Electron transport chain glycerol 3-phosphate 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. 

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. 

E. There are two shuttle mechanisms, the malate-aspartate shutde and the glycerol 3-phosphate shuttle, that transport electrons to the inner mitochondrial matrix to be used in the electron transport chain. 

Figure 7-4. The electron transport chain. Electrons enter from NADH to complex I or succinate dehydrogenase, which is complex II. Electrons derived from glycolysis through the glycerol-3-phosphate shuttle, complex I, and complex II join at coenzyme Q and are transferred to oxygen as shown. As electrons pass through complexes I, III, and IV, protons are transported across the membrane, creating a pH gradient.

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. 

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. 

These carriers transfer electrons into the electron-transport chain independently of and bypassing the NAD+/NADH couple. The main shuttle for cytoplasmic reducing equivalents is the glycerol 3-phosphate shuttle that is shown in Fig. 11-20 (page 334). 

Figure 18.37. Glycerol 3-Phosphate Shuttle. Electrons from NADH can enter the mitochondrial electron transport chain by being used to reduce dihydroxyacetone phosphate to glycerol 3-phosphate. Glycerol 3-phosphate is reoxidized by electron transfer to an FAD prosthetic group in a membrane-bound glycerol 3-phosphate dehydrogenase. Subsequent electron transfer to Q to form QH2 allows these electrons to enter the electron-transport chain.

Electron shuttles Enzymatic processes whereby electrons from NADH can be transferred across the mitochondrial barrier. The glycerol 3-phosphate shuttle uses the reduction of dihydroxyacetone phosphate to glycerol 3-phosphate and reoxidation to transfer electrons from cytosolic NADH to coenzyme Q in the electron transport chain. The malate-aspartate shuttle uses malate and aspartate in a two-member transfer exchange to transfer electrons from cytosolic NADH to mitochondrial NADH (see Figures 27-2 and 27-3). 

The NADH that is produced in the mitochondrion thus passes electrons to the electron transport chain. With the malate-aspartate shuttle, 2.5 moles of ATP are produced for each mole of cytosolic NADH rather than 1.5 moles of ATP in the glycerol-phosphate shutde, which uses FADHg as a carrier. The Biochemical Connections box on page 600 discusses some practical applications of our understanding of the catabolic pathways. 

Approximately how many ATP are formed for each extramitochondrial NADFI that is oxidized to NAD+ by O2 via the electron transport chain. Assume that the glycerol phosphate shuttle is operating. 

In the cytoplasm, oxaloacetate is reduced by NADH to malate via cytoplasmic malate dehydrogenase. Malate can pass into the mitochondrial matrix via special dicarboxylic acid transporters that are in the inner mitochondrial membrane. Once in the matrix, oxaloacetate is reoxidized to malate by mitochondrial malate dehydrogenase. Thus this series of enzyme and transporter reactions has effectively shuttled reducing equivalents in NADH from the cytoplasm to the matrix. This shuttle constitutes the most efficient way of transferring hydrogen atoms from NADH in the cytoplasm to the mitochondrial matrix, and hence into the electron transport chain (see Sec. 10.12 for the glycerol 3-phosphate shuttle). 

Carnitine is not involved in the movement of fatty acids into microbodies. Either free fatty acids or acyl-CoAs appear to be able to cross the organelle s membrane. Moreover, because of the absence of an electron transport chain in microbodies there is no internal means of regenerating NAD". The reoxidation of NADH is thought to occur either by a glycerol phosphate shuttle or by movement of NADH to the cytosol and NAD back. 

---