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)

The involvement of the carboxyl groups in the membrane-anchoring protein (QPs) in reconstitution of succinate dehydrogenase to form succinate-ubiquinone reductase is studied by using a carboxyl group modifying reagent, dicyclohexylcarbodiimide (DCCD). Inactivation of QPs by DCCD is found to be dependent on the temperature, pH, detergent, and DCCD concentration used. When QPs is treated with 300 molar excess DCCD at room temperature for 10 min, about 90% of the original reconstitutive activity is lost. When intact or reconstituted succinate-ubiquinone reductase formed from reconstitutively active succinate dehydrogenase and QPs is treated with DCCD under the same conditions, no loss of succinate-ubiquinone reductase activity is observed. However, when a mixture of reconstitutively inactive succinate dehydrogenase and QPs is treated with DCCD before being reconstituted with active succinate dehydrogenase, an inactivation behavior similar to that with QPs alone is observed. These results indicate that DCCD modifies the carboxyl groups of QPs which are essential for the interaction with succinate dehydrogenase to form succinate-ubiquinone reductase. Inactivation of QPs by DCCD parallels the incorporation of DCCD into QPs. About two carboxyl groups per molecule of QPs are essential for the interaction with succinate dehydrogenase. These essential carboxyl groups are located in the smaller subunit (Mr 13,000) of QPs. Modification of QPs by DCCD also alters the heme environment of cytochrome b560.
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PMID:Involvement of a carboxyl group in the interaction between succinate dehydrogenase and its membrane-anchoring protein (QPs) fraction. 342 98

Data on succinate-ubiquinone reductase are critically reviewed. The structural and catalytic properties of succinate dehydrogenase and succinate-ubiquinone reductase are compared. The redox components, active centers and proteins involved in the enzyme interaction with ubiquinone are described. Some structural and kinetic features of the succinate-ubiquinone reductase as the respiratory chain component and feasible mechanisms of regulation of the succinate-ubiquinone reductase activity are discussed.
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PMID:[Succinate-ubiquinone reductase site of the respiratory chain]. 354 59

The inhibitory effect of pyridoxal phosphate on the Triton X-100 solubilized purified bovine heart succinate-ubiquinone reductase (Choudhry, Z.M., Gavrikova, E.V., Kotlyar, A.B., Tushurashvilli, P.R. and Vinogradov, A.D. (1985) FEBS Lett. 182, 171-175) was studied. The kinetics of the enzyme inactivation by pyridoxal phosphate was found to be strongly dependent both qualitatively and quantitatively on the concentration of the protein-detergent complexes. In the diluted system the inactivation of the ubiquinone-depleted enzyme was completely prevented by the saturating concentrations of Q2, carboxin, thenoiltrifluoroacetone and pentachlorophenol, i.e., by the substrate and specific inhibitors of the enzyme. The protective effects of Q2 and the inhibitors was employed to quantitate the affinities of the ligands to their specific binding sites. Strong difference in the affinity of Q2 to the reduced and oxidized enzyme was found. When the soluble reconstitutively active succinate dehydrogenase was treated with pyridoxal phosphate, the reactivity of the enzyme towards low ferricyanide concentrations and its reconstitutive activity was significantly protected against aerobic inactivation.
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PMID:Studies on the succinate dehydrogenating system. Interaction of the mitochondrial succinate-ubiquinone reductase with pyridoxal phosphate. 370 47

