Malate—aspartate shuttle

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. 

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... 

Electrogenic antiport, can only operate in the direction of aspartate efflux as import of H is a requirement for the malate/aspartate shuttle... 

Electrons from NADH outside the mitochondria are transported into the mitochondria by the malate-aspartate shuttle or the a-glycerol phosphate shuttle. 

The other shuttle is the malate-aspartate shuttle. The advantage of this shuttle is that it gives you 3 ATPs for the oxidation of each cytoplasmic NADH. In red muscle, heart, and brain tissues the malate-aspartate shuttle is the major pathway for shuttling electrons into mitochondria. In white muscle, the a-glycerol phosphate shuttle predominates (Fig. 14-2). 

The MALATE-ASPARTATE SHUTTLE gets reducing equivalents (electrons) from cytosolic NADH into the mitochondria so that 3 ATPs can be made. 

THE MALATE-ASPARTATE SHUTTLE HAS A KEY ROLE IN BRAIN METABOLISM 541... 

The malate-aspartate shuttle is the most important pathway for transferring reducing equivalents from the cytosol to the mitochondria in brain 541... 

The malate-aspartate shuttle has a role in linking metabolic pathways in brain 542... 

The malate-aspartate shuttle is the most important pathway for transferring reducing equivalents from the cytosol to the mitochondria in brain. This shuttle involves both the cytosolic and mitochondrial forms of aspartate aminotransferase and malate dehydrogenase, the mitochondrial aspartate-glutamate carrier and the dicarboxylic acid carrier in brain (Fig. 31-5) [69]. The electrogenic exchange of aspartate for glutamate and a... 

The activity of the malate-aspartate shuttle increases during development in parallel with synaptogenesis, which is consistent with the high activity and importance of this shuttle in neurons and synaptic terminals. Evidence of highly regulated malate-aspartate shuttle in adult human brain has been documented [73 and references therein]. 

Cheeseman, A. J. and Clark, J. B. Influence of the malate-aspartate shuttle on oxidative metabolism in synaptosomes. /. Neurochem. 50 1559-1565,1988. 

In the malate-aspartate shuttle, two electrons are transferred to form NADH in the inner mitochondrial matrix (Figure 6-2A). 

While the glycerol 3-phosphate shuttle appears to be less efficient than the malate-aspartate shuttle because fewer ATP molecules are synthesized (see Chapter 7), its advantage is that it enables the cell to transport electrons in the presence of high amounts of NADH. 

Skeletal muscle and brain use a different NADH shuttle, the glycerol 3-phosphate shuttle (Fig. 19-28). It differs from the malate-aspartate shuttle in that it delivers the reducing equivalents from NADH to ubiquinone and thus into Complex III, not Complex I (Fig. 19-8), providing only enough energy to synthesize 1.5 ATP molecules per pair of electrons. 

The inner mitochondrial membrane is impermeable to NADH and NAD+, but NADH equivalents are moved from the cytosol to the matrix by either of two shuttles. NADH equivalents moved in by the malate-aspartate shuttle enter the respiratory chain at Complex I and yield a P/O ratio of 2.5 those moved in by the glycerol 3-phosphate shuttle enter at CoQ and give a P/O ratio of 1.5. 

Shuttle pathways for the transport of electrons across the inner mitochondrial membrane. A. Glycerophosphate shuttle. B. Malate-aspartate shuttle. 

Transaminases participate in metabolism of most of the amino acids, over 60 different enzymes have been identified.142163 Best studied are the aspartate aminotransferases, a pair of cytosolic and mitochondrial isoenzymes which can be isolated readily from animal hearts. Their presence in heart muscle and brain in high concentration is thought to be a result of their functioning in the malate-aspartate shuttle... 

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