oxidative phosphorylation - wikipedia, the free encyclopedia.pdf

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6/17/2016 Oxidative phosphorylation - W ikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Oxidative_phosphorylation

The electron transport chain in the cell is the site of oxidative

phosphorylation in prokaryotes. The NADHand succinate generated

in the citric acid cycle are oxidized, releasing energy to power the

ATP synthase.

Oxidative phosphorylationFrom Wikipedia, the free encyclopedia

Oxidative phosphorylation(or OXPHOS in

short) is the metabolic pathwayin which cells

use enzymes to oxidize nutrients, thereby

releasing energywhich is usedto reform ATP.In most eukaryotes, this takes place inside

mitochondria. Almost all aerobic organisms

carry out oxidative phosphorylation. This

pathway is probably so pervasive because it is a

highly efficient way of releasing energy,

compared to alternative fermentation processes

such as anaerobic glycolysis.

During oxidative phosphorylation, electrons are

transferred from electron donors to electron

acceptors such as oxygen, in redox reactions.These redox reactions release energy, which is

used to form ATP. In eukaryotes, these redox

reactions are carried out by a series ofprotein

complexes within the inner membrane of the

cell's mitochondria, whereas, in prokaryotes,

these proteins are located in the cells'

intermembrane space. These linked sets of

proteins are called electron transport chains. In

eukaryotes, five main protein complexes are

involved, whereas in prokaryotes many

different enzymes are present, using a variety

of electron donors and acceptors.

The energy released by electrons flowing through this electron transport chain is used to transport protons across

the inner mitochondrial membrane, in a process called electron transport. This generates potential energy in the

form of a pH gradient and an electricalpotential across this membrane. This store of energy is tapped by allowing

protons to flow back across the membrane and down this gradient, through a large enzyme called ATP synthase

this process is known as chemiosmosis. This enzyme uses this energy to generate ATP from adenosine diphospha

(ADP), in a phosphorylation reaction. This reaction is driven by the proton flow, which forces the rotation of a pa

of the enzyme the ATP synthase is a rotary mechanical motor.

Although oxidative phosphorylation is a vital part of metabolism, it produces reactive oxygen species such as

superoxide and hydrogen peroxide, which lead to propagation of free radicals, damaging cells and contributing to

disease and, possibly, aging (senescence). The enzymes carrying out this metabolic pathway are also the target of

many drugs and poisons that inhibit their activities.

Contents

1 Overview of energy transfer by chemiosmosis2 Electron and proton transfer molecules
https://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Enzyme_inhibitorhttps://en.wikipedia.org/wiki/Diseasehttps://en.wikipedia.org/wiki/Aginghttps://en.wikipedia.org/wiki/Senescencehttps://en.wikipedia.org/wiki/Superoxidehttps://en.wikipedia.org/wiki/Hydrogen_peroxidehttps://en.wikipedia.org/wiki/Chemiosmosishttps://en.wikipedia.org/wiki/PHhttps://en.wikipedia.org/wiki/Membrane_potentialhttps://en.wikipedia.org/wiki/Electron_transport_chainhttps://en.wikipedia.org/wiki/Prokaryotehttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Protein_complexhttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Protein_complexhttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Oxidizing_agenthttps://en.wikipedia.org/wiki/Oxygenhttps://en.wikipedia.org/wiki/Oxidizing_agenthttps://en.wikipedia.org/wiki/Redox_reactionhttps://en.wikipedia.org/wiki/Oxidizing_agenthttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Glycolysishttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Adenosine_triphosphatehttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Enzymehttps://en.wikipedia.org/wiki/Oxidizehttps://en.wikipedia.org/wiki/Nutrienthttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Metabolic_pathwayhttps://en.wikipedia.org/wiki/Cell_(biology)https://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svghttps://en.wikipedia.org/wiki/Wikipedia:Featured_articleshttps://en.wikipedia.org/wiki/Enzyme_inhibitorhttps://en.wikipedia.org/wiki/Senescencehttps://en.wikipedia.org/wiki/Aginghttps://en.wikipedia.org/wiki/Diseasehttps://en.wikipedia.org/wiki/Radical_(chemistry)https://en.wikipedia.org/wiki/Hydrogen_peroxidehttps://en.wikipedia.org/wiki/Superoxidehttps://en.wikipedia.org/wiki/Reactive_oxygen_specieshttps://en.wikipedia.org/wiki/Rotationhttps://en.wikipedia.org/wiki/Phosphorylationhttps://en.wikipedia.org/wiki/Adenosine_diphosphatehttps://en.wikipedia.org/wiki/Chemiosmosishttps://en.wikipedia.org/wiki/ATP_synthasehttps://en.wikipedia.org/wiki/Membrane_potentialhttps://en.wikipedia.org/wiki/PHhttps://en.wikipedia.org/wiki/Potential_energyhttps://en.wikipedia.org/wiki/Electron_transporthttps://en.wikipedia.org/wiki/Inner_mitochondrial_membranehttps://en.wikipedia.org/wiki/Protonhttps://en.wikipedia.org/wiki/Electron_transport_chainhttps://en.wikipedia.org/wiki/Prokaryotehttps://en.wikipedia.org/wiki/Protein_complexhttps://en.wikipedia.org/wiki/Eukaryotehttps://en.wikipedia.org/wiki/Redox_reactionhttps://en.wikipedia.org/wiki/Oxygenhttps://en.wikipedia.org/wiki/Oxidizing_agenthttps://en.wikipedia.org/wiki/Reducing_agenthttps://en.wikipedia.org/wiki/Glycolysishttps://en.wikipedia.org/wiki/Fermentation_(biochemistry)https://en.wikipedia.org/wiki/Aerobic_organismhttps://en.wikipedia.org/wiki/Mitochondriahttps://en.wikipedia.org/wiki/Eukaryoteshttps://en.wikipedia.org/wiki/Adenosine_triphosphatehttps://en.wikipedia.org/wiki/Nutrienthttps://en.wikipedia.org/wiki/Oxidizehttps://en.wikipedia.org/wiki/Enzymehttps://en.wikipedia.org/wiki/Cell_(biology)https://en.wikipedia.org/wiki/Metabolic_pathwayhttps://en.wikipedia.org/wiki/Wikipedia:Featured_articleshttps://en.wikipedia.org/wiki/ATP_synthasehttps://en.wikipedia.org/wiki/Citric_acid_cyclehttps://en.wikipedia.org/wiki/Prokaryotehttps://en.wikipedia.org/wiki/Cell_(biology)https://en.wikipedia.org/wiki/Electron_transport_chainhttps://en.wikipedia.org/wiki/File:Mitochondrial_electron_transport_chain%E2%80%94Etc4.svg


