Glycerol 3-phosphate shuttle, mechanisms

A summary of the sources of ATP produced from one molecule of glucose is provided in Table 10.2. ATP production from fatty acids, the other important energy source, is discussed in Chapter 12. Several aspects of this summary require further discussion. Recall that two molecules of NADH are produced during glycolysis. When oxygen is available, the oxidation of this NADH by the ETC is preferable (in terms of energy production) to lactate formation. The inner mitochondrial membrane, however, is impermeable to NADH. Animal cells have evolved several shuttle mechanisms to transfer electrons from cytoplasmic NADH to the mitochrondrial ETC. The most prominent examples are the glycerol phosphate shuttle and the malate-aspartate shuttle. 

Although the malate-aspartate shuttle (Figure 10.17b) is a more complicated mechanism than the glycerol phosphate shuttle, it is more energy efficient. The shuttle begins with the reduction of cytoplasmic oxaloacetate to malate by NADH. 

One carrier system that has been extensively studied in insect flight muscle is the glycerol-phosphate shuttle. This mechanism uses the presence on the outer face of the inner mitochondrial membrane of an FAD-dependent enzyme... 

How do shuttle mechanisms differ from one another Two shuttle mechanisms—the glycerol—phosphate shuttle and the malate—aspartate shuttle—transfer the electrons, but not the NADH, produced in cytosolic reactions into the mitochondrion. In the hrst of the two shuttles, which is found in muscle and brain, the electrons are transferred to FAD in the second, which is found in kidney, hver, and heart, the electrons are transferred to NAD. With the malate-aspartate shuttle, 2.5 molecules of ATP are produced for each molecule of cytosolic NADH, rather than 1.5 ATP in the glycerol-phosphate shuttle, a point that affects the overall yield of ATP in these tissues. 

E. There are two shuttle mechanisms, the malate-aspartate shutde and the glycerol 3-phosphate shuttle, that transport electrons to the inner mitochondrial matrix to be used in the electron transport chain. 

Although mitochondria contain both NAD+ and NADH, as does the cytoplasm, the mitochondrial and cytoplasmic pools are unable to exchange their contents directly, as the mitochondrial membranes are impermeable to the cytoplasmic compounds. The shuttle mechanisms allow the H on cytoplasmic NADH to be transported on other compounds into the mitochondria, where it is donated to NAD+ (to form mitochondrial NADH) or to FAD (to form mitochondrial FADH2). There are several shuttle mechanisms that are used by mammalian cells two of the most important are the malate-aspartate shuttle and the glycerol 3-phosphate shuttle. 

Fig. 11-20 The glycerol 3-phosphate shuttle, a mechanism for the transfer-ral of reducing equivalents (H s) between the cytoplasm and mitochondria.

As noted above, however, NAD must be regenerated from the NADH produced or the glycolytic cycle would cease. Under aerobic conditions regeneration of cytosohc NAD+ from cytosolic NADH is accomplished by transferring electrons across the mitochondrial membrane barrier to the electron transfer chain where the electrons are transferred to oxygen. There are two different shuttle mechanisms whereby this transfer of electrons across the membrane to regenerate cytosohc NAD+ can be accomplished, the glycerol 3-phosphate shuttle and the malate-aspartate shuttle. 

The malate—aspartate shuttle is the mechanism by which electrons from NADH produced in the cytosol are transported into mitochondria, as the inner membrane is impermeable to NADH itself. Oxaloacetate is reduced to malate in the cytosol by malate dehydrogenase, in the process oxidizing NADH to replenish cytosolic NAD. The malate-aspartate shuttle is found mainly in cardiac muscle and liver cells, while the glycerol 3-phosphate shuttle operates mainly in brain and skeletal muscle cells. Once malate has entered the mitochondria it is oxidized to oxaloacetate, generating NADH within the mitochondrial matrix. Oxaloacetate is then converted to aspartate, which is transported out of the mitochondria in exchange for glutamate. 

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