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)

The real-time kinetics of the release of ascorbyl free radicals in the coronary perfusate from isolated rat hearts submitted to an ischemia/reperfusion sequence has been achieved by continuous-flow ESR using high-speed acquisition techniques. Enhanced ESR detection of ascorbyl free radicals was obtained by addition of dimethyl sulfoxide (Me2SO), a strong cation chelator and oxidizing agent. A continuous-flow device allowed a direct monitoring of the ascorbyl free radical and/or ascorbate leakage in coronary perfusate by observation of the ascorbyl radical doublet (aH = 0.188 mT and g = 2.0054). 1. The results showed that ascorbyl free radical release occurred mainly during sequences of low-flow ischemia (90 min) coupled or not with 30 min of zero-flow ischemia followed by reperfusion (60 min). The kinetic profiles of ascorbyl-free-radical detection confirm in quantitative terms the expected correlation between the duration of the ischemic insult and the magnitude of ascorbate extracellular release upon reperfusion. There is indication that ascorbyl free radical depletion could be secondary to oxygen-derived-free-radical-induced cellular damage. 2. The amount of residual ascorbic acid was quantitated on myocardial tissue at the end of reperfusion using Me2SO as extracting solvent. Intense oxidation of ascorbate and chemical stabilization of the resulting free radical species provided by Me2SO allowed ESR measurement of a marked tissue ascorbate depletion related to the duration of ischemia. 3. Perfusion of superoxide dismutase during low-flow ischemia and the first 10 min of reperfusion greatly inhibited both extracellular release and endogenous ascorbate depletion. These results suggest that the ascorbate redox system constitutes a major protective mechanism against free-radical-induced myocardial injury. 4. The proposed direct ESR detection of ascorbyl free radicals in the coronary perfusates or in tissue extracts does not require extensive chemical preparation and conditioning of effluent or tissue samples. It provides an interesting straightforward alternative to the evaluation of detrimental free radical processes affecting the myocardium during ischemia and reperfusion.
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PMID:Ascorbyl free radical as a reliable indicator of free-radical-mediated myocardial ischemic and post-ischemic injury. A real-time continuous-flow ESR study. 217 67

Nifurtimox analogues bearing triazol-4-yl, benzimidazol-1-yl, triazin-4-yl or related groups as counterpart of the (5-nitro-2-furfurylidene) amino group were reduced to their nitro anion radicals by ascorbate in anaerobic solutions at high pH. The ESR spectra of the radical anions showed hyperfine spin couplings restricted to the nitrofuran moiety. With these compounds, the spin density at the nitro group was greater than with nifurtimox, nitrofurazone and nitrofurantoin. At neutral pH, solutions containing ascorbate and nitrofuran derivatives consumed oxygen, the compounds bearing unsaturated nitrogen heterocycles being the most effective. Superoxide dismutase and catalase decreased the rate of oxygen consumption, thus demonstrating the production of superoxide and hydrogen peroxide, respectively. NMR spectra of the triazol-4-yl and triazin-4-yl nitrofuran derivatives showed a deshielding effect for the azomethine proton, which was undetectable with nifurtimox and nitrofurazone.
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PMID:Generation of radical anions of nifurtimox and related nitrofuran compounds by ascorbate. 217 83

The nonenzymatic oxidation of NADH was studied spectrophotometrically in the presence of two vanadium compounds, sodium orthovanadate and vanadyl sulfate. At physiological pH 7.4, in 25 mM sodium phosphate buffer, addition of the synthetic thiol, dithioerythritol (DTE) results in a marked increase of NADH oxidation in the presence of sodium orthovanadate, but not in the presence of vanadyl sulfate. Other reductants, such as dithiothreitol and cysteine, can also increase NADH oxidation, whereas glutathione and ascorbate cannot. In all reactions, superoxide dismutase and catalase completely inhibit the vanadium-stimulated oxidation of NADH. Inhibition occurs in a concentration-dependent manner, and the boiled enzymes do not inhibit the thiol reaction. The hydroxyl radical scavenger, thiourea, inhibits the reaction, whereas urea cannot. ESR studies show that the ability of the thiol to reduce vanadate can be correlated with the degree of NADH oxidation. Using spin trapping techniques, hydroxyl radicals are detected during the course of the reaction. Addition of hydrogen peroxide to vanadyl in the presence of DTE greatly increases NADH oxidation; however, no NADH oxidation occurs when hydrogen peroxide is added to vanadyl and ascorbic acid. These results provide a partial explanation for the ability of vanadium compounds to both decrease cellular reducing equivalents and promote lipid peroxidation.
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PMID:Oxidation of NADH by vanadium compounds in the presence of thiols. 254 Jul 16

