Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myeloperoxidase (MPO), H2O2 and a halide form a powerful antimicrobial system effective against bacteria, fungi, viruses and mammalian cells. After phagocytosis, MPO is released into the phagosome from adjacent granules where it interacts with H2O2 generated either by leukocytic or microbial metabolism and a halide such as chloride or iodide to form agents toxic to the ingested organisms. Evidence for H2O2 and MPO participation in the microbicidal activity of polymorphonuclear leukocytes (PMNs) has been obtained from patients with neutrophil dysfunction. In chronic granulomatous disease, PMNs have a microbicidal defect associated with the absence of the respiratory burst. The importance of H2O2 deficiency in the PMN dysfunction is emphasized by its reversal by H2O2. PMNs which lack MPO also have a major fungicidal and bactericidal defect. Bactericidal activity is particularly low during the early postphagocytic period, after which the organisms are killed. Although emphasizing the importance of MPO-mediated antimicrobial systems particularly during the early postphagocytic period, these findings also indicate the presence of MPO-independent systems which develop slowly but are ultimately effective. The MPO-independent antimicrobial systems may be oxygen-dependent or oxygen-independent. The acetaldehyde-xanthine oxidase system has been used as a model of the MPO-independent, oxygen-dependent antimicrobial systems of the PMN. A microbicidal effect by this system was observed which was inhibited by superoxide dismutase, catalase and scavengers of hydroxyl radicals (OH') and singlet oxygen (1O2). The microbicidal activity of acetaldehyde and xanthine oxidase is increased considerably by MPO and chloride. The formation of ethylene from methional or 2-oxo-4-methylthiobutyric acid by PMNs has been regarded as evidence for OH' formation. We have found ethylene formation to be largely dependent on MPO and evidence for the initiation of ethylene formation by 1O2 has been obtained. Both the xanthine oxidase system and the MPO-H2O2-halide system convert diphenylfuran into cis-dibenzoylethylene, an effect which is compatible with, although not proof of, the formation of 1O2 by these systems.
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PMID:The role of myeloperoxidase in the microbicidal activity of polymorphonuclear leukocytes. 22 42

Aqueous solutions of engine exhaust condensation products were derived from cars powered by diesel or four-stroke gasoline engines (with and without three-way catalytic converter). The cars were operated on a static test platform. Samples of the different exhaust solutions accumulated in a Grimmer-type distillation trap (VDI 3872) during standard test programs (Federal Test Procedure) were incubated with important biomolecules. As indicators of reactive oxygen species or oxidative destruction, ascorbic acid, cysteine, glutathione, serum albumin, the enzymes glycerinaldehyde phosphate dehydrogenase and xanthine oxidase, and the oxygen free-radical indicator keto-methylthiobutyrate were used. During and after the incubations, oxygen activation (consumption) and oxidative destruction were determined. Comparison of the oxidative activities of the different types of exhaust condensates clearly showed that the exhaust condensate derived from the four-stroke car equipped with a three-way catalytic converter exhibited by far the lowest oxidative and destructive power.
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PMID:Oxidative destruction of biomolecules by gasoline engine exhaust products and detoxifying effects of the three-way catalytic converter. 128 38

Hydroxyl radicals have been generated from hydrogen peroxide and superoxide (produced with xanthine oxidase), and an iron (EDTA) catalyst, and detected with deoxyribose, or in some cases with benzoate or alpha-keto-gamma-methiolbutyric acid. Purified myeloperoxidase, and neutrophils stimulated with fMet-Leu-Phe and cytochalasin B, strongly inhibited this hydroxyl radical production in a concentration-dependent manner. Supernatants from stimulated cells also inhibited, and inhibition by cells or supernatant was prevented by azide. There was much less inhibition by myeloperoxidase-deficient neutrophils. Inhibition thus was due to myeloperoxidase released by the cells. With neutrophils stimulated with phorbol myristate acetate, which release very little myeloperoxidase, hydroxyl radical production was enhanced due to the additional superoxide produced by the cells. It is concluded that under conditions where neutrophils release myeloperoxidase as well as superoxide and hydrogen peroxide, breakdown of hydrogen peroxide by myeloperoxidase would make conditions unfavorable for hydroxyl radical production.
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PMID:Myeloperoxidase as an effective inhibitor of hydroxyl radical production. Implications for the oxidative reactions of neutrophils. 301 31

