Electron transfer flavoprotein

FeS Iron-sulfur protein ETF Electron-transferring flavoprotein Ep Elavoprotein Q Ubiquinone Cyt Cytochrome... 

Ma, Y.C., Funk, M., Dunham, W.R. and Komuniecki, R. (1993) Purification and characterization of electron-transfer flavoprotein rhodoquinone oxidoreduc-tase from anaerobic mitochondria of anaerobic mitochondria of the adult parasitic nematode, Ascaris suum. Journal of Biological Chemistry 268, 20360-20365. 

Glutaric acidurias Type I Primary defect of glutarate oxidation Type II Defect of electron transfer flavoprotein Type I Severe basal ganglia/cerebellar disease with macrocephaly. Onset 1-2 years Type II Fulminant neurological syndrome of the neonate. Often with renal/hepatic cysts. Usually fatal Diet low in lysine and tryptophan Supplementation with coenzyme Q, riboflavin, carnitine... 

This enzyme [EC 1.3.99.13] catalyzes the reaction of a long-chain acyl-CoA with an electron-transferring fla-voprotein to produce a 2,3-dehydroacyl-CoA and the reduced electron-transferring flavoprotein. 

Table 3.2.5 Disorders detectable by the in vitro probe assay. ETF Electron transfer flavoprotein, MADD multiple acyl-CoA dehydrogenase deficiency...

The oxidation of fatty acids is catalyzed by the FAD-containing acyl coenzyme A dehydrogenases which transfer reducing equivalents to the mitochondrial respiratory chain via a flavin-containing electron transfer flavoprotein (ETF) and subsequently via an ETF dehydrogenase (an Fe/S flavoprotein In addition to the mammalian... 

Some electrons enter this chain of carriers through alternative paths. Succinate is oxidized by succinate dehydrogenase (Complex II), which contains a flavoprotein that passes electrons through several Fe-S centers to ubiquinone. Electrons derived from the oxidation of fatty acids pass to ubiquinone via the electron-transferring flavoprotein. 

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...

As described before, also the formation of branched-chain fatty acids by enoyl-CoA reductase activity is coupled to electron transport (Komuniecki and Harris 1995). In this case electrons are transported from NADH to rhodoquinone via complex I and subsequently to the electron-transfer flavoprotein (ETF) via ETF-reductase (Fig. 5.3). The soluble, non-membrane-bound ETF then transfers electrons to enoyl-CoA reductase, which uses the electrons for the condensation of two short-chain (C2-C3) acyl-CoA moieties for the formation of branched-chain fatty acids. 

Komuniecki R, McCrury J, Thissen J, Rubin N (1989) Electron-transfer flavoprotein from anaerobic Ascaris suum mitochondria and its role in NADH-dependent 2-methyl branched-chain enoyl-CoA reduction. Biochim Biophys Acta 975 127-131 Komuniecki R, Harris BG (1995) Carbohydrate and energy metabolism in helminths. In Marr JJ, Muller M (eds) Biochemistry and molecular biology of parasites. Academic, London, pp 49-66... 

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.)...

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).

Because reduced redox cofactors, NADH and FADH2, are produced in the mitochondria, there is no need for shuttle mechanisms to reoxidize them via oxidative phosphorylation. NADH is reduced directly by complex I. FADH2 is reduced by the electron transfer flavoprotein, which then reduces ubiquinone. See Chapter 17 for details. 

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