Oxidative phosphorylation glycerol 3-phosphate shuttle

Oxidation of 2 molecules each of isocitrate, n-ketoglutarate, and malate yields 6 NADH Oxidation of 2 molecules of succinate yields 2 [FADHg] Oxidative phosphorylation (mitochondria) 2 NADH from glycolysis yield 1.5 ATP each if NADH is oxidized by glycerol-phosphate shuttle 2.5 ATP by malate-aspartate shuttle + 3 + 5... 

Because the 2 NADH formed in glycolysis are transported by the glycerol phosphate shuttle in this case, they each yield only 1.5 ATP, as already described. On the other hand, if these 2 NADH take part in the malate-aspartate shuttle, each yields 2.5 ATP, giving a total (in this case) of 32 ATP formed per glucose oxidized. Most of the ATP—26 out of 30 or 28 out of 32—is produced by oxidative phosphorylation only 4 ATP molecules result from direct synthesis during glycolysis and the TCA cycle. 

Cytoplasmic NADH oxidized by the glycerol phosphate shuttle produces a mitochondrial FADHj and yields approximately 2 ATP by oxidative phosphorylation. 

Many enzymes in the mitochondria, including those of the citric acid cycle and pyruvate dehydrogenase, produce NADH, aU of which can be oxidized in the electron transport chain and in the process, capture energy for ATP synthesis by oxidative phosphorylation. If NADH is produced in the cytoplasm, either the malate shuttle or the a-glycerol phosphate shuttle can transfer the electrons into the mitochondria for delivery to the ETC. Once NADH has been oxidized, the NAD can again be used by enzymes that require it. 

Figure 5-23. The glycerol phosphate and malate aspartate shuttles. Left, the glycerol phosphate shuttle produces FADH2, each of which generates approximately 2 ATP by oxidative phosphorylation. Right, the malate aspartate shuttle produces NADH, each of which generates approximately 3 ATP.

Under aerobic conditions, a greater energy yield may be derived from the electrons contained within the NADH molecule by their participation in the process of oxidative phosphorylation (Section 10.4). The location of the electron-transport assemblies within the inner mitochondrial membrane necessitates the penetration of the membrane by NADH (Section 9.5). The inner mitochondrial membrane is, however, impermeable to NADH molecules. This obstacle is circumvented by the use of shuttle systems (Section 10.5) which do not transport the NADH molecules across the membrane but transfer the electrons as components of another substance which can transverse the membrane. Two shuttle systems exist for this purpose the glycerol phosphate shuttle and the malate-aspartate shuttle. Their relative activities are tissue dependent, e.g. the glycerol phosphate shuttle predominates in the cells of mammalian skeletal muscle and brain whilst the malate-aspartate shuttle is... 

Note that, under aerobic conditions, the two NADH molecules that are synthesized are reoxidized via the electron transport chain generating ATP. Given the cytoplasmic location of these NADH molecules, each is reoxidized via the glycerol 3-phosphate shuttle (see Topic L2) and produces approximately two ATPs during oxidative phosphorylation or via the malate-aspartate shuttle (see Topic L2) and produces approximately three ATPs during oxidative phosphorylation. 

In fact, the glyceraldehyde 3-phosphate dehydrogenase reaction also consumes NADH, equivalent to two molecules of NADH for each molecule of glucose synthesized. Since each cytosolic NADH would normally be used to generate approximately two ATP molecules via the glycerol 3-phosphate shuttle and oxidative phosphorylation (see Topic L2), this is equivalent to the input of another four ATPs per glucose synthesized. 

It is often necessary to move electrons into mitochondria for disposal via oxidative phosphorylation. However, NADH and FADH2 do not penetrate the inner mitochondrial membrane. Instead, such electrons may first be passed to dihydroxyacetone phosphate or to oxaloacetate to make glycerol-3-phosphate and malate, respectively. These compounds can penetrate the inner mitochondrial membrane via the porters described earlier and oxidized there by mitochondrial NAD+ or FAD. These systems are termed the glycerol-3-phosphate and malate shuttles, respectively, and they are described in greater detail in Chapter 18. 

The main drawback of the glycerol-3-phosphate shuttle is that only two ATP are produced for each cytoplasmic NADH. The reason is that the electrons are shuttled to FADHj, which )delds only two ATP by oxidative phosphorylation. (The energy yield of the oxidation of mitochondrial NADH is three ATP.) Thus the total energy yield from glycolysis imder aerobic conditions in muscle and nerve cells is two ATP, produced by substrate level phosphorylation, plus four ATP (two ATP per NADH), produced by oxidative phosphorylation. This provides an energy yield of six ATP per glucose. 

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