This reaction does not involve the transfer of electrons, nor does it pump out protons, providing less energy to compare with the oxidation process of NADH. The third entry to the proton on the electron transport chain is electron transfer flavin-coenzyme Q oxidoreductase, also known as electron transfer flavin dehydrogenase, which reduces Q10 by using electrons from electron transfer flavin in the mitochondrial matrix. Coenzyme Q-cytochrome C reductase, also known as complex III, catalyzes the oxidation of QH2, and the reduction of cytochrome c and ferritin.
In this reaction, cytochrome C carries an electron. Coenzyme Q is reduced to QH2 on one side of the mitochondrial membrane, while QH2 is oxidized to coenzyme Q10 on the other side, resulting in the transfer of protons on the membrane, which also contributes to the formation of proton gradients. The last protein complex in the electron transport chain is cytochrome c oxidase, also called complex IV. It mediates the final reaction on the electron transport chain - transferring electrons to the final electron receptor oxygen - oxygen reduces to water - pumping protons through the membrane.
At the end of this reaction, protons that directly pumped out and that consumed by the reduction of oxygen to water increase the proton gradient. There is another electron-donating molecule - FADH2 in eukaryotes. FADH2 is also the intermediate metabolite during the earlier stage of cellular respiration such as glycolysis or citric acid cycle. And this reaction does not pump out protons either. The subsequent reactions are nearly the same as those in the NADH2 electron transport chain.
Prokaryotes such as bacteria and archaea have many electron transfer enzymes that can use a very wide range of chemicals as substrates. As the same with eukaryotes, electron transport in prokaryotic cells also uses the energy released by oxidation from the substrate to pump protons across the membrane to create an electrochemical gradient, which drives ATP synthase to generate ATP.
The difference is that bacteria and archaea use many different substrates as electron donors or electron receptors. This also helps prokaryotes to survive and grow in different environments. Under normal conditions, electron transfer and phosphorylation are tightly coupled. Some compounds can affect electron transport or interfere with phosphorylation reactions, all of which cause oxidative phosphorylation abnormalities.
Here introduce four factors affecting oxidative phosphorylation. The greater the gradient, the greater the energy needed to pump protons out of the mitochondrion. Eventually, if nothing relieves the gradient, it becomes too large and the energy of electron transport is insufficient to perform the pumping.
When pumping stops, so too does electron transport. In the absence of ADP, the ATP synthase stops functioning and when it stops, so too does movement of protons back into the mitochondrion.
With this information, it is possible to understand the link between energy usage and metabolism. The root of this, as noted, is respiratory control. To illustrate these links, let us first consider a person, initially at rest, who then suddenly jumps up and runs away.
ATP synthase begins working and protons begin to come back into the mitochondrial matrix. The proton gradient decreases, so electron transport re-starts. Electron transport needs an electron acceptor, so oxygen use increases and when oxygen use increases, the person starts breathing more heavily to supply it.
With little or no proton movement, electron transport stops because the proton gradient is too large. When electron transport stops, oxygen use decreases and the rate of breathing slows down.
The really interesting links to metabolism occur relative to whether or not electron transport is occurring. From the examples, we can see that electron transport will be relatively slowed when not exercising and more rapid when exercise or other ATP usage is occurring.
If one does not have the proper amount of exercise, reduced carriers remain high in concentration for long periods of time. This means we have an excess of energy and then anabolic pathways, particularly fatty acid synthesis, are favored, so we get fatter.
One might suspect that altering respiratory control could have some very dire consequences and that would be correct. These alterations can be achieved using compounds with specific effects on particular components of the system.
All of the chemicals described here are laboratory tools and should never be used by people. The first group for discussion are the inhibitors. In tightly coupled mitochondria, inhibiting either electron transport or oxidative phosphorylation has the effect of inhibiting the other one as well.
Common inhibitors of electron transport include rotenone and amytal, which stop movement of electrons past Complex I, malonate, malate, and oxaloacetate, which inhibit movement of electrons through Complex II, antimycin A which stops movement of electrons past Complex III, and cyanide, carbon monoxide, azide, and hydrogen sulfide, which inhibit electron movement through Complex IV Figure 5.
All of these compounds can stop electron transport directly no movement of electrons and oxidative phosphorylation indirectly proton gradient will dissipate. While some of these compounds are not commonly known, almost everyone is aware of the hazards of carbon monoxide and cyanide, both of which can be lethal. It is also possible to use an inhibitor of ATP synthase to stop oxidative phosphorylation directly no ATP production and electron transport indirectly proton gradient not relieved so it becomes increasingly difficult to pump protons out of matrix.
