Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carbon monoxide complex of ascorbate-reduced dopamine beta-hydroxylase has been prepared and characterized by Fourier transform infrared, fluorescence, and x-ray absorption spectroscopies. CO has previously been shown to be a competitive inhibitor with respect to O2, and binds to only one of the two copper atoms/active site (Blackburn, N. J., Pettingill, T. M., Seagraves, K. S., and Shigeta, R. T. (1990) J. Biol. Chem. 265, 15383-15386). Thus, it acts as an excellent probe of the O2-binding site. A single C-O infrared absorption band is observed at 2089 cm-1, shifting by 46 cm-1 to lower energy on substitution with either 13C16O or 12C18O. The 13C isotope shift is reversed to the position expected for 12CO upon vacuum flushing with 12CO gas, indicating that formation of the CO adduct is a fully reversible process. Binding of the substrate tyramine does not eliminate the infrared peak but causes a 3-cm-1 shift to lower energy. On the other hand, binding of a bifunctional inhibitor which cross-links the substrate and O2-binding site does eliminate the CO peak. These data, in conjunction with the competitive nature of CO binding with respect to O2, identify the CO-binding site as the O2-binding site, and place it in close proximity to the substrate-binding site. CO-dopamine beta-hydroxylase exhibits no luminescence in the visible region, suggesting a structure different from carbonmonoxy hemocyanin, and in all probability mononuclear. Analysis of extended x-ray absorption spectroscopy data is most consistent with an average coordination per Cu of 2-3 histidines, 0.5 CO, and 0.5 S atoms as ligands, and absorption edge comparisons indicates pseudo-4 coordination as the most likely geometry at each Cu(I) center. The results can be interpreted by a model involving inequivalent 4-coordination at each Cu(I) center in the CO adduct with CuAHis3S...CuBHis2CO-X as the coordination most consistent with all of the data.
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PMID:Carbonmonoxy dopamine beta-hydroxylase. Structural characterization by Fourier transform infrared, fluorescence, and x-ray absorption spectroscopy. 189 98

Ascorbate reversibly inhibits catalase, and this inhibition is enhanced and rendered irreversible by the prior addition of copper(II)-bishistidine. In the absence of copper, the inhibition was prevented and reversed by ethanol, but not by superoxide dismutase, benzoate, mannitol, thiourea, desferrioxamine, or DETAPAC. In the presence of the copper complex mannitol, benzoate, and superoxide dismutase still had no effect, but thiourea, desferrioxamine, DETAPAC, or additional histidine decreased the extent of inactivation to that seen in the absence of copper. In the presence of copper, ethanol protected at [ascorbate] less than 1 mM, but was ineffective at [ascorbate] greater than 2 mM, even in the absence of oxygen. Although in the absence of copper, complete removal of oxygen provided full protection against inactivation by ascorbate, this protection was not seen if the catalase was briefly preincubated with H2O2 prior to flushing with nitrogen, or if copper was present. In fact, if copper was present, inactivation was enhanced by the removal of oxygen. Increasing the concentration of oxygen from ambient to 100% slowed the inactivation, whether or not copper was present. It is concluded that the initial reversible inactivation involves reaction with H2O2 to form compound I, followed by one electron reduction of compound I to compound II. In the presence of added copper, the initial (reversible) inactivation allows H2O2 to accumulate sufficiently to permit irreversible inactivation. Since in the presence of copper oxygen is not required, and neither the reversible nor the irreversible inactivation was prevented by conventional scavengers of active forms of oxygen, the inactivation is likely mediated by semidehydroascorbate, and/or it may involve site-specific generation of the damaging intermediates.
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PMID:Mechanism of the inhibition of catalase by ascorbate. Roles of active oxygen species, copper and semidehydroascorbate. 300 60

Dog kidneys were preserved by simple hypothermic storage in UW-lactobionate organ preservation solution for 48 h and analyzed for evidence of lipid peroxidation. The antioxidant function of the UW solution was evident in stored kidney tissues which had significant reductions in conjugated dienes, lipid peroxides, and Schiff base content compared to fresh controls without vascular flushing. Aerobic incubation of kidney cortex homogenates at 37 degrees C for 60 min resulted in increases in conjugated dienes, lipid peroxides, and Schiff bases in UW-stored kidneys. Schiff base production was markedly higher in UW-stored kidneys during warm incubation than in controls. Addition of Trolox (200 microM) to UW solution resulted in significant reductions in Schiff base production during warm aerobic incubation after preservation. In contrast, adding ascorbate (1 mM) to UW solution potentiated oxidative stress during aerobic incubation, with significant increases in conjugated dienes, lipid peroxides, and Schiff bases which were only partially reversed by further addition of Trolox. Increased oxidative stress was correlated with decreased respiratory function (decreased uncoupled respiration rates and sensitivity to oligomycin inhibition) in aerobically incubated homogenates. This study showed that although the UW solution does have an antioxidant function during hypothermic preservation there remains an increased oxidative stress during warm reoxygenation even in optimally harvested kidneys. The antioxidant effect of the UW solution after preservation can be significantly enhanced using the water-soluble vitamin E analogue Trolox. Antioxidant supplementation of UW solution may be advantageous in preserving kidneys with increased oxidative stresses obtained from suboptimal donors in clinical practice.
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PMID:The effect of simple hypothermic preservation with Trolox and ascorbate on lipid peroxidation in dog kidneys. 867 54

