Ubiquinone reductase

NADH-ubiquinone reductase) and the second one was complex II (succinate-ubiquinone reductase). Chiesi and Schwaller [101] found that quercetin and tannin inhibited neuronal constitutive endothelial NO synthase. 

This mechanism is now considered to be of importance for the protection of LDL against oxidation stress, Chapter 25.) The antioxidant effect of ubiquinones on lipid peroxidation was first shown in 1980 [237]. In 1987 Solaini et al. [238] showed that the depletion of beef heart mitochondria from ubiquinone enhanced the iron adriamycin-initiated lipid peroxidation whereas the reincorporation of ubiquinone in mitochondria depressed lipid peroxidation. It was concluded that ubiquinone is able to protect mitochondria against the prooxidant effect of adriamycin. Inhibition of in vitro and in vivo liposomal, microsomal, and mitochondrial lipid peroxidation has also been shown in studies by Beyer [239] and Frei et al. [240]. Later on, it was suggested that ubihydroquinones inhibit lipid peroxidation only in cooperation with vitamin E [241]. However, simultaneous presence of ubihydroquinone and vitamin E apparently is not always necessary [242], although the synergistic interaction of these antioxidants may take place (see below). It has been shown that the enzymatic reduction of ubiquinones to ubihydroquinones is catalyzed by NADH-dependent plasma membrane reductase and NADPH-dependent cytosolic ubiquinone reductase [243,244]. 

Deficiency of electron transport flavoprotein or of ETF ubiquinone reductase Biotinidase... 

In the hydrogenosomal membranes, EPR spectra showed no trace of the highly characteristic features of the iron-sulfur clusters of complex I (NADH ubiquinone reductase) and the Rieske protein of complex III of the mitochondrial respiratory chain. This is consistent with the absence of... 

I NADH ubiquinone reductase 8 X 10 FMN, Fe-S protein NADH ubiquinol (QH2)... 

NADH dehydrogenase (ubiquinone) [EC 1.6.5.3] (also called ubiquinone reductase, type I dehydrogenase, and complex I dehydrogenase) catalyzes the reaction of NADH with ubiquinone to produce NAD and ubiqui-nol. The complex, which uses EAD and iron-sulfur proteins as cofactors, is found in mitochondrial membranes and can be degraded to form NADH dehydrogenase [EC... 

H. Ueno, H. Miyoshi, K. Ebisui, H. Iwamura, Comparison of the inhibitory action of natural rotenone and its stereoisomers with various NADH-ubiquinone reductases, Eur. J. Biochem. 225 (1994) 411-417. 

The Tte of the 3Fe-4S centre in succinate ubiquinone reductase between 4 and 8 K is decreased by interaction with paramagnetic cytochrome b.98 To mitigate the impact of spectral diffusion the relaxation times were measured by a picket-fence sequence with 100 pulses. Analysis of the powder pattern distribution of relaxation times indicated that the anisotropic dipolar interaction dominated over isotropic scalar interaction and a lower limit of 10 A was estimated for the distance between the iron-sulfur cluster and the heme. 

Ahammadsahib, K.I., Hollingworth, R.M., McGovren, P.J., Hui, Y.-H., and McLaughlin, J.L. Inhibition of NADH ubiquinone reductase (mitochondrial complex I) by bullatacin, a potent antitumor and pesticidal Annonaceous acetogenin. Life Sci., 53, 1113, 1993. 

Both the presence of methyl substituents in the tocopherols and their chromanol structures increase the ability of these compounds to form relatively stable radicals.498 499 This ability is doubtless probably important also in the function of ubiquinones and plastoquinones. Ubiquinone radicals (semiquinones) are probably intermediates in mitochondrial electron transport (Chapter 18) and radicals amounting to as much as 40% of the total ubiquinone in the NADH-ubiquinone reductase of heart mito-... 

Two instructive examples of the use of phospholipid reagents are the labeling of succinate-ubiquinone reductase (complex II) (Girdlestone et al., 1981) and the labeling of glycophorin A (Ross et al., 1982). 