A new ESR assay has been developed for the characterization of unilamellar lipid vesicles. It is based on the reduction by photogenerated FADH2 of amphiphilic spin-labels having the spin in the polar group. FADH2 is generated in situ under anaerobic conditions from its oxidized form (FAD) by photoreduction in the presence of excess EDTA as the reducing agent. Photoreduction is induced by exposing the FAD/EDTA mixture to white light of a commercial slide projector. FADH2 as an impermeable agent reduces spin-label molecules located on the outer layer of the bilayer that are readily accessible in a first fast reaction; spin-label located on the inner layer of the bilayer is reduced in a second slow reaction. The ESR assay is suitable for the routine characterization of unilamellar membrane vesicles: it allows the determination of the vesicle size, the entrapped volume, the bilayer asymmetry, the bilayer integrity, and the vesicle stability. The ESR assay developed is of general applicability: it can be used with charged and uncharged bilayers which may be labeled with either neutral or charged spin-labels. An assessment of the new ESR assay is given in comparison to the existing ascorbate method which uses sodium ascorbate as the reducing agent. Various other potential reducing agents for spin-labels have been tested and found unsuitable for the ESR assays discussed here.
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PMID:A new electron spin resonance assay for membrane asymmetry and entrapped volume of unilamellar lipid vesicles based on photoreduced flavin adenine dinucleotide. 254 82

Pulsed electron-spin-resonance techniques were applied to the hydrogenase of the purple photosynthetic bacterium Thiocapsa roseopersicina, an enzyme which contains nickel and iron-sulphur clusters but no flavin. The linear electric field effect profile of the spectrum in the region of g = 2.01 indicated that the strong ESR signal in the oxidized protein is due to a [3Fe-4S] cluster. The electron spin-echo envelope of this spectrum was modulated by hyperfine interactions with 1H and 14N nuclei, probably from the polypeptide chain. The ESR spectrum of this species shows a complex pattern arising from spin-spin interaction with another paramagnet. When the protein was partially reduced by ascorbate plus phenazine methosulphate, the complexity of the spectrum was abolished but the form of the electron spin-echo envelope modulation (ESEEM) pattern was unchanged. This indicates that the reversible disappearance of the spin-spin interaction pattern on partial reduction is not due to cluster interconversion to a [4Fe-4S] cluster. In the ESR spectrum of nickel(III), weak hyperfine interactions with 1H and 14N were also observed by ESEEM. The nature of the interacting nuclei is discussed.
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PMID:Spectroscopic characterization of the nickel and iron-sulphur clusters of hydrogenase from the purple photosynthetic bacterium Thiocapsa roseopersicina. 2. Electron spin-echo spectroscopy. 254 25

alpha-Tocopherol (vitamin E) is a lipophilic chain-breaking antioxidant which inhibits lipid peroxidation in isolated mitochondrial membranes and protects membranes from oxidative damage. The primary oxidation product of vitamin E is the tocopheroxyl radical. Reduction of the tocopheroxyl radical can occur by reactions with water-soluble anti-oxidants such as ascorbate or glutathione, resulting in the recycling of vitamin E. Physiological concentrations of vitamin E are too low to allow detection of tocopheroxyl radical by ESR. After dietary supplementation with vitamin E, a 10-20-fold increase in the rat liver mitochondrial membrane content of vitamin E was achieved and this allowed for direct detection of the tocopheroxyl radical by ESR, after treatment with an oxidizing system composed of lipoxygenase and arachidonic acid. By using submitochondrial particle membranes, it was shown that NADH, succinate, and reduced cytochrome c-linked oxidation reduce the tocopheroxyl radical, preventing both accumulation of the radical and vitamin E consumption. As the electron transport chain can reduce tocopheroxyl radical it may have an important physiological role in recycling vitamin E.
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PMID:Mitochondrial electron transport-linked tocopheroxyl radical reduction. 255 30

