Aerobic respiration is a series of enzyme-catalyzed reactions in which electrons are transferred from fuel molecules such as glucose to oxygen as a final electron acceptor. This pathway is the principal energy-yielding scheme for aerobic heterotrophs, and it provides both ATP and metabolic intermediates for many other pathways in the cell, including those of protein, lipid, and carbohydrate synthesis.
Aerobic respiration in microorganisms can be summarized by this equation:
The seeming simplicity of the equation for aerobic respiration conceals the complexity of the process. Fortunately we do not have to present all of the details to address some important concepts concerning its reactants and products, as follows: 1. the steps in the oxidation of glucose,
2. the involvement of coenzyme carriers and the final electron acceptor,
3. where and how ATP originates,
4. where carbon dioxide originates, and
5. where oxygen is required.
Glucose: The Starting Compound
Carbohydrates such as glucose are good fuels because these com pounds are readily oxidized; that is, they are superior electron donors. The electrons they donate can be used in energy transfers. The end products of the oxidation of such organic compounds are energy-rich ATP and energy-poor carbon dioxide and water. Polysaccharides (starch, glycogen) and disaccharides (maltose, sucrose) are stored sources of glucose also available for the respiratory pathways. Although we use glucose as the main starting compound, other hexoses (fructose, galactose) and fatty acid subunits can enter the path ways of aerobic respiration as well.
Glycolysis: The Starting Lineup
The process called glycolysis (EMP) is a pathway that converts glucose through several steps into pyruvic acid. Depending on the organism and the conditions, it may be only the first phase of respiration, or it may serve as the primary metabolic pathway for fermentative microbes. Glycolysis provides a way to synthesize a small amount of ATP, to release another potential source of energy—NADH, and to generate pyruvic acid, an essential inter mediary metabolite. None of these reactions involve the direct input of oxygen.
Steps in the Glycolytic Pathway Glycolysis proceeds along nine linear steps. The first portion of glycolysis involves activation of glucose, which is followed by oxidation reactions of the glucose fragments, the synthesis of ATP, and the formation of pyruvic acid. Although each step of metabolism is catalyzed by a specific enzyme, we will mention only certain key ones. The following outline lists the principal steps of glycolysis. To see an overview of glycolysis, go to process figure 1. Detailed illustrations appear in Appendix A.
Fig1. Summary of the steps in glycolysis. (1) Glucose is phosphorylated to form glucose-6-phosphate. (2) Glucose- 6-phosphate is converted to fructose-6-phosphate. (3) Fructose-6-phosphate is phosphorylated to produce fructose-1,6-bisphosphate. (4) Fructose 1,6-bisphosphate is split into two 3-carbon molecules, glyceraldehyde-3-phosphate (G3P), and dihydroxyacetone phosphate (DHAP). (5) DHAP is converted to G3P, resulting in the production of two molecules of G3P from each molecule of glucose (because of this, each of the reactions past this point occur twice for each molecule of glucose). (6) G3P is converted to 1,3-bisphosphoglyceric acid, yielding one NADH (two per glucose molecule). (7) 1,3-bisphosphoglyceric acid is converted to 3-phosphoglyceric acid, yielding one ATP (two per glucose molecule). (8) 3-phosphoglyceric acid is converted to 2-phosphoglyceric acid. (9) 2-phosphoglyceric acid is converted to phosphoenolpyruvic acid (PEP), producing a high-energy phosphate bond, along with a molecule of water (two per glucose molecule). (10) A high-energy phosphate is transferred from PEP to ADP to produce ATP (two ATP per glucose molecule) and a molecule of pyruvic acid. A more detailed version of glycolysis can be found in Appendix A.
1. First, glucose is phosphorylated at the number six carbon by an ATP to produce glucose-6-phosphate (see figure 8.14). This is a way of “priming” the system and preventing the glucose from being transported out of the cell.
2. Glucose-6-phosphate is converted to its isomer, fructose 6-phosphate.
3. Another ATP is spent in phosphorylating the first carbon of fructose-6-phosphate, which yields a molecule with two phosphates called fructose-1,6-diphosphate. Up to this point, no energy has been released, no oxidation-reduction has occurred, and, in fact, 2 ATPs have been used and the molecules remain in the 6-carbon state.
4. Fructose-1,6-diphosphate is split into two 3-carbon fragments: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
5. Glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP) are isomers, and DHAP is converted to G3P, which is the more reactive form for the following reactions.
The effect of the splitting of fructose diphosphate is to double every subsequent reaction, because where there was once a single molecule, there are now two to be fed into the remainder of glycolysis and other pathways.
6. Each molecule of glyceraldehyde-3-phosphate becomes involved in the single oxidation-reduction reaction of glycolysis. This sets the scene for ATP synthesis. The NAD+ coenzyme complex picks up hydrogens from G3P, forming NADH. This step is ac companied by the addition of an inorganic phosphate (PO4 3−) to form an unstable bond on the third carbon of the G3P substrate. The product of these reactions is diphosphoglyceric acid (DPGA).
7. One of the high-energy phosphates of diphosphoglyceric acid is donated to ADP via substrate-level phosphorylation, resulting in a molecule of ATP. The other product of this reac tion is 3-phosphoglyceric acid (3-PGA).
8. During this phase, the 3-phosphoglyceric acid is converted to 2-phosphoglyceric acid (2-PGA) through the shift of a phosphate from the third to the second carbon. 9. The removal of a water molecule from 2-phosphoglyceric acid converts it to phosphoenolpyruvic acid (PEPA). The result gives rise to a high-energy phosphate bond.
10. In the final reaction of glycolysis, phosphoenolpyruvic acid gives up its high-energy phosphate to form a second ATP, again via substrate-level phosphorylation. This reaction also produces pyruvic acid (pyruvate), a compound with many roles in metabolism.
The reactions of glycolysis thus give rise to two pyruvic acids per glucose. The two substrate-level phosphorylations produce a total of 4 ATPs. However, 2 ATPs were expended for steps 1 and 3, so the net number of ATPs available to the cell from these reactions is 2.
In aerobic organisms, the two NADHs formed during step 5 are shuttled to the electron transport system, where the final electron acceptor will be oxygen, and additional ATPs will be generated. In organisms that ferment glucose, the NADH will be oxidized back to NAD+, and the electron acceptor will be an organic compound.
