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 alpha-ketoglutarate dioxygenase, thymine 7-hydroxylase (EC 1.14.11.6), has been purified from cultures of Rhodotorula glutinis grown with thymine as a nitrogen source. The purification scheme developed yielded essentially homogeneous preparations of the 7-hydroxylase and also purified another alpha-ketoglutarate dioxygenase, pyrimidine deoxyribonucleoside 2'-hydroxylase (EC 1.14.11.3). The purity of the 7-hydroxylase was determined with analytical disc gel electrophoresis in which runs were varied with respect to pH, extent of cross-linking, and the presence of sodium dodecyl sulfate-mercaptoethanol. The 7-hydroxylase apparently exists as a monomer since its molecular weight was 42,700 when determined by molecular gel filtration chromatography and was 40,300 when determined by analytical disc gel electrophoresis under denaturing conditions. Gel filtration chromatography under nondenaturing conditions was used to show that the 2'-hydroxylase has a molecular weight of 64,600. The essentially homogeneous preparations of the 7-hydroxylase were shown to catalyze the thymine-, 5-hydroxymethyluracil-, and 5-formyluracil-dependent oxygenations that are coupled to the decarboxylation of alpha-ketoglutarate, as well as a putative uncoupled decarboxylation which is dependent on uracil. Furthermore, these enzyme preparations were used to show that ATP stimulated the 7-hydroxylase reaction in the absence of ascorbate. Even though it is attractive to consider the four pyrimidine-dependent reactions as being catalyzed by the same active site, they were shown to differ markedly in their dependencies on ascorbate or ATP. The effects of ascorbate and ATP on these reactions, and on the 2'-hydroxylase reaction, are discussed in terms of the possible roles of ascorbate and ATP.
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PMID:Markedly different ascorbate dependencies of the sequential alpha-ketoglutarate dioxygenase reactions catalyzed by an essentially homogeneous thymine 7-hydroxylase from Rhodotorula glutinis. 668 17

The divalent cations, Ca++ and Mg++, are known to competitively inhibit a large number of aminoglycoside-membrane interactions, so that Ca++ prevents both the neurotoxic and ototoxic effects of these antibiotics acutely in vitro. Since gentamicin-induced plasma and subcellular membrane damage appear to be critical pathogenetic events in gentamicin nephrotoxicity, Ca++ may play a similar protective role in gentamicin-induced acute renal failure. To test this possibility in vivo, rats (group 2) were given a 4% calcium (in the form of CaCO3) supplemented diet to increase delivery of Ca++ to the kidney and administered single daily subcutaneous injections of gentamicin, 100 mg/kg, for 10 d. Compared with a simultaneously studied group (group 1) of rats receiving identical gentamicin dosages and normal diets, Ca++ supplementation ameliorated gentamicin-induced acute renal failure. After 10 doses of gentamicin, blood-urea nitrogen values in group 1 averaged 213 +/- 15 (SE) and 25 +/- 3 (P less than 0.001) in group 2. The progressive decline in renal excretory function, as measured by BUN, in group 1 animals was accompanied by simultaneous declines in renal cortical mitochondrial function and elevations in renal cortex and mitochondrial Ca++ content, quantitative indices of the degree of renal tubular cell injury. Oral Ca++ loading markedly attenuated these gentamicin-induced derangements. After eight and 10 doses of gentamicin, mitochondria isolated from the renal cortex of group 2 rats had significantly higher rates of respiration supported by pyruvate-malate, succinate and N,N,N',N'-tetramethyl-p-phenyldiamine-ascorbate, higher rates of dinitrophenol-uncoupled respiration and greater acceptor control ratios than those measured in mitochondria isolated from the renal cortex of group 1 animals. Similarly, after 8 and 10 doses, renal cortex and renal cortical mitochondrial Ca++ content of group 2 was significantly lower than values observed in group 1. Thus, dietary calcium supplementation significantly protected against gentamicin-induced renal tubular cell injury and, consequently, gentamicin-induced acute renal failure. The mechanism for this protective effect of Ca++ may relate to the manner in which this polycationic antibiotic interacts with anionic sites, primarily the acidic phospholipids of renal membranes. In this regard, Ca++ was found to be a competitive inhibitor both of 125I-gentamicin binding to renal brush border membranes, the initial site of interaction between gentamicin and renal proximal tubule cells, with a composite inhibition constant (Ki) of 12 mM and of 125I-gentamicin binding to phosphatidic acid, an important membrane acidic phosph
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PMID:Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity. 669 Apr 74

