During electron transport, electrons are released from NADH and FADH2 and eventually transferred to O2, forming H2O, according to the following overall reactions:
Recall that the conversion of 1 glucose molecule to CO2 via the glycolytic pathway and citric acid cycle yields 10 NADH and 2 FADH2 molecules (see Table 1). Oxidation of these reduced coenzymes has a total ΔG°′ of −613 kcal/mol [10(−52.6) + 2(−43.4)]. Thus of the total potential free energy present in the chemical bonds of glucose (−686 kcal/mol), about 90 percent is conserved in the reduced coenzymes. Why should there be two different coenzymes, NADH and FADH2? Although many of the reactions involved in glucose and fatty acid oxidation are sufficiently energetic to reduce NAD+, several are not. To capture the energy released by those reactions, they are coupled to re duction of FAD, which requires less energy.
Table1. Net Result of the Glycolytic Pathway and the Citric Acid Cycle
The energy carried in the reduced coenzymes can be released by oxidizing them. The biochemical challenge faced by the mitochondrion is to transfer, as efficiently as possible, the energy released by this oxidation into the energy in the terminal phosphoanhydride bond in ATP.
A relatively simple one-to-one reaction involving reduction of one coenzyme molecule and synthesis of one ATP molecule would be terribly inefficient because the ΔG°′ for ATP generation from ADP and Pi is substantially less than that for the coenzyme oxidation, and much energy would be lost as heat. To efficiently recover that energy, the mitochondrion converts the energy of coenzyme oxidation into a proton motive force using a series of electron carriers, all but one of which are integral components of the inner membrane (see stage III in Figure 1). The proton-motive force can then be used to generate ATP very efficiently.
Fig1. Summary of aerobic oxidation of glucose and fatty acids. Stage I: In the cytosol, glucose is converted to pyruvate (glycolysis) and fatty acid to fatty acyl CoA. Pyruvate and fatty acyl CoA then move into the mitochondrion. Mitochondrial porins make the outer membrane permeable to these metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow) and fatty acids (blue) into the matrix. Fatty acyl groups are transferred from fatty acyl CoA to an intermediate carrier, transported across the inner membrane, and then reattached to CoA on the matrix side. Stage II: In the mitochondrial matrix, pyruvate and fatty acyl CoA are converted to acetyl CoA and then oxidized, releasing CO2. Pyruvate is converted to acetyl CoA with the formation of NADH and CO2; two carbons from fatty acyl CoA are converted to acetyl CoA with the formation of FADH2 and NADH. Oxidation of acetyl CoA in the citric acid cycle generates NADH and FADH2, GTP, and CO2. Stage III: Electron transport reduces O2 to H2O and generates a proton motive force. Electrons (blue) from reduced coenzymes are transferred via electron-transport complexes (blue boxes) to O2 concomitant with transport of H+ ions (red) from the matrix to the intermembrane space, generating the proton-motive force. Electrons from NADH flow directly from complex I to complex III, bypassing complex II. Electrons from FADH2 flow directly from complex II to complex III, bypassing com plex I. Stage IV: ATP synthase, also called the F0F1 complex (orange), harnesses the proton-motive force to synthesize ATP in the matrix. Antiporter proteins (purple and green ovals) transport ADP and Pi into the matrix and export hydroxyl groups and ATP. NADH generated in the cytosol is not transported directly to the matrix because the inner membrane is impermeable to NAD+ and NADH; instead, a shuttle system (red) transports electrons from cytosolic NADH to NAD+ in the matrix. O2 diffuses into the matrix, and CO2 diffuses out.
