Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ascorbate-reduced horse heart cytochrome c reduces photo-oxidized bacterial reaction centres with a second-order rate constant of (5-8) X 10(8) M-1 X s-1 at an ionic strength of 50 mM. In the absence of cytochrome c, the cytochrome c1 in the ubiquinol:cytochrome c oxidoreductase is oxidized relatively slowly (k = 3.3 X 10(5) M-1 X s-1). Ferrocytochrome c binds specifically to ascorbate-reduced reductase, with a Kd of 0.6 microM, and only the free cytochrome c molecules are involved in the rapid reduction of photo-oxidized reaction centres. The electron transfer between ferricytochrome c and ferrocytochrome c1 of the reductase is rapid, with a second-order rate constant of 2.1 X 10(8) M-1 X s-1 at an ionic strength of 50 mM. The rate of electron transfer from the Rieske iron-sulphur cluster to cytochrome c1 is even more rapid. The cytochrome b of the ubiquinol:cytochrome c oxidoreductase can be reduced by electrons from the reaction centres through two pathways: one is sensitive to antimycin and the other to myxothiazol. The amount of cytochrome b reduced in the absence of antimycin is dependent on the redox potential of the system, but in no case tested did it exceed 25% of the amount of photo-oxidized reaction centres.
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PMID:Kinetics of flash-induced electron transfer between bacterial reaction centres, mitochondrial ubiquinol:cytochrome c oxidoreductase and cytochrome c. 631 49

In a system containing reaction centres isolated from Rhodopseudomonas sphaeroides mutant R26, and variable amounts of horse-heart cytochrome c and bovine-heart mitochondrial QH2: cytochrome c oxidoreductase in a medium containing 2 mM ascorbate and 0.1 microM phenazine methosulphate, electron transfer was induced by a single flash. Three distinct phases of electron transfer can be distinguished: the first event is the oxidation of cytochrome c, and this is followed by an equilibration between cytochrome c, cytochrome c1 and the Rieske [2Fe-2S] cluster. The actual rates of these processes depend on the concentrations of cytochrome c and the reductase. The slower third phase is the oxidation of ubiquinol, which can follow two pathways: one sensitive to antimycin and one sensitive to myxothiazole. The antimycin-sensitive pathway (t1/2 approximately equal to 10 ms) is an equilibration between the Q/QH2 couple and cytochrome b, but may also include a direct reduction of cytochrome b by the QB of the reaction centres. The myxothiazole-sensitive pathway is a coupled reduction of cytochrome b and the Rieske [2Fe-2S] cluster which rapidly equilibrates with cytochromes c1 and c. Both pathways are sensitive to 7-(n-heptadecyl)mercapto-6-hydroxy-5,8-quinoline quinone, but with different affinities. In the absence of inhibitors the initial reduction of cytochrome b (via both pathways) is followed by a net oxidation which is the resultant of a continuing reduction (together with the reduction of the Rieske [2Fe-2S] cluster) and an oxidation (via the antimycin-sensitive site) by quinone. The results are discussed in the light of linear and cyclic models proposed to explain electron transfer between cytochromes b and c. It is concluded that only the Q-cycle model fits the present experimental data.
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PMID:Flash-induced electron transfer through mitochondrial QH2: cytochrome c oxidoreductase in the presence of bacterial reaction centres and cytochrome c. Analysis of subsequent processes and effect of inhibitors. 632 66

In the presence of ascorbate, hexaamineruthenium mediates rapid reduction of cytochrome b-562 in submitochondrial particles but not in mitochondria. The reaction is observed in the combined presence of antimycin (or funiculosin) and myxothiazol, which implies direct interaction of Ru(NH3)2+6 with b cytochrome(s). We assume that contrary to previous conclusions (Case and Leigh (1976) Biochem. J., 160, 769-783) redox centre of at least one of the oxidized cytochromes b, most probably of b-562, is exposed to the M-aqueous phase.
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PMID:Cytochrome b reduction by hexaammineruthenium in mitochondria and submitochondrial particles. Evidence for heme b-562 localization at the M-side of the mitochondrial membrane. 647 28

The bioenergetic capacity of skeletal muscle in a 17-year-old patient with a severe defect in complex III of the electron transport chain has been examined by 31P NMR measurements of the molar ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Resting ratios were 1.3-2.5, which can be compared with roughly 8.6 for a young, normal female control at rest. Quantitative evaluation of the activity of oxidative metabolism was afforded by the rate of recovery of PCr/Pi from exercise and was found to be 2.5% of normal. After administration of menadione and ascorbate, we found a 21-fold increase of the recovery rate relative to the pretherapy value, to within 56% of the recovery rate of the young female control. Thus, NMR examinations of skeletal muscle at rest and in recovery from activity document marked improvement to specific drug therapy in the electron transport capabilities and the ATP synthesis rate of a patient with a deficiency in a cytochrome b-containing complex III. Improvements in functional ability, although not as dramatic as biochemical changes, are also apparent.
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PMID:31P NMR study of improvement in oxidative phosphorylation by vitamins K3 and C in a patient with a defect in electron transport at complex III in skeletal muscle. 658 67