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https://en.wikipedia.org/wiki/Oxidative_phosphorylation 2

u aryo c e ec ron ranspor c a ns3.1 NADH-coenzyme Q oxidoreductase (complex I)3.2 Succinate-Q oxidoreductase (complex II)3.3 Electron transfer flavoprotein-Q oxidoreductase3.4 Q-cytochrome c oxidoreductase (complex III)3.5 Cytochrome c oxidase (complex IV)3.6 Alternative reductases and oxidases3.7 Organization of complexes

4 Prokaryotic electron transport chains

5 ATP synthase (complex V)6 Reactive oxygen species7 Inhibitors8 History9 See also10 Notes11 References12 Further reading

12.1 Introductory12.2 Advanced

13 External links

13.1 General resources13.2 Structural resources

Overview of energy transfer by chemiosmosis

Oxidative phosphorylation works by using energy-releasing chemical reactions to drive energy-requiring reaction

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 process, whic

requires an input of energy. Both the electron transport chain and the ATP synthase are embedded in a membraneand energy is transferred from electron transport chain to the ATP synthase by movements of protons across this

membrane, in a process called chemiosmosis.[1]In practice, this is like a simple electric circuit, with a current of

protons being driven from the negative N-side of the membrane to the positive P-side by the proton-pumping

enzymes of the electron transport chain. These enzymes are like a battery, as they perform work to drive current

through the circuit. The movement of protons creates an electrochemical gradient across the membrane, which is

often called theproton-motive force. It has two components: a difference in proton concentration (a H+gradient,

pH) and a difference in electric potential, with the N-side having a negative charge.[2]

ATP synthase releases this stored energy by completing the circuit and allowing protons to flow down the

electrochemical gradient, back to the N-side of the membrane.

[3]

This kinetic energy drives the rotation of part ofthe enzymes structure and couples this motion to the synthesis of ATP.

The two components of the proton-motive force are thermodynamically equivalent: In mitochondria, the largest

part of energy is provided by the potential in alkaliphile bacteria the electrical energy even has to compensate for

counteracting inverse pH difference. Inversely, chloroplasts operate mainly on pH. However, they also require a

small membrane potential for the kinetics of ATP synthesis. At least in the case of the fusobacterium P. modestum

it drives the counter-rotation of subunits a and c of the FOmotor of ATP synthase.[2]
https://en.wikipedia.org/wiki/Fusobacteriahttps://en.wikipedia.org/wiki/Chloroplasthttps://en.wikipedia.org/wiki/Alkaliphilehttps://en.wikipedia.org/wiki/Thermodynamichttps://en.wikipedia.org/wiki/Electric_potentialhttps://en.wikipedia.org/wiki/PHhttps://en.wikipedia.org/wiki/Electrochemical_gradienthttps://en.wikipedia.org/wiki/Work_(thermodynamics)https://en.wikipedia.org/wiki/Battery_(electricity)https://en.wikipedia.org/wiki/Electrical_networkhttps://en.wikipedia.org/wiki/Chemiosmosishttps://en.wikipedia.org/wiki/Endergonichttps://en.wikipedia.org/wiki/Exergonichttps://en.wikipedia.org/wiki/Oxygenhttps://en.wikipedia.org/wiki/Electron_acceptorhttps://en.wikipedia.org/wiki/NADHhttps://en.wikipedia.org/wiki/Energy


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Reduction of coenzyme Q from its

ubiquinone form (Q) to the reduced

ubiquinol form (QH2).

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,[4]while each cycle of beta oxidation of a fatty acid yields about

14 ATPs. These ATP yields are theoretical maximum values in practice, some protons leak across the membrane

lowering the yield of ATP.[5]

Electron and proton transfer moleculesThe electron transport chain carries both protons and electrons, passin

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 protei

cytochrome c.[6]This carries only electrons, and these are transferred

by the reduction and oxidation of an iron atom that the protein holds

within a heme group in its structure. Cytochrome c is also found in

some bacteria, where it is located within the periplasmic space.[7]

Within the inner mitochondrial membrane, the lipid-soluble electron

carrier coenzyme Q10 (Q) carries both electrons and protons by a

redox cycle.[8]This small benzoquinone molecule is very hydrophobi

so it diffuses freely within the membrane. When Q accepts two

electrons and two protons, it becomes reduced to the ubiquinolform

(QH2) when QH2releases 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 QH2oxidized on

the other, ubiquinone will couple these reactions and shuttle protons across the membrane.[9]Some bacterial

electron transport chains use different quinones, such as menaquinone, in addition to ubiquinone.[10]

Within proteins, electrons are transferred between flavin cofactors,[3][11]ironsulfur clusters, and cytochromes.

There are several types of ironsulfur cluster. The simplest kind found in the electron transfer chain consists of tw

iron atoms joined by two atoms of inorganic sulfur these are called [2Fe2S] clusters. The second kind, called

[4Fe4S], contains a cube of four iron atoms and four sulfur atoms. Each iron atom in these clusters is coordinate

by an additional amino acid, usually by the sulfur atom of cysteine. Metal ion cofactors undergo redox reactions

without binding or releasing protons, so in the electron transport chain they serve solely to transport electrons

through proteins. Electrons move quite long distances through proteins by hopping along chains of these

cofactors.[12]This occurs by quantum tunnelling, which is rapid over distances of less than 1.4 109m.[13]

