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At least 19 recordsLinked to original sources
PubMed1979

[Comparative study of chicken liver xanthine dehydrogenase and bovine liver xanthine oxidase. dehydrogenase activity of xanthine oxidase (author's transl)].

A method to purify bovine liver xanthine oxidase in described, with which samples of 256-fold specific activity with respect to the initial homogenate are obtained. Bovine liver xanthine oxidase and chicken liver xanthine dehydrogenase with oxygen as electron acceptor exhibit similar profile in pKM and log V versus pH plots. With NAD+ as electron acceptor a different profile in the pKM xanthine plot is obtained for chicken liver xanthine dehydrogenase. However three inflection points at the same pH values appear in all plots. Both enzymes are irreversibly inhibited by pCMB and reversibly by N-ethylmaleimide and by iodoacetamide, with competitive and uncompetitive type inhibitions respectively. These results suggest that NAD+ alters the enzymatic action since its binding to the enzyme antecedes the binding of xanthine to the xanthine oxidase molecule, without undergoing itself any modification. 0.15 M DDT of DTE treatment of bovine liver xanthine oxidase gives to the enzyme a permanent activity with NAD+ without modifying its activity with oxygen. The enzyme thus treated produces parallel straight lines in Lineweaver-Burk plots.

Animals↗
PubMed1992

Mechanism of neutrophil-induced xanthine dehydrogenase to xanthine oxidase conversion in endothelial cells: evidence of a role for elastase.

Activated neutrophils cause conversion of xanthine dehydrogenase to its oxidase form (xanthine oxidase) in endothelial cells, the mechanism of which may be related to the cytotoxic effect of activated neutrophils. The elastase inhibitors, elastatinal, alpha 1-antitrypsin, and MeO-Suc-(Ala)2-Pro-Val-CH2Cl, significantly inhibited xanthine dehydrogenase to oxidase conversion by phorbol myristate acetate-stimulated neutrophils without inhibition of neutrophil adherence to the endothelial cell monolayer. The role of elastase in this enzyme conversion process was confirmed by the ability of purified elastase to cause conversion of xanthine dehydrogenase to xanthine oxidase in intact endothelial cells (or cell extracts) without causing cytotoxicity. In contrast, cathepsin G failed to cause conversion. The kinetics of conversion induced by elastase was relatively rapid, being essentially completed by 30 min. Upon removal of elastase, the effect was slowly (greater than 12 h) reversible and could be inhibited by cycloheximide treatment. Exposure of endothelial cells to hypoxia failed to enhance the elastase-induced conversion. Treatment of endothelial cells with Ca2+ ionophores failed to cause conversion of xanthine dehydrogenase to oxidase, suggesting that intracellular Ca(2+)-activated proteases are not sufficient to induce this process. Neutrophil-induced xanthine dehydrogenase to oxidase conversion was inhibited by concomitant treatment with antibodies to CD11b. The results suggest that activated neutrophils induce conversion of xanthine dehydrogenase to oxidase by secretion of elastase in close proximity to the endothelial cells and that this intimate contact between the two cell types enables high local concentrations of elastase to be attained, which are sufficient to cause xanthine dehydrogenase to xanthine oxidase conversion.

Animals↗
PubMed1992

Change of xanthine dehydrogenase and xanthine oxidase activities in rat brain following complete ischaemia.

We studied the activities of xanthine dehydrogenase and xanthine oxidase in rat forebrain after complete ischaemia. Complete ischaemia was induced by decapitation after transcardiac infusion with saline. The activities of xanthine dehydrogenase and xanthine oxidase immediately after ischaemia were 93.3 +/- 38.7 and 18.8 +/- 7.7 microU/mg protein, respectively, and at 24 h after ischaemia were 183.5 +/- 75.1 and 60.8 +/- 15.2 microU/mg protein, respectively. The ratios of xanthine dehydrogenase/xanthine oxidase immediately and 24 h after ischaemia were 5.04 +/- 1.03 and 3.04 +/- 0.99, respectively. These data indicate that xanthine dehydrogenase and xanthine oxidase activities were maintained even 24 h after complete ischaemia. Conversion of xanthine dehydrogenase to xanthine oxidase proceeds slowly during complete ischaemia.

Animals↗
PubMed1978

Bovine milk xanthine oxidase: purification by ultrafiltration and conventional methods which omit addition of proteases: some criteria for homogeneity of native xanthine oxidase.

Methodological difficulties have been encountered when proteases were omitted from the conventional isolation of bovine milk xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2). The use of these conventional methods has been studied and modified to reduce the problems encountered. Some of the difficulties may be due to the presence of high concentrations of caseins, which exhibit a wide range of charges and sizes, thereby making separations based on charge and size more complicated. In addition, non-covalent interactions may occur between the caseins and xanthine oxidase leading to the formation of casein-xanthine oxidase micellar aggregates. The difficulties encountered in this conventional isolation have been circumvented by purifying the enzyme directly from milk fat globule membranes that first have been washed free of most casein and other milk proteins. The xanthine oxidase is isolated by ultrafiltration through an Amicon XM-100A membrane at 5 degrees C in 0.25 M sucrose/5 mM sodium salicylate. The largest molecular size of globular proteins which can penetrate this ultrafiltration membrane has been previously estimated to be around 100 000 daltons. Xanthine oxidase thus appears to be smaller than 100 000 daltons in its native state. The size observed for active xanthine oxidase previously isolated by other methods has been around 275 000--300 000 daltons. Xanthine oxidase isolated by ultrafiltration appears similar to xanthine oxidase from conventional isolation methods according to empirical criteria of homogeneity based on size and also on the absorbances at 280 and 450 nm. Criteria based on charge were found to be less reliable.

