The electron transport chain, in cellular biology is one of the steps that your cells use to make energy from the food you eat.
It is the third stage of aerobic cellular respiration. Cellular respiration refers to the process by which your cells use food to generate energy. The electron transport chain is the place where most of energy required to run cells is generated. This “chain” actually refers to a collection of protein complexes as well as electron carrier molecules in the inner membrane cell mitochondria. Also known as the cell’s powerhouse,
Aerobic respiration requires oxygen because the electron transfer to oxygen ends the chain.
Three parts make up aerobic cellular respiration: glycolysis (Krebs), oxidative phosphorylation, and citric acid cycle. Glycolysis is where glucose is converted into two molecules of pyruvate. This produces ATP and nicotinamide adenine nucleotide(NADH) respectively. Each pyruvate is oxidized into acetyl CoA, along with an additional molecule each of NADH (CO2) and carbon dioxide. The acetyl CoA can then be used in the citric Acid Cycle, which is a series of chemical reactions that produces CO2, NADH and flavin adenine dinucleotide (2FADH2), as well as ATP. The three NADH2 and one FADH2 accumulated from previous steps are used for oxidative phosphorylation to produce water and ATP.
The electron transport chain (ETC), and chemiosmosis are two components of oxidative phosphorylation. The ETC is composed of proteins that are bound to the outer mitochondrial membrane and organic molecules. Electrons then pass through these molecules in a series redox reactions and release energy. The proton gradient is formed by the energy that is released. This is used in chemiosmosis for large amounts of ATP production by the protein ATP–synthase.
Photosynthesis is a metabolic process in which light energy is converted into chemical energy to make sugars. Light energy and water are used in light-dependent reactions to create ATP, NADPH and oxygen (O2). An electron transport chain is used to form the proton gradient that makes ATP. The light-independent reactions produce sugar from the ATP or NADPH of the previous reactions.
Key Takeaways: Electron Transport Chain
- The electron transport chain is a collection of protein complexes as well as electron carrier molecules that are found within the inner membrane mitochondrial. They generate ATP.
- The electrons travel along the chain, passing from one protein complex to another until they reach oxygen. Protons are pumped from the mitochondrial matrix across to the inner membrane and into the intermembrane space.
- An electrochemical gradient is created when protons accumulate in the intermembrane area. This causes protons to flow downwards through ATP synthase and back into the matrix. This proton’s movement provides energy for the production ATP.
- The third stage of aerobic cellular respiration is the electron transport chain. The Krebs cycle and glycolysis are the two first steps in cellular respiration.
Electron Transport Chain Definition
The Electron Transport Chain is also known as the Electron Transport System. It is a series of reactions that converts redox energy available from oxidation NADH and FADH2 into proton-motive force. This is used to synthesize ATP via conformational changes within the ATP synthase compound through a process known as oxidative phosphorylation.
- The final step in cellular respiration is oxidative phosphorylation.
- This stage involves a series electron transfer from organic compounds into oxygen, while simultaneously releasing energy.
- Aerobic respiration has molecular oxygen as the final electron acceptor, while anaerobic respiration has sulfate and sulfate as other acceptors.
- This chain of reactions is crucial because it involves the breaking down of ATP to ADP and resynthesizing it. The body thus uses the limited ATPs it has about 300 times per day.
- Four large protein complexes embedded in the inner mitochondrial membrane are responsible for electron flow. They are called the electron-transport or respiratory chains.
- This is a crucial stage in energy synthesis, as all oxidative reactions in the degradation and amino acid degradation converge at this last stage of cellular respiration. In which the energy from oxidation drives ATP synthesis, it is vital.
Electron Transport Chain Animation Video
Equation of Electron Transport Chain
The electron transport chain is a collection of oxidation-reduction processes that result in the release of energy. The following summarizes the electron transport chain reactions:
NADH + 1/2O2 + H+ + ADP + Pi → NAD+ + ATP + H2O
Where does electron transport chain occur?
- The mitochondria also house the high-energy electrons, as the citric acid cycle is carried out in them. The electron transport chain that is used in eukaryotes’ cells also occurs in mitochondria.
- The mitochondrion, a double-membraned organelle, consists of outer and inner membranes that are folded into a series of ridges known as cristae.
