NADH-ubiquinone oxidoreductase

Electrons from NADH, together with two protons, are transferred to ubiquinone to form ubiquinol by complex I (NADH ubiquinone oxidoreductase). Complex I... 

Complexes of the Mitochondrial Electron-Transport Chain Complex I (NADH Ubiquinone Oxidoreductase)... 

Barker CD, Reda T, Hirst J. 2007. The flavoprotein suhcomplex of complex I (NADH ubiquinone oxidoreductase) from bovine heart mitochondria Insights into the mechanisms of NADH oxidation and NAD reduction from protein film voltammetry. Biochemistry 46 3454-3464. 

In the mitochondria, ONOO- can mediate damage to OXPHOS by nitrosylat-ing/oxidizing tyrosine or thiol functional groups, rendering catalytic inactivation of complex I [NADH ubiquinone oxidoreductase], complex II [succinate ubiquinone oxidoreductase] and complex V (FI, FO-ATPase), thereby impeding ETC/ OXPHOS... 

Albracht SPJ, Hedderich R. 2000. Learning from hydrogenases location of a proton pump and of a second FMN in bovine NADH ubiquinone oxidoreductase (complex I) FEBS Lett 485 1-6. 

H. Ueno, H. Miyoshi, M. Inoue, Y. Niidome, H. Iwamura, Structural factors of rotenone required for inhibition of various NADH-ubiquinone oxidoreductases, Biochim. Biophys. Acta 1276 (1996) 195-202. 

In NADH-ubiquinone oxidoreductase, there are several sites for ubiquinone binding, and the semiquinone relaxation times are different at these sites.99Analysis of P1/2 of the CW power saturation curve for the fastest relaxing semiquinone signal, SQnf, gave a distance of 11 A between the semiquinone and iron-sulfur cluster N2. 

Gabaldon T, Rainey D, Huynen MA (2005) Tracing the evolution of a large protein complex in the eukaryotes, NADH ubiquinone oxidoreductase (complex I). J Mol Biol 348 857-870... 

Friedrich, T., VanHeek, P., Leif, H., Ohnishi, T., Forche, E., Kunze, B., Jansen, R., Trowitzsch-Kienast, W., Holfe, G., Reichenbach, H., and Weiss, H. Two binding sites of inhibitors in NADH ubiquinone oxidoreductase (complex I) relationship of one site with the ubiquinone oxido-reductase. Eur. J. Biochem., 219, 691, 1994. 

Brandt, U. (1997) Proton-translocation by membrane-bound NADH ubiquinone-oxidoreductase (complex I) through redoxgated ligand conduction. Biochim Biophys. Acta 1318, 79-91. Advanced discussion of models for electron movement through Complex I. 

NADH-methemoglobin reductase 826 NADH ubiquinone oxidoreductase 788 oxidation by ferricyanide 780 NADP+ (NADP) 507, 765 - 771, 767s, 779 in catalase 853 isolation of 767... 

These complexes are usually named as follows I, NADH-ubiquinone oxidoreductase II, succinate-ubiquinone oxidoreductase III, ubiquinol-cytochrome c oxidoreductase IV, cytochrome c oxidase. The designation complex V is sometimes applied to ATP synthase (Fig. 18-14). Chemical analysis of the electron transport complexes verified the probable location of some components in the intact chain. For example, a high iron content was found in both complexes I and II and copper in complex IV. 

Figure 18-7 Three-dimensional image of bovine NADH-Ubiquinone oxidoreductase (complex I) reconstructed from individual images obtained by electron cyro-microscopy.

Engler M, Anke T, Sterner O, Brandt U (1997) Pterulinic Acid and Pterulone, Two Novel Inhibitors of NADH Ubiquinone Oxidoreductase (Complex I) Produced by a Pterula Species I. Production, Isolation and Biological Activities. J Antibiot 50 325... 

T Yagi, Y Hatefi. Identification of the dicyclohexylcarbodiimide-binding subunit of NADH-ubiquinone oxidoreductase (Complex I). J Biol Chem 263 16150-16155, 1988. 

Oxidation of NADH begins with complex I, also termed NADH dehydrogenase or NADH ubiquinone oxidoreductase. It contains 25 polypeptide chains, flavine mononucleotide (FMN), and several iron-sulfur centers. The function of this complex is to reduce a substance called ubiquinone (UQ or CoQ), whose structure is shown in Figure 17.5. UQ is not protein bound and can move about freely. In the process of reducing UQ, the NADH is oxidized to NAD+. It is now accepted that in complex I, NADH first reduces FMN, and the resulting FMNH2 then transfers its electrons through at least three iron-sulfur centers to UQ. As the electrons pass from NADH to UQ, two to four protons are extruded from the mitochondrial matrix across the inner membrane. 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

NAADP, nicotinic acid adenine dinucleotide 2 -phosphate NAADP-R, nicotinic acid adenine dinucleotide 2 -phosphate receptor nACh-R, nicotinic acetylcholine receptor NADH DH, NADH dehydrogenase NADH/NAD"1", reduced/oxidized nicotinamide adenine dinucleotide NADH-U() OR, NADH-ubiquinone oxidoreductase... 

Kim, S. H., Vlkolinsky, R., Cairns, N., Fountoulakis, M., Lubec, G. (2001e). The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer s disease. 

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. 

Nicolaou K, et al. Combinatorial synthesis of novel and potent inhibitors of NADH ubiquinone oxidoreductase. Chem. Biol. 2000 7 979-992. 

N. Grigorieff. 1998. Three-dimensional structure of bovine NADH ubiquinone oxidoreductase (complex I) at 22 A in ice J. Mol. Biol. 211 1033-1046. (PubMed)... 

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