Electron transfer flavoprotein transport chain

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. 

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.)...

A distinct electron transfer flavoprotein (ETF) is the single-electron acceptor for a variety of flavoprotein dehydrogenases, including acyl CoA, glutaryl CoA, sarcosine, and dimethylglycine dehydrogenases. It then transfers the electrons to ETF-ubiquinone reductase, the iron-sulfur flavoprotein that reduces ubiquinone in the mitochondrial electron transport chain. 

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. 

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-...

Most compounds oxidized by the electron transport chain donate hydrogen to NAD+, and then NADH is reoxidized in a reaction coupled to reduction of a flavoprotein. During this transformation, sufficient energy is released to enable synthesis of ATP from ADP. The reduced flavoprotein is reoxidized via reduction of coenzyme Q subsequent redox reactions then involve cytochromes and electron transfer processes rather than hydrogen transfer. In two of these cytochrome redox reactions, there is sufficient energy release to allow ATP synthesis. In... 

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... 

The system depends on an electron transport pathway that transfers electrons from NADPH through a flavoprotein (NADPH cytochrome P-450 reductase) to cytochrome P-450 that is the terminal oxidase of the chain (10). The xenobiotic first forms a complex with the oxidized form o cytochrome P-450 which is reduced by an electron passing down the chain from NADPH. The reduced cytochrome P-450/substrate complex then reacts with and activates molecular oxygen to an electrophilic oxene species (an electron deficient species similar to singlet oxygen) that is transferred to the substrate with the concommitant formation of water. Cytochrome P-450 thus acts primarily as an oxene transferase (2). Substrate binding is a relatively nonspecific, passive process that serves to bring the xenobiotic into close association with the active center and provide the opportunity for the oxene transfer to occur. 

Flavoproteins catalyzing single -electron transfer provide the link between substrate oxidation catalyzed by dehydrogenases and the mitochondrial electron transport chain. 

The answer is d. (Murray, pp 123—148. Scriver, pp 2367—2424. Sack, pp 159—175. Wilson, pp 287-317.) Some monooxygenases found in liver endoplasmic reticulum require cytochrome P450. This cytochrome acts to transfer electrons between NADPH, O2, and the substrate. It can be an electron acceptor from a flavoprotein. In the mitochondrial electron transport chain, flavoproteins donate electrons to coenzyme Q, which then transfers them to other cytochromes. Flavoproteins that are oxidases often react directly with molecular oxygen to form hydrogen peroxide. Flavoproteins can be NADH dehydrogenases that oxidize NADH and transfer the electrons to coenzyme Q. The electron transfer centers of flavoproteins in the electron transport chain contain nonheme iron and sulfur. 

Electron transfer flavins, ETF flavoproteins (see Flavin enzymes) which mediate electron transport from reduced FADH to the cytochrome system. Flavoproteins oxidize those substrates of the Respiratory chain (see) whose oxidation does not involve pyridine nucleotides. However, the substrate must have a more positive redox potential than the NADH -I- H /NAD system. ETF from pork liver has 6 molecules flavin per atom of iron, and copper is also present. 

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