Kinetic analysis has been used to access how well scavenger inhibition can characterize the reactivity of oxidants produced in the iron-catalyzed reaction of H2O2 with xanthine oxidase-derived O2-.. Formate oxidation to CO2, deoxyribose oxidation, benzoate hydroxylation, and ethylene production from alpha-keto-gamma-methiolbutyric acid (KMB) were measured. With Fe(EDTA) as catalyst, inhibition by most scavengers was quantitatively as expected for OH. involvement. Exceptions were urate and thiourea, which inhibited excessively and appeared to scavenge intermediates of the detection reactions. With nonchelated iron, there was minimal formate oxidation, but benzoate, KMB, and deoxyribose gave, respectively, 17%, 25%, and approximately the same product yield as with Fe(EDTA). Deoxyribose oxidation was not inhibited by some scavengers and excessively inhibited by others. However, scavengers that did not inhibit deoxyribose oxidation did inhibit with KMB and benzoate, and differences in scavenger effects in the presence and absence of EDTA in these assays were relatively minor. The results with formate and deoxyribose, but not KMB and benzoate, can therefore exclude free OH. as a significant oxidant product of the nonchelated iron-catalyzed Haber-Weiss reaction. It is proposed that the different patterns of scavenger inhibition arise in the different assays because scavengers can react with intermediates in the detection reactions, all of which are multistep chains. Thus, inhibition may not signify OH. involvement, and similarities with inhibition expected for OH. my be fortuitous.
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PMID:The ability of scavengers to distinguish OH. production in the iron-catalyzed Haber-Weiss reaction: comparison of four assays for OH. 304 May 37

The role of free radicals in the conversion of 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene by a membrane-bound enzyme from carnation petals was studied. The membrane preparation oxidized ACC more effectively than it oxidized cyclopropaneamine or 2-keto-4-methylthiobutyric acid (KMB). All these substrates were oxidized chemically by NaOCl to ethylene very effectively. Free radicals generated by the xanthine/xanthine oxidase system oxidized KMB far more effectively than it oxidized ACC; only 0.004% of the ACC included in the reaction mixture was oxidized in 1 h, compared with 0.9% of the KMB. Conversion of ACC to ethylene by the membrane-bound enzyme was inhibited by Co2+, ATP and EDTA, while the inhibition of the oxidation of KMB by the same inhibitors was much less pronounced. These results suggest that ACC, the natural immediate precursor of ethylene, is specifically oxidized by the membrane-bound enzyme rather than through a nonspecific oxidation by free radicals.
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PMID:Free radicals play little role in the conversion of 1-aminocyclopropane-1-carboxylic acid to ethylene in carnation membrane fraction. 314 43

The generation of hydroxyl radicals by the xanthine-xanthine oxidase reaction (C. Beauchamp and I. Fridovich (1970) J. Biol. Chem. 245, 4641-1616) has been shown to be increased by iron-saturated lactoferrin isolated from pig neutrophils. Hydroxyl radical production, measured by EPR spin trapping and by ethylene production from alpha-keto-gamma-methiol butyric acid, has been demonstrated to be produced by a Fenton-type Haber-Weiss reaction catalysed by lactoferrin. The possibility that lactoferrin catalyses such a reaction in vivo is considered.
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PMID:Enhanced production of hydroxyl radicals by the xanthine-xanthine oxidase reaction in the presence of lactoferrin. 628 Jul 74

During phagocytosis, neutrophils take oxygen from the surrounding medium and convert it to superoxide anion (O2-) and hydrogen peroxide (H2O2). Hydroxyl radical (.OH), a particularly potent oxidant, is believed to be produced by interaction between O2- and H2O2 in the presence of iron, according to the Haber-Weiss reactions. Production of .OH by whole human neutrophils, by particulate fractions from human neutrophils disrupted after stimulation, and by a xanthine oxidase system was measured by conversion of alpha-keto-gamma-methiol butyric acid to ethylene. FeCl3 or ferric EDTA enhanced ethylene production in all three systems by 155--406% of base line at a concentration of 50--100 microM. Iron-saturated human milk lactoferrin, 100 nM, increased ethylene generation by 127--296%; and purified human neutrophil lactoferrin, 10 nM, enhanced ethylene production by 167--369%. Thus, iron bound to lactoferrin was approximately 5,000 times more effective in producing an enhancement in ethylene generation than iron derived from FeCl3 or ferric EDTA. O2- and H2O2 were required for ethylene production in the presence of lactoferrin, since superoxide dismutase inhibited ethylene formation in the three systems by 76--97% and catalase inhibited by 76--98%. Ethylene production in the presence of lactoferrin was inhibited by the .OH scavengers mannitol, benzoate, and thiourea by 43--85, 45--94, and 76--96%, respectively. Thus, most of the ethylene production could be attributed to oxidation of alpha-keto-gamma-methiol butyric acid by .OH. The ability of neutrophil lactoferrin to provide iron efficiently to the oxygen radical-generating systems is compatible with a role for lactoferrin as regulator of .OH production. As such, lactoferrin may be an important component in the microbicidal activity of neutrophils.
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PMID:Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system. 678 Jun 7