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, consistin

of complexes I through IV, is called the electron transport chain and is found in the inner membrane of the

mitochondrion. Succinate is also oxidized by the electron transport chain, but feeds into the pathway at a different

point.
https://en.wikipedia.org/wiki/Succinic_acidhttps://en.wikipedia.org/wiki/Standard_electrode_potentialhttps://en.wikipedia.org/wiki/NADHhttps://en.wikipedia.org/wiki/Coenzymehttps://en.wikipedia.org/wiki/Beta_oxidationhttps://en.wikipedia.org/wiki/Citric_acid_cyclehttps://en.wikipedia.org/wiki/Glycolysishttps://en.wikipedia.org/wiki/Catabolichttps://en.wikipedia.org/wiki/Quantum_tunnellinghttps://en.wikipedia.org/wiki/Cysteinehttps://en.wikipedia.org/wiki/Amino_acidhttps://en.wikipedia.org/wiki/Sulfurhttps://en.wikipedia.org/wiki/Flavin_grouphttps://en.wikipedia.org/wiki/Vitamin_Khttps://en.wikipedia.org/wiki/Hydroquinonehttps://en.wikipedia.org/wiki/Hydrophobehttps://en.wikipedia.org/wiki/1,4-Benzoquinonehttps://en.wikipedia.org/wiki/Redoxhttps://en.wikipedia.org/wiki/Coenzyme_Q10https://en.wikipedia.org/wiki/Lipidhttps://en.wikipedia.org/wiki/Periplasmic_spacehttps://en.wikipedia.org/wiki/Hemehttps://en.wikipedia.org/wiki/Ironhttps://en.wikipedia.org/wiki/Cytochrome_chttps://en.wikipedia.org/wiki/Solublehttps://en.wikipedia.org/wiki/Fatty_acidhttps://en.wikipedia.org/wiki/Beta_oxidationhttps://en.wikipedia.org/wiki/Glucosehttps://en.wikipedia.org/wiki/Glycolysishttps://en.wikipedia.org/wiki/Anaerobic_fermentationhttps://en.wikipedia.org/wiki/Ubiquinonehttps://en.wikipedia.org/wiki/Coenzyme_Qhttps://en.wikipedia.org/wiki/File:Ubiquinone%E2%80%93ubiquinol_conversion.svg


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Complex I or NADH-Q oxidoreductase. The abbreviations

are discussed in the text. In all diagrams of respiratory

complexes in this article, the matrix is at the bottom, with

the intermembrane space above.

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. Oxidative phosphorylation in the eukaryotic

mitochondrion is the best-understood example of this process. The mitochondrion is present in almost all

eukaryotes, with the exception of anaerobic protozoa such as Trichomonas vaginalisthat instead reduce protons t

hydrogen in a remnant mitochondrion called a hydrogenosome.[14]

Typical respiratory enzymes and substrates in eukaryotes.

Respiratory enzyme Redox pair

Midpoint potential

(Volts)

NADH dehydrogenase NAD+/ NADH 0.32[15]

Succinate dehydrogenase FMN or FAD / FMNH2or FADH2 0.20[15]

Cytochrome bc1complex Coenzyme Q10ox/ Coenzyme Q10red +0.06[15]

Cytochrome bc1complex Cytochrome box/ Cytochrome bred +0.12[15]

Complex IV Cytochrome cox/ Cytochrome cred +0.22[15]

Complex IV Cytochrome aox/ Cytochrome ared +0.29[15]

Complex IV O2/ HO

+0.82[15]

Conditions: pH = 7[15]

NADH-coenzyme Q oxidoreductase (complex I)

NADH-coenzyme Q oxidoreductase, also known as

ADH dehydrogenaseor complex I, is the first proteinin the electron transport chain.[16]Complex I is a giant

enzyme with the mammalian complex I having 46

subunits and a molecular mass of about 1,000

kilodaltons (kDa).[17]The structure is known in detail

only from a bacterium[18][19]in most organisms the

complex resembles a boot with a large "ball" poking

out from the membrane into the mitochondrion.[20][21]

The genes that encode the individual proteins are

contained in both the cell nucleus and the

mitochondrial genome, as is the case for manyenzymes present in the mitochondrion.

The reaction that is catalyzed by this enzyme is the two

electron oxidation of NADH by coenzyme Q10 or

ubiquinone(represented as Q in the equation below), a

lipid-soluble quinone that is found in the

mitochondrion membrane:

(
https://en.wikipedia.org/wiki/Quinonehttps://en.wikipedia.org/wiki/Coenzyme_Q10https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotidehttps://en.wikipedia.org/wiki/Mitochondrial_genomehttps://en.wikipedia.org/wiki/Cell_nucleushttps://en.wikipedia.org/wiki/Atomic_mass_unithttps://en.wikipedia.org/wiki/Enzymehttps://en.wikipedia.org/wiki/NADH_dehydrogenasehttps://en.wikipedia.org/wiki/Cytochrome_ahttps://en.wikipedia.org/wiki/Cytochrome_chttps://en.wikipedia.org/wiki/Cytochrome_c_oxidasehttps://en.wikipedia.org/wiki/Cytochrome_bhttps://en.wikipedia.org/wiki/Coenzyme_Q10https://en.wikipedia.org/wiki/Coenzyme_Q_-_cytochrome_c_reductasehttps://en.wikipedia.org/wiki/FADhttps://en.wikipedia.org/wiki/Flavin_mononucleotidehttps://en.wikipedia.org/wiki/Succinate_dehydrogenasehttps://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotidehttps://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotidehttps://en.wikipedia.org/wiki/NADH_dehydrogenasehttps://en.wikipedia.org/wiki/Standard_electrode_potential#Non-standard_conditionhttps://en.wikipedia.org/wiki/Redoxhttps://en.wikipedia.org/wiki/Hydrogenosomehttps://en.wikipedia.org/wiki/Trichomonas_vaginalishttps://en.wikipedia.org/wiki/Electrochemical_gradienthttps://en.wikipedia.org/wiki/Intermembrane_spacehttps://en.wikipedia.org/wiki/Protonhttps://en.wikipedia.org/wiki/Eukaryotehttps://en.wikipedia.org/wiki/NADH_dehydrogenasehttps://en.wikipedia.org/wiki/File:Complex_I.svg


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Complex II: Succinate-Q oxidoreductase.

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 ironsulfur clusters: the second kind of prosthetic group present i

the complex.[18]There are both [2Fe2S] and [4Fe4S] ironsulfur clusters in complex I.

