 In this video, I will describe the overall result in terms of molecules produced in the breakdown of glucose by cellular respiration, describe how electrons move through the electron transport chain, explain how a proton gradient is established and maintained by the electron transport chain, and define oxidative phosphorylation and explain the chemiosmotic mechanism for the production of ATP. In aerobic cellular respiration, following glycolysis, pyruvate will enter the mitochondria, where the pyruvate dehydrogenase complex will convert pyruvate to acetylcoenzyme A, and acetylcoenzyme A will then enter the citric acid cycle, which is also known as the Krebs cycle. Then following the citric acid cycle, high energy electrons will be transferred into oxidative phosphorylation and provide the energy required for ATP synthesis. So the mitochondria are the locations where aerobic cellular respiration will proceed following glycolysis. The pyruvate dehydrogenase complex located in the mitochondria will catalyze oxidation of pyruvate forming acetylcoenzyme A. High energy electrons are transferred from pyruvate onto the oxidizing agent NAD+, producing NADH, and one of the three carbons of pyruvate is released as a carbon dioxide molecule. Following the pyruvate dehydrogenase complex, acetylcoenzyme A, which is commonly abbreviated acetylcoA, enters into the Krebs cycle, which is more commonly known as the citric acid cycle. There are eight steps in the citric acid cycle, each catalyzed by a distinct enzyme. The first step in the citric acid cycle is catalyzed by citric synthase, where acetylcoA and oxaloacetate are converted into citrate. The second step of the citric acid cycle is an isomerization reaction, converting citrate to isocitrate, which is catalyzed by a connotase. The third step of the citric acid cycle is the first redox reaction, where isocitrate dehydrogenase catalyzes the oxidation of isocitrate and the reduction of NAD+, forming alpha-ketoglutarate carbon dioxide and NADH as products. Then the fourth step of the citric acid cycle is catalyzed by alpha-ketoglutarate dehydrogenase, which catalyzes the oxidation of alpha-ketoglutarate, forming succinyl-CoA, while NAD+, is reduced, forming NADH, and another carbon dioxide molecule is produced. Notice, at this step, two carbon dioxide molecules have been generated in the citric acid cycle, corresponding to the two carbon atoms that entered the citric acid cycle as acetyl-CoA. Next, succinyl-CoA dehydrogenase converts succinyl-CoA into succinate and forms a high-energy GTP molecule. This GTP molecule can then transfer a phosphate to ADP, producing an ATP. The sixth step of the citric acid cycle, catalyzed by succinate dehydrogenase, will oxidize succinate, producing fumarate, and transferring electrons onto an electron carrier, known as FAD, forming FADH2. The seventh step of the citric acid cycle, which is catalyzed by the enzyme fumarase, converts fumarate to malate. Then the eighth and final step of the citric acid cycle, where malate dehydrogenase, catalyzes the oxidation of malate, forming oxaloacetate, and transferring electrons to NAD+, forming another NADH molecule. To summarize, at this point in aerobic cellular respiration, one molecule of glucose entered glycolysis and was converted into two molecules of pyruvate. In the process, two molecules of ATP were generated, and two molecules of NADH were generated. Then each molecule of pyruvate entered the pyruvate dehydrogenase complex, which produced two more molecules of NADH, and converted pyruvate to acetyl-coenzyme A. Then the citric acid cycle generated three molecules of NADH, as well as a molecule of FADH2, for every acetyl-coA that entered. From one glucose, there would be two molecules of acetyl-coA that entered the citric acid cycle, so we would have six molecules of NADH and two molecules of FADH2. There was also a GTP that was produced in the citric acid cycle that can be converted to ATP. However, NADH needs to be transported into the mitochondria in order to be used in oxidative phosphorylation after the citric acid cycle to complete aerobic cellular respiration. And the transport of NADH into the mitochondria will consume one ATP per NADH. The two molecules of NADH produced in glycolysis will cost two ATP to transport into the mitochondria. Therefore, we lose the two molecules of ATP from glycolysis in order to get those two molecules of NADH into the mitochondria, giving us an overall net two ATP that came from the citric acid cycle directly, plus 10 NADH, six from the citric acid cycle directly, two from the pyruvate dehydrogenase complex, and two that were transported into the mitochondria from glycolysis. And then we have our two molecules of FADH2 that are produced directly in the citric acid cycle. Now, the high energy electrons that have been stored as NADH and FADH2 will be used in oxidative phosphorylation to produce ATP. Energy which has been released from glucose oxidation will be stored in chemical bonds as the endergonic reaction of ATP synthesis is fueled by glucose oxidation. Oxidative phosphorylation occurs in the mitochondria following the citric acid cycle in aerobic cellular respiration. Oxidative phosphorylation is a metabolic pathway that uses oxygen and will release the energy stored in electron carrier molecules NADH and FADH2 in order to produce a large amount of ATP and as oxygen becomes reduced, it will be converted to water. There are two parts of oxidative phosphorylation. The first part known as the electron transport chain is where electron carrier molecules NADH and FADH2 will be oxidized and oxygen will function as the final electron acceptor that becomes reduced forming water. Then the second part of oxidative phosphorylation is the chemiosmotic mechanism of ATP synthesis which is catalyzed by the enzyme ATP synthase. The electron transport chain is a series of four enzymes that will oxidize the electron carrier molecules NADH and FADH2. Complex one of the electron transport chain is also known as NADH ubiquinone oxido reductase and it catalyzes the oxidation of NADH and the reduction of ubiquinone forming the products NAD plus and ubiquinol. In the process, four hydrogen ions are pumped from the mitochondrial matrix to the intermembrane