Several pathological situations are characterized by the production of reactive oxygen species (ROS), whereby different sources such as activated leukocytes and xanthine oxidase seem to be mainly responsible. The contribution of immigrating activated neutrophils to symptom development during inflammatory processes or after reperfusion of ischemic tissues is a matter of continuing discussion. We present a simple method for the differentiation between oxygen activating reactions in which neutrophil-derived myeloperoxidase is involved. The method is based on the gas chromatographic detection of ethylene, which is formed by the reaction of alpha-keto-gamma-methylthiobutyric acid (KMB) or 1-amino-cyclopropane-1-carboxylic acid (ACC) with ROS. In the presence of OH-radical-type oxidants, only KMB yields ethylene whereas ACC is fragmented by myeloperoxidase-derived species (OCl-, chloramines). The amounts of ethylene may be used as an indicator for the relative contribution of Fenton-type or myeloperoxidase-catalyzed reactions.
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PMID:Gas chromatographic differentiation between myeloperoxidase activity and Fenton-type oxidants. 764 86

Hemolymph of M. Edulis is rich in phagocytic hemocytes. Hemocytes contain numerous lysosomes which, in turn, contain various hydrolytic enzymes. Phagocytic activity of M. edulis hemocytes is thought to be associated with NAD(P)H-oxidase activity of the plasma membrane. The laser dye, dihydrorhodamine 123 (DHR), was used for cytochemical and biochemical detection of the generation of reactive oxygen species (ROS) by isolated M. edulis hemocytes. Hemocytes readily take up DHR from the suspension medium and selectively concentrate it in the lysosomes, wherein DHR is oxidized to fluorescent rhodamine 123. Concomitant uptake of DHR with superoxide dismutase or the spin-trap, tert-phenylbutyl nitrone, but not catalase markedly reduced fluorescence in the lysosomes implicating superoxide anion (O2-) but not hydrogen peroxide (H2O2) in DHR oxidation. Uptake of the anthraquinone, purpurin, and FeEDTA with DHR greatly amplified fluorescence within the lysosomes. These data are consistent with uptake of xenobiotics by hemocytes and their concentration in lysosomes wherein, ROS are generated in response to their accumulation. The rate of DHR oxidation by hemocytes was not stimulated by zymosan, a known stimulator of the oxidative burst. In vitro studies using the xanthine oxidase/hypoxanthine reaction to generate O2- and selective inhibitors of ROS production indicated that DHR is oxidized by O2- and H2O2 but not by .OH and that iron can participate in the reaction. Incubating isolated hemocytes promoted low-level, SOD-sensitive, FeEDTA-stimulated production of ethylene from alpha-keto-gamma-methiolbutyric acid, indicating the in situ formation of .OH via production of O2-. The above suggest that enhanced production of ROS in M. edulis hemocytes by xenobiotic accumulation within the lysosomal compartment should be considered in the toxic sequelae of exposure of marine molluscs to chemical pollutants.
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PMID:Production of reactive oxygen species by hemocytes from the marine mussel, Mytilus edulis: lysosomal localization and effect of xenobiotics. 864 15

Reactive oxygen species such as OH, peroxynitrite and the non-radical, hypochlorous acid, play outstanding roles in many disease. The formation of OH (Fenton)-type radicals is catalyzed by enzymes such as xanthine oxidase (XOD) via one-electron reduction of molecular oxygen producing superoxide radical anions (O2). Subsequent transfer of one electron to hydrogen peroxide by Fe2+ or Cu+ -ions yields OH-radicals measurable as ethene release from 1-keto-4-methylthiobutyrate (KMB). Xanthine oxidase or activated neutrophils are prominent sources of this strong oxidant produced at inflammatory sites. Many natural compounds such as salicylates or flavonoids interfere either with the production of these activated oxygen species or function as radical scavengers and thus as antioxidants. Extracts from willow-bark (Salix spec.) and also other species such as ash-tree (Fraxinus spec.) or poplar (Populus spec.) have been used as antiinflammatory drugs since a long time. In this communication we wish to report on model reactions to demonstrate a) the radical scavenging activities of such plant extracts inhibiting ethene release from KMB induced by Fenton-type oxidants and b) the inhibition of the formation of nitrogen monoxide (NO) from hydroxylamine including XOD either in the presence or absence of myoglobin (MYO) measurable as nitrite formation: In the absence of MYO, superoxide dismutase is an excellent inhibitor of nitrite formation but is inactive in its presence. Extracts from the willow-bark or the drug Phytodolar however, are inhibitory both in the presence and absence of MYO. As active principle, the flavonoid rutin included in these extracts is likely to function as one inhibitor of the XOD-mediated reaction.
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PMID:Superoxide-dependent and -independent nitrite formation from hydroxylamine: inhibition by plant extracts. 968 63


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