Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.5.3 (complex I)
8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane-bound quinoprotein glucose dehydrogenase (GDH) in Escherichia coli donates electrons directly to ubiquinone during the oxidation of d-glucose as a substrate, and these electrons are subsequently transferred to ubiquinol oxidase in the respiratory chain. To determine whether the specific ubiquinone-reacting site of GDH resides in the N-terminal transmembrane domain or in the large C-terminal periplasmic catalytic domain (cGDH), we constructed a fusion protein between the signal sequence of beta-lactamase and cGDH. This truncated GDH was found to complement a GDH gene-disrupted strain in vivo. The signal sequence of the fused protein was shown to be cleaved off, and the remaining cGDH was shown to be recovered in the membrane fraction, suggesting that cGDH has a membrane-interacting site that is responsible for binding to membrane, like peripheral proteins. Kinetic analysis and reconstitution experiments revealed that cGDH has ubiquinone reductase activity nearly equivalent to that of the wild-type GDH. Thus, it is likely that the C-terminal periplasmic domain of GDH possesses a ubiquinone-reacting site and transfers electrons directly to ubiquinone.
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PMID:C-terminal periplasmic domain of Escherichia coli quinoprotein glucose dehydrogenase transfers electrons to ubiquinone. 1160

This work was focused on distinguishing the contribution of mitochondrial redox complexes to the production of reactive oxygen species (ROS) during cellular respiration. We were able to accurately measure, for the first time, the basal production of ROS under uncoupled conditions by using a very sensitive method, based on the fluorescent probe dichlorodihydrofluorescein diacetate. The method also enabled the detection of the ROS generated by the oxidation of the endogenous substrates in the mitochondrial preparations and could be applied to both mitochondria and live cells. Contrary to the commonly accepted view that complex III (ubiquinol:cytochrome c reductase) is the major contributor to mitochondrial ROS production, we found that complex I (NADH-ubiquinone reductase) and complex II (succinate-ubiquinone reductase) are the predominant generators of ROS during prolonged respiration under uncoupled conditions. Complex II, in particular, appears to contribute to the basal production of ROS in cells.
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PMID:The contribution of mitochondrial respiratory complexes to the production of reactive oxygen species. 1176 48

Propionic and methylmalonic acidemic patients have severe neurologic symptoms whose etiopathogeny is still obscure. Since increase of lactic acid is detected in the urine of these patients, especially during metabolic decompensation when high concentrations of methylmalonate (MMA) and propionate (PA) are produced, it is possible that cellular respiration may be impaired in these individuals. Therefore, we investigated the effects of MMA and PA (1, 2.5 and 5mM), the principal metabolites which accumulate in these conditions, on the mitochondrial respiratory chain complex activities succinate: 2,6-dichloroindophenol (DCIP) oxireductase (complex II); succinate: cytochrome c oxireductase (complexII+CoQ+III); NADH: cytochrome c oxireductase (complex I+CoQ+complex III); and cytochrome c oxidase (COX) (complex IV) from cerebral cortex homogenates of young rats. The effect of MMA on ubiquinol: cytochrome c oxireductase (complex III) and NADH: ubiquinone oxireductase (complex I) activities was also tested. Control groups did not contain MMA and PA in the incubation medium. MMA significantly inhibited complex I+III (32-46%), complex I (61-72%), and complex II+III (15-26%), without affecting significantly the activities of complexes II, III and IV. However, by using 1mM succinate in the assay instead of the usual 16mM concentration, MMA was able to significantly inhibit complex II activity in the brain homogenates. In contrast, PA did not affect any of these mitochondrial enzyme activities. The effect of MMA and PA on succinate: phenazine oxireductase (soluble succinate dehydrogenase (SDH)) was also measured in mitochondrial preparations. The results showed significant inhibition of the soluble SDH activity by MMA (11-27%) in purified mitochondrial fractions. Thus, if the in vitro inhibition of the oxidative phosphorylation system is also expressed under in vivo conditions, a deficit of brain energy production might explain some of the neurological abnormalities found in patients with methylmalonic acidemia (MMAemia) and be responsible for the lactic acidemia/aciduria identified in some of them.
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PMID:Inhibition of the mitochondrial respiratory chain complex activities in rat cerebral cortex by methylmalonic acid. 1190 Aug 54