Oligomycin A Figure 5. Rotenone, which is a plant product, is used as a natural insecticide that is permitted for organic farming. When mitochondria are treated with this, electron transport will stop at Complex I and so, too, will the pumping of protons out of the matrix. When this occurs, the proton gradient rapidly dissipates, stopping oxidative phosphorylation as a consequence.
There are other entry points for electrons than Complex I, so this type of inhibition is not as serious as using inhibitors of Complex IV, since no alternative route for electrons is available. It is for this reason that cyanide, for example, is so poisonous.
Imagine a dam holding back water with a turbine generating electricity through which water must flow. When all water flows through the turbine, the maximum amount of electricity can be generated. If one pokes a hole in the dam, though, water will flow through the hole and less electricity will be created. The generation of electricity will thus be uncoupled from the flow of water. If the hole is big enough, the water will all drain out through the hole and no electricity will be made. Imagine, now, that the proton gradient is the equivalent of the water, the inner membrane is the equivalent of the dam and the ATP synthase is the turbine.
It is important to recognize, though, that uncoupling by 2,4 DNP works differently from the electron transport inhibitors or the ATP synthase inhibitor.
In those situations, stopping oxidative phosphorylation resulted in indirectly stopping electron transport, since the two processes were coupled and the inhibitors did not uncouple them. Similarly, stopping electron transport indirectly stopped oxidative phosphorylation for the same reason.
Such is not the case with 2,4 DNP. Stopping oxidative phosphorylation by destroying the proton gradient allows electron transport to continue unabated it actually stimulates it , since the proton gradient cannot build no matter how much electron transport runs. Consequently, electron transport runs like crazy but oxidative phosphorylation stops. The reason such a scenario is dangerous is because the body is using all of its nutrient resources, but no ATP is being made.
Lack of ATP leads to cellular and organismal death. In addition, the large amounts of heat generated can raise the temperature of the body to unsafe levels. One of the byproducts of uncoupling electron transport is the production of heat.
The faster metabolic pathways run, the more heat is generated as a byproduct. Since 2,4 DNP causes metabolism to speed up, a considerable amount of heat can be produced. Controlled uncoupling is actually used by the body in special tissues called brown fat. In this case, brown fat cells use the heat created to help thermoregulate the temperature of newborn children. Permeabilization of the inner membrane is accomplished in brown fat by the synthesis of a protein called thermogenin also known as uncoupling protein.
Thermogenin binds to the inner membrane and allows protons to pass through it, thus bypassing the ATP synthase. As noted for 2,4 DNP, this results in activation of catabolic pathways and the more catabolism occurs, the more heat is generated. In uncoupling, whether through the action of an endogenous uncoupling protein or DNP, the energy that would have normally been captured in ATP is lost as heat.
In the case of uncoupling by thermogenin, this serves the important purpose of keeping newborn infants warm. But in adults, uncoupling merely wastes the energy that would have been harvested as ATP. In other words, it mimics starvation, even though there is plenty of food, because the energy is dissipated as heat. This fact, and the associated increase in metabolic rate, led to DNP being used as a weight loss drug in the s.
Touted as an effortless way to lose weight without having to eat less or exercise more, it was hailed as a magic weight loss pill. It quickly became apparent, however, that this was very dangerous. Many people died from using this drug before laws were passed to ban the use of DNP as a weight loss aid. They use an alternative electron transport.
In these organisms, there is an enzyme called alternative oxidase Figure 5. Alternative oxidase is able to accept electrons from CoQ and pass them directly to oxygen. The process occurs in coupled mitochondria. Its mechanism of action is to reduce the yield of ATP, since fewer protons are being pumped per reduced electron carrier. The byproduct of this increased catabolism is more heat. Not surprisingly, the alternative oxidase pathway can be activated by cold temperatures.
Nothing we know is. Consequently, cells do not get as much energy out of catabolic processes as they put into anabolic processes. A good example is the synthesis and breakdown of glucose, something liver cells are frequently doing. This difference must be made up in order for the organism to meet its energy needs. It is for this reason that we eat. In addition, the inefficiency of our capture of energy in reactions results in the production of heat and helps to keep us warm, as noted.
It is also noteworthy that cells do not usually have both catabolic and anabolic processes for the same molecules occurring simultaneously inside of them for example, breakdown of glucose and synthesis of glucose because the cell would see no net production of anything but heat and a loss of ATPs with each turn of the cycle. Such cycles are called futile cycles and cells have controls in place to limit the extent to which they occur.
Since futile cycles can, in fact, yield heat, they are used as sources of heat in some types of tissue. Brown adipose tissue of mammals uses this strategy, as described earlier. See also HERE for more on heat generation with a futile cycle. Endogenous production of ROS is directed towards intracellular signaling H2O2 and nitric oxide, for example and defense. It produces superoxides in the reaction below to kill bacteria.
