Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several inherited metabolic disorders of the transsulfuration pathway are discussed. They are hypermethioninemia, homocystinuria, cystathioninuria, beta-mercaptolactate cysteine disulfideuria and sulfite oxidase deficiency (SOD). Primary coverage is given to homocystinuria and SOD. In the case of homocystinuria, metabolic defects include cystathionine beta-synthase deficiency, methylenetetrahydroforate reductase deficiency, and mutations in cobalamin metabolism. Their main clinical pictures, metabolic abnormalities, and treatment are also described. SOD appears in two cases as an isolated enzyme defect and a combined deficiency of sulfite oxidase and xanthine dehydrogenase that share a common molybdenum cofactor. The clinical, biochemical and neurological features of the two disorders are reviewed.
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PMID:[Inherited metabolic disorders of the transsulfuration pathway]. 140 82

Clinical evidence has suggested that mitomycin C (MMC) potentiates doxorubicin (DOX) induced cardiotoxicity. In this study a mouse model was used to examine the effect of DOX on the ability of cardiac tissue to bioactivate MMC to generate oxygen radicals. Cardiac damage was assessed by measuring serum CPK-MB isoenzyme levels and thiobarbituric acid reactive substances (TBARS) in the cardiac tissue. The exposure of animals to DOX or DOX and MMC over a three week period led to an increase in serum CPK-MB isoenzyme levels as well as TBARS. Treatment with DOX led to an increase in MMC-dependent, NADH-dependent, cyanide insensitive oxygen consumption, compared to control animals, thereby suggesting increased MMC-dependent oxygen radical generation. Levels of xanthine oxidase (XO; EC 1.1.3.22) and NADPH:cytochrome C reductase, two enzymes known to bioactivate MMC with subsequent oxygen radical generation, were measured in cardiac tissue with a 4.5 x increase in XO activity seen in DOX treated animals vs controls and no change in NADPH:cytochrome C reductase activity. Cardiac levels of xanthine dehydrogenase (XDH; EC 1.1.1.204) activity in DOX treated animals decreased while the XO/XDH ratio increased, suggesting a conversion of XDH to XO following DOX treatment.
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PMID:Role of xanthine oxidase in the potentiation of doxorubicin-induced cardiotoxicity by mitomycin C. 191 Oct 46

During the reductive process in the tissues, the aerobes generate a number of oxidants. Unless these oxidants are reduced, oxidative damage and cell death would occur. Oxidation of plasma membrane lipids leads to autocatalytic chain reactions which eventually alter the permeability of the cell. The role of oxidative damage in the pathophysiology of diabetic complications and ischemic reperfusion injury of myocardium, especially the changes in the channel activity which may lead to arrhythmia have been studied. Hyperglycemia activates aldose reductase which could efficiently reduce glucose to sorbitol in the presence of NADPH. Since NADPH is also aldose required by glutathione reductase for reducing oxidants, its diversion would lead to membrane lipid oxidation and permeability changes which are probably responsible for diabetic complications such as cataractogenesis, retinopathy, neuropathy etc. Antioxidants such as butylated hydroxy toluene (BHT) and also reductase inhibitors prevent or delay some of these complications. By using patch-clamp technique in isolated frog myocytes, we have shown that hydroxy radicals generated by ferrous sulfate and ascorbate as well as lipid peroxides such as t-butyl hydroperoxide facilitate the entry of Na+ by oxidizing Na+-channels. Increased intracellular Na+ leads to an increase in Na+/Ca2+ exchange. The increased Na+ concentration by itself may produce electrical disturbance which would result in arrhythmia. Increased Ca2+ may affect proteases and may help in the conversion of xanthine dehydrogenase to xanthine oxidase, consequently increased production of super oxide radicals. Increased membrane lipid peroxidation and other oxygen free-radical associated membrane damage in myocytes has been demonstrated.
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PMID:The effect of oxidants on biomembranes and cellular metabolism. 251 41

Native FAD was removed from chicken liver xanthine dehydrogenase (XDH) and replaced with a number of artificial flavins of different redox potential. Dithionite titration of the 2-thio-FAD- or 4-thio-FAD (high potential)-containing enzymes showed that the first center to be reduced was the flavin. With native enzyme, iron-sulfur centers are the first to be reduced. With the low potential flavin, 6-OH-FAD, the enzyme-bound flavin was the last center to be reduced in reductive titration with xanthine. These shifts in the reduction profile support the hypothesis that the distribution of reducing equivalents in multi-center oxidation-reduction enzymes of this type is determined by the relative potentials of the centers. The reaction of molecular oxygen with fully reduced 2-thio-FAD XDH or 4-thio-FAD XDH resulted in 5 electron eq being released in a fast phase and one in a slow phase. Reduction of these enzymes by xanthine was limited at a rate comparable to that for the release of urate from native XDH. Xanthine/O2 turnover with these enzymes (and native XDH) resulted in approximately 40-50% of the xanthine reducing equivalents appearing as superoxide. Steady state turnover experiments involving all modified flavin-containing enzymes, as well as native enzyme, showed that shifting the flavin potential either positive or negative relative to FAD caused a decrease in catalytic activity in the xanthine/NAD reductase reaction. In the case of the xanthine/O2 reductase activity, there is no simple obvious relationship between the activity and the redox potential of the reconstituted flavin.
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PMID:Reactivity of chicken liver xanthine dehydrogenase containing modified flavins. 253 67

