Oxidative phosphorylation malate-aspartate shuttle

NADH (oxidative phosphorylation malate-aspartate shuttle) 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. 

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... 

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. 

Citrin is an aspartate-glutamate antiporter that has a role both in the urea cycle and in the malate aspartate shuttle. It is necessary for the transport of aspartate produced in the mitochondria into the cytosol, where it is used by AS. Its role in the malate-aspartate shuttle is to transport cytosolic NADH reducing equivalents into the mitochondria, where they are used in oxidative phosphorylation. Defects in citrin cause citrullinemia type II. Patients manifest later-onset intermittent hyperammonemic encephalopathy as in HHH syndrome. 

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... 

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