electron transport chain carries both protons and electrons, passing electrons from donors to acceptors, and transporting protons across a membrane.
-These processes use both soluble and protein-bound transfer molecules.
-In mitochondria, electrons are transferred within the intermembrane space by the water-soluble electron transfer protein cytochrome c
-Within the inner mitochondrial membrane, the lipid-soluble electron carrier coenzyme Q10 (Q) carries both electrons and protons by a redox cycle.
-When Q accepts two electrons and two protons, it becomes reduced to the ubiquinol form (QH2);
-When QH2 releases two electrons and two protons, it becomes oxidized back to the ubiquinone (Q) form.
-As a result, if two enzymes are arranged so that Q is reduced on one side of the membrane and QH2 oxidized on the other, ubiquinone will couple these reactions and shuttle protons across the membrane.

-Within proteins, electrons are transferred between flavin cofactors,iron–sulfur clusters, and cytochromes.
-There are several types of iron–sulfur cluster
*The simplest kind found in the electron transfer chain consists of two iron atoms joined by two atoms of inorganic sulfur; these are called [2Fe–2S] clusters.
*The second kind, called [4Fe–4S], contains a cube of four iron atoms and four sulfur atoms.
-Each iron atom in these clusters is coordinated by an additional amino acid, usually by the sulfur atom of cysteine
4.Eukaryotic electron transport chains
-Many catabolic biochemical processes, such as glycolysis, the citric acid cycle, and beta oxidation, produce the reduced coenzyme NADH
-. This coenzyme contains electrons that have a high transfer potential; in other words, they will release a large amount of energy upon oxidation
-However, the cell does not release this energy all at once, as this would be an uncontrollable reaction.
Instead, the electrons are removed from NADH and passed to oxygen through a series of enzymes that each release a small amount of the energy.
-This set of enzymes, consisting of complexes I through IV, is called the electron transport chain and is found in the inner membrane of the mitochondrion.
-In eukaryotes, the enzymes in this electron transport system use the energy released from the oxidation of NADH to pump protons across the inner membrane of the mitochondrion.
-This causes protons to build up in the intermembrane space, and generates an electrochemical gradient across the membrane
-The energy stored in this potential is then used by ATP synthase to produce ATP.
a. 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 the mammalian complex I having 46 subunits and a molecular mass of about 1,000 kilodaltons (kDa).
-The reaction that is catalyzed by this enzyme is the two electron reduction by NADH of coenzyme Q10 or ubiquinone (represented as Q in the equation below), a lipid-soluble quinone that is found in the mitochondrion membrane:
-The start of the reaction, and indeed of the entire electron chain, is the binding of a NADH molecule to complex I and the donation of two electrons .
-The electrons enter complex I via a prosthetic group attached to the complex, flavin mononucleotide (FMN). The addition of electrons to FMN converts it to its reduced form, FMNH2.
-The electrons are then transferred through a series of iron–sulfur clusters: the second kind of prosthetic group present in the complex. There are both [2Fe–2S] and [4Fe–4S] iron–sulfur clusters in complex I.
-As the electrons pass through this complex, four protons are pumped from the matrix into the intermembrane space.
-Finally, the electrons are transferred from the chain of iron–sulfur clusters to a ubiquinone molecule in the membrane.
-Reduction of ubiquinone also contributes to the generation of a proton gradient, as two protons are taken up from the matrix as it is reduced to ubiquinol (QH2)
b.Succinate-Q oxidoreductase (complex II)
-Succinate-Q oxidoreductase, also known as complex II or succinate dehydrogenase, is a second entry point to the electron transport chain
-it is the only enzyme that is part of both the citric acid cycle and the electron transport chain.
-Complex II consists of four protein subunits and contains a bound flavin adenine dinucleotide (FAD) cofactor, iron–sulfur clusters, and a heme group that does not participate in electron transfer to coenzyme Q.
-It oxidizes succinate to fumarate and reduces ubiquinone.
c.Electron transfer flavoprotein-Q oxidoreductase
-Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-Q oxidoreductase), also known as electron transferring-flavoprotein dehydrogenase, is a third entry point to the electron transport chain.
-It is an enzyme that accepts electrons from electron-transferring flavoprotein in the mitochondrial matrix, and uses these electrons to reduce ubiquinone.
-This enzyme contains a flavin and a [4Fe–4S] cluste