Air pollution may affect athletic performance. In Los Angeles, contaminants include carbon monoxide, ozone, peroxyacetylnitrate (PAN) and nitrogen oxides, whereas in older European cities, such as Sarajevo, "reducing smog" of sulfur dioxide is the main hazard. The carbon monoxide and ozone levels expected in Los Angeles this summer could affect the athletes' performance in endurance events at the Olympic Games. Carbon monoxide may also impair psychomotor abilities, and PAN causes visual disturbances. The only likely physiologic consequence from reducing smog is an increase in the workload of the respiratory system and thus a decrease in endurance performance. While carbon monoxide has been blamed for myocardial infarctions, nitrogen oxides for pulmonary edema and sulfur dioxide for deaths due to respiratory failure, the only illnesses that are likely to be more frequent than usual among young athletes exposed to high levels of these pollutants are upper respiratory tract infections. Therapeutic tactics include the avoidance of pollution, the administration of oxygen, vitamin C and vitamin E, and general reassurance.
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PMID:Athletic performance and urban air pollution. 674 56

In ulcerative colitis, total colectomy with ileo-rectal anastomosis is commonly performed in Europe. Whether this procedure induces a protein caloric malnutrition and/or a radical modification of diet is not known. Twenty-one patients with ileo-rectal anastomosis and 21 normal subjects who were matched for age, sex, social behavior and habitat were therefore studied concomitantly. In all subjects, the diet contents in energy, nitrogen, glucids, lipids, proteins, dietary fibers and vitamin C, were quantitatively determined. Evaluation of nutritional status included body weight measurement and determination of biological markers: serum albumin, prealbumin, transferrin, hemoglobin and urinary creatinine. The energy and nitrogen intakes of the patients were not different from those of control subjects: respectively 2,187 +/- 612 versus 2,038 +/- 589 kcal/day and 15.4 +/- 5.9 versus 16.0 +/- 5.2 g/day. In contrast, the dietary fiber and vitamin C contents of the diet were significantly lower in patients than in control subjects: respectively 9.7 +/- 5.5 versus 14.6 +/- 5.6 g/day and 43.5 +/- 29.9 versus 72.4 +/- 23.7 mg/day (p less than 0.05). There was no difference in nutritional status between patients and the control group. Thus, in ulcerative colitis, ileorectal anastomosis seems to cause neither protein caloric malnutrition nor radical modifications in diet. Nevertheless, the low intake in vitamin C suggests that supplementation with ascorbic acid may be useful in these patients.
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PMID:[Dietary behavior and nutritional status of patients with ileorectal anastomosis after total colectomy for hemorrhagic rectocolitis]. 674 76

2-Bromohydroquinone was identified as a metabolite of both bromobenzene and o-bromophenol in the rat in vivo and in vitro. Identification was based on high-pressure liquid chromatography and gas chromatography-mass spectrometry. Formation of 2-bromohydroquinone by rat liver microsomes from both bromobenzene and o-bromophenol was increased by treatment of rats with either phenobarbital or 3-methylcholanthrene. Covalent binding of o-bromophenol to rat liver microsomes was inhibited by glutathione and ascorbate but not by superoxide dismutase or catalase. Liver microsomes converted o-bromophenol to 2-bromohydroquinone and covalently bound material, whereas kidney and lung microsomes metabolized o-bromophenol less rapidly. Administration of 2-bromohydroquinone to rats caused a dose- and time-dependent decrease in hepatic and renal glutathione levels, an increase in blood urea nitrogen levels and histopathological changes in kidney without causing any alterations to the liver. The histological changes in the kidney were indistinguishable from those observed after either bromobenzene or o-bromophenol administration. However, the dose of 2-bromohydroquinone required to elicit a similar nephrotoxicity was less than 10% of that of bromobenzene. Thus, 2-bromohydroquinone may play a role in the nephrotoxicity observed after bromobenzene administration. Although the nature of the nephrotoxic metabolite of 2-bromohydroquinone is not known, our present results suggest that 2-bromohydroquinone or a conjugate thereof may be formed in the liver and transported to the kidney where it elicits toxicity.
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PMID:Identification of 2-bromohydroquinone as a metabolite of bromobenzene and o-bromophenol: implications for bromobenzene-induced nephrotoxicity. 674 40

The kinetics of the reduction of metmyoglobins by ascorbic acid (H2A) were studied under a nitrogen atmosphere at 25 degrees C, at an ionic strength of 0.30 M (NaCl), and between pH 7.18 and 8.09. Neither Tris-HCl nor phosphate buffers had any effect on the reduction of metmyoglobin. Imidazol and 1-methylimidazol accelerated this reaction, but N3- and CN- ions inhibited it. It is concluded that the reduction of imidazolmetmyoglobin or 1-methylimidazolmetmyoglobin is faster than that of aquametmyoglobin and that neither azidometmyoglobin nor cyanometmyoglobin can be reduced by ascorbate under the present experimental conditions. The second-order rate constants were determined for the reductions of aqua-, imidazol-, and 1-methylimidazolmetmyoglobin by ascorbate (HA- and A2-). The higher reactivity of imidazolmetmyoglobin with ascorbate may be due to the easy transfer of an electron of ascorbate to partially exposed imidazol or porphyrin ring because of expansion of the heme pocket induced by the coordination of imidazol.
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PMID:Kinetic studies on the reduction of metmyoglobins by ascorbic acid. 684 27