- The mitochondria has two compartments: the matrix and intermembrane.
- The outer membrane is extremely permeable to ions. It is home to enzymes that are necessary for the production of citric acid cycles. The inner membrane, however, is impermeable and inaccessible to various ions.
- The location and function of a cell will determine the number of electron transport chains in its mitochondria. The liver mitochondria has 10, 000 sets of electron transportation chains, while the heart mitochondria has three times as many electron transport chains.
- Intermembrane space is home to enzymes such as adenylate kinase. The matrix also contains ATP, ADP and AMP, and various ions like Ca2+, Mg2+, etc.
Importance of the Electron Transport Chain
Electron transport chain (ETC) is essential to the process of respiration in cells. It results in:
- The production of the majority of ATP molecules is a result of the process of oxidative phosphorylation. Synthesized ATP molecules are then utilized in various energy-consuming processes including the biosynthesis of macromolecules that are complex.
- The complete oxidation process of NADH and FADH2 replenishes the metabolic pool of cells via NAD+ as well as FAD+. Both act as cofactors and substrates in various catabolic as well as anabolic pathways that aid in the metabolism of cellular energy.
- ETC makes use of FADH2, NADH, and H+ to generate the equivalent of 30 and 32 ATP, based on the specific compounds involved (I, III and IV, or II, III and IV processes).
Deficient, excessive, or absence of ETC function may cause mitochondrial dysfunction and stress. Examples of the negative consequences and effects of disrupted ETC functions are:
- The cells are depleted of ATP is a risk that can result in an increase in ETC processes and an excessive amount of temperatures that increase the body’s temperature. This is evident by an excessive dose of salicylic acid, or aspirin that dissociates the electron transport chain from the oxidative phosphorylation. In the end, the ETC is overloaded in order to compensate for a decrease in cell ATP. In extreme cases that have low levels of ATP could trigger lactate fermentation in certain tissues, which can result in the condition known as type-b lactic acidosis because of the elevated levels of lactate present in blood.
- The inhibition of the Complex I activity through chemicals like barbiturates and rotenone results in the inability of electrons to move, which leads to decreased oxidative phosphorylation. Incomplete ETC causes the formation of radicals, such as reactive oxygen species that can cause damage to mitochondria. The decreased oxidative phosphorylation decreases cell ATP production. This in turn decreases the metabolic rate of cells. The end result is that the reduction of Complex I activity suppresses cell growth and triggers apoptosis. the process of killing cells. However, in small quantities, these chemicals can be utilized for positive effects. Rotenone is known as a pesticide and piscicide, and it has anti-carcinogenic effects. Barbiturates can be used for anesthetics and anticonvulsants as well as neuroprotective substances.
- The mutations in the genes that encode succinate dehydrogenase may result in reduced electron flow as well as an increase in oxygen-related toxicity. For humans, these effects may manifest in a variety of types of clinical conditions, including encephalomyopathy, tumors, and the optic atrophy that are typical associated with Leigh syndrome.
What are the Components/ Electron carriers of Electron Transport Chain?
The electrons in the chain are transported from substrate to oxygen via a number of electronic carriers. There are around 15 chemical groups that can accept electrons or transfer them through the chain of electrons.
FMN (Flavin Mononucleotide)
The electrons of NADH are transferred to flavin Mononucleotide (FMN) at the beginning of the electron transfer chain. This reduces the NADH to FMN2.
NAD + H+ + FMN → NAD + FMNH2
NADH dehydrogenase is responsible for the transfer of electrons. The electrons are then transferred into a variety of complexes that contain iron and sulfur (FeS), which have a higher affinity for electrons.
Other electron carriers, called ubiquinone (UQ), are found between the flavoproteins or cytochromes. Ubiquinone, the electron carrier in the respiratory system, is not attached to any protein. This allows the molecule to move between the flavoproteins as well as the cytochromes. After electrons have been transferred from FMNH2 to the Fe-S centres to the ubiquinone it becomes UQH2 then the oxidized flavoprotein (FMN), is released.
FMNH2 + UQ → FMN + UQH2
Cytochromes, which are proteins of red or brown color and contain a heme group that transports electrons in a sequence that runs from ubiquinone to the molecular oxygen, are the next electron carriers. Each cytochrome (like Fe-S centres) transfers one electron, while other electron carriers, such as FMN or ubiquinone, transfer two electrons.