A truncated human c-Ha-ras gene product, ras(1-171) protein, was prepared and chemically modified with maleimide spin-label (MSL). By trypsin digestion of the MSL-labeled ras(1-171) protein, MSL-labeled peptide fragments were isolated and sequenced. The cysteine residue in position 118 of the protein, but not the other cysteine residues, Cys-51 or Cys-80, was found to be specifically labeled by MSL. The ESR spectrum of the MSL-labeled ras(1-171) protein indicates that the MSL group attached to Cys-118 is strongly immobilized. Proton NMR spectra at 400-MHz were measured for this MSL-labeled ras(1-171) protein and also for a control sample of a labeled ras(1-171) protein whose MSL was reduced by sodium ascorbate. In the difference spectra for these two proteins, resonances of protons in the vicinity of the MSL group attached to Cys-118 of the ras(1-171) protein were observed. Thus, the MSL group was found to be in the vicinity of the protein-bound GDP. A phenylalanine residue and two histidine residues, which were characterized by 2D HOHAHA and DQF-COSY spectra, were also found to be in the vicinity of MSL. NOE and pH titration analyses indicate that this phenylalanine residue is close to the bound GDP and one of the two histidine residues. By carboxypeptidase digestion, the two histidine residues near MSL were identified as His-27 and His-94.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spin-labeling proton NMR study on aromatic amino acid residues in the guanine nucleotide binding site of human c-Ha-ras(1-171) protein. 255 24

The kinetics of reduction of nitroxides including 4-hydroxy-TEMPO, 4-methoxy-TEMPO and 4-hexanoyloxy-TEMPO, which are of different lipophilicities, by vitamin C in cationic, non-ionic and anionic micelles, i.e. CTAB, Triton X-100 and SDS, respectively, have been studied by FSR spectroscopy by a stopped-flow technique. A mechanism for the reaction conducted in micelles is proposed and the rate constants for the elementary reactions are evaluated. It is found that the rates of single electron transfer reactions involving the nitroxides are dependent on the nature of the micelle and the lipophilicity of the nitroxide. The rates are increased in CTAB, decreased in SDS, whereas unaffected in Triton X-100. And the greater the lipophilicity of the nitroxide, the more pronounced the rate variation. As high as a 3600-fold increase in the rate was observed for 4-hexanoyloxy-TEMPO in CTAB over that in SDS. The micellar effects are rationalized on the basis of analysis of parameters and line shape of the ESR spectra for the nitroxides in the micelles.
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PMID:Studies on bio-antioxidants--micellar effects on the reduction of nitroxides by vitamin C. 261 Aug 66

Glycylglycylhistidine (GGH) was synthesized using mixed anhydride method, and Cu(II): GGH = 1:1 complex was identified using UV, ESR, CD, ORD and FAB/MS technique. The oxidation of ascorbate catalyzed by cupric ion in RPMI 1640 medium (pH 7.40) was studied. The activation energy E = 39.2 kJ/mol. The addition of GGH inhibited the oxidation of ascorbate catalyzed by cupric ion. The investigations with ESR and fluorimetry indicate that there are Cu(I), ascorbate radical (AH), O2-., H2O2 and .OH during the oxidation.
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PMID:[Effect of diglycylhistidine on the oxidation of ascorbate catalyzed by Cu(II)]. 280 Nov 40

For the first time we have synthesized spin-labeled nitrosoureas and have studied their properties--reduction of the iminoxyl group by vitamin C leading to the formation of the corresponding hydroxylamine derivatives and degradation in the presence of an aminoradical, leading to biradicals. The ESR spectra of biradicals in methanol have nine hyperfine resonance lines. The spin-labeled nitrosoureas have shown a high antitumor activity against the L 1210 lymphoid leukemia and P 388 lymphocytic leukemia in BDF1 mice. A study of a broad range of transplantable tumors is in progress.
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PMID:Synthesis and study of spin-labeled nitrosoureas. 298 81


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