The objective of the present communication is to describe the role played by combinations between diethydithiocarbamate (DDC) and divalent metals in hemolysis of human RBC. RBC which had been treated with DDC (10-50 microM) were moderately hemolyzed (about 50%) upon the addition of subtoxic amounts of Cu2+ (50 microM). However, a much stronger and a faster hemolysis occurred either if mixtures of RBC-DDC were immediately treated either by Co2+ (50 microM) or by a premixture of Cu2+ and Co2+ (Cu:Co) (50 microM). While Fe2+ and Ni2+, at 50 microM, initiated 30-50% hemolysis when combined with DDC (50 microM), on a molar basis, Cd2+ was at least 50 fold more efficient than any of the other metals in the initiation of hemolysis by DDC. On the other hand, neither Mn2+ nor Zn2+, had any hemolysis-initiating effects. Co2+ was the only metal which totally blocked hemolysis if added to DDC prior to the addition of the other metals. Hemolysis by mixtures of DDC + (Cu:Co) was strongly inhibited by anaerobiosis (flushing with nitrogen gas), by the reducing agents glutathione, N-acetyl cysteine, mercaptosuccinate, ascorbate, TEMPO, and alpha-tocopherol, by the PLA2 inhibitorbromophenacylbromide (BrPACBr), by tetracycline as well as by phosphatidyl choline, cholesterol and by trypan blue. However, TEMPO, BrPACBr and PC were the only agents which inhibited hemolysis induced by DDC: Cd2+ complexes. On the other hand, none of the classical scavengers of reactive oxygen species (ROS) employed e.g dimethylthiourea, catalase, histidine, mannitol, sodium benzoate, nor the metal chelators desferal and phenanthroline, had any appreciable inhibitory effects on hemolysis induced by DDC + (Cu:Co). DDC oxidized by H2O2 lost its capacity to act in concert either with Cu2+ or with Cd2+ to hemolyze RBC. While either heating RBC to temperatures greater than 37 degrees C or exposure of the cells to glucose-oxidase-generated peroxide diminished their susceptibility to hemolysis, exposure to the peroxyl radical from AAPH, enhanced hemolysis by DDC + (Cu:Co). The cyclovoltammetry patterns of DDC were drastically changed either by Cu2+, Co2+ or by Cd2+ suggesting a strong interaction of the metals with DDC. Also, while the absorbance spectrum of DDC at 280 nm was decreased by 50% either by Co2+, Cd2+ or by H2O2, a 90% reduction in absorbance occurred if DDC + H2O2 mixtures were treated either by Cu2+ or by Co2+, but not by Cd2+. Taken together, it is suggested that DDC-metal chelates can induce hemolysis by affecting the stability and the integrity of the RBC membrane, and possibly also of the cytoskeleton and the role played by reducing agents as inhibitors might be related to their ability to deplete oxygen which is also supported by the inhibitory effects of anaeobiosis.
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PMID:Hemolysis of human red blood cells induced by the combination of diethyldithiocarbamate (DDC) and divalent metals: modulation by anaerobiosis, certain antioxidants and oxidants. 1049 Feb 37

Ascorbic acid (vitamin C) induced hydroxyl radical formation was measured in household drinking water samples using the hydroxyl radical sensitive probe coumarin-3-carboxylic acid. Vitamin C, a reducing agent that is commonly used as a food additive, triggered a significant hydroxyl radical generating reaction when added to the tap-water samples tested. The capacity of ascorbic acid to trigger hydroxyl radical formation in the tap-water samples was dependent on the flushing time before the samples were taken indicating that the water in the copper piping had been contaminated by copper ions. In line with this, high concentrations of copper were measured in the hydroxyl radical generating first-draw samples. Moreover, a strong correlation was found between the hydroxyl radical generation capacity seen in the coumarin-3-carboxylic acid based microplate assay and the DNA damage seen in an agarose gel assay using the pBluescript plasmid. In the water samples showing high capacity to hydroxylate coumarin-3-carboxylic acid, a rapid formation of the open circular form of the plasmid could also be seen indicating a copper assisted hydroxyl radical attack on the DNA. In conclusion, our results show that addition of vitamin C to household tap water that is contaminated with copper ions, results in Fenton type reactions that continuously generate harmful and reactive hydroxyl radicals.
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PMID:Measurement of ascorbic acid (vitamin C) induced hydroxyl radical generation in household drinking water. 1260 17