Mitochondrial chemiosmotic mechanism of oxidative phosphorylation for forming large quantities of ATP. This figure shows the relationship of the oxidative and phosphorylation steps at the outer and inner membranes of the mitochondrion.
this sequence of oxidative reactions, tremendous quantities of energy are released to form ATP. Formation of ATP in this manner is called oxidative phospho-rylation. This occurs entirely in the mitochondria by a highly specialized process called the chemiosmotic mechanism.
Chemiosmotic Mechanism of the Mitochondria to Form ATP
Ionization of Hydrogen, the Electron Transport Chain, and Formation of Water. The first step in oxidative phosphorylation in the mitochondria is to ionize the hydrogen atoms that have been removed from the food substrates. As described earlier, these hydrogen atoms are removed in pairs: one immediately becomes a hydrogen ion, H+; the other combines with NAD+ to form NADH. The upper portion of Figure 67-7 shows the subsequent fate of the NADH and H+. The initial effect is to release the other hydrogen atom from the NADH to form another hydrogen ion, H+; this process also reconstitutes NAD+ that will be reused again and again.
The electrons that are removed from the hydrogen atoms to cause the hydrogen ionization immediately enter an electron transport chain of electron acceptors that are an integral part of the inner membrane (the shelf membrane) of the mitochondrion. The electron acceptors can be reversibly reduced or oxidized by accepting or giving up electrons. The important members of this electron transport chain include flavo-protein, several iron sulfide proteins, ubiquinone, and cytochromes B, C1, C, A, and A3. Each electron is shuttled from one of these acceptors to the next until it finally reaches cytochrome A3, which is called cytochrome oxidase because it is capable of giving up two electrons and thus reducing elemental oxygen to form ionic oxygen, which then combines with hydrogen ions to form water.
Thus, Figure 67-7 shows the transport of electrons through the electron chain and then their ultimate use by cytochrome oxidase to cause the formation of water molecules. During the transport of these electrons through the electron transport chain, energy is released that is used to cause the synthesis of ATP, as follows.
Pumping of Hydrogen Ions into the Outer Chamber of the Mitochondrion, Caused by the Electron Transport Chain. As the electrons pass through the electron transport chain, large amounts of energy are released. This energy is used to pump hydrogen ions from the inner matrix of the mitochondrion (to the right in Figure 67-7) into the outer chamber between the inner and outer mitochon-drial membranes (to the left). This creates a high concentration of positively charged hydrogen ions in this chamber; it also creates a strong negative electrical potential in the inner matrix.
Formation of ATP. The next step in oxidative phosphorylation is to convert ADP into ATP. This occurs in conjunction with a large protein molecule that protrudes all the way through the inner mitochondrial membrane and projects with a knoblike head into the inner mitochondrial matrix. This molecule is an ATPase, the physical nature of which is shown in Figure 67-7. It is called ATP synthetase.
The high concentration of positively charged hydrogen ions in the outer chamber and the large electrical potential difference across the inner membrane cause the hydrogen ions to flow into the inner mitochondrial matrix through the substance of the ATPase molecule. In doing so, energy derived from this hydrogen ion flow is used by ATPase to convert ADP into ATP by combining ADP with a free ionic phosphate radical (Pi), thus adding another high-energy phosphate bond to the molecule.
The final step in the process is transfer of ATP from the inside of the mitochondrion back to the cell cytoplasm. This occurs by facilitated diffusion outward through the inner membrane and then by simple diffusion through the permeable outer mitochondrial membrane. In turn, ADP is continually transferred in the other direction for continual conversion into ATP. For each two electrons that pass through the entire electron transport chain (representing the ionization of two hydrogen atoms), up to three ATP molecules are synthesized.
Summary of ATP Formation During the Breakdown of Glucose
We can now determine the total number of ATP molecules that, under optimal conditions, can be formed by the energy from one molecule of glucose.
1. During glycolysis, four molecules of ATP are formed, and two are expended to cause the initial phosphorylation of glucose to get the process going. This gives a net gain of two molecules of ATP.
2. During each revolution of the citric acid cycle, one molecule of ATP is formed. However, because each glucose molecule splits into two pyruvic acid molecules, there are two revolutions of the cycle for each molecule of glucose metabolized, giving a net production of two more molecules of ATP.
3. During the entire schema of glucose breakdown, a total of 24 hydrogen atoms are released during glycolysis and during the citric acid cycle. Twenty of these atoms are oxidized in conjunction with the chemiosmotic mechanism shown in Figure 67-7, with the release of three ATP molecules per two atoms of hydrogen metabolized. This gives an additional 30 ATP molecules.