Bovine heart mitochondrial NADH----ubiquinone reductase (complex I), contains two disulfide-linked subunits of 75 and 33 kDa as revealed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with beta-mercaptoethanol omitted from preparation of the sample for the first dimension. Two unidentified polypeptides (110-115 and 69 kDa) are also found in disulfide linkage with the two complex I subunits. The 110-115-kDa polypeptide appears to be pyridine dinucleotide transhydrogenase by several criteria including selective precipitation with an antibody raised to the purified transhydrogenase. The two disulfide-linked subunits were also found in a product cross-linked for 2 min with dithiobis (succinimidyl propionate) (DSP) along with five other complex I subunits of 53-57, 42, 24-27, 17-18, and 12.5-15.5 kDa (Gondal, J.A., and Anderson, W.M. (1985) J. Biol. Chem. 260, 5931-5935) indicating that these seven subunits lie within 11-12 A of each other at one or more points in space in the enzyme's interior. Cross-linking of complex I with DSP for 2 min in the presence of 1 microM rotenone yielded a cross-linked product consisting of the two natural disulfide-linked subunits and the 110-115- and 69-kDa polypeptides. This suggests that rotenone induces a conformational change in the enzyme that moves the seven DSP cross-linked subunits away from each other and outside the 11-12 A bridging distance of DSP. This alteration in conformation may be communicated to iron-sulfur center N-2 within the hydrophobic outer shell of the enzyme to prevent electron transfer to its natural electron acceptor, ubiquinone. A model of rotenone action based upon these observations is presented.
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PMID:The molecular morphology of bovine heart mitochondrial NADH----ubiquinone reductase. Native disulfide-linked subunits and rotenone-induced conformational changes. 393 May 1

The polypeptide composition of isolated mitochondrial NADH:ubiquinone reductase (NADH dehydrogenase) is very similar to that of material immunoprecipitated from detergent-solubilized bovine heart submitochondrial particles by antisera to the holoenzyme. The specificity of the antisera for dehydrogenase polypeptides was determined by immunoblotting, which showed that antisera reacting with only a few proteins were able to immunoprecipitate all others in parallel. The polypeptide compositions of rat, rabbit and human NADH dehydrogenase were determined by immunoprecipitation of the enzyme from solubilized submitochondrial particles and proved to be very similar to that of the bovine heart enzyme, particularly in the high-Mr region. Further homologies in these and other species were explored by immunoblotting with antisera to the holoenzyme and monospecific antisera raised against iron-sulphur-protein subunits of the enzyme.
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PMID:The polypeptide composition of the mitochondrial NADH: ubiquinone reductase complex from several mammalian species. 393 83

Treatment of the soluble ubiquinone-deficient succinate: ubiquinone reductase with pyridoxal phosphate results in the inhibition of the carboxin-sensitive ubiquinone-reductase activity of the enzyme. The inactivation is prevented by the soluble homolog of ubiquinone (Q2) but is insensitive to the dicarboxylates interacting with the substrate binding site of succinate dehydrogenase. The reactivity of the pyridoxal phosphate-inhibited enzyme with different electron acceptors suggests that the observed inhibition is due to the dissociation of succinate dehydrogenase from the enzyme complex. The soluble succinate dehydrogenase was recovered in the supernatant after treatment of the insoluble succinate: ubiquinone reductase with pyridoxal phosphate. The data obtained strongly suggest the participation of amino groups in the interaction between succinate dehydrogenase and the ubiquinone reactivity conferring peptide within the complex.
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PMID:Pyridoxal phosphate-induced dissociation of the succinate: ubiquinone reductase. 397 21

Thenoyltrifluoroacetone (TTA) and carboxin inhibit soluble ubiquinone-deficient succinate: ubiquinone reductase according to the mixed type (with respect to added Q2) inhibition. pattern. The Ki values for the inhibitors are mutually dependent, thus indicating the presence of a single binding site for both TTA and carboxin. The enolic form of TTA was shown to be the species interacting with the enzyme. Carboxin prevents the alkali-induced inactivation of the membrane-bound succinate dehydrogenase without having any effect on the reconstitution of succinate: ubiquinone reductase from the soluble dehydrogenase and b-c1 complex. The reduction of the respiratory chain by succinate protects succinate dehydrogenase against inactivation (solubilization) by alkali; under these conditions, carboxin does not affect the inactivation process. The cumulative data suggest that the degree of the mutual mobility of the succinate dehydrogenase smaller subunit and ubiquinone reactivity-conferring protein (QPs) is a prerequisite for the catalytic mechanism of succinate: ubiquinone reductase. A mechanism of the enzyme inhibition by TTA and carboxin is proposed, which consists in non-covalent cross-linking of the subunits by the inhibitors.
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PMID:[Interaction of mitochondrial succinate:ubiquinone reductase with thenoyltrifluoroacetone and carboxin]. 399 1