There are five types of cytochromes between ubiquinone and the molecular oxygen, such as the a, b and c. These are named based on their ability to absorb different wavelengths of light (cytochrome A absorbs the longest wavelength while cytochrome b absorbs the next-longest wavelength, so on).
- These are discovered by John S. Rieske, that’s why it is called Rieske iron-sulfur proteins.
- These iron-sulfur (Fe-S) centers range from simple structures with a single Fe atom coordinated to four Cys—SH groups to more complex Fe-S centers with two or four Fe atoms.
Electron Transport Chain Complexes
The electron transport chain contains four enzyme complexes. They catalyze the electron transfer through various electron carriers to molecular oxygen.
a. Complex I (Mitochondrial complex I)
- Complex I is also known as NADH:ubiquinone dehydrogenase or NADH oxidoreductase.
- It is a large enzyme which is composed of 42 polypeptide chains. This includes an FMN-containing flavoprotein. There are also at least six iron-sulfur centres.
- High-resolution electron microscopes show Complex I to have an L shape. One arm of the L is found in the membrane, the other extends into the matrix.
- The NADH that was donated by glycolysis and the citric acid cycle can be oxidized here, transfer 2 electrons from NADH into FMN.
- They are then transferred to Fe-S clusters, and finally to coenzyme Q.
- During the process, 4 hydrogen ions move from the mitochondrial matrix into the intermembrane area, contributing to an electrochemical gradient.
- Complex I could also play a significant role in the activation of apoptosis in programmed cell death.
(NADH + H+) + CoQ + 4 H+(matrix) -> NAD+ + CoQH2 + 4 H+(intermembrane)
b. Complex II (Mitochondrial complex II)
- Complex II is simpler and smaller than Complex I.
- It includes four types of protein subunits and two types of 5 prosthetic groups.
- Subunits C, and D are integral membrane protein with three transmembrane-helices.
- They contain a heme-group, heme b, and a binding site to ubiquinone (the flnal electron accepting agent in Complex II).
- Subunits A, and B extend into the matrix. They contain three 2Fe-2S centers bound to FAD and a site to bind the substrate, succinate.
- Complex II, also called succinate dehydrogenase (or succinate dehydrogenase), accepts electrons form succinate (an intermediate of the citric acid cycle) and acts as a second entry point to the ETC.
- FAD within Complex II accepts 2 electrons when succinate is oxidized to fumarate.
- FAD then passes them on to Fe-S clusters, and then to coenzymeQ, which is similar to complex I.
- Complex II does not translocate protons across the membrane, so less ATP can be produced through this pathway.
Succinate + FAD -> Fumarate + 2 H+(matrix) + FADH2
FADH2 + CoQ -> FAD + CoQH2
- Acyl-CoA and Glycerol-3Phosphate Dehydrogenase accept electrons from glycerol-3-P, and fatty acyl-CoA, respectively.
- These protein complexes allow for donation to the ETC via cytosolic NADH (glycerol-3P acts as a shuttle and regenerates cytosolic NADH from NADH), and fatty acids that are undergoing beta-oxidation within mitochondria (acylCoA is oxidized into enoylCoA in step one, producing FADH2).
c. Complex III (Mitochondrial complex III)
- Complex III, also called cytochrome bcq complex or ubiquinone:cytochrome c oxidoreductase.
- It combines the transfer electrons from ubiquinol (QH2) to cytochrome C with vectorial transport protons from matrix to intermembrane.
- Between 1995 and 1998, the determination of the entire structure of this complex and Complex IV by x-ray crystallography was a landmark in the study mitochondrial electron transfer. It provided the structural framework for integrating many biochemical observations about the functions of respiratory complexes.
- Complex III’s functional unit is a dimer. It has the monomeric units of Cytochrome b and surrounds a “cavern” in the middle of the membrane. This “cavern”, in which ubiquinone can freely move from the matrix side (site QN for one monomer) to the intermembrane area (site QP for the other monomer), as it shuttles electrons across the inner mitochondrial membrane.
- A cytochrome, a protein that is involved in electron transfer, contains a heme-group.
- During electron transfer, the heme group alternates between ferrous (Fe2+), and ferric (Fe3+) states.