-This metabolic pathway is important in beta oxidation of fatty acids and catabolism of amino acids and choline, as it accepts electrons from multiple acetyl-CoA dehydrogenases.
d.Q-cytochrome c oxidoreductase (complex III)
-The two electron transfer steps in complex III: Q-cytochrome c oxidoreductase
-This enzyme is a dimer, with each subunit complex containing 11 protein subunits, an [2Fe-2S] iron–sulfur cluster and three cytochromes: one cytochrome c1 and two b cytochromes
-A cytochrome is a kind of electron-transferring protein that contains at least one heme group.
-The reaction catalyzed by complex III is the oxidation of one molecule of ubiquinol and the reduction of two molecules of cytochrome c, a heme protein loosely associated with the mitochondrion.
-Unlike coenzyme Q, which carries two electrons, cytochrome c carries only one electron.
-In the first step, the enzyme binds three substrates, first, QH2, which is then oxidized, with one electron being passed to the second substrate, cytochrome c.
-The two protons released from QH2 pass into the intermembrane space.
-The third substrate is Q, which accepts the second electron from the QH2 and is reduced to Q.- ubisemiquinone free radical
-In the second step, a second molecule of QH2 is bound and again passes its first electron to a cytochrome c acceptor.
-The second electron is passed to the bound ubisemiquinone, reducing it to QH2 as it gains two protons from the mitochondrial matrix.
-This QH2 is then released from the enzyme.
e.Cytochrome c oxidase (complex IV)
-Cytochrome c oxidase, also known as complex IV, is the final protein complex in the electron transport chain
-Contains 13 subunits, two heme groups, as well as multiple metal ion cofactors – in all three atoms of copper, one of magnesium and one of zinc.
-This enzyme mediates the final reaction in the electron transport chain and transfers electrons to oxygen.
-The final electron acceptor oxygen, which is also called the terminal electron acceptor, is reduced to water in this step.
-. The reaction catalyzed is the oxidation of cytochrome c and the reduction of oxygen:

f.ATP synthase (complex V)
-ATP synthase, also called complex V, is the final enzyme in the oxidative phosphorylation pathway
-This enzyme contains 16 subunits and has a mass of approximately 600 kilodaltons.
5.Alternative reductases and oxidases
-plants have alternative NADH oxidases, which oxidize NADH in the cytosol rather than in the mitochondrial matrix, and pass these electrons to the ubiquinone pool
-Another example of a different electron transport chain is the alternative oxidase, which is found in plants, as well as some fungi, protists, and possibly some animals
-This enzyme transfers electrons directly from ubiquinol to oxygen.
6. Prokaryotic electron transport chains
-In contrast to the general similarity in structure and function of the electron transport chains in eukaryotes, bacteria and archaea possess a large variety of electron-transfer enzymes.
-Prokaryotic electron transport uses the energy released from the oxidation of a substrate to pump ions across a membrane and generate an electrochemical gradient.
-The main difference between eukaryotic and prokaryotic oxidative phosphorylation is that bacteria and archaea use many different substances to donate or accept electrons.
-This allows prokaryotes to grow under a wide variety of environmental conditions
-In E. coli, for example, oxidative phosphorylation can be made by a large number of pairs of reducing agents and oxidizing agents, which are listed below..
-The midpoint potential of a chemical measures how much energy is released when it is oxidized or reduced, with reducing agents having negative potentials and oxidizing agents positive potentials.

-As shown above, E. coli can grow with reducing agents such as formate, hydrogen, as electron donors, or oxygen as acceptors .
-The larger the difference in midpoint potential between an oxidizing and reducing agent, the more energy is released when they react.
-Prokaryotes control their use of these electron donors and acceptors by varying which enzymes are produced, in response to environmental conditions.
-Addition to this metabolic diversity, prokaryotes also possess a range of isozymes– different enzymes that catalyze the same reaction .
8.Reactive oxygen species
-Molecular oxygen is an ideal terminal electron acceptor because it is a strong oxidizing agent.
-These reactive oxygen species and their reaction products, such as the hydroxyl radical, are very harmful to cells, as they oxidize proteins and cause mutations in DNA.
-This cellular damage might contribute to disease and is proposed as one cause of aging.
-To counteract these reactive oxygen species, cells contain numerous antioxidant systems, including antioxidant vitamins such as vitamin C and vitamin E, and antioxidant enzymes such as superoxide dismutase, catalase, and peroxidases which detoxify the reactive species, limiting damage to the cell.
14. Inhibitors
-There are several well-known drugs and toxins that inhibit oxidative phosphorylation.
-For example, if oligomycin inhibits ATP synthase, protons cannot pass back into the mitochondrion.
Reference
-Biochemistry book
-some information in the website:
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