In the immune system, cells called phagocytes engulf foreign cells and then use ROS to kill them. ROS can serve as signals for action. In zebrafish, damaged tissues have increased levels of H2O2 and this is thought to be a signal for white blood cells to converge on the site. In fish lacking the genes to produce hydrogen peroxide, white blood cells do not converge at the damage site. Sources of hydrogen peroxide include peroxisomes, which generate it as a byproduct of oxidation of long chain fatty acids.
Reactive oxygen species are at the heart of the free radical theory of aging, which states that organisms age due to the accumulation of damage from free radicals in their cells. In yeast and Drosophila, there is evidence that reducing oxidative damage can increase lifespan. In mice, increasing oxidative damage decreases life span, though in Caenorhabditis, blocking production of superoxide dismutase actually increases lifespan, so the role of ROS in aging is not completely clear.
It is clear, though, that accumulation of mitochondrial damage is problematic for individual cells. Bcl-2 proteins on the surface of mitochondria monitor damage and if they detect it, will activate proteins called Bax to stimulate the release of cytochrome c from the mitochondrial membrane, stimulating apoptosis programmed cell death. Eventually the dead cell will be phagocytosed. A common endogenous source of superoxide is the electron transport chain.
Under these circumstances, semi-reduced CoQ can donate an electron to O2 to form superoxide O Superoxide can react with many molecules, including DNA where it can cause damage leading to mutation. Countering the effects of ROS are enzymes, such as catalase, superoxide dismutase, and anti-oxidants, such as glutathione and vitamins C and E. Glutathione protects against oxidative damage by being a substrate for the enzyme glutathione peroxidase.
Glutathione peroxidase catalyzes the conversion of hydrogen peroxide to water next page. The enzyme, which employs four heme groups in its catalysis, works extremely rapidly, converting up to 40,, molecules of hydrogen peroxide to water and oxygen per enzyme per second.
In addition, we must consider the reduction reaction gaining of electrons that accompanies the oxidation of NADH. Oxidation reactions are always accompanied by reduction reactions, because an electron given up by one group must be accepted by another group. In this case, molecular oxygen O 2 is the electron acceptor, and the oxygen is reduced to water Equation 10, below. The molecular changes that occur upon oxidation are shown in red. In this tutorial, we have seen that nonspontaneous reactions in the body occur by coupling them with a very spontaneous reaction usually the ATP reaction shown in Equation 3.
But we have not yet answered the question: by what mechanism are these reactions coupled? Every day your body carries out many nonspontaneous reactions. As discussed earlier, if a nonspontaneous reaction is coupled to a spontaneous reaction, as long as the sum of the free energies for the two reactions is negative, the coupled reactions will occur spontaneously.
How is this coupling achieved in the body? Living systems couple reactions in several ways, but the most common method of coupling reactions is to carry out both reactions on the same enzyme. Consider again the phosphorylation of glycerol Equations Glycerol is phosphorylated by the enzyme glycerol kinase, which is found in your liver. The product of glycerol phosporylation, glycerolphosphate Equation 2 , is used in the synthesis of phospholipids. Glycerol kinase is a large protein comprised of about amino acids.
X-ray crystallography of the protein shows us that there is a deep groove or cleft in the protein where glycerol and ATP attach see Figure 6, below. Because the enzyme holds the ATP and the glycerol in place, the phosphate can be transferred directly from the ATP to glycerol. Instead of two separate reactions where ATP loses a phosphate Equation 3 and glycerol picks up a phosphate Equation 2 , the enzyme allows the phosphate to move directly from ATP to glycerol Equation 4.
The coupling in oxidative phosphorylation uses a more complicated and amazing! This is a schematic representation of ATP and glycerol bound attached to glycerol kinase. The enzyme glycerol kinase is a dimer consists of two identical subuits.
There is a deep cleft between the subunits where ATP and glycerol bind. Since the ATP and phosphate are physically so close together when they are bound to the enzyme, the phosphate can be transferred directly from ATP to glycerol. Hence, the processes of ATP losing a phosphate spontaneous and glycerol gaining a phosphate nonspontaneous are linked together as one spontaneous process.
Neglecting any differences in difficulty synthesizing or accessing these molecules by biological systems, rank the molecules in order of their efficiency as a free-energy currency i. In order to couple the redox and phosphorylation reactions needed for ATP synthesis in the body, there must be some mechanism linking the reactions together.
In cells, this is accomplished through an elegant proton-pumping system that occurs inside special double-membrane-bound organelles specialized cellular components known as mitochondria. A number of proteins are required to maintain this proton-pumping system and catalyze the oxidative and phosphorylation reactions. There are three key steps in this process:. Note: Steps a and b show cytochrome oxidase, the final electron-carrier protein in the electron-transport chain described above.