Measurements were made of the stoicheiometry of proton-translocation coupled to NAD(P)H oxidation by several quinones (duroquinone, ubiquinone(0), ubiquinone(1), ubiquinone(2)) in mitochondria from rat liver and ox heart. Observed stoicheiometries of protons translocated per mol of NADH oxidized (-->H(+)/2e(-) ratios; Mitchell, 1966) ranged from 0.75 (rat liver mitochondria with ubiquinone(1)) to 1.55 (ox heart mitochondria with ubiquinone(1) or ubiquinone(2)). Only the rotenone-sensitive pathway of NADH oxidation by quinone was able to support proton translocation. Correction of the observed -->H(+)/2e(-) ratios for the loss of reducing equivalents to the rotenone-insensitive pathway increased their value to approx. 2.0. It is concluded that the rotenone-sensitive NADH- ubiquinone reductase activity of the respiratory chain may be organized in the mitochondrial membrane as a proton-translocating oxidoreduction loop. The number of such loops between NADH and ubiquinone is one, and not two, as initially proposed by Mitchell (1966).
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PMID:Proton translocation coupled to quinone reduction by reduced nicotinamide--adenine dinucleotide in rat liver and ox heart mitochondria. 414 94

A synthetic analogue of ubiquinone, 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole, inhibits oxidation of succinate and NADH-linked substrates by rat liver mitochondria. Inhibition occurs both in the presence (state 3) and absence (state 4) of ADP. With isolated succinate-cytochrome c reductase complex from bovine heart mitochondria the quinone analogue inhibits succinate-cytochrome c reductase and ubiquinol-cytochrome c reductase activities but does not inhibit succinate-ubiquinone reductase activity. Inhibition of cytochrome c reductase activities is markedly dependent on pH in the range pH 7-8. At pH 7.0 inhibition occurs with an apparent Ki less than or equal to 1 x 10(-8) M, while at pH 8.0 the apparent Ki is more than an order of magnitude greater than this. Spectrophotometric titrations of 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole show a visibly detectable pKa at pH 6.5 attributable to ionization of the 6-hydroxy group. These results indicate that this quinone derivative is a highly specific and potent inhibitor of electron transfer in the b-c1 segment of the respiratory chain. Because of the structural analogy, it is likely that the mechanism of inhibition involves disruption of normal ubiquinone function. In addition, this inhibition depends on protonation of the ionizable hydroxy group of the inhibitory analogue or on protonation of a function group in the b-c1 segment.
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PMID:Inhibition of electron transfer in the cytochrome b-c, segment of the mitochondrial respiratory chain by a synthetic analogue of ubiquinone. 626 Jul 66

1. Evidence is presented for the presence of a stable ubisemiquinone pair in the vicinity of iron-sulphur centre S-3, based on its thermodynamic and spin relaxation properties. 2. These semiquinones are coupled by dipolar interaction; quantitative analysis of the signals of the spin-coupled semiquinones (at pH 7.4) gives midpoint redox potentials E1 (oxidized to semiquinone state) and E2 (semiquinone to fully reduced state) of 140 and 80mV, respectively, for individual ubiquinones. 3. Values of pKS (pK of the semiquinone form) below 6.5 and pKR (pK of the fully reduced ubiquinone) of about 8.0 or above were estimated from the pH-dependence of the midpoint potentials of the spin coupled signals. Thus the ubisemiquinone associated with succinate dehydrogenase (designated as SQS) functions mostly in the anionic form of the physiological pH range. 4. Theonyltrifluoroacetone, a specific inhibitor of the succinate-ubiquinone reductase segment of the respiratory chain, destabilized the intermediate redox state; thus it quenches both the g = 2.00 signal and ubisemiquinone (SQS) and split signals from the spin coupled pair. This inhibitor has no significant effect on another bound ubisemiquinone species present in the cytochrome bc1 region (designated as SQC). 5. The possible function and location of these stabilized ubisemiquinone species were discussed in connection with Site-II energy transduction.
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PMID:Studies on the stabilized ubisemiquinone species in the succinate-cytochrome c reductase segment of the intact mitochondrial membrane system. 626 61


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