As the electrons pass through this complex, four protons are pumped from the matrix into the intermembrane

space. Exactly how this occurs is unclear, but it seems to involve conformational changes in complex I that cause

the protein to bind protons on the N-side of the membrane and release them on the P-side of the membrane.[22]

Finally, the electrons are transferred from the chain of ironsulfur clusters to a ubiquinone molecule in the

membrane.[16]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).

Succinate-Q oxidoreductase (complex II)

Succinate-Q oxidoreductase, also known as complex IIorsuccinate

dehydrogenase, is a second entry point to the electron transport

chain.

[23]

It is unusual because it is the only enzyme that is part of boththe citric acid cycle and the electron transport chain. Complex II

consists of four protein subunits and contains a bound flavin adenine

dinucleotide (FAD) cofactor, ironsulfur clusters, and a heme group

that does not participate in electron transfer to coenzyme Q, but is

believed to be important in decreasing production of reactive oxygen

species.[24][25]It oxidizes succinate to fumarate and reduces

ubiquinone. As 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.

(2)

In some eukaryotes, such as the parasitic wormAscaris suum, an

enzyme similar to complex II, fumarate reductase (menaquinol:fumarate oxidoreductase, or QFR), operates in

reverse to oxidize ubiquinol and reduce fumarate. This allows the worm to survive in the anaerobic environment o

the large intestine, carrying out anaerobic oxidative phosphorylation with fumarate as the electron acceptor.[26]

Another unconventional function of complex II is seen in the malaria parasitePlasmodium falciparum. Here, the

reversed action of complex II as an oxidase is important in regenerating ubiquinol, which the parasite uses in an

unusual form of pyrimidine biosynthesis.[27]

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.[28]This enzyme contains a flavin and a [4Fe4S] cluster, but, unlike the other respiratory

complexes, it attaches to the surface of the membrane and does not cross the lipid bilayer.[29]

(
https://en.wikipedia.org/wiki/Flavin_grouphttps://en.wikipedia.org/wiki/Electron-transferring_flavoproteinhttps://en.wikipedia.org/wiki/Electron-transferring-flavoprotein_dehydrogenasehttps://en.wikipedia.org/wiki/Pyrimidinehttps://en.wikipedia.org/wiki/Plasmodium_falciparumhttps://en.wikipedia.org/wiki/Malariahttps://en.wikipedia.org/wiki/Large_intestinehttps://en.wikipedia.org/wiki/Large_roundworm_of_pigshttps://en.wikipedia.org/wiki/Parasitic_wormhttps://en.wikipedia.org/wiki/Fumaric_acidhttps://en.wikipedia.org/wiki/Succinic_acidhttps://en.wikipedia.org/wiki/Hemehttps://en.wikipedia.org/wiki/FADhttps://en.wikipedia.org/wiki/Succinate_-_coenzyme_Q_reductasehttps://en.wikipedia.org/wiki/Ubiquinolhttps://en.wikipedia.org/wiki/Conformational_changehttps://en.wikipedia.org/wiki/Iron-sulfur_clusterhttps://en.wikipedia.org/wiki/Flavin_mononucleotidehttps://en.wikipedia.org/wiki/Prosthetic_grouphttps://en.wikipedia.org/wiki/Succinate_-_coenzyme_Q_reductasehttps://en.wikipedia.org/wiki/File:Complex_II.svg


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The two electron transfer steps in complex III: Q-cytochrome coxidoreductase. After each step, Q (in the upper part of the figure) leave

the enzyme.

In mammals, 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.[30][31]In plants, ETF-Q

oxidoreductase is also important in the metabolic responses that allow survival in extended periods of darkness.[3

Q-cytochrome c oxidoreductase (complex III)

Q-cytochrome c oxidoreductase is also

known as cytochrome c reductase,

cytochrome bc1complex, or simply complex

III.[33][34]In mammals, this enzyme is a

dimer, with each subunit complex

containing 11 protein subunits, an [2Fe-2S]

ironsulfur cluster and three cytochromes:

one cytochrome c1and two b

cytochromes.[35]A cytochrome is a kind of

electron-transferring protein that contains at

least one heme group. The iron atoms inside

complex IIIs heme groups alternatebetween a reduced ferrous (+2) and oxidized

ferric (+3) state as the electrons are

transferred through the protein.

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.

(

As only one of the electrons can be transferred from the QH2donor to a cytochrome c acceptor at a time, thereaction mechanism of complex III is more elaborate than those of the other respiratory complexes, and occurs in

two steps called the Q cycle.[36]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

QH2pass into the intermembrane space. The third substrate is Q, which accepts the second electron from the QH2

and is reduced to Q., which is the ubisemiquinone free radical. The first two substrates are released, but this

ubisemiquinone intermediate remains bound. In the second step, a second molecule of QH2is bound and again

passes its first electron to a cytochrome c acceptor. The second electron is passed to the bound ubisemiquinone,

reducing it to QH2as it gains two protons from the mitochondrial matrix. This QH2is then released from the

enzyme.[37]

As coenzyme Q is reduced to ubiquinol on the inner side of the membrane and oxidized to ubiquinone on the othe

a net transfer of protons across the membrane occurs, adding to the proton gradient.[3]The rather complex two-st

mechanism by which this occurs is important, as it increases the efficiency of proton transfer. If, instead of the Q

cycle, one molecule of QH2were used to directly reduce two molecules of cytochrome c, the efficiency would be

halved, with only one proton transferred per cytochrome c reduced.[3]

Cytochrome c oxidase (complex IV)
https://en.wikipedia.org/wiki/Free_radicalhttps://en.wikipedia.org/wiki/Semiquinonehttps://en.wikipedia.org/wiki/Q_cyclehttps://en.wikipedia.org/wiki/Cytochrome_chttps://en.wikipedia.org/wiki/Ubiquinolhttps://en.wikipedia.org/wiki/Hemehttps://en.wikipedia.org/wiki/Cytochromeshttps://en.wikipedia.org/wiki/Cytochromehttps://en.wikipedia.org/wiki/Cytochromehttps://en.wikipedia.org/wiki/Protein_dimerhttps://en.wikipedia.org/wiki/Coenzyme_Q_-_cytochrome_c_reductasehttps://en.wikipedia.org/wiki/Acetyl-CoAhttps://en.wikipedia.org/wiki/Cholinehttps://en.wikipedia.org/wiki/Amino_acidhttps://en.wikipedia.org/wiki/Fatty_acidhttps://en.wikipedia.org/wiki/Beta_oxidationhttps://en.wikipedia.org/wiki/Coenzyme_Q_-_cytochrome_c_reductasehttps://en.wikipedia.org/wiki/File:Complex_III_reaction.svg


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Complex IV: cytochrome c oxidase.