Cytokine-mediated regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) non-hypoxic stabilization, translocation and activation is not well characterized. Furthermore, evidence that reactive oxygen species (ROS) signaling mediates interleukin (IL)-1 beta-dependent regulation of HIF-1 alpha has yet to be ascertained in alveolar epithelial cells. Recombinant human IL-1 beta induced, in a time-dependent manner, the nuclear translocation of HIF-1 alpha, an effect associated with up-regulating the activity of this transcription factor under normoxic conditions. In addition, analysis of the mode of action of IL-1 beta revealed a novel induction of intracellular ROS, including hydrogen peroxide (H(2)O(2)), the superoxide anion (O(2)(-*)) and the hydroxyl radical (*OH). The antioxidants, dimethyl sulfoxide (DMSO) and 1,3-dimethyl-2-thiourea (DMTU), purported to be prototypical scavengers of H2O2 and *OH, attenuated, in a dose-dependent manner, IL-1 beta-induced HIF-1 alpha nuclear translocation and activation. The NADPH-oxidase inhibitor, 4'-hydroxy-3'-methoxy-acetophenone (HMAP), which may affect mitochondrial ROS production, attenuated IL-1 beta-mediated nuclear translocation and activation of HIF-1 alpha. Inhibition of the mitochondrion complex I nicotinamide adenine dinucleotide phosphate-dependent oxidase by diphenylene iodonium (DPI), which blocks the conversion of ubiquinone --> ubiquinol, abrogated IL-1 beta-dependent nuclear translocation and activation of HIF-1 alpha. Similarly, interrupting the respiratory chain with potassium cyanide reversed the excitatory effect of IL-1 beta on HIF-1 alpha nuclear translocation and activation. These results indicate that a non-hypoxic pathway mediates cytokine-dependent regulation of HIF-1 alpha translocation and activation in a ROS-sensitive mechanism.
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PMID:Recombinant human interleukin (IL)-1 beta-mediated regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) stabilization, nuclear translocation and activation requires an antioxidant/reactive oxygen species (ROS)-sensitive mechanism. 1210 Oct 82

The selenoprotein thioredoxin reductase (TrxR1) is an essential antioxidant enzyme known to reduce many compounds in addition to thioredoxin, its principle protein substrate. Here we found that TrxR1 reduced ubiquinone-10 and thereby regenerated the antioxidant ubiquinol-10 (Q10), which is important for protection against lipid and protein peroxidation. The reduction was time- and dose-dependent, with an apparent K(m) of 22 microm and a maximal rate of about 12 nmol of reduced Q10 per milligram of TrxR1 per minute. TrxR1 reduced ubiquinone maximally at a physiological pH of 7.5 at similar rates using either NADPH or NADH as cofactors. The reduction of Q10 by mammalian TrxR1 was selenium dependent as revealed by comparison with Escherichia coli TrxR or selenium-deprived mutant and truncated mammalian TrxR forms. In addition, the rate of reduction of ubiquinone was significantly higher in homogenates from human embryo kidney 293 cells stably overexpressing thioredoxin reductase and was induced along with increasing cytosolic TrxR activity after the addition of selenite to the culture medium. These data demonstrate that the selenoenzyme thioredoxin reductase is an important selenium-dependent ubiquinone reductase and can explain how selenium and ubiquinone, by a combined action, may protect the cell from oxidative damage.
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PMID:The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. 1243 34

Enzymes in the mitochondrial respiratory chain are involved in various physiological events in addition to their essential role in the production of ATP by oxidative phosphorylation. The use of specific and potent inhibitors of complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c reductase), such as rotenone and antimycin, respectively, has allowed determination of the role of these enzymes in physiological processes. However, unlike complexes I, III, and IV (cytochrome c oxidase), there are few potent and specific inhibitors of complex II (succinate-ubiquinone reductase) that have been described. In this article, we report that atpenins potently and specifically inhibit the succinate-ubiquinone reductase activity of mitochondrial complex II. Therefore, atpenins may be useful tools for clarifying the biochemical and structural properties of complex II, as well as for determining its physiological roles in mammalian tissues.
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PMID:Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase). 1251 59

We show here sodium ion cycling between complex I from Klebsiella pneumoniae and the F(1)F(0) ATP synthase from Ilyobacter tartaricus in a reconstituted proteoliposome system. In the course of NADH oxidation by complex I, an electrochemical sodium ion gradient was established and served as a driving force for the synthesis of ATP from ADP and phosphate. In the opposite direction, the deltamu(Na(+)) generated by ATP hydrolysis could be coupled to NADH formation by reversed electron transfer from ubiquinol to NAD. For reverse electron transfer, a transmembrane voltage larger than 30 mV was obligatory. No NADH-driven proton transport into the lumen of proteoliposomes was detected. We conclude that Na(+) is used as the exclusive coupling ion by the enterobacterial complex I.
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PMID:Sodium ion cycling mediates energy coupling between complex I and ATP synthase. 1255 38

