Electron transfer flavoprotein: ubiquinone oxidoreductase

J.-J. P. Kim, J. Zhang, and F. E. Frerman, Three-Dimensional Structure of Pocine Electron Transfer Flavoprotein-Ubiquinone Oxidoreductase, in Flavins and Flavoproteins 2002 , eds. S. K. Chapman, R. N. Perham, and N. S. Scrutton, Rudolf Weber, Berlin, 2002, p. 77. 

Figure 37.2 Cartoon depicting enzymes participating in mitochondrial P-oxidation and part of the respiratory chain. Acyl-CoA substrates derived from fatty acid and amino acid metabolism are oxidized by several flavin-containing acyl-CoA dehydrogenases (ACAD). Electrons obtained from this reaction are shuttled to the respiratory chain via the ETF/ETF QO hub (electron-transfer flavoprotein and electron-transfer flavoprotein ubiquinone oxidoreductase). ETF QO is able to transfer electrons to ubiquinone (Q) (such as respiratory complexes I and II) whose subsequent transfer down to complex IV will result in energy conservation and ATP production. See list of abbreviations for definitions.

Figure 37.5 Crystallographic structure of pig electron-transfer flavoprotein ubiquinone oxidoreductase (ETF QO). The flavin and iron-sulfur cluster cofactors, as well as the ubiquinone substrate are shown in white sticks. An amphipatic region of ETF QO establishes interactions with membrane and accommodates the ubiquinone substrate.

Zhang, J., Frerman, F.E., and Kim, J.J., 2006. Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. Proceedings of the National Academy of Sciences of the United States of America. 103 16212-16217. 

Fig. 5.2. Possible metabolic pathways in facultative anaerobic mitochondria. Shaded boxes show components of the electron-transport chain used during hypoxia, open boxes are components used during aerobiosis, and the hatched boxes (complex I and ATP-synthase) are components used under aerobic as well as anaerobic conditions. ASCT acetate succinate CoA-transferase, C cytochrome c, Cl, CIII and CIV complexes I, III and IV of the respiratory chain, CITR citrate, ECR enoyl-CoA reductase (such as present in Ascaris suum), ETF electron-transfer flavoprotein, ETF RQ OR electron-transfer flavoproteimrhodoquinone oxidoreductase, FRD fumarate reductase, FUM fumarate, MAE malate, OXAC oxaloacetate, PYR pyruvate, RQ rhodoquinone, SDH succinate dehydrogenase, SUCC succinate, Succ-CoA succinyl-CoA, TER trans-2-enoyl-CoA reductase (such as present in E. gracilis), UQ ubiquinone...

Figure 17.4 The electron transport chain of mitochondria. Triangles indicate sites of inhibition by various compounds. Cyt, cytochrome ETF, electron transfer flavoprotein. (Reproduced with permission from Moreadith RW, Batshaw ML, Ohnishi T, Kerr D, Knox B, Jackson D, Hruben R, Olson J, Reynafarje B, Lehninger AL. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis J Clin Invest 74 685-697, 1984.)...

The mitochondrial respiratory chain, which contains at least 13 Fe-S clusters (Figure 6), perhaps best illustrates the importance of Fe-S clusters in membrane-bound electron transport. Electrons enter via three principal pathways, from the oxidation of NADH to NAD+ (NADH-ubiquinone oxidoreductase or Complex I) and succinate to fumarate (succinate ubiquinone oxidoreductase or Complex II), and from the /3-oxidation of fatty acids via the electron transferring flavoprotein (ETF-ubiquinone oxidoreductase). All three pathways involve a complex Fe S flavoprotein dehydrogenase, that is, NADH dehydrogenase, succinate dehydrogenase, and ETF dehydrogenase, and in each case the Fe-S clusters mediate electron transfer from the flavin active site to the ubiquinone pool via protein-associated ubiquinone. 

Frerman FE, Goodman SI. Defects of the electron transfer flavoprotein and electron transfer flavopro-tein-ubiquinone oxidoreductase glutaric acidemia type II. In Scriver CR, Beaudet AL, Valle D, Sly WS, Childs B, Kinzler KW, et al, eds. The metabofic molecular bases of inherited disease, 8th ed. New York McGraw-Hill, 2001 2357-65. 

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). 

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