- Cytochrome c is able to accept one electron at a given time so this process takes place in two steps (the Q cycle), in contrast to the single-step complex I and II pathways.
- Complex III also releases four protons into intermembrane space after a full Q cycle. This contributes to the gradient.
- The electrons are then transferred one by one to complex IV by Cytochrome C.
- In Step 1 of the Q cycle ubiquinol (CoQH2) or ubiquinone(CoQ) binding two different sites on complex III. Each electron is transferred to a different pathway by CoQH2. One electron goes to FeS, then cytochrome C. The second electron is transferred first to cytochrome B and then to the CoQ bound at another site. 2 H+ ions are also released into intermembrane space while this is happening, which contributes to the proton gradient. CoQH2 has now been oxidized to Ubiquinone, and is dissociated from the complex. From accepting one electron, the CoQ bound to the second site enters a transitional CoQH-2 radical state.
- The second stage of the cycle is a repeat of the previous: A new CoQH2 binds the first site and transfers 2 electrons (plus 2 additional H+ ions released). One electron is transferred to cytochrome C and one to Cytochrome B, which works to reduce CoQH- to CoQH2. This allows it to dissociate from complex III and can then be recycled. This complete cycle is shown as follows:
2 CoQH2(site 1) + CoQ(site 2) + 2 Cyt c(ox) + 2 H+(matrix) -> 2 CoQ(site 1) + CoQH2(site 2) + 2 Cyt c(red) + 4 H+(intermembrane)
d. Complex IV (Mitochondrial complex IV)
- Complex IV is a large enzyme (13 subunits, Mr 204,000) of the inner mitochondrial membrane.
- Bacteria have a simpler form, with just three to four subunits but still capable of catalyzing electron transfer and proton pumping. Comparing the mitochondrial and bacteria complexes shows that the function requires three subunits.
- Two Cu ions are found in the Mitochondrial Subunit II. They are combined with the -SH group of two Cys residues. This binuclear center is similar to the 2Fe-2S iron-sulfur protein centers.
- Subunit I includes two heme groups (a and a3) and another copper ion.
- Heme a3 is combined with Cus to form a second Complex IV. Also known as cytochrome C oxidase. This oxidizes Cytochrome C and then transfers electrons to oxygen.
- The cytochrome proteins a and a3, along with the heme, copper groups in complex IV transfer the donated electrons to the bound dioxygen species. This converts it into water molecules.
- Four protons are able to travel into the intermembrane space due to the electron transfer, generating free energy that contributes to the proton gradient. The following reactions reduce oxygen:
2 cytochrome c(red) + ½O2 + 4 H+(matrix) -> 2 cytochrome c(ox) + 1 H2O + 2 H+(intermembrane)
- Complex V is also known as ATP synthase.
- It uses the ETC-generated proton gradient across inner mitochondrial membrane to create ATP.
- F0 and F1 subunits are act as the rotational motor system in ATP-synthase.
- F0 is hydrophobic and is embedded in the inner mitochondrial cell membrane. It is composed of a proton corridor, which is protonated and then deprotonated frequently as H+ ions flow from intermembrane to matrix.
- Rotation is caused by the alternating ionization F0, which alters F1’s orientation.
- F1 is hydrophilic, and it faces the mitochondrial matrix.
- F1 subunits undergo conformational changes that catalyze the production of ATP from ADP or Pi.
- Each 4 H+ ions produces 1 ATP.
- ATP-synthase may also be forced into reverse by consuming ATP in order to create a hydrogen gradient. This is similar to what you see in bacteria.
Electron Transport Chain Products
The Products of Electron Transport Chain are 30-32 ATPs and 44 moles of H2O.
|Stage||Direct products (net)||Ultimate ATP yield (net)|
|Glycolysis||2 ATP||2 ATP|
|2 NADH||3-5 ATP|
|Pyruvate oxidation||2 NADH||5 ATP|
|Citric acid cycle||2 ATP/GTP||2 ATP|
|6 NADH||15 ATP|
|2 FADH2||3 ATP|
Electron Transport Chain Steps and Components
The electron transport chain consists of four different complexes such as Complex I, Complex, II, Complex, III, and Complex, IV. Complex I transfers the electron from NADH to ubiquinone and Complex II transfers the electron from Succinate to Ubiquinone.
