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 rates of reactive absorption of ozone by various biomolecule solutions were measured. At pH 7, the ability of various biomolecules to reactively absorb ozone was in the following sequence: thiosulfate > ascorbate > cysteine approximately methionine > glutathione. The rates of reactive absorption under a variety of conditions were then analyzed using a mathematical model in order to estimate the reaction rate constants for the various ozone-biomolecule reactions. Compared to the ozone-methionine rate constant, the relative rate constants for thiosulfate, ascorbate, cysteine, and glutathione reactions were 18 +/- 2, 12 +/- 1, 1.1 +/- 0.1, and 0.62 +/- 0.03, respectively. Using an ozone-methionine reaction rate constant of 4 x 10(6) M-1 s-1, the rate constants for thiosulfate, ascorbate, cysteine, and glutathione were 7.2 x 10(7), 4.8 x 10(7), 4.4 x 10(6), and 2.5 x 10(6) M-1 s-1, respectively. Competitive studies using tryptophan as a standard ozone target were consistent with these rate constants. Compared to tryptophan, the relative ozone reaction rate constants for methionine, cysteine, and glutathione were 0.77 +/- 0.08, 0.88 +/- 0.19, and 0.42 +/- 0.01, respectively. These relative rate constants refer to ozone consumption rather than biomolecule consumption, so they may be compared with the relative rate constants obtained from reactive absorption. In addition, various inconsistencies in the literature regarding the rates of the ozone-cysteine and the ozone-glutathione reactions were reviewed.
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PMID:Reactive absorption of ozone by aqueous biomolecule solutions: implications for the role of sulfhydryl compounds as targets for ozone. 784 Jun 60

Aqueous humor from children with retinoblastoma obtained at enucleation and from eyes with adult cataracts were assayed with electrochemical liquid chromatography (Model 5500 Coulochem electrode array system) for metabolites of tyrosine, tryptophan metabolic pathways, catecholamine degradation pathways and ascorbate. More than 20 metabolites were identified in human aqueous for the first time. High levels of ascorbate were found in aqueous of eyes with adult cataracts (254, 336 ng/ml). Tyrosine metabolism in both sets of eyes was through dopamine. Vandylmandelic acid (VMA), homovanillic acid (HVA), and 3-methoxy, 4-hydroxyphenylglycol (MHPG) were all detected in retinoblastoma eyes. Although eyes with either adult cataracts or childhood retinoblastoma convert tryptophan through the serotonin pathway, retinoblastoma eyes metabolize tryptophan through the kynurenine pathway to a greater degree than adult cataract eyes.
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PMID:Retinoblastoma aqueous humor: aromatic amino acids. 811 19

The effect of dietary supplementation with acetylsalicylic acid on the increased modification, and susceptibility to modification, of lens crystallins from the streptozocin diabetic rat, has been determined. This was done by the measurement of characteristic markers of protein post-translational oxidative modification and glycation, in beta L crystallins purified from the lenses of control, diabetic and acetylsalicylic acid-supplemented diabetic animals, with no further manipulations, and again following the application of an in vitro graded oxidative insult. Crystallins prepared from the diabetic, in comparison with control animals, exhibited a higher level of bityrosine- and AGEP-like fluorescence as well as a loss of tryptophan fluorescence and sulphydryl groups. Exposure to an oxidative insult (in the form of CuSO4 and ascorbate) increased all parameters in beta L crystallins, irrespective of their source. However, the effects were most pronounced in the diabetic in which the effects of oxidative stress were always greater than the control crystallin. Dietary supplementation of the diabetic group with acetylsalicylic acid (100 mg kg-1 body weight day-1) had a marked effect in decreasing the level of modification induced in diabetic crystallins, by in vitro metal catalysed oxidative stress, lowering the levels of AGEP- and bityrosine-like fluorescence and carbonyl group formation. Increasing the oxidative stress by addition of increasing concentrations of H2O2, induced stress proportional increases in the indicators of protein modification in all beta L crystallins, irrespective of source. The increase in damage in relation to H2O2 concentration was greater in those crystallins from diabetic animals, revealing a greater susceptibility to such oxidative stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased susceptibility to metal catalysed oxidation of diabetic lens beta L crystallin: possible protection by dietary supplementation with acetylsalicylic acid. 815 30

The level of characteristic markers of protein oxidative modification (tryptophan oxidation and sulfhydryl group loss as well as carbonyl and bityrosine formation) and glycation (AGEP formation) have been measured in beta L crystallin purified from the lenses of control, diabetic, and ascorbate-supplemented diabetic animals. These markers were also determined following the application of an in vitro graded oxidative insult. Prior to the application of stress, diabetic lens crystallins, in comparison with control, exhibited a higher content of bityrosine and AGEPs, a lower level of nonoxidized tryptophan, and a loss of sulfhydryl groups. After exposure to the oxidative insult there was a stress-proportional increase of the parameters in all beta L crystallins, irrespective of their source. The effects were most pronounced in the diabetic, in which the already-elevated indicators of oxidative damage were further increased. Dietary supplementation of the diabetic group with ascorbate had a marked effect in preventing beta L crystallin modification in vivo, alleviating the loss of sulfhydryl groups and the oxidation of tryptophan, partially preventing the formation of AGEP and carbonyl groups, but not affecting the formation of bityrosine. Supplementation also inhibited the increase in susceptibility of diabetic beta L crystallin to in vitro oxidative stress, preventing sulfhydryl group loss as well as carbonyl and AGEP group formation. The results are discussed in relation to the proposal that diabetes renders lens crystallins more susceptible to oxidative stress and that this may be a causative factor in cataractogenesis. The possible role of ascorbate in the inhibition, or attenuation, of cataractogenesis is examined.
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PMID:The effect of diabetes and dietary ascorbate supplementation on the oxidative modification of rat lens beta L crystallin. 826 Jan 97