Cytochrome c oxidase, also known as complex IV, is the final protein

complex in the electron transport chain.[38]The mammalian enzyme has an

extremely complicated structure and 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.[39]

This enzyme mediates the final reaction in the electron transport chain and

transfers electrons to oxygen, while pumping protons across the

membrane.[40]The final electron acceptor oxygen, which is also called the

terminal electron acceptor, is reduced to water in this step. Both the direct

pumping of protons and the consumption of matrix protons in the reduction

of oxygen contribute to the proton gradient. The reaction catalyzed is the

oxidation of cytochrome c and the reduction of oxygen:

(

Alternative reductases and oxidases

Many eukaryotic organisms have electron transport chains that differ from the much-studied mammalian enzyme

described above. For example, plants have alternative NADH oxidases, which oxidize NADH in the cytosol rathe

than in the mitochondrial matrix, and pass these electrons to the ubiquinone pool.[41]These enzymes do not

transport protons, and, therefore, reduce ubiquinone without altering the electrochemical gradient across the inner

membrane.[42]

Another example of a divergent electron transport chain is the alternative oxidase, which is found in plants, as we

as some fungi, protists, and possibly some animals.[43][44]This enzyme transfers electrons directly from ubiquino

to oxygen.

[45]

The electron transport pathways produced by these alternative NADH and ubiquinone oxidases have lower ATP

yields than the full pathway. The advantages produced by a shortened pathway are not entirely clear. However, th

alternative oxidase is produced in response to stresses such as cold, reactive oxygen species, and infection by

pathogens, as well as other factors that inhibit the full electron transport chain.[46][47]Alternative pathways might

therefore, enhance an organisms' resistance to injury, by reducing oxidative stress.[48]

Organization of complexes

The original model for how the respiratory chain complexes are organized was that they diffuse freely and

independently in the mitochondrial membrane.[49]However, recent data suggest that the complexes might form

higher-order structures called supercomplexes or "respirasomes."[50]In this model, the various complexes exist as

organized sets of interacting enzymes.[51]These associations might allow channeling of substrates between the

various enzyme complexes, increasing the rate and efficiency of electron transfer.[52]Within such mammalian

supercomplexes, some components would be present in higher amounts than others, with some data suggesting a

ratio between complexes I/II/III/IV and the ATP synthase of approximately 1:1:3:7:4. [53]However, the debate ov

this supercomplex hypothesis is not completely resolved, as some data do not appear to fit with this model.[17][54]

Prokaryotic electron transport chains
https://en.wikipedia.org/wiki/Respirasomehttps://en.wikipedia.org/wiki/Oxidative_stresshttps://en.wikipedia.org/wiki/Reactive_oxygen_specieshttps://en.wikipedia.org/wiki/Adenosine_triphosphatehttps://en.wikipedia.org/wiki/Protisthttps://en.wikipedia.org/wiki/Fungushttps://en.wikipedia.org/wiki/Planthttps://en.wikipedia.org/wiki/Alternative_oxidasehttps://en.wikipedia.org/wiki/Planthttps://en.wikipedia.org/wiki/Electron_acceptorhttps://en.wikipedia.org/wiki/Zinchttps://en.wikipedia.org/wiki/Magnesiumhttps://en.wikipedia.org/wiki/Copperhttps://en.wikipedia.org/wiki/Cytochrome_c_oxidasehttps://en.wikipedia.org/wiki/Cytochrome_c_oxidasehttps://en.wikipedia.org/wiki/File:Complex_IV.svg


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In contrast to the general similarity in structure and function of the electron transport chains in eukaryotes, bacteri

and archaea possess a large variety of electron-transfer enzymes. These use an equally wide set of chemicals as

substrates.[55]In common with eukaryotes, prokaryotic electron transport uses the energy released from the

oxidation of a substrate to pump ions across a membrane and generate an electrochemical gradient. In the bacteria

oxidative phosphorylation inEscherichia coliis understood in most detail, while archaeal systems are at present

poorly understood.[56]

The main difference between eukaryotic and prokaryotic oxidative phosphorylation is that bacteria and archaea us

many different substances to donate or accept electrons. This allows prokaryotes to grow under a wide variety of

environmental conditions.[57]InE. coli, for example, oxidative phosphorylation can be driven by a large number o

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.

Respiratory enzymes and substrates inE. coli.[58]

Respiratory enzyme Redox pair

Midpoint potential

(Volts)

Formate dehydrogenase Bicarbonate / Formate 0.43

Hydrogenase Proton / Hydrogen 0.42

NADH dehydrogenase NAD+/ NADH 0.32

Glycerol-3-phosphate dehydrogenase DHAP / Gly-3-P 0.19

Pyruvate oxidase Acetate + Carbon dioxide / Pyruvate ?

Lactate dehydrogenase Pyruvate / Lactate 0.19

D-amino acid dehydrogenase 2-oxoacid + ammonia / D-amino acid ?