The differences in the effects of two similar electron transfer inhibitors, antimycin and 2-nonyl-4-hydroxyquinoline N-oxide (HOQNO) on the reactions of cytochromes b are described. In the cyanide-inhibited submitochondrial particles of bovine heart, HOQNO strongly stimulates cytochrome b reduction by ascorbate in the presence of redox mediators, e. g. N,N,N',N'-tetramethylparaphenylene diamine, 2,6-dichlorophenolindophenol, diaminodurol and phenazine methosulfate; this effect can be reversed by antimycin. Addition of both inhibitors to the submitochondrial particles aerobically equilibrated with succinate/fumarate redox buffer at E = +54 mV in the presence of cyanide results in a similar reduction of cytochromes b, which in the case of antimycin is readily reversed by phenazine methosulfate but is resistant to this redox mediator in the presence of HOQNO. The latter causes additional reduction of cytochrome b562 in the argone atmosphere, the effect being reversed by antimycin. In the presence of HOQNO the anaerobic redox titration curve of cytochrome b562 is shifted towards a high potential region by 20-30 mV. An additional reduction of cytochromes b induced by HOQNO can be due to superposition of two effects, i. e. extra-reduction of cytochromes b566 and b562 requiring O2 and a true positive shift of E0 of cytochrome b562.
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PMID:[Differences in the action of antimycin and 2-nonyl-4-hydroxyquinoline N-oxide on oxidation-reduction of mitochondrial cytochromes b]. 662 6

The respiratory components of the envelope membrane preparation of Neisseria meningitidis were investigated. Oxidase activities were demonstrated in this fraction in the presence of succinic acid, reduced nicotinamide adenine dinucleotide, and ascorbate-N,N,N',N'-tetramethyl-p-phenylene-diamine (TMPD). Differences in the kinetics of inhibition by terminal oxidase inhibitors on the three oxidase activities indicated that ascorbate-TMPD oxidation involved only an azide-sensitive oxidase, whereas oxidation of the physiological substrates involved two oxidases, one of which was relatively azide resistant. Spectrophotometric studies revealed that ascorbate-TMPD donated its electrons exclusively to cytochrome o, whereas the physiological substrates were oxidized via both cytochromes o and a. The effects of class II inhibitors on the oxidases suggest terminal branching of the electron transport chain at the cytochrome b level. A model of the respiratory system in N. meningitidis is proposed.
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PMID:Terminal branching of the respiratory electron transport chain in Neisseria meningitidis. 676 15

The effect of trifluoperazine on the respiration of porcine liver and skeletal muscle mitochondria was investigated by polarographic and spectroscopic techniques. Low concentrations of trifluoperazine (88 nmol/mg protein) inhibited both the ADP- and Ca2+-stimulated oxidation of succinate, and reduced the values of the respiratory control index and the ADP/O and Ca2+/O ratio. High concentrations inhibited both succinate and ascorbate plus tetramethyl-p-phenylenediame (TMPD) oxidations, and uncoupler (carbonyl cyanide p-trifluromethoxyphenylhydrazone) and Ca2+-stimulated respiration. Porcine liver mitochondria were more sensitive to trifluoperazine than skeletal muscle mitochondria. Trifluoperazine inhibited the electron transport of succinate oxidation of skeletal muscle mitochondria within the cytochrome b-c1 and cytochrome c1-aa3 segments of the respiratory chain system. 233 nmol trifluoperazine/mg protein inhibited the aerobic steady-state reduction of cytochrome c1 by 92% with succinate as substrate, and of cytochrome c and cytochrome aa3 by 50-60% with ascorbate plus TMPD as electron donors. Trifluoperazine can thus inhibit calmodulin-independent reactions particularly when used at high concentrations.
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PMID:Effect of trifluoperazine on skeletal muscle mitochondrial respiration. 683 Jul 68

DBHBM (3,5-dibromo-4-hydroxy-benzylidenemalonitrile) inhibited the NADH- or succinate-supported rate of O2 consumption in beef heart submitochondrial particles (Ki = 7 x 10(-7) M). Oxygen comsumption was restored with the addition of ascorbate/TMPD, indicating that the inhibitory effect was on the ubiquinol-cytochrome c reductase activity of the respiratory chain. Difference spectra with submitochondrial particles indicated that DBHBM blocked electron transport through the cytochrome bc1 complex, in a mode closely similar to that of antimycin A. The reduction rates of cytochrome b by succinate were strongly inhibited in the presence of DBHBM plus myxothiazol, but not by DBHBM plus antimycin A. These data suggest that DBHBM may bind primarily to the QN center. In the purified bc1 complex, DBHBM and antimycin A induced a red shift from 562 to 566 nm of the alpha peak of cytochrome b, supporting the idea that DBHBM influences predominantly the ligand field of the b562 (bh) heme. Difference spectra in the presence or absence of myxothiazol showed that DBHBM induced the same red shift with a maximum at 565 nm and a minimum at 559 nm. We conclude that DBHBM blocks electron transfer at the QN center and thus may be considered a novel group III inhibitor of the bc1 complex.
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PMID:DBHBM (3,5-dibromo-4-hydroxy-benzylidenemalonitrile) is a novel inhibitor of electron transfer through the QN center of the mitochondrial bc1 complex. 772 62

