NADH quinone oxidoreductase

Yano T (2002) The energy-transducing NADH quinone oxidoreductase, complex I. Mol Asp Med 23 345-368... 

Yagi, T., and Matsuno-Yagi, A. 2003. The proton-translocating NADH-quinone oxidoreductase in the respiratory chain The secret unlocked, Biochemistry 42 2266-2274. 

Yagi, T., Inhibition by capsaicin of NADH-quinone oxidoreductases is correlated with the presence of energy-coupling site 1 in various organisms. Arch. Biochem. Biophys., 281, 305, 1990. 

Shimada, H. Hirai, K. Simamura, E. Pan, J. Mitochondrial NADH-quinone oxidoreductase of the outer membrane is responsible for paraquat cytotoxicity in rat livers. Arch. Biochem. Biophys. 1998, 351, 75-81. 

Constam, D., Muheim, A., Zinunermaim, W., Fiechter, A. (1991). Purification and characterization of an intracellular NADH quinone oxidoreductase from Phanero-chaete chrysosporium. J. Gen. Microbial. 137,2209-2214. 

The electron carriers in the respiratory assembly of the inner mitochondrial membrane are quinones, flavins, iron-sulfur complexes, heme groups of cytochromes, and copper ions. Electrons from NADH are transferred to the FMN prosthetic group of NADH-Q oxidoreductase (Complex I), the first of four complexes. This oxidoreductase also contains Fe-S centers. The electrons emerge in QH2, the reduced form of ubiquinone (Q). The citric acid cycle enzyme succinate dehydrogenase is a component of the succinate-Q reductase complex (Complex II), which donates electrons from FADH2 to Q to form QH2.This highly mobile hydrophobic carrier transfers its electrons to Q-cytochrome c oxidoreductase (Complex III), a complex that contains cytochromes h and c j and an Fe-S center. This complex reduces cytochrome c, a water-soluble peripheral membrane protein. Cytochrome c, like Q, is a mobile carrier of electrons, which it then transfers to cytochrome c oxidase (Complex IV). This complex contains cytochromes a and a 3 and three copper ions. A heme iron ion and a copper ion in this oxidase transfer electrons to O2, the ultimate acceptor, to form H2O. 

Special electron carriers ferry the electrons from one complex to the next. Electrons are carried from NADH-Q oxidoreductase to Q-cytochrome c oxidoreductase, the second complex ot the chain, by the reduced form of coeti2 ymt2 Q (Q), also known as ubiquinone because it is a ubiquitous quinone in biological systems. Ubiquinone is a hydrophobic quinone that diffuses rapidly within the inner mitochondrial membrane. Cytochrome c. a small soluble protein, shuttles electrons from Q-cytochrome c oxidoreductase to cytochrome c oxidase, the final component in the chain and the one that catalyses the reduction of Oi. Electrons from the FADH generated bv... 

Studies on metabolic stability using hepatocyte suspensions are not feasible for automation/HTS, but these studies do provide rather complete profiles of hepatic biotransformation without the supplements of cofactors and cosubstrates. The use of S9 in metabolic stability studies can be evaluated in a manner similar to that used for the microsomal assays, but with the possible addition of a broader panel of cofactors or cosubstrates. These include NADPH for CYP/FMO-mediated reactions, NADH for xanthine oxidoreductase and quinone oxidoreductase 2, NADPH-dependent reductions by carbonyl reductases, and NADPH/NADH-dependent reductions catalyzed by aldo-keto reductases, uridine 5 -diphosphate... 

While isolated rat hepatocytes do not hberate appreciable amounts of 02 , simple quinones, such as 2,5-dimethyl-p-benzoquinone stimulate the formation of O2 up to 15 nmoles per min and 10 cells (Powis et al. 1981). Hepatocyte 02 formation stimulated by a variety of simple quinones and more complex antitumor quinones is maximal at a qui-none one-electron reduction potential (E, ) of -70 mV and quahtatively similar to the pattern of 02 formation seen with mitochondrial NADH ubi-quinone oxidoreductase and microsomal NADH-cytochrome bs reductase. 02 production, by microsomal NADPH-cytochrome P-450 reductase is maximal at a quinone E of -200 mV. Phenobarbital induction, which increases NADPH-cytochrome P-450 reductase, had no effect on O2 formation by hepatocytes. 

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). 

The second step in nitrification is the oxidation of nitrite to nitrate and is catalyzed by the enzyme nitrite oxidoreductase (NOR) (Eq. 3). In this reaction, the oxygen atom is derived from water. NOR is located in the cytoplasmic membrane and is composed of cytochromes a and c, a quinone and a deshydrogenase dependent on NADH (Aleem Sewel, 1981 Spieck... 

Besides the permselective properties, the electrocatalytic properties of ECP films can be also used for the amperometric detection of some target molecules. Accordingly, electrodes modified with PPy, polythiophene (PTh), PAni, and their derivatives were found to catalyze the electrochemical oxidation of ascorbic acid [127-129], NADH [115, 116,130], dopamine [128], pyrrolo-quinoline quinone [131] as a coenzyme of some oxidoreductases, and quinone and derivatives [132, 133]. Selectivity exhibited by these materials could be enhanced by the introduction of an appropriate substituent onto the polymer backbone. So, a facilitated electron transfer between cytochrome c and carboxylic acid or carboxylate-substituted PPy [134] or polyindole [135] has been observed. As such an effect was not obtained with unsubstituted polymer films, the cytochrome c-polymer interaction was e lained on the basis of binding between the polymer substituents and the lysine residues on the redox protein. 

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