The reaction of 6-electron reduced chicken liver xanthine dehydrogenase (XDH) with molecular oxygen was studied using both stopped flow and steady-state turnover techniques at pH 7.8, 4 degrees C. Oxidation of fully reduced XDH proceeded via four phases, three of which were detected with the stopped flow spectrophotometer. The fastest phase was second order in oxygen (1900 M-1 s-1), resulted in the appearance of flavin semiquinone and yielded no superoxide. The next phase was also second order in oxygen (260 M-1 s-1), involved the loss of flavin semiquinone and yielded, on average, 1 mol of superoxide/mol of XDH oxidized. The last 2 electron equivalents were located in the iron-sulfur centers. They were released one equivalent at a time in the form of superoxide. Steady-state kinetics were found to be critically dependent on temperature and oxygen concentration. When these factors were carefully controlled, both the xanthine-oxygen and NADH-oxygen reductase reactions gave linear Lineweaver-Burk plots. The xanthine-oxygen data yielded a turnover number of 43 min-1, which was 42% of that for xanthine-NAD turnover. During turnover, with xanthine and O2, 40-44% of the electron equivalents introduced by xanthine appeared as superoxide. Reduced pyridine nucleotides, NAD and 3-aminopyridine adenine dinucleotide, dramatically reduced the formation of superoxide at levels which did not seriously inhibit oxygen reactivity.
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PMID:The reactivity of chicken liver xanthine dehydrogenase with molecular oxygen. 291 19

Reduced nicotinamide adenine dinucleotide (NADH):ferricyanide reductase and DT-diaphorase specific activity in total homogenates of rat liver are markedly decreased as a very early biochemical event of hepatocarcinogenesis induced by the carcinogen 2-acetylaminofluorene (AAF). A 50 to 75% decrease in NADH:ferricyanide reductase was observed after 1 day of AAF (0.025% in the diet) feeding and persisted throughout a 7-week continuum of AAF administration. Carcinogen added directly to cell extracts had no effect. Similar results were obtained with single injections of either AAF or diethylnitrosamine. Xanthine dehydrogenase was also reduced in liver following AAF administration to nearly the same extent as NADH:ferricyanide reductase and DT-diaphorase. Total NADH-cytochrome c reductase and mitochondrial activity as estimated from succinic dehydrogenase were not affected by carcinogen administration relative to basal dietary controls. The reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase that functions in drug detoxification was elevated. With livers of animals fed 4-acetamidophenol, a hepatotoxin chemically related to AAF, small decreases were noted in NADH:ferricyanide reductase, but not in xanthine dehydrogenase nor in DT-diaphorase. Initial lowering of these activities in the livers of the carcinogen-treated animals is preceded by or concomitant with a reduction in the levels of extramitochondrial pyridine nucleotides known from other studies to result from DNA damage.
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PMID:Decreased NADH-oxidoreductase activities as an early response in rat liver to the carcinogen 2-acetylaminofluorene. 396 29

The chemistry of Se suggests that, in biological systems, it is most likely present as the selenol (selenomercaptan)R-SeH, or, as the Se ether analogous to sulfur in the amino acid methionine. Selenols are stronger acids than mercaptans and, at physiological pH, exist mainly in anionic form (R-Se-) whereas the sulfhydryl group exists mainly in the protonated form. The anionic form of the selenohydryl group is a good nucleophile as well as a good leaving group. Also, it binds metals strongly, which is the principle behind the use of Se compounds for heavy metal detoxification. Conversely, metal ions can strip Se from organoselenium compounds and Hg, Cd, Pb, and Cu are highly effective in this capacity. In vivo, Se compounds tend to undergo reduction in contrast to sulfur compounds which are acquired in reduced form and generally undergo oxidation. Biosynthesis of methylated Se compounds, yielding dimethyl selenide, dimethyl diselenide, or trimethyl selenonium ion, appears to be the major pathway of Se metabolism/detoxification in animals. The highest activity of the pathway has been found in liver and kidney followed by lung, skeletal muscle, spleen, and heart. Selenium (Se) appears to be incorporated into proteins via post transcriptional modification of polypeptides. Six proteins that incorporate/require Se have been isolated: Se-dependent glutathione peroxidase (GSH-Px), the selenoprotein of muscle, selenoflagellin, Se-transport protein, and the bacterial enzymes formate dehydrogenase and glycin reductase. There is evidence also that Se is an essential component of nicotinic acid hydroxylase, xanthine dehydrogenase, and a bacterial thiolase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemistry of selenium: a brief overview. 635 27