space. As these hydrogen ions which are also known as protons accumulate in the intermembrane space, this will create a potential energy source that will fuel ATP synthesis. Complex two of the electron transport chain is also known as succinate dehydrogenase and is one of the enzymes of the citric acid cycle that oxidizes succinate to produce fumarate and FADH2. This enzyme will then oxidize FADH2, transferring the high energy electrons to the oxidizing agent ubiquinone, producing ubiquinol. So the ubiquinol from complex one and complex two will enter into complex three of the electron transport chain which is also known as ubiquinol cytochrome C oxido reductase, which catalyzes the oxidation of ubiquinol forming ubiquinone and reduces a molecule known as cytochrome C. The fourth and final enzyme in the electron transport chain will then accept electrons from cytochrome C, and this is known as cytochrome C oxidase. And the electrons that are transferred from cytochrome C will be accepted by oxygen. And so oxygen is the oxidizing agent that accepts the electrons as cytochrome C becomes oxidized. Oxygen will be reduced producing water. Complex three of the electron transport chain pumps four hydrogen ions into the intermembrane space, and then complex four pumps two hydrogen ions into the intermembrane space. This accumulation of hydrogen ions in the intermembrane space is a potential energy source that will drive the final step of oxidative phosphorylation, where ADP is phosphorylated to produce ATP in the mechanism of chemiosmosis. Chemiosmosis is where protons, also known as hydrogen ions, move by facilitated diffusion through the enzyme ATP synthase. As those hydrogen ions move down their concentration gradient through ATP synthase, they create kinetic energy that will then be converted into the chemical potential energy of the bonds in ATP. Three hydrogen ions enter the mitochondrial matrix through ATP synthase for every ATP that's generated by ATP synthase. However, most of the ATP produced in the mitochondria will need to be transported out of the mitochondria to be used for sustaining life, being used by a variety of proteins throughout the cell that are going to need ATP in order to fuel the work that they have to do. And ATP is too large of a molecule to be able to simply diffuse out of the mitochondria. The antiporter that transports ATP out will require one hydrogen ion to move into the mitochondrial matrix for every ATP molecule that's transported out, and one molecule of ADP and one inorganic phosphate will also enter the mitochondrial membrane, providing the reagents necessary to synthesize another molecule of ATP. This means that four hydrogen ions will be removed from the intermembrane space and enter the mitochondrial matrix for every one molecule of ATP that's synthesized and transported out of the mitochondria. And so to summarize oxidative phosphorylation, high-energy electron carriers NADH and FADH2 enter the electron transport chain from the citric acid cycle. And as those high-energy electron carriers become oxidized, electrons are transferred through the electron transport chain, and as those high-energy electrons are passed down the electron transport chain, energy released is used to pump hydrogen ions out of the mitochondrial matrix into the intermembrane space. That high concentration of hydrogen ions in the intermembrane space then is the potential energy that will fuel ATP synthesis as hydrogen ions move down their concentration gradient by facilitated diffusion through ATP synthase. They're converting the potential energy of the concentration gradient to the kinetic energy of motion through ATP synthase, and then ATP synthase will convert that kinetic energy into the chemical potential energy of ATP as the bond is formed between inorganic phosphate and ADP. So chemiosmosis is specifically the synthesis of ATP by ATP synthase, which is fueled by the facilitated diffusion of hydrogen ions into the mitochondrial matrix from the intermembrane space. And the concentration gradient for chemiosmosis is generated in the electron transport chain, the other half of oxidative phosphorylation. To summarize, the overall maximum yield of ATP produced by aerobic cellular respiration of glucose is around 36 ATP. Now, how do we get to that number? There's two ATPs that are produced from the process of glycolysis and the citric acid cycle overall. Although two ATPs were generated from glycolysis, those two ATPs were spent to transport NADH into the mitochondria where it would need to be transported in order to enter the electron transport chain. And so we get the overall two ATP from the citric acid cycle. Then oxidative phosphorylation generates another 28 to 34 ATP, 28 ATP if those ATPs need to be transported out of the mitochondria and 34 if the ATP is used locally within the mitochondria. This is because the oxidation of NADH by the electron transport chain can pump 10 hydrogen ions across the inner mitochondrial matrix, and it will require three hydrogen ions to pass into the matrix for every ATP synthesized. Then if that ATP is going to be used outside of the mitochondria, another hydrogen ion will enter the matrix to transport that ATP out. For every FADH, six hydrogen ions will be pumped across the inner mitochondrial membrane, and so those six hydrogen ions could be used to generate two ATPs that are used inside of the mitochondria or one and a half if the ATPs transported out of the mitochondria. So overall if we have 10 NADH molecules that get oxidized and we can transport that ATP out of the mitochondria, we'll have 25 ATP generated from NADH, and then for our two molecules of FADH we'll be able to transport three molecules of ATP out of the mitochondria. That gives us the total 28 ATP from oxidative phosphorylation and two ATP from the citric acid cycle. So a net of about 30 ATP is a realistic estimate for the maximum ATP production by cellular respiration of glucose. However, it's unlikely that cells actually achieve that theoretical maximum. Efficiency can vary from cell to cell based on a variety of factors. As I pointed out, one of those factors has to do with the transport of ATP in and out of the mitochondria or the transport of NADH in and out of the mitochondria.