Glucose dehydrogenase Gluconate / Glucose 0.14

Succinate dehydrogenase Fumarate / Succinate +0.03

Ubiquinol oxidase Oxygen / Water +0.82

Nitrate reductase Nitrate / Nitrite +0.42

Nitrite reductase Nitrite / Ammonia +0.36

Dimethyl sulfoxide reductase DMSO / DMS +0.16

TrimethylamineN-oxide reductase TMAO / TMA +0.13

Fumarate reductase Fumarate / Succinate +0.03

As shown above,E. colican grow with reducing agents such as formate, hydrogen, or lactate as electron donors,and nitrate, DMSO, or oxygen as acceptors.[57]The larger the difference in midpoint potential between an

oxidizing and reducing agent, the more energy is released when they react. Out of these compounds, the

succinate/fumarate pair is unusual, as its midpoint potential is close to zero. Succinate can therefore be oxidized t

fumarate if a strong oxidizing agent such as oxygen is available, or fumarate can be reduced to succinate using a

strong reducing agent such as formate. These alternative reactions are catalyzed by succinate dehydrogenase and

fumarate reductase, respectively.[59]

Some prokaryotes use redox pairs that have only a small difference in midpoint potential. For example, nitrifying

bacteria such asNitrobacteroxidize nitrite to nitrate, donating the electrons to oxygen. The small amount of

energy released in this reaction is enough to pump protons and generate ATP, but not enough to produce NADH o
https://en.wikipedia.org/wiki/Nitrobacterhttps://en.wikipedia.org/wiki/Nitrificationhttps://en.wikipedia.org/wiki/Fumarate_reductasehttps://en.wikipedia.org/wiki/Succinate_-_coenzyme_Q_reductasehttps://en.wikipedia.org/wiki/Succinic_acidhttps://en.wikipedia.org/wiki/Fumaric_acidhttps://en.wikipedia.org/wiki/Fumarate_reductasehttps://en.wikipedia.org/wiki/Trimethylaminehttps://en.wikipedia.org/wiki/Trimethylamine_N-oxidehttps://en.wikipedia.org/wiki/Trimethylamine_N-oxide_reductasehttps://en.wikipedia.org/wiki/Dimethyl_sulfidehttps://en.wikipedia.org/wiki/Dimethyl_sulfoxidehttps://en.wikipedia.org/wiki/DMSO_reductasehttps://en.wikipedia.org/wiki/Ammoniahttps://en.wikipedia.org/wiki/Nitritehttps://en.wikipedia.org/wiki/Nitrite_reductasehttps://en.wikipedia.org/wiki/Nitritehttps://en.wikipedia.org/wiki/Nitratehttps://en.wikipedia.org/wiki/Nitrate_reductasehttps://en.wikipedia.org/wiki/Waterhttps://en.wikipedia.org/wiki/Oxygenhttps://en.wikipedia.org/wiki/Ubiquinol_oxidasehttps://en.wikipedia.org/wiki/Succinic_acidhttps://en.wikipedia.org/wiki/Fumaric_acidhttps://en.wikipedia.org/wiki/Succinate_-_coenzyme_Q_reductasehttps://en.wikipedia.org/wiki/Glucosehttps://en.wikipedia.org/wiki/Gluconic_acidhttps://en.wikipedia.org/wiki/Quinoprotein_glucose_dehydrogenasehttps://en.wikipedia.org/wiki/Amino_acidhttps://en.wikipedia.org/wiki/Ammoniahttps://en.wikipedia.org/wiki/Oxoacidhttps://en.wikipedia.org/wiki/D-amino_acid_dehydrogenasehttps://en.wikipedia.org/wiki/Lactic_acidhttps://en.wikipedia.org/wiki/Pyruvic_acidhttps://en.wikipedia.org/wiki/Lactate_dehydrogenasehttps://en.wikipedia.org/wiki/Pyruvic_acidhttps://en.wikipedia.org/wiki/Carbon_dioxidehttps://en.wikipedia.org/wiki/Acetic_acidhttps://en.wikipedia.org/wiki/Pyruvate_dehydrogenase#Other_formshttps://en.wikipedia.org/wiki/Glycerol_3-phosphatehttps://en.wikipedia.org/wiki/Dihydroxyacetone_phosphatehttps://en.wikipedia.org/wiki/Glycerol-3-phosphate_dehydrogenasehttps://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotidehttps://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotidehttps://en.wikipedia.org/wiki/NADH_dehydrogenasehttps://en.wikipedia.org/wiki/Hydrogenhttps://en.wikipedia.org/wiki/Protonhttps://en.wikipedia.org/wiki/Hydrogenasehttps://en.wikipedia.org/wiki/Formatehttps://en.wikipedia.org/wiki/Bicarbonatehttps://en.wikipedia.org/wiki/Formate_dehydrogenasehttps://en.wikipedia.org/wiki/Standard_electrode_potential#Non-standard_conditionhttps://en.wikipedia.org/wiki/Redoxhttps://en.wikipedia.org/wiki/Standard_electrode_potential#Non-standard_conditionhttps://en.wikipedia.org/wiki/Escherichia_colihttps://en.wikipedia.org/wiki/Archaeahttps://en.wikipedia.org/wiki/Bacteria


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NADPH directly for use in anabolism.[60]This problem is solved by using a nitrite oxidoreductase to produce

enough proton-motive force to run part of the electron transport chain in reverse, causing complex I to generate

NADH.[61][62]

Prokaryotes control their use of these electron donors and acceptors by varying which enzymes are produced, in

response to environmental conditions.[63]This flexibility is possible because different oxidases and reductases use

the same ubiquinone pool. This allows many combinations of enzymes to function together, linked by the commo

ubiquinol intermediate.[58]These respiratory chains therefore have a modular design, with easily interchangeable

sets of enzyme systems.

In addition to this metabolic diversity, prokaryotes also possess a range of isozymes different enzymes that

catalyze the same reaction. For example, inE. coli, there are two different types of ubiquinol oxidase using oxyge

as an electron acceptor. Under highly aerobic conditions, the cell uses an oxidase with a low affinity for oxygen

that can transport two protons per electron. However, if levels of oxygen fall, they switch to an oxidase that

transfers only one proton per electron, but has a high affinity for oxygen.[64]

ATP synthase (complex V)

ATP synthase, also called complex V, is the final enzyme in the oxidative phosphorylation pathway. This enzyme

is found in all forms of life and functions in the same way in both prokaryotes and eukaryotes.[65]The enzyme us

the energy stored in a proton gradient across a membrane to drive the synthesis of ATP from ADP and phosphate

(Pi). Estimates of the number of protons required to synthesize one ATP have ranged from three to four,[66][67]wi

some suggesting cells can vary this ratio, to suit different conditions. [68]

