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)

Cu-catalyzed oxidation of ascorbate has been studied in the absence and the presence of superoxide dismutase, catalase, mannitol, glycerol, ethanol, formate, and thiourea. None of these agents except thiourea inhibited the reaction. Therefore, the role of the Haber-Weiss reaction in the ascorbate oxidation could not be demonstrated. Electron spin resonance studies demonstrated that the preventive effect of the thiol is primarily due to the chelation of the reduced copper ions with the sulphur atom. The oxidation was also prevented by the chelation of copper with physiological levels of bovine serum albumin. These observations are consistent with the concept that a metal-oxygen complex is perhaps directly involved in the oxidative process. Measurements of the peroxide produced during oxidation indicated that significant amounts of this compound accumulates only at lower levels of ascorbate and in the absence of a protein or other chelating agents. At higher ascorbate levels no peroxide accumulation takes place. These results are, thus, useful in predicting the conditions under which the nutrient may act as a pro-oxidant or as an anti-oxidant. The observations suggest that under normal conditions low levels of ascorbate may act as a pro-oxidant through H2O2 production if the system has transition metal ions devoid of chelating agents. At higher concentrations ascorbate acts predominantly as an antioxidant.
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PMID:Copper catalyzed oxidation of ascorbate: chemical and ESR studies. 217 51

Superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (.OH) produced from the "autoxidation" of biomolecules, such as ascorbate, catecholamines, or thiols, have been implicated in numerous toxicities. However, the direct reaction of dioxygen with the vast majority of biomolecules, including those listed above, is spin forbidden, a condition which imposes a severe kinetic limitation on this reaction pathway. Therefore, an alternate mechanism must be invoked to explain the "autoxidations" reactions frequently reported. Transition metals are efficient catalysts of redox reactions and their reactions with dioxygen are not spin restricted. Therefore it is likely that the "autoxidation" observed for many biomolecules is, in fact, metal catalyzed. In this paper we discuss: 1) the quantum mechanic, thermodynamic, and kinetic aspects of the reactions of dioxygen with biomolecules; 2) the involvement of transition metals in biomolecule oxidation; and 3) the biological implications of metal catalyzed oxidations. We hypothesize that true autoxidation of biomolecules does not occur in biological systems, instead the "autoxidation" of biomolecules is the result of transition metals bound by the biomolecules.
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PMID:Transition metals as catalysts of "autoxidation" reactions. 218 96

A review of some of Dr Kinoshita's contributions to our understanding of lens protein and glutathione biochemistry is presented. Particular emphasis is placed on Dr Kinoshita's work involved with the relationship of carbohydrate metabolism and the maintenance of reduced glutathione, the question of the biological function of glutathione in the lens, the effect of oxidative stress provided by diamide and azoester on glutathione, membrane pump function and protein and also ascorbate and H2O2 effects on Na+, K(+)-ATPase. The importance of oxidative stress was recognized early by Dr Kinoshita and he has continued to make significant contributions in this area as illustrated by his work with Dr Zigler on posterior subcapsular cataracts and with Drs Garland and Zigler on mixed function oxidation. It is concluded that Dr Kinoshita's overall contributions in the areas mentioned above have been broad and of considerable importance.
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PMID:Some aspects of Dr Kinoshita's contributions to lens protein chemistry. 219 9

Horseradish peroxidase in the presence of hydrogen peroxide mediates the activation of carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I) to DNA-bound products in vitro. The peroxidase activating system is greater than 10 times more effective with respect to DNA modification by Sudan I than the microsomal enzymes containing cytochrome P450. The DNA-binding reaction of the Sudan I metabolite(s) formed by the peroxidase system is dependent on Sudan I and H2O2 concentration and pH. Reactive intermediate(s) or product(s) of the Sudan I oxidation by peroxidase with a short half-life are responsible for the DNA modification. DNA modified by peroxidase-activated Sudan I becomes colored and has an absorption maximum at approximately 480 nm. The modification of DNA by Sudan I metabolites(s) formed by the peroxidase system is inhibited by some compounds of physiological importance (ascorbate, glutathione, Mg2+ ions) and by radical trapping agents (nitrosobenzene, methyl viologen). 32P-Postlabeling assay of the DNA modified by Sudan I activated by the peroxidase system indicates that the covalent DNA adduct formation is the principal type of the DNA modification. Four major and several minor adducts of deoxyribonucleotide 3',5'-bisphosphate from DNA with Sudan I metabolite(s) were detected by the classical Randerath 32P-postlabelling assay as well as by the nuclease P1 version of the same method.
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PMID:Mechanism of formation and 32P-postlabeling of DNA adducts derived from peroxidative activation of carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxynaphthalene (Sudan I). 220 98