The riboflavin-sensitized photooxidation of ascorbate ion (HA-) to ascorbate radical (A.-) was followed by electron spin resonance (ESR) spectroscopy in conjunction with oxygen depletion measurements. In air-saturated aqueous media, steady-state amounts of A.- are rapidly established upon irradiation. The ESR signal disappears within a few seconds after the light is extinguished--more slowly under constant irradiation as oxygen is depleted. No photooxidation was observed in deaerated media. Similar results were obtained with other flavins and when ascorbyl palmitate was substituted for HA-. The effect of added superoxide dismutase, catalase, desferrioxamine, and singlet oxygen scavengers (NaN3 and tryptophan) was studied, as was replacement of water by D2O and saturation with O2. The results are indicative of ascorbate free radical production via direct reaction between ascorbate ion and triplet riboflavin in the presence of O2. While the presence of superoxide ion tends to reduce the steady-state concentration of A.-, competition from the reaction of HA- with singlet oxygen is less apparent in this system (at HA- > or = 1 mM) than in the previously studied aluminum phthalocyanine tetrasulfonate-photosensitized reaction.
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PMID:Photosensitized formation of ascorbate radicals by riboflavin: an ESR study. 839 95

Soluble calf lens proteins were extensively glycated during a 4 week incubation with ascorbic acid in the presence of oxygen. Amino acid analysis of the dialyzed proteins removed at weekly intervals showed an increasing loss of lysine, arginine and histidine, consistent with the extensive protein cross-linking observed. Irradiation of the dialyzed samples with UVA light (1.0 kJ/cm2 total illumination through a 338 nm cutoff filter) caused an increasing loss of tryptophan, an additional loss of histidine and the production of micromolar concentrations of hydrogen peroxide. No alteration in amino acid content and no photolytic effects were seen in proteins incubated without ascorbic acid or in proteins incubated with glucose for 4 weeks. The rate of hydrogen peroxide formation was linear with each glycated sample with a maximum production of 25 nmol/mg protein illuminated. The possibility that the sensitizer activity was due to an ascorbate-induced oxidation of tryptophan was eliminated by the presence of a heavy metal ion chelator during the incubation and by showing equivalent effects with ascorbate-incubated ribonuclease A, which is devoid of tryptophan. The ascorbate-incubated samples displayed increasing absorbance at wavelengths above 300 nm and increasing fluorescence (340/430) as glycation proceeded. The spectra of the 4 week glycated proteins were identical to those obtained with a solubilized water-insoluble fraction from human lens, which is known to have UVA sensitizer activity. The incubation of lens proteins with dehydroascorbic acid or L-threose, but not fructose, produced equivalent glycation, protein crosslinking and sensitizer activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ascorbic acid glycation of lens proteins produces UVA sensitizers similar to those in human lens. 857 Jul 5

Measurement of urinary xanthurenic acid (XA) has been used clinically to study a variety of disorders caused by vitamin B6 deficiency. To obviate some cumbersome steps of current methods for measuring XA in human urine, we have developed a simple fluorometric method. We apply the urine sample to a solid-phase extraction column containing trimethylaminopropyl group bound to silica, which enables us to purify and concentrate the XA from the urine without contamination from various tryptophan metabolites. The XA in the acidic eluate can then be quantified fluorometrically. The linearity of the proposed method extends from 0.2 to 10.0 mg/L. The method is precise, yielding day-to-day CVs for two pooled control specimens (1.08 and 1.90 mg/L) of 1.2% and 2.6%, respectively. Correlation studies with an established HPLC method and with a spectrophotometric procedure showed correlation coefficients of 0.99 and 0.98, respectively. Interference from vitamin C, uric acid, salicylate, acetaminophen, vanillylmandelic acid, and homovanillic acid was insignificant. The proposed method for urinary XA is rapid, simple, and suitable for routine use in the clinical laboratory.
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PMID:Improved fluorometric quantification of urinary xanthurenic acid. 859 2

