Mitochondrial glycerol-3-phosphate dehydrogenase

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. 

Another pathway is the L-glycerol 3-phosphate shuttle (Figure 11). Cytosolic dihydroxyacetone phosphate is reduced by NADFl to s.n-glycerol 3-phosphate, catalyzed by s,n-glycerol 3-phosphate dehydrogenase, and this is then oxidized by s,n-glycerol 3-phosphate ubiquinone oxidoreductase to dihydroxyacetone phosphate, which is a flavoprotein on the outer surface of the inner membrane. By this route electrons enter the respiratory chain.from cytosolic NADH at the level of complex III. Less well defined is the possibility that cytosolic NADH is oxidized by cytochrome bs reductase in the outer mitochondrial membrane and that electrons are transferred via cytochrome b5 in the endoplasmic reticulum to the respiratory chain at the level of cytochrome c (Fischer et al., 1985). 

The lipid-soluble ubiquinone (Q) is present in both bacterial and mitochondrial membranes in relatively large amounts compared to other electron carriers (Table 18-2). It seems to be located at a point of convergence of the NADH, succinate, glycerol phosphate, and choline branches of the electron transport chain. Ubiquinone plays a role somewhat like that of NADH, which carries electrons between dehydrogenases in the cytoplasm and from soluble dehydrogenases in the aqueous mitochondrial matrix to flavoproteins embedded in the membrane. Ubiquinone transfers electrons plus protons between proteins within the... 

Cytosolic NADH cannot cross the inner mitochondrial membrane and enter mitochondria to be reoxidized. However, it can be reoxidized via the glycerol 3-phosphate shuttle. Cytosolic glycerol 3-phosphate dehydrogenase oxidizes the NADH and reduces dihydroxyacetone phosphate to glycerol 3-phosphate. 

FAD Sucdnate —> furmarate3 Fatty acyl CoA —> enoyl CoAb Glycerol-3-phosphate —> dihydroxyacetone phosphate (mitochondrial)c Succinate dehydrogenase Fatty acyl CoA dehydrogenase Glycerol-3-phosphate dehydrogenase... 

Figure 18.5 The glycerol-3-phosphate shuttle. This shuttle is used to bring electrons from cytosolic NADH into mitochondria. The mitochondrial glycerol-3-phosphate dehydrogenase with its FAD prosthetic group is bound to the inner mitochondrial membrane. ETF is electron transfer flavoprotein, which extracts electrons from the FADH2 of mitochondrial glycerol-3-phosphate dehydrogenase and with it reduces ubiquinone (UQ).

Muscle tissue contains two glycerol-3-phosphate dehydrogenases a cytosolic enzyme, which uses NADH, and a flavin-nucleotide-dependent mitochondrial enzyme. What is the metabolic significance of these two enzymes ... 

Nguyen, N.H., Brathe, A., Hassel, B. (2003). Neuronal uptake and metabolism of glycerol and the neuronal expression of mitochondrial glycerol-3-phosphate dehydrogenase. J. Neurochem. 85 831-42. 

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.

If glycerol 3-phosphate dehydrogenase is embedded in inner mitochondrial membrane, e- passed to ubiquinone. 

Brown, L., MacDonald, M., Lehn, D., and Moran, S. M. (1994]. Sequence of rat mitochondrial glycerol-3 phosphate dehydrogenase cDNA. /. Bioi. Chem. 269,14363-14366. 

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