The amino acid sequence of chicken liver xanthine dehydrogenase (EC 1.1.1.204) was determined by cDNA cloning and partial amino acid sequencing of the purified enzyme. The enzyme consisted of 1358 amino acids with calculated molecular mass of 149,633 Da. In order to compare the structure of the chicken and rat enzymes, limited proteolysis was performed with the purified chicken liver xanthine dehydrogenase. When the enzyme was digested with subtilisin, it was not converted from the NAD-dependent dehydrogenase type to the O2-dependent oxidase type, in contrast with the mammalian enzyme. However, the enzyme was cleaved mainly into three fragments in a manner similar to that for the rat enzyme at pH 8.2 (20, 37, and 84 kDa) and retaining a full complement of redox centers. The cleavage sites were identified by determination of amino-terminal sequences of the produced fragments. It was concluded that the 20-kDa fragment was amino-terminal, the 84-kDa fragment carboxyl-terminal, and the 37-kDa fragment an intermediate portion in the enzyme protein. On the other hand, when the enzyme was digested with the same protease at pH 10.5, the sample contained only the 20- and 84-kDa portions and lacked the 37-kDa portion. The resultant sample possessed xanthine dichlorophenol indophenol reductase activity, indicating that the molybdenum center remained intact. The absorption spectrum showed the sample was very similar to deflavo-enzyme. From these results and sequence analyses, the domain structure of the enzyme is discussed.
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PMID:The structure of chicken liver xanthine dehydrogenase. cDNA cloning and the domain structure. 785 55

In this report, we describe the isolation of a 4020-bp genomic PstI fragment of Desulfovibrio gigas harboring the aldehyde oxido-reductase gene. The aldehyde oxido-reductase gene spans 2718 bp of genomic DNA and codes for a protein with 906 residues. The protein sequence shows an average 52% (+/- 1.5%) similarity to xanthine dehydrogenase from different organisms. The codon usage of the aldehyde oxidoreductase is almost identical to a calculated codon usage of the Desulfovibrio bacteria.
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PMID:Molecular cloning and sequence analysis of the gene of the molybdenum-containing aldehyde oxido-reductase of Desulfovibrio gigas. The deduced amino acid sequence shows similarity to xanthine dehydrogenase. 814 44

The effects of anoxic submergence (20 h at 5 degrees C) and subsequent 24 h aerobic recovery on the antioxidant systems of six organs were examined in freshwater turtles, Trachemys scripta elegans. Both xanthine oxidase and xanthine dehydrogenase were detected in turtle tissues with xanthine oxidase composing 36-75% of the total activity. Turtle organs displayed high constitutive activities of catalase (CAT), superoxide dismutase (SOD), and alkyl hydroperoxide reductase (AHR). Measurements of lipid peroxidation damage products (conjugated dienes, lipid hydroperoxides, thiobarbituric acid reactive substances) showed minimal changes during anoxia or recovery suggesting that natural anoxic-aerobic transitions occur without the free radical damage that is seen during ischemia-reperfusion in mammals. Anoxia exposure led to selected decreases in enzyme activities in organs, consistent with a reduced potential for oxidative damage during anoxia: SOD decreased in liver by 30%, CAT decreased in heart by 31%, CAT and total glutathione peroxidase (GPOX) decreased in kidney (by 68 and 41%), and CAT and SOD decreased in brain (by 80 and 15%). AHR, however, increased 2 and 3.5 fold during anoxia in heart and kidney respectively. Most anoxia-induced changes were reversed during aerobic recovery although brain enzyme activities remained suppressed. Some specific changes occurred during the recovery period: SOD increased from controls in heart by 45%, AHR increased to 200 and 168% of control values in red and white muscle respectively, and total GPOX decreased from controls in heart and white muscle by 75 and 77% respectively. The results show that biochemical adaptation for natural anoxia tolerance in turtles includes well-developed antioxidant defenses that minimize or prevent damage by reactive oxygen species during the reoxygenation of organs after anoxic submergence.
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PMID:Antioxidant systems and anoxia tolerance in a freshwater turtle Trachemys scripta elegans. 914 33


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