We report here the effect of oxygen free radicals, OFR (superoxide, O2-; hydroxy, OH; t-butylhydroperoxide, H2O2) lipid peroxides (malondialdehyde, MDA), free radical scavengers (superoxide dismutase, catalase, allopurinol) and generator (ferrous chloride) antioxidants (ascorbate, glutathione) spin traps (5,5-dimethyl-1-pyroline-N-oxide, N-t-butyl-L-pheny nitrone) on the cardiac isoenzyme (CK, CK-MB, LDH, LD1) concentrations in the sera of patients with acute myocardial infarction. CK-MB and LD1 were rapidly and completely inactivated by O2- (50 nmol/ml), OH (1 nmol/ml) and MDA (0.6 microM). Butylhydroperoxide (600 microM), and ferrous chloride (200 microM) selectively inhibited CK-MB. The free radical scavengers, antioxidants and spin traps all had minimal effects, and H2O2 had none.
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PMID:Effect of oxygen free radicals and lipid peroxides on cardiac isoenzymes. 227 17

To clarify the significance of catalase in peroxisomes, we have examined the effect of aminotriazole treatment of rats on the activity of beta-hydroxybutyryl-CoA dehydrogenase in liver peroxisomes. When the effect of H2O2 on the dehydrogenase activity was examined using an extract of liver peroxisomes from aminotriazole-treated rats, the acetoacetyl-CoA-dependent oxidation of NADH was found to increase considerably on the addition of dilute H2O2. Such an effect of H2O2 was not seen on the beta-hydroxybutyryl-CoA-dependent reduction of NAD nor with extracts from untreated animals. We then noticed that similar NADH oxidation was caused non-enzymatically by a mixture of acetoacetyl-CoA and H2O2. The oxidation was dependent on both acetoacetyl-CoA and H2O2, and was blocked by scavengers of oxyradicals such as ascorbate and ethanol. Degradation products formed during the reaction of acetoacetyl-CoA with H2O2 had no NADH oxidizing activity, indicating that effective oxidant(s) were generated during the reaction of H2O2 with acetoacetyl-CoA. No other fatty acyl-CoA so far examined nor acetoacetate could replace acetoacetyl-CoA in this reaction. Therefore, if H2O2 were to be accumulated in peroxisomes, it would decrease both NADH and acetoacetyl-CoA, thus affecting the fatty acyl-CoA beta-oxidation system. These results, together with our previous finding that peroxisomal thiolase was significantly inactivated by H2O2 [Hashimoto, F. & Hayashi, H. (1987) Biochim. Biophys. Acta 921, 142-150] suggest that the role of catalase in peroxisomes is at least in part to protect the fatty acyl-CoA beta-oxidation system from the deleterious action of H2O2.
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PMID:Significance of catalase in peroxisomal fatty acyl-CoA beta-oxidation: NADH oxidation by acetoacetyl-CoA and H2O2. 227 34

Chondrocytes in dense suspension culture in agarose survive in serum-free DME because they secrete low molecular mass compounds supporting their own viability. This activity can be replaced by pyruvate, or sulfhydryl compounds, e.g., cysteine or dithioerythritol. Catalase, an enzyme decomposing H2O2, also protects the cells, whereas superoxide dismutase has no effect. Therefore, chondrocytes in culture are sensitive to toxic compounds derived from molecular oxygen, i.e., hydroxyl radicals or hydrogen peroxide spontaneously generated in DME containing ascorbate and ferrous ions. Poly-ADP-ribosylation is an important step in the cascade of events triggered by these compounds. To survive, chondrocytes do not require stimulation by growth factors. They remain resting cells in fully defined, serum-free culture also at low density. Proliferation and hypertrophy can be induced by serum, but not by low cell density alone.
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PMID:Resting chondrocytes in culture survive without growth factors, but are sensitive to toxic oxygen metabolites. 236 33