Piericidins are the first compounds obtained by the screening search for insecticidal natural products among microbial metabolites.10 They were isolated from Streptomyces mobaraensis in 1963,11 and many piericidin derivatives have been found in microbial metabolites until now.12 Piericidins are not used as insecticides practically, but are important biological reagents because they have specific inhibitory activity toward the mitochondrial electron transport chain protein nicotinamide adenine dinucleotide (NADH)-ubiquinone reductase (complex I).13 Piericidin Ax (1 in Figure 1) is biosynthesized as a polyketide,14 but genes responsible for its biosynthesis are not yet identified. Total synthesis of piericidins A (1) was reported recently.15... 

It is also of considerable interest thatNADH-ubiquinone reductase (Complex 1) is reported to be significantly reduced in the substantia nigra of PD patients (S6). Importantly, this biochemical defect is the same as that produced in animal models by l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (see below). 

Preparations of NADH dehydrogenase from mammalian mitochondria may be divided into three types (1) NADH-ubiquinone reductase or complex I of the electron transport system, (2) the high molecular weight NADH dehydrogenases, and (3) the low molecular weight NADH dehy-... 

NADH-ubiquinone reductase was isolated by Hatefi et al. in 1961 (27-B9). A procedure was developed for the resolution of the mitochondrial electron transport system into four enzyme complexes. Recently, a fifth fraction, which is capable of energy conservation and ATP-Pi exchange, was also isolated (30, 31). The overall scheme for the isolation of the five component enzyme complexes of the mitochondrial electron transport-oxidative phosphorylation system is given in Fig. 1. It is seen... 

It has been shown by Ragan and Racker (36) that phospholipids are necessary for the ubiquinone, but not the ferricyanide, reductase activity of complex I. Thus, removal of about 50% of complex I lipids by extraction with cholate under special conditions resulted in a reversible loss of ubiquinone reductase activity without affecting the ferricyanide reductase activity. More phosphatidylcholine and phosphatidylethanolamine were removed by this procedure than cardiolipin. Readdition of either phosphatidylcholine or phosphatidylethanolamine restored considerable rotenone-sensitive ubiquinone-1 reductase activity, which was further augmented when small amounts of cardiolipin were also added. Using preparations depleted of ubiquinone-10 by pentane extraction, these authors have also shown that enzyme-bound ubiquinone-10 is not necessary for the reduction of added ubliquinone-1 by complex I or the inhibition of this reaction by rotenone. 

The ubiquinone reductase activity of their low molecular weight dehydrogenase led Pharo et al. (64, 75) to conclude that the enzyme represented the mitochondrial NADH-ubiquinone reductase. However, it has been shown that the quinone reductase activity of the low molecular weight dehydrogenase is different from that of intact respiratory particles or complex I in many important respects, including kinetic constants, re-... 

As stated above, the low molecular weight NADH dehydrogenase of Pharo et al. (64) was considered incorrectly to be the NADH-ubiquinone reductase of the respiratory chain. This was in part because the ubiquinone reductase activity of the preparation could be partially inhibited by Amytal and by very low concentations of rotenone. It was demonstrated by others that these effects were different from the inhibitions... 

It has been shown recently that the mitochondrial electron transport system contains at least three different fe-type cytochromes 178). Two of these cytochromes are found in complex III, and under appropriate conditions are reducible with substrates. The third 6-type cytochrome was discovered by Davis et al. 178), and shown to fractionate exclusively into complex II. At 77°K, the cytochrome 6 of complex II exhibits a double a band at 557.5 and 550 nm, a prominent band at 531 nm, and a Soret band at 422 nm (Fig. 29). Cytochrome 6557.5 appears to have a low reduction potential. It is not detectably reduced by succinate in either complex II or respiratory particles, but its dithionite reduced form is rapidly oxidized by either fumarate or ubiquinone. The role of this cytochrome in mammalian mitochondria is not known. Davis et al. 178) have suggested that it might be an electron entry point for an unknown ancillary tributary of the respiratory chain. Further, Bruni and Racker 179) have shown that a preparation of cytochrome 6 is required for reconstitution of succinate-ubiquinone reductase activity (see below). 

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