Groups of 3-5 Swiss CD1 mice were gavaged with aqueous solutions of sodium nitrite (250 micrograms), followed immediately by morpholine (5 micrograms) or dimethylamine (250 micrograms). At subsequent intervals, up to 30-60 min, mice were frozen, pulverized in liquid nitrogen and extracted with methylene chloride. Volatile nitrosamines were then quantitatively determined using a Thermal Energy Analyzer, interfaced to GC or HPLC. Biosynthesis of both N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) showed a time-dependent increase for 3 and 9 min, respectively, followed by a steady decline. Levels of NDMA and NMOR were generally less than 0.1 ng/g in control mice gavaged with amine or nitrite alone. Zero-time recovery of NDMA and NMOR ranged from 50-70% and 70-90%, respectively. Biosynthesis of NDMA and NMOR was inhibited by prior administration of ascorbic acid, sodium ascorbate or ammonium sulfamate.
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PMID:Kinetics of nitrosamine formation in mice following oral administration of trace-level precursors. 722 50

The laws by which a number of substances fix nitrogen oxide and sodium nitrite were studied. Nitrogen oxide leads to the formation of compounds of the N O X type, characterised by the following equilibrium constants: 1.93 X 10(-2) for sodium ascorbate, 1.96 X 10(-2) for cysteine, 2.79 X 10(-2) for guanidine, 1.43 X 10(-3) for glutathion, 0.384 for sarcosin, 4.6 X 10(-2) for galacturonic acid, and 1.8 X 10(-3) for neuraminic acid. Mucic, benzoic, lactic and gallic acid do not fix this oxide, nor do glycerol and imidazole. Of all the substances listed above, only ascorbate and cysteine fix nitrite. It was not possible to establish any direct fixing law. This fact, taken with the conditions of the medium, leads to the conclusion that nitrite is fixed only after reduction, in the form of nitrogen oxide NO, according to the laws referred to above.
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PMID:[Blockade of nitrogen oxide and nitrites by various substances]. 725 4

The effects of galacturonic, gallic, acetylneuraminic acid, ascorbate, cysteine, glutathion and imidazole on the formation of dimethylnitrosamine and diethylnitrosamine was studied in a simple aqueous medium with four different nitrite contents (50, 100, 500 and 1 000 ppm) and the two amines, compared with control samples. The nitrosamines were determined by the TELLING method (confirmed by photolysis). The results observed were compared with the laws of fixing nitrite in the form of nitrogen oxide, studied previously. For sarcosin and imidazole, the fixing takes into account the phenomena observed. The other substances lead to a conclusion that there are two stages in the process: 1) fixing of the nitrite to a greater or lesser degree in the form of a nitrogen oxide complex, 2) direct effect on the nitrosation reaction which is catalysed or slowed down. The discussion based on the literature, concludes that the final nitrosation reaction give rise to free radicals, even in an aqueous medium.
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PMID:[Effect of various blockers of nitrite and nitrogen oxide on the formation of nitrosamines]. 725 5

Epidemiologic evidence suggests that cigarette smoking is a major risk factor for chronic obstructive pulmonary diseases such as chronic bronchitis and emphysema, for carcinogenesis, and for cardiovascular disease. However, the precise mechanisms of these effects are incompletely understood. The gas phase of cigarette smoke contains abundant free radicals including nitric oxide. Hence, cigarette smoke may induce some of its damaging effects by free radical mechanisms. We report that exposure of plasma, a model for respiratory tract lining fluids, to gas-phase cigarette smoke causes depletion of antioxidants, including ascorbate, urate, ubiquinol-10, and alpha-tocopherol, and a variety of carotenoids, including beta-carotene. Gas-phase cigarette smoke induced some lipid peroxidation, as measured by cholesteryl linoleate hydroperoxide (18:2OOH) formation. Ascorbate was effective in preventing 18:2OOH formation. In contrast to the low concentrations of lipid hydroperoxides measured (< 1 mumol/L), protein carbonyl formation, a measure of protein modification, increased by approximately 400 mumol/L after nine puffs of cigarette smoke. Reduced glutathione inhibited protein carbonyl formation, whereas other plasma antioxidants, including ascorbate, were ineffective. alpha, beta-Unsaturated aldehydes (acrolein and crotonaldehyde) in cigarette smoke may react with protein -SH and -NH2 groups by a Michael addition reaction that results in a protein-bound aldehyde functional group. Gas-phase cigarette smoke is capable of converting tyrosine to 3-nitrotyrosine and dityrosine, indicating free radical mechanisms of protein damage by nitrogen oxides. Aldehydes and nitrogen oxides in cigarette smoke may be significant contributors to biomolecular damage, and endogenous antioxidants can attenuate some of these adverse effects.
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PMID:Dietary antioxidants and cigarette smoke-induced biomolecular damage: a complex interaction. 749 50


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