4. The remaining four hydrogen atoms are released by their dehydrogenase into the chemiosmotic oxidative schema in the mitochondrion beyond the first stage of Figure 67-7. Two ATP molecules are usually released for every two hydrogen atoms oxidized, thus giving a total of four more ATP molecules.
Now, adding all the ATP molecules formed, we find a maximum of 38 ATP molecules formed for each molecule of glucose degraded to carbon dioxide and water.Thus, 456,000 calories of energy can be stored in the form of ATP, whereas 686,000 calories are released during the complete oxidation of each gram-molecule of glucose. This represents an overall maximum efficiency of energy transfer of 66 per cent. The remaining 34 per cent of the energy becomes heat and, therefore, cannot be used by the cells to perform specific functions.
Control of Energy Release from Stored Glycogen When the Body Needs Additional Energy: Effect of ATP and ADP Cell Concentrations in Controlling the Rate of Glycolysis
Continual release of energy from glucose when energy is not needed by the cells would be an extremely wasteful process. Instead, glycolysis and the subsequent oxidation of hydrogen atoms are continually controlled in accordance with the cells' need for ATP. This control is accomplished by multiple feedback control mechanisms within the chemical schemata. Among the more important of these are the effects of cell concentrations of both ADP and ATP in controlling the rates of chemical reactions in the energy metabolism sequence.
One important way in which ATP helps control energy metabolism is to inhibit the enzyme phospho-fructokinase. Because this enzyme promotes the formation of fructose-1,6-diphosphate, one of the initial steps in the glycolytic series of reactions, the net effect of excess cellular ATP is to slow or even stop glycolysis, which in turn stops most carbohydrate metabolism. Conversely, ADP (and AMP as well) causes the opposite change in this enzyme, greatly increasing its activity. Whenever ATP is used by the tissues for energizing a major fraction of almost all intracellular chemical reactions, this reduces the ATP inhibition of the enzyme phosphofructokinase and at the same time increases its activity as a result of the excess ADP formed. Thus, the glycolytic process is set in motion, and the total cellular store of ATP is replenished.
Another control linkage is the citrate ion formed in the citric acid cycle. An excess of this ion also strongly inhibits phosphofructokinase, thus preventing the glycolytic process from getting ahead of the citric acid cycle's ability to use the pyruvic acid formed during glycolysis.
A third way by which the ATP-ADP-AMP system controls carbohydrate metabolism, as well as controlling energy release from fats and proteins, is the following: Referring back to the various chemical reactions for energy release, we see that if all the ADP in the cell has already been converted into ATP, additional ATP simply cannot be formed. As a result, the entire sequence involved in the use of foodstuffs—glucose, fats, and proteins—to form ATP is stopped. Then, when ATP is used by the cell to energize the different physiologic functions in the cell, the newly formed ADP and AMP turn on the energy processes again, and ADP and AMP are almost instantly returned to the ATP state. In this way, essentially a full store of ATP is automatically maintained, except during extreme cellular activity, such as very strenuous exercise.
Anaerobic Release of Energy— "Anaerobic Glycolysis"
Occasionally, oxygen becomes either unavailable or insufficient, so that oxidative phosphorylation cannot take place. Yet even under these conditions, a small amount of energy can still be released to the cells by the glycolysis stage of carbohydrate degradation, because the chemical reactions for the breakdown of glucose to pyruvic acid do not require oxygen.
This process is extremely wasteful of glucose, because only 24,000 calories of energy are used to form ATP for each molecule of glucose metabolized, which represents only a little over 3 per cent of the total energy in the glucose molecule. Nevertheless, this release of glycolytic energy to the cells, which is called anaerobic energy, can be a lifesaving measure for up to a few minutes when oxygen becomes unavailable.
Formation of Lactic Acid During Anaerobic Glycolysis Allows Release of Extra Anaerobic Energy. The law of mass action states that as the end products of a chemical reaction build up in a reacting medium, the rate of the reaction decreases, approaching zero. The two end products of the glycolytic reactions (see Figure 67-5) are (1) pyruvic acid and (2) hydrogen atoms combined with NAD+ to form NADH and H+. The buildup of either or both of these would stop the glycolytic process and prevent further formation of ATP When their quantities begin to be excessive, these two end products react with each other to form lactic acid, in accordance with the following equation:
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.