Complex III transfers the electron from Ubiquinone to Cytochrome C and then Complex IV completes the process by transferring the electron to the O2 molecules.
- Complex I is known as NADH: Ubiquinone oxidoreductase or NADH:Dehydrogenase.
- The complex I is the largest complex molecule within the ETC. It consists of 42 polypeptide chains, FMN-containing flavoprotein, and 6 iron-sulfur centers.
- Under the electron microscope the Complex I appears in L-shape. The one arm of this L-shape is embedded within the inner membrane and the second arm is extended within the matrix.
- Complex I performs two processes simultaneously such as (a) The exergonic transfer of electrons from NADH to Quinone and a hydrogen atom from matrix, and (b) endergonic transfer of 4 protons from matrix to intermembrane space.
- Due to the transfer of electrons from matrix to intermembrane space, the matrix becomes negatively charged and the intermembrane space becomes positively charged.
- The Cyanide and Carbon monoxide Inhibit cytochrome oxidase; Antimycin A Blocks electron transfer from cytochrome b to cytochrome c1; Myxothiazol, Rotenone, Amytal, and Piericidin A Prevent electron transfer from Fe-S center to ubiquinone.
- Complex II is much smaller and simpler than complex I and it contains 5 prosthetic groups of two different types and 4 protein subunits.
- The four subunits are Subunit A, Subunit B, Subunit C and Subunit D.
- The subunits C and D are integral membrane proteins, these contain heme b protein and ubiquinone binding site.
- Subunit A and B contain a Substrate (Succinate) binding site. Bound FAD, three 2Fe-2S centers.
- In complex II the electrons are transferred from the Substrate binding site to FAD then pass through the Fe-S centers to Ubiquinone.
- Complex III transfers the electron from the ubiquinone to cytochrome C.
- This complex is also known as Cytochrome bc1 complex or Ubiquinone: Cytochrome C oxidoreductase.
- The X-ray crystallography shows the detailed structure of Complex III.
- Complex III is a dimer, containing two Subunits of Cytochrome b, which are surrounding the cavern. Through this quinone can freely move from matrix to intermembrane space by releasing protons and electrons.
- Except transfer of electrons, complex III also transfers 4 proton or Hydrogen molecules from the matrix to intermembrane space.
- In complex III the Ubiquinol releases 2 hydrogen and electrons to form Quinone. Then these 2 hydrogen atoms move toward the intermembrane space and one electron moves towards the Fe-S centers, then cytochrome C1, and finally to Cytochrome C.
- Another electron moves toward the Heme bL, to heme bH and then to Q, which is then formed semiubiquinone. Then semiubiquinone accept 2 hydrogen atom from the matrix and form ubiquinol.
The net redox reaction in complex III is;
QH2 + 2Cyt C (oxidized) + 2H = Q + 2 Cyt C (Reduced) + 4H
- The complex IV transfers the electron from Cytochrome C to oxygen and forms the H2O.
- Complex IV is also known as the Cytochrome oxidase.
- Complex IV contains 13 subunits in mitochondria. In a bacterial cell the complex IV is much simpler and contains three to four subunits.
- In complex IV the 4 electron is transferred from 4 Cytochrome C to a CuA center, then to heme a, to the heme a3–CuB center, and finally to O2.
- During the transfer of four electrons, the complex IV also consumed 4 hydrogen (substrate) atoms to form H2O from O2.
- It also pumps 4 hydrogen atoms from the matrix to intermembrane space.
The net redox reaction in complex IV is;
4Cyt c (reduced) + 8H + O2 = 2H2O + 4 Cyt c (oxidized) + 4 H
Formation of Reactive Oxygen Species (ROS)
During the transfers of electrons through the ETC different highly reactive free radicals are generated which can damage the cells.
The passage of electrons from complex I to QH2 and QH2 to Complex III leads to the formation of an intermediate called Ubiquinol. Ubiquinol with low probability can pass an electron to the O2 and lead to the formation of Superoxide free radical.
This superoxide free radical can form more reactive hydroxyl free radicals which can damage the cells. To prevent the oxidative damage by these radicals the cell releases an enzyme called superoxide dismutase which converts the superoxide into H2O2.