It has recently been shown that cyanide-resistant respiration (CRR) is very common in Crabtree-negative yeasts (incapable of aerobic fermentation) and in non-fermentative yeasts. It is conferred by a salicylhydroxamic acid-sensitive alternative oxidase that transfers electrons from ubiquinol to oxygen, bypassing the cytochrome chain. An interesting finding is that, in general, whenever CRR is present, complex I is also present. In this article we briefly review the occurrence of CRR, the biochemistry and molecular biology of the alternative oxidase, and summarise the putative functions that have been attributed to this ubiquitous metabolic pathway, whose usefulness for the yeast cells still remains obscure.
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PMID:Cyanide-resistant respiration, a very frequent metabolic pathway in yeasts. 1268 32

Pure mitochondria of the photosynthetic alga Chlamydomonas reinhardtii were analyzed using blue native-polyacrylamide gel electrophoresis (BN-PAGE). The major oxidative phosphorylation complexes were resolved: F(1)F(0)-ATP synthase, NADH-ubiquinone oxidoreductase, ubiquinol-cytochrome c reductase, and cytochrome c oxidase. The oligomeric states of these complexes were determined. The F(1)F(0)-ATP synthase runs exclusively as a dimer, in contrast to the C. reinhardtii chloroplast enzyme, which is present as a monomer and subcomplexes. The sequence of a 60-kD protein, associated with the mitochondrial ATP synthase and with no known counterpart in any other organism, is reported. This protein may be related to the strong dimeric character of the algal F(1)F(0)-ATP synthase. The oxidative phosphorylation complexes resolved by BN-PAGE were separated into their subunits by second dimension sodium dodecyl sulfate-PAGE. A number of polypeptides were identified mainly on the basis of their N-terminal sequence. Core I and II subunits of complex III were characterized, and their proteolytic activities were predicted. Also, the heterodimeric nature of COXIIA and COXIIB subunits in cytochrome c oxidase was demonstrated. Other mitochondrial proteins like the chaperone HSP60, the alternative oxidase, the aconitase, and the ADP/ATP carrier were identified. BN-PAGE was also used to approach the analysis of the major chloroplast protein complexes of C. reinhardtii.
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PMID:Identification of novel mitochondrial protein components of Chlamydomonas reinhardtii. A proteomic approach. 1274 37

A project to systematically investigate respiratory supercomplexes in plant mitochondria was initiated. Mitochondrial fractions from Arabidopsis, potato (Solanum tuberosum), bean (Phaseolus vulgaris), and barley (Hordeum vulgare) were carefully treated with various concentrations of the nonionic detergents dodecylmaltoside, Triton X-100, or digitonin, and proteins were subsequently separated by (a) Blue-native polyacrylamide gel electrophoresis (PAGE), (b) two-dimensional Blue-native/sodium dodecyl sulfate-PAGE, and (c) two-dimensional Blue-native/Blue-native PAGE. Three high molecular mass complexes of 1,100, 1,500, and 3,000 kD are visible on one-dimensional Blue native gels, which were identified by separations on second gel dimensions and protein analyses by mass spectrometry. The 1,100-kD complex represents dimeric ATP synthase and is only stable under very low concentrations of detergents. In contrast, the 1,500-kD complex is stable at medium and even high concentrations of detergents and includes the complexes I and III(2). Depending on the investigated organism, 50% to 90% of complex I forms part of this supercomplex if solubilized with digitonin. The 3,000-kD complex, which also includes the complexes I and III, is of low abundance and most likely has a III(4)I(2) structure. The complexes IV, II, and the alternative oxidase were not part of supercomplexes under all conditions applied. Digitonin proved to be the ideal detergent for supercomplex stabilization and also allows optimal visualization of the complexes II and IV on Blue-native gels. Complex II unexpectedly was found to be composed of seven subunits, and complex IV is present in two different forms on the Blue-native gels, the larger of which comprises additional subunits including a 32-kD protein resembling COX VIb from other organisms. We speculate that supercomplex formation between the complexes I and III limits access of alternative oxidase to its substrate ubiquinol and possibly regulates alternative respiration. The data of this investigation are available at http://www.gartenbau.uni-hannover.de/genetik/braun/AMPP.
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PMID:New insights into the respiratory chain of plant mitochondria. Supercomplexes and a unique composition of complex II. 1297 Apr 93


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