Glycerol-3-phosphate shuttle

FIGURE 21.33 The glycerophosphate shuttle (also known as the glycerol phosphate shuttle) couples the cytosolic oxidation of NADH with mitochondrial reduction of [FAD]. 

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. 

The net stoichiometric equation for the oxidation of glucose, using the glycerol phosphate shuttle, is... 

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... 

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). 

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. 

FADH is produced by succinate dehydrogenase in the citric acid cycle and by the a-glycerol phosphate shuttle. Both enzymes are located in the inner membrane and can reoxidize FADHj directly by transferring electrons into the ETC. Once FADH2 has been oxidized, the FAD can be made available once again for use by the enzyme. 

All these components are in the inner membrane of the mitochondria as shown in Figure I-I3-3. Succinate dehydrogenase and the a-glycerol phosphate shuttle enzymes reoxidize their FADHj and pass electrons directly to CoQ. 

Two biochemically distinct shuttles, the malate/aspar-tate shuttle (Figure 9.17) and the glycerol phosphate shuttle (Figure 9.18) are involved in the transfer (Appendix 9.7). 

Figure 9.18 The glycerol phosphate shuttle. In the cytosol, NADH is oxidised in a reaction in which dihydroxyacetone phosphate is reduced to glycerol 3-phosphate, catalysed by glycerol-3-phosphate dehydrogenase (NAD linked) ...

B. The calculated ATP yield is somewhat variable because glycolytic electrons transferred by the glycerol phosphate shuttle bypass complex I of the electron transport chain. 

Six ATPs will be synthesized if the aspartate-malate shuttle is used to transfer NADH generated through glycolysis to NADH in the mitochondrial matrix four molecules of ATP will be made if the glycerol phosphate shuttle delivers the electrons to ubiquinone in the inner mitochondrial membrane. 

Tire glycerol-phosphate shuttle, because it depends upon a mitochondrial flavoprotein, provides 2 ATP per electron pair (P/O = 2), whereas the malate-aspartate shuttle may provide a higher yield of ATP. Tire glycerol-phosphate shuttle is essentially irreversible, but the reactions of the malate-aspartate shuttle can be reversed and utilized in gluconeogenesis (Chapter 17). 

Figure 18-18 (A) The glycerol-phosphate shuttle and (B) the malate-aspartate shuttle for transport from cytoplasmic NADH into mitochondria. The heavy arrows trace the pathway of the electrons (as 2H) transported.

What is the mitochondrial glycerol phosphate shuttle Is it utilized by plant cells Explain. 

Mitochondria employ a host of carriers, or transporters, to move molecules across the inner mitochondrial membrane. The electrons of cytoplasmic NADH are transferred into the mitochondria by the glycerol phosphate shuttle to form FADH2 from FAD. The entry of ADP into the mitochondrial matrix is coupled to the exit of ATP by ATP-ADP translocase, a transporter driven by membrane potential. 

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 ... 

Bissell, M. J., Rambock, W. A., White, R. C., and Bassham, J. A. (1976), Glycerol phosphate shuttle in vims-transformed cells in culture. Science 191,856-858. 

Glycerol phosphate shuttle (Figure 5-23, left side)... 

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.

Overall, when 1 mole of glucose is oxidized to C02 and H20, approximately 36 moles of ATP are produced if the glycerol phosphate shuttle is used, or 38 moles if the malate aspartate shuttle is used. 

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