Now H2O2 is converted into H2O with the help of an enzyme called glutathione peroxidase. The glutathione reductase recycles the oxidized glutathione to reduce glutathione with the help of NADPH, which is generated from the pentose phosphate pathway.
- In anaerobic respiration Nitrate, Sulfate, Co2 functions as a final electron acceptor in ATC.
- Anaerobic respiration produces less energy or ATP as compared to aerobic respiration.
- The aerobic respiration is performed by few bacteria, archaea, and some eukaryotic microbes.
- Paracoccus denitrificans performs both anaerobic respiration in presence of O2 and anaerobic respiration in absence of O2.
- The anaerobic respiration carried out different enzymes such as nitrate reductase (Nar), nitrite reductase (Nir), nitric oxide reductase (Nor), and nitrous oxide reductase (Nos) for the formation of gaseous Nitrogen from Nitrate.
- Nitrite is reduced to nitric oxide (NO) by the periplasmic enzyme nitrite reductase. Nitric oxide reductase catalyzes the formation of nitrous oxide (N20) from NO. It is part of the membrane-bound cytochrome b complex. Finally, the periplasmic enzyme nitrous oxide reductase catalyzes the formation of N2 from N20.
Why is the energy yield or ATP yield in Anaerobic respiration is Low?
The final electron acceptor of anaerobic respiration is nitrate, which has a low positive reduction potential as compared to oxygen(electron acceptor of aerobic respiration). The difference in standard reduction potential of NADH and Nitrate is lower than the difference of reduction potential between the NADH and O2.
That’s why the energy yield of anaerobic respiration is low, because the energy yield is directly related to the magnitude of reduction potential difference.
Alternative Respiratory Pathways of Plants
- The plant mitochondria contain an alternative pathway for the transfer of electrons from ubiquinone to O2.
- They contain an alternative NADH dehydrogenase, it is insensitive to the complex I inhibitor rotenone that’s why it is called rotenone insensitive NADH dehydrogenase complex. This complex transfers the electrons from NADH to Ubiquinone directly.
- Except alternative NADH dehydrogenase, the plant contains another NADH dehydrogenase at the external face of the inner membrane, which functions the transfer of electrons from the NADPH or NADH to the matrix and then to Ubiquinone.
- Both these external NADH dehydrogenase and alternative NADH dehydrogenase bypass the complex I.
- Now the electron is transferred to O2 via the cyanide-resistant alternative oxidase and generates H2O. In this process energy is not conserved as ATP but is released as heat.
- A skunk cabbage can use the heat to melt snow, produce a foul stench, or attract beetles or flies.
ATP Synthase Definition
- The synthesis of ATP is accomplished by the ATP synthase. ATP synthase is made of two structural subunits called F1 and F0.
- These ATP synthases are found in mitochondria, chloroplasts, and bacteria.
- The F1 complex is spherical in shape and attached on the mitochondria inner membrane with the help of stalk.
- F1 complex is composed of three α subunits which are alternate with three β subunits, and it also contains a γ subunit which is located at the center.
- The γ subunit is extended from the F1 to F0 complex and it can rotate.
- A stalk (γ and ε subunit) connects the F1 complex and F0 complex and serves as a proton channel.
- The F0 complex is composed of one a subunit, two b sunits and 8 -12 c subunits.
- A stator arm is embedded within the membrane and also attached with the F1 complex. This stator arm is made of one a subunit, two b sunit and δ subunit.
- A ring of c subunits in F0 is connected with the stalk (γε). When the ring turns it results in the rotation of Shaft or stalk (γε).
Binding-change model for ATP synthase/ How does ATP synthase produce ATP?
- The binding change mechanism is a widely accepted model of ATP synthesis. This simplified drawing of the model shows the three catalytic β subunits and the γ subunit, which is located at the center of the F1 complex.
- The β subunit contains three catalytic sites such as βE, βDP, and βTP. The βE site is open conformation which does not bind with the nucleotides.
- When the γ subunit rotates it results in conformational change in catalytic sites of β subunits. In one turn of γ subunit the βE is changed to βHC as a result the ADP and Pi bind to this catalytic site.
- The 2nd turn of γ subunit results in a three conformational change in catalytic site of β subunits.
- The βTP is changed to βE as a result the ATP is released from the ATP synthase.
