Electron transfer flavoprotein oxidoreductase

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. 

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. 

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. 

Ma, Y., Funk. M., Dunham, W. and Komuniecki, R. (1993) Purification and characterization of electron-transfer flavoprotein rhodoquinone oxidoreductase from anaerobic mitochondria of the adult parasitic nematode, Ascaris suum. J. Biol. Chem. 268 20360-20365. 

Like the FAD in all flavoproteins, FAD(2H) bound to the acyl CoA dehydrogenases is oxidized back to FAD without dissociating from the protein (Fig. 23.8). Electron transfer flavoproteins (RTF) in the mitochondrial matrix accept electrons from the enzyme-bound FAD(2H) and transfer these electrons to ETF-QO (electron transfer flavoprotein -CoQ oxidoreductase) in the inner mitochondrial membrane. ETF-QO, also a flavoprotein, transfers the electrons to CoQ in the electron transport chain. Oxidative phosphorylation thus generates approximately 1.5 ATP for each FAD(2H) produced in the (3-oxidation spiral. 

Fig. 23.8. Transfer of electrons from acyl CoA dehydrogenase to the electron transport chain. Abbreviations ETF, electron-transferring flavoprotein ETF-QO, electron-transferring flavoprotein-Coenzyme Q oxidoreductase.

Fig. 13.1.1. Schematic overview of mitochondrial oxidative phosphorylation. A part of the mitochondrion is represented, showing the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM) and crista (an invagination of the inner membrane). Substrates for oxidation enter the mitochondrion through specific carrier proteins, e.g., the pyruvate transporter, (PyrT). Reducing equivalents from fatty acyl CoA dehydrogenases, pyruvate dehydrogenase and the TCA cycle are delivered to the electron transport chain through NADH, succinate ubiquinol oxidoreductase (SQO), electron transfer flavoprotein (ETF) and its ubiquinol-...

FIGURE 9.2 Physiology of ABE fermentation metabolism of Clostridium acetobutylicum with the respective enzymes and products. CoA, coenzyme A Ldh, lactate dehydrogenase Pdc, pyruvate decarboxylase Pfor, pyruvate ferredoxin oxidoreductase Fdred, ferredoxin reduced Thl, thiolase Hbd, p-hydroxybutyryl-CoA dehydrogenase Crt, crotonase Bed, butyryl-CoA dehydrogenase Etf, electron transfer flavoprotein Pta, phosphotransacetylase Ack, acetate kinase Ptb, phosphotransbutyrylase Buk, butyrate kinase Ctf A/B, acetoacetyl-CoA acyl-CoA transferase Adc, acetoacetate decarboxylase AdhE, aldehyde/alcohol dehydrogenase Bdh, butanol dehydrogenase. 

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. 

NADH-coenzyme Q (CoQ) oxidoreductase, transfers electrons stepwise from NADH, through a flavoprotein (containing FMN as cofactor) to a series of iron-sulfur clusters (which will be discussed in Chapter 13) and ultimately to CoQ, a lipid-soluble quinone, which transfers its electrons to Complex III. A If, for the couple NADH/CoQ is 0.36 V, corresponding to a AG° of —69.5 kJ/mol and in the process of electron transfer, protons are exported into the intermembrane space (between the mitochondrial inner and outer membranes). 

Capeillere-Blandin, C., Barber, M. J., Bray, R. C. Differences in electron transfer rates among prosthetic groups between two homologous flavocytochrome b2 (L-lactate cytochrome c oxidoreductase) from different yeasts. In Flavins and flavoproteins (Massey, V., Williams, C. H. eds.) pp. 838-843, New York, Amsterdam, Oxford, Elsevier/North Holland 1982... 

Another flavoprotein that makes use of both one-and two-electron transfer reactions is ferredoxin-NADP+ oxidoreductase (Eq. 15-28). Its bound FAD accepts electrons one at a time from each of the two... 

The Z scheme. [(Mn)4 = a complex of four Mn atoms bound to the reaction center of photosystem II Yz = tyrosine side chain Phe a = pheophytin a QA and Qb = two molecules of plastoquinone Cyt b/f= cytochrome hf,f complex PC = plastocyanin Chi a = chlorophyll a Q = phylloquinone (vitamin K,) Fe-Sx, Fe-SA, and Fe-SB = iron-sulfur centers in the reaction center of photosystem I FD = ferredoxin FP = flavoprotein (ferredoxin-NADP oxidoreductase).] The sequence of electron transfer through Fe-SA and Fe-SB is not yet clear. 

ACP = acyl carrier protein ACPA D = ACPA desat-urase AlkB = octane 1-monooxygenase AOX = alternative oxidase DMQ hydroxylase = 5-demethoxyquinone hydroxylase EXAFS = extended X-ray absorption fine structure spectroscopy FMN = flavin mononucleotide FprA = flavoprotein A (flavo-diiron enzyme homologue) Hr = hemerythrin MCD = magnetic circular dichroism MME hydroxylase = Mg-protophorphyrin IX monomethyl ester hydroxylase MMO = methane monooxygenase MMOH = hydroxylase component of MMO NADH = reduced nicotinamide adenine dinucleotide PAPs = purple acid phosphatases PCET = proton-coupled electron transfer, PTOX = plastid terminal oxidase R2 = ribonucleotide reductase R2 subunit Rbr = rubrerythrin RFQ = rapid freeze-quench RNR = ribonucleotide reductase ROO = rubredoxin oxygen oxidoreductase XylM = xylene monooxygenase. 

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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