Changes in activities of ascorbate free radical (AFR) reductase (NADH:AFR oxidoreductase) and H2O2-dependent NADH oxidation were correlated with levels of insoluble protein in senile cataractous human lenses. The H2O2-dependent NADH oxidation activity was measured to reflect the content of free glutathione. AFR reductase activities in all the cataractous lenses assayed here tended to decrease with increase of insoluble protein contents. A similar tendency in the relationship between lens protein aggregation and H2O2-dependent NADH oxidation activities, i.e. free glutathione contents was recognized in the lenses with pale yellow, yellow or dark yellow nucleus. However, for the highest levels of insoluble protein, some of the brunescent cataractous lenses exhibited very high activities of H2O2-dependent NADH oxidation, and some brunescent lenses had very low activities. From the above results, it is suggested that lens protein aggregates in the brunescent and non-brunescent cataractous lenses may be formed through significantly different oxidation processes, respectively. The possible mechanisms such as free radical reaction and disulfide bond formation are discussed.
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PMID:Activities of ascorbate free radical reductase and H2O2-dependent NADH oxidation in senile cataractous human lenses. 237 70

It has been indicated recently that ascorbic acid is responsible for the hemoglobin-mediated oxidative damage to the central nervous system (Sadrzadeh & Eaton, J. Clin. Invest. 82:1510-1515, 1988). In this paper we describe the changes in chemiluminescence accompanying hemoglobin- and ascorbate-dependent oxidative injury to brain tissue. Addition of either hemoglobin (15 microM) or ascorbate (1 or 2 mM) to rat brain homogenates stimulated spontaneous chemiluminescence in a synergistic manner. This increase in chemiluminescence was inhibited by desferrioxamine indicating that free iron was involved in the reactions leading to lipid peroxidation. Preincubation with ascorbate oxidase inhibited both spontaneous and hemoglobin-dependent chemiluminescence, suggesting that ascorbate was required for the reactions leading to lipid peroxidation. Supplementation with aminotriazole (an irreversible inhibitor of the catalase-H2O2 complex) increased chemiluminescence in a time-dependent manner, as catalase reacted with accumulated H2O2, suggesting that ascorbic acid has a dual action being involved in the production of H2O2 and also maintaining Fe in the reduced state to catalyze a Fenton-like reaction. The excited species responsible for the chemiluminescence were partially characterized by adding specific fluorescent energy acceptors: dibromoanthracene (DBA) and diphenylanthracene (DPA). Both DBA and DPA stimulated chemiluminescence several-fold indicating that triplet and singlet species are responsible for the observed chemiluminescence. Excited singlet carbonyls (identified with DPA) may be produced during the collision of two ROO.. Singlet oxygen may also be generated during the same reaction. It decays to the triplet state (emitting chemiluminescence at 634 nm) and reacts with double bonds producing dioxetanes, which may breakdown generating triplet carbonyls (identified with DBA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ascorbate- and hemoglobin-dependent brain chemiluminescence. 237 61

Perfusate, blood plasma and tissue homogenate were investigated by H2O2-stimulated chemiluminescence (CL) and photochemiluminescence (PCL) during experimental liver and kidney transplantation. The canine kidneys were perfused prior to reimplantation for 68 h at 4 degrees C. The increase of the H2O2 CL of the perfusate correlated positively with the LDH activity. After ischemic load of the liver, the antioxidative capacity (AC) of the tissue as determined by PCL decreases. After transplantation of the stored liver (1 h, 4 degrees C) an increased AC is observed in peripheral blood. This increase is lower after addition of ascorbate to the preservation solution. The results allow to conclude that both methods are suitable for the characterization of the organ status after hypoxic injury during conservation.
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PMID:Local and systemic effects of organ hypoxia detected by chemiluminescence and photochemiluminescence. 240 43


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