Shuttle systems malate-aspartate

Figure 15.11b shows the malate/aspartate shuttle system, which is particularly active in liver and heart. It uses malate, aspartate, and oxaloacetate to shuttle cytoplasmic electrons from NADH into the mitochondrial matrix. In this shuttle, NADH reduces oxaloacetate to malate, which travels through an inner membrane transport system that ultimately exchanges the malate for an ot-ketoglutarate. To do... 

The second electron shuttle system, called the malate-aspartate shuttle, is shown in Figure 21.34. Oxaloacetate is reduced in the cytosol, acquiring the electrons of NADH (which is oxidized to NAD ). Malate is transported across the inner membrane, where it is reoxidized by malate dehydrogenase, converting NAD to NADH in the matrix. This mitochondrial NADH readily enters the electron transport chain. The oxaloacetate produced in this reaction cannot cross the inner membrane and must be transaminated to form aspartate, which can be transported across the membrane to the cytosolic side. Transamination in the cytosol recycles aspartate back to oxaloacetate. In contrast to the glycerol phosphate shuttle, the malate-aspartate cycle is reversible, and it operates as shown in Figure 21.34 only if the NADH/NAD ratio in the cytosol is higher than the ratio in the matrix. Because this shuttle produces NADH in the matrix, the full 2.5 ATPs per NADH are recovered. 

This transfer of reducing equivalents is essential for maintaining the favorable NAD+/NADH ratio required for the oxidative metabolism of glucose and synthesis of glutamate in brain (McKenna et al., 2006). The malate-aspartate shuttle is considered the most important shuttle in brain. It is particularly important in neurons. It has low activity in astrocytes. This shuttle system is fully reversible and linked to amino acid metabolism with the energy charge and citric acid cycle of neuronal cells. 

Malate-aspartate Shuttle This is the common shuttle in mammalian systems. It is both more complex and more efficient than the glycerol phosphate shuttle, yielding 2.5 ATP/NADH. It can be thought of as occurring in two phases ... 

The malate-aspartate shuttle is quantitatively more significant in all vertebrate tissues. It is unidirectional, requiring cytoplasmic and mitochondrial malate dehydrogenases and aspartate aminotransferases as well as two membrane-bound carrier systems (Figure 14-22). In this process, the reducing equivalents of NADH are... 

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... 

The final reactions to be considered in the metabolism of ethanol in the liver are those involved in reoxidation of cytosolic NADH and in the reduction of NADP. The latter is achieved by the pentose phosphate pathway which has a high capacity in the liver (Chapter 6). The cytosolic NADH is reoxidised mainly by the mitochondrial electron transfer system, which means that substrate shuttles must be used to transport the hydrogen atoms into the mitochondria. The malate/aspartate is the main shuttle involved. Under some conditions, the rate of transfer of hydrogen atoms by the shuttle is less than the rate of NADH generation so that the redox state in the cytosolic compartment of the liver becomes highly reduced and the concentration of NAD severely decreased. This limits the rate of ethanol oxidation by alcohol dehydrogenase. 

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