- The βDP is changed into The βTP as results the ATP is generated.
- The βHC is changed to The βDP, where ADP is bounded.
Inhibitors of Oxidative Phosphorylation
Some poisons, such as antimycin A, carboxin, and antimycin B, can block cellular oxidative proteinrylation. Complex I is inhibited by rotenone, complex II by carboxin, complex III by antimycin A, and complex IV in turn, by cyanide or CO. Oligomycin blocks ATP synthase.
Rotenone (and some barbiturates) – inhibits complex I (coenzyme Q binding site)
- Rotenone is a widely used pesticide. However, it is more commonly used in the US as piscicide (fish).
- Complex I is prevented by Rotenone from passing electrons between the Fe-S clusters and ubiquinone.
- Although it is not well absorbed through skin, it is rarely fatal as poisoning can lead to vomiting and the removal of the substance. But intentional ingestion can prove fatal.
Carboxin – inhibits complex II (coenzyme Q binding site)
- Carboxin, a fungicide, is no longer being used due to newer agents that have a broader spectrum.
- Carboxin, similar to rotenone interferes with ubiquinone’s binding site.
Doxorubicin – coenzyme Q (theoretical)
- Doxorubicin can be used for cancer chemotherapy, primarily breast and bladder carcinomas and lymphoma.
- Dilated cardiomyopathy is a well-known side effect caused by doxorubicin.
- One mechanism that could explain the causation of the disease is the formation of reactive oxygen species in myocardial tissue, where the drug impairs electron transfer by coenzyme Q.
Antimycin A – inhibits complex III (cytochrome c reductase)
- Antimycin A is a piscicide which binds to the Qi binding site of cytochrome C reductase.
- This activity blocks ubiquinone’s ability to accept an electron and bind to it, thus preventing the Q cycle from recycling ubiquinol (CoQH2) through the Q cycle.
Carbon Monoxide (CO) – inhibits complex IV (cytochrome c oxidase)
- Carbon monoxide binds and inhibits the cytochrome C oxidase complex IV. Carbon monoxide not only disrupts the ETC but also binds hemoglobin to an oxygen-binding site, converting it into carboxyhemoglobin. This state causes hemoglobin to lose oxygen and blocks its delivery to the body’s tissues. Common signs of CO poisoning include symptoms in the central nervous system and cardiac systems. These organ systems are heavily dependent on oxygen intake. You may experience symptoms such as hypotension, tachycardia, or arrhythmias, along with fatigue, nausea, vomiting and changes in vision. Seizure, coma or retinal hemorhages may be more severe in cases. However, autopsy is often more useful for determining the cause.
- Paint strippers, house fires and wood-burning stoves are all sources of CO. A CO saturation monitor can detect CO levels. A ratio of carboxyhemoglobin to hemoglobin greater than 10% is likely to be symptomatic. The percent of hemoglobin bound by regular pulse oximetry devices is measured, regardless of the type of hemoglobin. If CO is bound, the patient’s pulse Ox might still look normal. However, it cannot be reliably used if O2 is bound. A co-oximeter is recommended. The best treatment for CO poisoning involves dissociating the bound CO with O2. There are two options for treating CO poisoning: 100% supplemental oxygen via nonrebreather, or hyperbaric oxygen.
Cyanide (CN) – inhibits complex IV (cytochrome c oxidase)
- Also, cyanide binds and inhibits complex IV (cytochrome C oxidase). Tissue hypoxia can cause similar symptoms in patients. These patients may experience hypoxia that isn’t responsive to supplemental oxygen and an almond breath smell. Common sources of cyanide are house fires (furniture and rugs), jewelry cleaning products, rubber manufacturing, plastic or rubber manufacturing, iatrogenic prescribed nitroprusside or some fruit seeds (apricots peaches, apples).
- The treatment can include the use of nitrites to convert hemoglobin iron to Fe2+ to Fe3+. Also known as methemoglobin. This conformation binds to cyanide and prevents it from reaching the ETC. This prevents blood cells transporting oxygen and requires further treatment with methyleneblue to reduce Fe3+ to Fe2+. Hydroxocobalamin is another option. Thiosulfate can also be administered. However, this is more time-consuming and often requires combination therapy with Nitrites.