The nitric oxide reductase (NOR) from Pseudomonas stutzeri is a cytochrome bc complex which shows on SDS/PAGE two subunits with apparent molecular masses of 17 kDa and 38 kDa. Two other species of approximately 45 kDa and 74-78 kDa represent the undissociated enzyme complex and an aggregate of the cytochrome b subunit, respectively. The cytochrome b subunit is highly hydrophobic and results in aberrant electrophoretic mobility. The stability of the enzyme in various detergents and at different pH was investigated. The highest specific activity of 60 mumol NO min-1 mg-1 protein was obtained after electrophoresis in the presence of laurylpropanediol-3-phosphorylcholine ether. Purified NOR contained cardiolipin, phosphatidylglycerol, and phosphatidylethanolamine, the latter as the major component. A phospholipid was required for high catalytic activity with either cardiolipin or phosphatidylglycerol increasing the activity of the enzyme as isolated by a factor of up to 5. Free fatty acids inhibited NOR, with cis-9-octadecenoic acid (oleic acid) showing the most pronounced effect. Certain detergents substituted for the phospholipid requirement of NOR. The enzyme, as isolated, in 0.1% Triton X-100, 20 mM Tris/HCl pH 8.5, exhibited a complex set of EPR resonances at low magnetic field, with a prominent peak at g 6.34 resulting from Fe(III) high-spin cytochrome b. The second prominent feature arose from a low-spin Fe(III) heme center with strong lines at apparent g values of 3.02 and 2.29, and a broad resonance at g approximately 1.5 which we assigned to the cytochrome c component of the enzyme. From spin quantitation and computer simulations of the various EPR signals a ratio close to 1:1 for the low-spin/high-spin heme centers in NOR was estimated. Shifting the pH from 8.5 to 5.0, replacing Triton X-100 by other detergents, or adding soybean phospholipids to the protein, led to pronounced changes of the EPR signals in the g = 6 region. In contrast, the strong inhibitor oleic acid did not cause significant spectral changes. NOR which had been reduced by L-ascorbate/phenazine methosulfate prior to incubation with its substrate NO gave the characteristic Fe(II) nitrosyl triplet centered at g approximately 2.01, with a hyperfine splitting of 1.70 mT. In the absence of dioxygen, NOR was quantitatively reduced by either sodium dithionite, or photochemically with deazaflavin and oxalate; the enzyme was reoxidizable by ferricyanide in a fully reversible reaction. Spectroelectrochemical oxidoreductive titrations gave E'o (versus standard hydrogen electrode) = +322 mV for the cytochrome b and +280 mV for the cytochrome c component.
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PMID:Nitric oxide reductase from Pseudomonas stutzeri, a novel cytochrome bc complex. Phospholipid requirement, electron paramagnetic resonance and redox properties. 802 Apr 68

The cytochrome bc1 complex purified from beef heart mitochondria was incorporated into potassium (K+)-loaded phospholipid vesicles by a cholate dialysis method to study the reverse reaction of electron transfer in the complex. The reduction of cytochrome b in the presence of sodium ascorbate was observed on addition of valinomycin to the K(+)-loaded proteoliposomes in a medium containing no external KCl; it was followed by the gradual oxidation. Nigericin accelerated the reoxidation of reduced cytochrome b, indicating that a K+ diffusion potential (negative inside) induced the reduction of cytochrome b. The extent of the cytochrome b reduction depended on the magnitude of the diffusion potential across the liposomal membranes, and its maximal reduction was attained at more than 210 mV of the diffusion potential. It was cytochrome b562 that was reduced during the establishment of the K+ diffusion potential in the presence of ascorbate, and about 90% of cytochrome b562 was estimated to be reduced. Antimycin A and myxothiazol inhibited the diffusion potential-induced reduction of cytochrome b562, and ubiquinone was proved to be essential for the reversed electron transfer. The K+ diffusion potential also induced the partial reduction of cytochrome b566 when cytochrome b562 had previously been reduced with ascorbate plus tetramethyl-p-phenylenediamine. These results were interpreted well based on the Q cycle scheme which assumed the energy-dependent reduction of ubiquinone at center o. Dicyclohexylcarbodiimide, which did not perturb the ability of proteoliposomes to generate the K+ diffusion potential, inhibited the energy-dependent reduction of cytochrome b562 without a significant loss in the catalytic activity of the complex. The half-inhibition was brought about by 200 mol of dicyclohexylcarbodiimide/mol of cytochrome c1. These results strongly suggest the coupling of a proton flow with the reversed electron transfer in the bc1 complex.
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PMID:Membrane potential-linked reversed electron transfer in the beef heart cytochrome bc1 complex reconstituted into potassium-loaded phospholipid vesicles. 829 31


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