(

This phosphorylation reaction is an equilibrium, which can be shifted by altering the proton-motive force. In the

absence of a proton-motive force, the ATP synthase reaction will run from right to left, hydrolyzing ATP andpumping protons out of the matrix across the membrane. However, when the proton-motive force is high, the

reaction is forced to run in the opposite direction it proceeds from left to right, allowing protons to flow down

their concentration gradient and turning ADP into ATP.[65]Indeed, in the closely related vacuolar type H+-

ATPases, the hydrolysis reaction is used to acidify cellular compartments, by pumping protons and hydrolysing

ATP.[69]

ATP synthase is a massive protein complex with a mushroom-like shape. The mammalian enzyme complex

contains 16 subunits and has a mass of approximately 600 kilodaltons.[70]The portion embedded within the

membrane is called FOand contains a ring of c subunits and the proton channel. The stalk and the ball-shaped

headpiece is called F1and is the site of ATP synthesis. The ball-shaped complex at the end of the F1portioncontains six proteins of two different kinds (three subunits and three subunits), whereas the "stalk" consists of

one protein: the subunit, with the tip of the stalk extending into the ball of and subunits.[71]Both the and

subunits bind nucleotides, but only the subunits catalyze the ATP synthesis reaction. Reaching along the side of

the F1portion and back into the membrane is a long rod-like subunit that anchors the and subunits into the ba

of the enzyme.

As protons cross the membrane through the channel in the base of ATP synthase, the FOproton-driven motor

rotates.[72]Rotation might be caused by changes in the ionization of amino acids in the ring of c subunits causing

electrostatic interactions that propel the ring of c subunits past the proton channel.[73]This rotating ring in turn
https://en.wikipedia.org/wiki/Electrostatichttps://en.wikipedia.org/wiki/Ionizationhttps://en.wikipedia.org/wiki/Kilodaltonhttps://en.wikipedia.org/wiki/V-ATPasehttps://en.wikipedia.org/wiki/Chemical_equilibriumhttps://en.wikipedia.org/wiki/Phosphorylationhttps://en.wikipedia.org/wiki/Phosphatehttps://en.wikipedia.org/wiki/Isozymehttps://en.wikipedia.org/wiki/Modular_designhttps://en.wikipedia.org/wiki/Nitrite_oxidoreductasehttps://en.wikipedia.org/wiki/Anabolism


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Mechanism of ATP synthase. ATP is

shown in red, ADP and phosphate in

pink and the rotating subunit in

black.

drives the rotation of the central axle (the subunit stalk) within the and subunits. The and subunits are

prevented from rotating themselves by the side-arm, which acts as a stator. This movement of the tip of the

subunit within the ball of and subunits provides the energy for the active sites in the subunits to undergo a

cycle of movements that produces and then releases ATP.[74]

This ATP synthesis reaction is called the binding change mechanismand

involves the active site of a subunit cycling between three states.[75]In

the "open" state, ADP and phosphate enter the active site (shown in brown

in the diagram). The protein then closes up around the molecules and bindsthem loosely the "loose" state (shown in red). The enzyme then changes

shape again and forces these molecules together, with the active site in the

resulting "tight" state (shown in pink) binding the newly produced ATP

molecule with very high affinity. Finally, the active site cycles back to the

open state, releasing ATP and binding more ADP and phosphate, ready for

the next cycle.

In some bacteria and archaea, ATP synthesis is driven by the movement of

sodium ions through the cell membrane, rather than the movement of

protons.[76][77]Archaea such asMethanococcusalso contain the A1

Ao

synthase, a form of the enzyme that contains additional proteins with little

similarity in sequence to other bacterial and eukaryotic ATP synthase

subunits. It is possible that, in some species, the A1Aoform of the enzyme is a specialized sodium-driven ATP

synthase,[78]but this might not be true in all cases.[77]

Reactive oxygen species

Molecular oxygen is an ideal terminal electron acceptor because it is a strong oxidizing agent. The reduction of

oxygen does involve potentially harmful intermediates.[79]Although the transfer of four electrons and four proton

reduces oxygen to water, which is harmless, transfer of one or two electrons produces superoxide or peroxide

anions, which are dangerously reactive.

(

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.[80][81]

The cytochrome c oxidase complex is highly efficient at reducing oxygen to water, and it releases very few partly

reduced intermediates however small amounts of superoxide anion and peroxide are produced by the electron

transport chain.[82]Particularly important is the reduction of coenzyme Q in complex III, as a highly reactive

ubisemiquinone free radical is formed as an intermediate in the Q cycle. This unstable species can lead to electron

"leakage" when electrons transfer directly to oxygen, forming superoxide.[83]As the production of reactive oxyge

species by these proton-pumping complexes is greatest at high membrane potentials, it has been proposed that
https://en.wikipedia.org/wiki/Coenzyme_Qhttps://en.wikipedia.org/wiki/Free-radical_theory_of_aginghttps://en.wikipedia.org/wiki/Diseasehttps://en.wikipedia.org/wiki/DNAhttps://en.wikipedia.org/wiki/Mutationhttps://en.wikipedia.org/wiki/Hydroxylhttps://en.wikipedia.org/wiki/Reactive_oxygen_specieshttps://en.wikipedia.org/wiki/Peroxidehttps://en.wikipedia.org/wiki/Superoxidehttps://en.wikipedia.org/wiki/Electron_acceptorhttps://en.wikipedia.org/wiki/Methanococcushttps://en.wikipedia.org/wiki/Dissociation_constanthttps://en.wikipedia.org/wiki/Statorhttps://en.wikipedia.org/wiki/Axlehttps://en.wikipedia.org/wiki/ATP_synthasehttps://en.wikipedia.org/wiki/File:ATPsyn.gif


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mitochondria regulate their activity to maintain the membrane potential within a narrow range that balances ATP

production against oxidant generation.[84]For instance, oxidants can activate uncoupling proteins that reduce

membrane potential.[85]

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,[79]which detoxify the reactive species, limiting damage to the cell.

Inhibitors

There are several well-known drugs and toxins that inhibit oxidative phosphorylation. Although any one of these

toxins inhibits only one enzyme in the electron transport chain, inhibition of any step in this process will halt the

rest of the process. For example, if oligomycin inhibits ATP synthase, protons cannot pass back into the

mitochondrion.[86]As a result, the proton pumps are unable to operate, as the gradient becomes too strong for the

to overcome. NADH is then no longer oxidized and the citric acid cycle ceases to operate because the

concentration of NAD+falls below the concentration that these enzymes can use.