Oligomycin – inhibits ATP-synthase (complex V)
- Oligomycin, a macrolide antibiotic that Streptomyces species have synthesized, inhibits the F0 unit of ATP-synthase and prevents ATP production. It is primarily used for research.
Uncoupling agents dissociate the electron transport chain from the phosphorylation of ATP-synthase. This prevents the formation ATP. The phospholipid bilayer of membranes is disrupted, resulting in a fluid-like state that allows protons to flow more freely. The proton leak reduces the electrochemical gradient and transfers protons without the need for ATP-synthase.
The cell will become deficient in ATP and the ETC will work overtime to try to shuttle more electrons to ATP synthase. As electrons move from one carrier to another, the ETC produces heat. This will cause the body to become more active. Cells will also adapt to fermentation, even in anaerobic conditions. This may lead to type B lactic acidosis.
Aspirin (Salicylic Acid)
- Salicylic acid can be uncoupler. Salicylate poisoning is not caused by uncoupling. However, signs such as tinnitus or early respiratory alkalosis are common. As the disease progresses, it can transition to a mixed metabolic acidosis or respiratory alkalosis. If activated charcoal is present within one hour of ingestion or sodium bicarbonate can be used to treat it.
- Brown adipose tissues contain thermogenin (also known as uncoupling proteins 1 (UCP1)). Brown adipose tissues have many small lipid droplets, and high levels of mitochondria (which give the “brown” colour). This contrasts with white adipose tissues which only has one droplet. This is a strong indication that brown fat is a common source of energy in hibernating newborns and animals that have deficient neurologic thermoregulation (ex. Hypothermia is possible in these animals, who are susceptible to shivering and may even be prone to it. These brown fat mitochondria have more thermogenin than any other cells. This allows for proton leakage and inner mitochondrial membrane disruption.
Plant Mitcchondria Have Alternative Meehanisms for Oxidizing NADH
- The plant mitochondria provide ATP to cells during low light or dark periods by using mechanisms that are very similar to those of nonphotosynthetic organisms.
- The light is the main source of mitochondrial NADH. This is because glycine is produced through a process called photorespiration and is then converted to serine.
2 Glycine + NAD+ —–> serine + CO2 + NH3 + NADH + H*
- Even though they don’t need NADH to produce ATP, plants must still perform this reaction.
- To regenerate NAD+ from unneeded NADH, plant mitochondria transfer electrons from NADH directly to ubiquinone and from ubiquinone directly to O2, bypassing Complexes III and IV and their proton pumps.
- This is where the NADH energy is converted to heat. Sometimes, this can be valuable for the plant.
- Cyanide does not inhibit the alternative QH2 oxygenase, unlike Complex IV’s cytochrome-oxidase.
- This unique electron-transfer pathway is characterized by cyanide-resistant NADH oxygenation.
Where does the electron transport chain take place?
It occurs in mitochondria in both cellular respiration and photosynthesis.
What is the electron transport chain?
An electron transport chain is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions and couples this electron transfer with the transfer of protons across a membrane.
Where is the electron transport chain located?
Where are the proteins of the electron transport chain located?
The electron transport chain is a series of proteins and organic molecules found in the inner membrane of the mitochondria.
What is the final electron acceptor in the electron transport chain?
The final electron acceptor is oxygen (O2). Oxygen has a high electronegativity; thus, oxygen’s high affinity for electrons makes it an ideal acceptor for low-energy electrons. With the electrons, hydrogen is added to oxygen forming water as the final product.
how many atp are produced in the electron transport chain?
34 ATP molecules are produced in the electron transport chain if we consider that one molecule of NADH produces 3 molecules of ATP and one molecule of FADH2 gives rise to 2 molecules of ATP.
what does the electron transport chain produce?
The electron transport chain produces an electrochemical gradient that drives the synthesis of ATP by chemiosmosis. The end products of the electron transport chains are ATP and water.
What is the purpose of the electron transport chain?
The main purpose of the electron transport chain is to build up a surplus of hydrogen ions (protons) in the intermembrane space sp that there will be a concentration gradient compared to the matrix of the mitochondria. This will drive ATP synthase.
Where does the electron transport chain get its electrons from?
All of the electrons that enter the transport chain come from NADH and FADH 2