Shiga toxin is a bacterial protein composed of one A and five B subunits. Its A chain possesses a protease sensitive loop (Cys-242-Cys-261) that is cleaved to produce an enzymatically active A1 domain and an A2 fragment associated with its B subunit pentamer. The proposed mode of action of the toxin is linked to its retrograde transport to the ER lumen followed by the translocation of its catalytic A1 chain to the cytoplasmic side of the ER membrane. A signal sequence-like domain (residues 220-246) which constitutes the C-terminus of the A1 chain precedes a region within the protease sensitive loop (residues 247-258) that contains known and putative cleavage sites. Two peptides corresponding to this C-terminus (residues 220-246) were chemically synthesized to investigate if this signal sequence-like domain can interact with membranes. Such a property may provide a clue to the mechanism of translocation of the A1 domain across the ER membrane. The first peptide represented the native sequence, which includes a naturally occurring cysteine at position 242 and provided a thiol moiety for the attachment of a spinlabel. A second peptide was designed to contain a single tryptophan residue (Ile232Trp) located within the hydrophobic core of the sequence which served as an intrinsic fluorescence probe. The interactions of both peptides with lipid vesicles were analyzed by circular dichroism, fluorescence, and EPR spectroscopy. The peptides lack structure in aqueous buffers and adopted an alpha-helical geometry when bound to negatively charged lipid vesicles. The addition of lipid vesicles to a solution of the tryptophan-containing peptide results in a blue shift in the wavelength of its fluorescence maxima as well as an increase in fluorescence intensity at 335 nm, suggesting that the hydrophobic core of this A1 peptide relocated to a nonpolar environment. EPR measurements of a proxyl-labeled analog of the peptide (introduced at Cys-242) indicated a decreased mobility of a fraction of the proxyl probe in the presence of lipid vesicles. At pH 7, the membrane-bound probe was completely reduced by ascorbate trapped inside vesicles but only partially reduced by ascorbate added outside the vesicles, suggesting that the C-terminal region of the peptide traversed the membrane bilayer or relocated close to the surface of its inner lipid leaflet. Finally, the peptide was shown to insert into lipid vesicles, causing the release of calcein at a high peptide:lipid ratio. These results suggest that the C-terminal tail of the A1 chain may anchor this domain into the ER membrane.
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PMID:Insertion and orientation of a synthetic peptide representing the C-terminus of the A1 domain of Shiga toxin into phospholipid membranes. 875 10

The pyridoindole derivative stobadine [(-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido(4,3b) indole] has been described as a drug with antihypoxic and antiarrhythmic cardioprotective properties. The antioxidative properties of this compound were studied during Cu(++)-mediated low-density lipoprotein (LDL) oxidation. Stobadine (concentration 0-5 microM) prolonged the lag phase (in min produced by one molecule antioxidant per LDL particle) as measured by diene formation more effectively than did ascorbate, trolox, or alpha-tocopherol. It also has the ability to decrease the rate of diene formation during the propagation phase very efficiently. Diene formation, Trp destruction, and alpha-tocopherol consumption were measured in the presence and absence of stobadine. Stobadine (10 microM) did not influence tocopherol consumption during oxidation and the Trp fluorescence quenching of Cu++ was not influenced by this compound. From these results, as well as polarographic measurements, we conclude that the antioxidative effect of stobadine is not simply a result of Cu(++)-ion complexation. In contrast to ascorbate, this compound is stable in the presence of Cu++. Stobadine inhibits the oxidation of LDL-Trp residues very efficiently via its radical scavenging properties, and may even have the ability to reduce Trp radicals to tryptophan. The concentration of stobadine used for LDL oxidation was in the range found in plasma (stobadine given p.o. in human and rats results in plasma concentrations between 0.2-3.9 microM.
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PMID:Effect of stobadine on Cu(++)-mediated oxidation of low-density lipoprotein. 878 42

Peroxynitrite (ONOO-), the reaction product of superoxide (O2.-) and nitric oxide (.NO), nitrates tyrosine and other phenolics. We report herein that tryptophan is also nitrated by peroxynitrite in the absence of transition metals to one predominant isomer of nitrotryptophan, as determined from spectral characteristics and liquid chromatography-mass spectrometry analysis. At high peroxynitrite to tryptophan ratios, other oxidation products were detected as well. The amount of nitrotryptophan formed from peroxynitrite increased at acidic pH, with an apparent pKa of 7.8. High concentrations of Fe(3+)-EDTA were required to enhance peroxynitrite-induced nitrotryptophan formation, while addition of up to 15 microM Cu/Zn superoxide dismutase had a minimal effect on tryptophan nitration. Cysteine, ascorbate, and methionine decreased nitrotryptophan yield to an extent similar to that predicted by their reaction rates with ground-state peroxynitrite, and typical hydroxyl radical scavengers partially inhibited nitration. Plots of the observed rate constant of nitrotryptophan formation vs tryptophan concentration presented downward curvatures. Thus, the kinetics of metal-independent nitration reactions were interpreted in terms of two parallel mechanisms. In the first one, ground-state peroxynitrous acid nitrated tryptophan with a second-order rate constant of 184 +/- 11 M-1 s-1 at 37 degrees C. The activation enthalpy was 9.1 +/- 0.3 kcal mol-1, and the activation entropy was -19 +/- 1 cal mol-1 K-1. In the second mechanism, ONOOH*, an activated intermediate derived from trans-peroxynitrous acid formed in a steady state, was the nitrating agent.
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PMID:Peroxynitrite-dependent tryptophan nitration. 883 40


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