Compounds Use Site ofaction Effect on oxidative phosphorylation

CyanideCarbon monoxideAzideHydrogen sulfide

Poisons Complex

IV

Inhibit the electron transport chain by binding more strongly thanoxygen to the FeCu center in cytochrome c oxidase, preventing the

reduction of oxygen.[87]

Oligomycin Antibiotic ComplexV

Inhibits ATP synthase by blocking the flow of protons through the Fo

subunit.[86]

CCCP

2,4-Dinitrophenol

Poisons,weight-

loss[N 1]

Inner

membrane

Ionophores that disrupt the proton gradient by carrying protons across membrane. This ionophore uncouples proton pumping from ATP

synthesis because it carries protons across the inner mitochondrialmembrane.[88]

Rotenone Pesticide Complex IPrevents the transfer of electrons from complex I to ubiquinone by

blocking the ubiquinone-binding site.[89]

Malonate andoxaloacetate

Poisons Complex

II Competitive inhibitors of succinate dehydrogenase (complex II).[90]

Antimycin A Piscicide Complex

IIIBinds to the Qi site of cytochrome c reductase, thereby inhibiting theoxidation of ubiquinol.

Not all inhibitors of oxidative phosphorylation are toxins. In brown adipose tissue, regulated proton channels

called uncoupling proteins can uncouple respiration from ATP synthesis.[91]This rapid respiration produces heat,

and is particularly important as a way of maintaining body temperature for hibernating animals, although these

proteins may also have a more general function in cells' responses to stress.[92]

History

The field of oxidative phosphorylation began with the report in 1906 by Arthur Harden of a vital role for phospha

in cellular fermentation, but initially only sugar phosphates were known to be involved.[93]However, in the early

1940s, the link between the oxidation of sugars and the generation of ATP was firmly established by Herman
https://en.wikipedia.org/wiki/Herman_Kalckarhttps://en.wikipedia.org/wiki/Sugar_phosphateshttps://en.wikipedia.org/wiki/Fermentation_(biochemistry)https://en.wikipedia.org/wiki/Arthur_Hardenhttps://en.wikipedia.org/wiki/Hibernationhttps://en.wikipedia.org/wiki/Body_temperaturehttps://en.wikipedia.org/wiki/Uncoupling_proteinhttps://en.wikipedia.org/wiki/Brown_adipose_tissuehttps://en.wikipedia.org/wiki/Ubiquinolhttps://en.wikipedia.org/wiki/Oxidationhttps://en.wikipedia.org/wiki/Coenzyme_Q_%E2%80%93_cytochrome_c_reductasehttps://en.wikipedia.org/wiki/Piscicidehttps://en.wikipedia.org/wiki/Antimycin_Ahttps://en.wikipedia.org/wiki/Oxaloacetatehttps://en.wikipedia.org/wiki/Malonatehttps://en.wikipedia.org/wiki/Pesticidehttps://en.wikipedia.org/wiki/Rotenonehttps://en.wikipedia.org/wiki/Uncoupleshttps://en.wikipedia.org/wiki/Ionophorehttps://en.wikipedia.org/wiki/2,4-Dinitrophenolhttps://en.wikipedia.org/wiki/Carbonyl_cyanide_m-chlorophenyl_hydrazonehttps://en.wikipedia.org/wiki/Antibiotichttps://en.wikipedia.org/wiki/Oligomycinhttps://en.wikipedia.org/wiki/Copperhttps://en.wikipedia.org/wiki/Ironhttps://en.wikipedia.org/wiki/Hydrogen_sulfidehttps://en.wikipedia.org/wiki/Azidehttps://en.wikipedia.org/wiki/Carbon_monoxidehttps://en.wikipedia.org/wiki/Cyanidehttps://en.wikipedia.org/wiki/Oligomycinhttps://en.wikipedia.org/wiki/Toxinhttps://en.wikipedia.org/wiki/Drughttps://en.wikipedia.org/wiki/Peroxidaseshttps://en.wikipedia.org/wiki/Catalasehttps://en.wikipedia.org/wiki/Superoxide_dismutasehttps://en.wikipedia.org/wiki/Vitamin_Ehttps://en.wikipedia.org/wiki/Vitamin_Chttps://en.wikipedia.org/wiki/Vitaminhttps://en.wikipedia.org/wiki/Antioxidanthttps://en.wikipedia.org/wiki/Uncoupling_protein


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Kalckar,[94]confirming the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann

in 1941.[95]Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that the coenzyme NADH linked

metabolic pathways such as the citric acid cycle and the synthesis of ATP.[96]The term oxidative phosphorylation

was coined by Volodymyr Belitser in 1939.[97][98]

For another twenty years, the mechanism by which ATP is generated remained mysterious, with scientists

searching for an elusive "high-energy intermediate" that would link oxidation and phosphorylation reactions.[99]

This puzzle was solved by Peter D. Mitchell with the publication of the chemiosmotic theory in 1961.[100]At firstthis proposal was highly controversial, but it was slowly accepted and Mitchell was awarded a Nobel prize in

1978.[101][102]Subsequent research concentrated on purifying and characterizing the enzymes involved, with majo

contributions being made by David E. Green on the complexes of the electron-transport chain, as well as Efraim

Racker on the ATP synthase.[103]A critical step towards solving the mechanism of the ATP synthase was provide

by Paul D. Boyer, by his development in 1973 of the "binding change" mechanism, followed by his radical

proposal of rotational catalysis in 1982.[75][104]More recent work has included structural studies on the enzymes

involved in oxidative phosphorylation by John E. Walker, with Walker and Boyer being awarded a Nobel Prize in

1997.[105]

See also

RespirometryTIM/TOM Complex

Notes

1. DNP was extensively used as an anti-obesity medication in the 1930s but was ultimately discontinued due to its

dangerous side effects. However, illicit use of the drug for this purpose continues today. See 2,4-Dinitrophenol#Dieting

aid for more information.

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