When this protein accepts an electron green from another protein in the electron-transport chain, an Fe III ion in the center of a heme group purple embedded in the protein is reduced to Fe II. Cells use a proton-pumping system made up of proteins inside the mitochondria to generate ATP.
Before we examine the details of ATP synthesis, we shall step back and look at the big picture by exploring the structure and function of the mitochondria, where oxidative phosphorylation occurs. The mitochondria Figure 8 are where the oxidative-phosphorylation reactions occur.
Mitochondria are present in virtually every cell of the body. They contain the enzymes required for the citric-acid cycle the last steps in the breakdown of glucose , oxidative phosphorylation, and the oxidation of fatty acids.
This is a schematic diagram showing the membranes of the mitochondrion. The purple shapes on the inner membrane represent proteins, which are described in the section below. An enlargement of the boxed portion of the inner membrane in this figure is shown in Figure 8, below. The mitochondrial membranes are crucial for this organelle's role in oxidative phosphorylation. As shown in Figure 8, mitochondria have two membranes, an inner and an outer membrane.
The outer membrane is permeable to most small molecules and ions, because it contains large protein channels called porins. The inner membrane is impermeable to most ions and polar molecules. The inner membrane is the site of oxidative phosphorylation. Recall the discussion of protein channels in the " Maintaining the Body's Chemistry: Dialysis in the Kidneys " Tutorial. As shown in Figure 8, inside the inner membrane is a space known as the matrix ; the space between the two membranes is known as the intermembrane space.
This charge difference is used to provide free energy G for the phosphorylation reaction Equation 8. Electrons are not transferred directly from NADH to O 2 , but rather pass through a series of intermediate electron carriers in the inner membrane of the mitochondrion.
This allows something very important to occur: the pumping of protons across the inner membrane of the mitochondrion. As we shall see, it is this proton pumping that is ultimately responsible for coupling the oxidation-reduction reaction to ATP synthesis. Two major types of mitochondrial proteins see Figure 9, below are required for oxidative phosphorylation to occur. Both classes of proteins are located in the inner mitochondrial membrane.
The electron carriers can be divided into three protein complexes NADH-Q reductase 1 , cytochrome reductase 3 , and cytochrome oxidase 5 that pump protons from the matrix to the intermembrane space, and two mobile carriers ubiquinone 2 and cytochrome c 4 that transfer electrons between the three proton-pumping complexes. Gold numbers refer to the labels on each protein in Figure 9, below. Overall, in living systems, these pathways of glucose catabolism extract about 34 percent of the energy contained in glucose.
Privacy Policy. Skip to main content. Cellular Respiration. Search for:. Oxidative Phosphorylation. Electron Transport Chain The electron transport chain uses the electrons from electron carriers to create a chemical gradient that can be used to power oxidative phosphorylation. Learning Objectives Describe how electrons move through the electron transport chain.
Key Takeaways Key Points Oxidative phosphorylation is the metabolic pathway in which electrons are transferred from electron donors to electron acceptors in redox reactions; this series of reactions releases energy which is used to form ATP.
Complex I establishes the hydrogen ion gradient by pumping four hydrogen ions across the membrane from the matrix into the intermembrane space. Complex IV reduces oxygen; the reduced oxygen then picks up two hydrogen ions from the surrounding medium to make water. Key Terms prosthetic group : The non-protein component of a conjugated protein. Chemiosmosis and Oxidative Phosphorylation Chemiosmosis is the movement of ions across a selectively permeable membrane, down their electrochemical gradient.
Learning Objectives Describe how the energy obtained from the electron transport chain powers chemiosmosis and discuss the role of hydrogen ions in the synthesis of ATP. Key Takeaways Key Points During chemiosmosis, the free energy from the series of reactions that make up the electron transport chain is used to pump hydrogen ions across the membrane, establishing an electrochemical gradient.
Hydrogen ions in the matrix space can only pass through the inner mitochondrial membrane through a membrane protein called ATP synthase. ATP Yield The amount of energy as ATP gained from glucose catabolism varies across species and depends on other related cellular processes. Learning Objectives Describe the origins of variability in the amount of ATP that is produced per molecule of glucose consumed.
Key Takeaways Key Points While glucose catabolism always produces energy, the amount of energy in terms of ATP equivalents produced can vary, especially across different species.
The number of hydrogen ions the electron transport chain complexes can pump through the membrane varies between species. The use of intermediates from glucose catabolism in other biosynthetic pathways, such as amino acid synthesis, can lower the yield of ATP.
Key Terms catabolism : Destructive metabolism, usually including the release of energy and breakdown of materials. Licenses and Attributions.
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