Ammonium Sulfate↗
PubMed1990

[The effect of immune antibodies and the xanthine oxidase-xanthine enzymatic link on Vibrio cholerae].

As revealed in experiments on V. cholerae, highly diluted cholera antiserum enhanced the inhibitory action of the enzymatic link xanthine oxidase-xanthine-Fe2+ on the multiplication of V. cholerae, while low dilutions of the antiserum weakened this action. Normal rabbit serum produced no such effect. The antivibrionic effectiveness of the immune molecular cycle, viz. antiserum--the xanthine oxidase enzymatic link, was found to depend also on the concentration of xanthine. Immune antibodies to cholera antigens activated the bacteriostatic action of the enzymatic link at the concentration of xanthine oxidase equal to 0.0125 g/l and its bactericidal action at the concentration of xanthine oxidase equal to 0.025 g/l. In this article the values of the specificity indices of immune interaction and immunological effectiveness, characterizing the effectiveness of immune molecular cycles (antibodies--the xanthine oxidase enzymatic link), are presented.

Animals↗
PubMed1990

Ischaemic brain oedema and xanthine-xanthine oxidase system.

The formation of oxygen-derived free radicals in cerebral ischaemia has been implicated in altering the BBB permeability, cause oedema and tissue damage. However little attention has been paid regarding the involvement of xanthine oxidase in the cerebral ischaemic events. Recently we demonstrated that cerebral ischaemia promotes the conversion of xanthine oxidase type D (nicotinamide adenine dinucleotide-dependent dehydrogenase) to type 0 (oxygen-dependent superoxide-producing oxidase). This investigation was concerned with elucidating the relationship between the conversion of xanthide oxidase and the duration of brain ischaemia. Four vessel-occlusion served as a model for the induction of cerebral ischaemia in rats. Xanthine oxidase was assayed by high pressure liquid chromatography using ultraviolet and electrochemical detection. The enzymatic conversion of xanthine oxidase from type D to type O increased with time from 7.6-15% during 5 min ischaemia to 27% and 36% at 15 min and 30 min after ischaemia, respectively. These results support the contention that xanthine oxidase may participate in free radical-induced ischaemic brain oedema.

Animals↗
PubMed1991

A xanthinuric family--the proposita having immunologically reactive xanthine oxidase but no xanthine oxidase activity.

The antibody was raised against purified human liver xanthine oxidase in a rabbit. In a xanthinuric patient, the double immunodiffusion method demonstrated the existence of an immunologically reactive duodenal mucosa xanthine oxidase which did not possess xanthine oxidase activity. These results indicated that xanthine oxidase protein is abnormal in structure and/or amino acid sequence.

Female↗
PubMed1976

Oxidation of N-methyl substituted hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives by bovine milk xanthine oxidase.

1. The oxidation of six series of purines (hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives) by a highly purified bovine milk xanthine oxidase (EC 1.2.3.2) has been studied, using a variety of N-methyl derivatives. 2. N-Methyl substituents can either enhance or reduce enzymic rates. Enhancement is ascribed to blockade of groups which mediate unfavorable modes of binding of substrate to enzyme. Introduction of N-methyl groups can also inhibit enzymic oxidation, either by occluding essential binding groups or by preventing spontaneous or enzyme-induced tautomerisation processes, which create suitable binding sites in the substrates. 3. In all purines which are rapidly attacked by xanthine oxidase, proper attachment to the active center is mediated by the groupings (3) NH, (9) N or (3) N, (9) NH. 4. Reduced rates usually express lowered substrate affinity, which finds its expression in weak competitive inhibition of xanthine oxidation.

Animals↗
PubMed1978

Magnetic coupling of the molybdenum and iron-sulphur centres in xanthine oxidase and xanthine dehydrogenases.

Magnetic interaction between molybdenum and one of the iron-sulphur centres in milk xanthine oxidase [Lowe, Lynden-Bell & Bray (1972) Biochem. J. 130, 239-249] was studied further, with particular reference to the newly discovered Mo(V) e.p.r.(electron-paramagnetic-resonance) signal, Resting II [Lowe, Barber, Pawlik & Bray (1976) Biochem. J. 155, 81-85]. E.p.r. measurements at 35GHz near to 4.2K showed that the interaction has the same sign at all molybdenum orientations and is ferromagnetic. The predicted splitting of the e.p.r. signal from the reduced iron-sulphur centre, Fe/S I, was observed, Providing positive identification of this as the other interacting species. Chemical modification of the molybdenum environment in xanthine oxidase can change the size of the interaction severalfold, but interaction always remains approximately isotropic. The interaction in turkey liver xanthine dehydrogenase is indistinguishable from that in the oxidase. However, a bacterial xanthine dehydrogenase with different iron-sulphur centres shows rather larger interaction. Guanidinium chloride disturbs the iron-sulphur centres of the oxidase, and when this occurs there is a parallel and relatively small change in the interaction. Removal of flavin from the molecule, or raising the pH to 12.0, changes the interaction slightly without affecting the chromophores themselves. It is concluded that the Fe/S I centre and the Mo are at least 1.0nm and probably nearer 2.5nm apart, and that the conformation of the protein between them is relatively stable up to pH 12.

Animals↗
PubMed1978

Electron-paramagnetic-resonance spectroscopy of complexes of xanthine oxidase with xanthine and uric acid.

Molybdenum(V) e.p.r. signals from reduced functional milk xanthine oxidase molecules (the Rapid signals), obtained in the presence of purine substrates and products, were further investigated [cf. Bray & Vänngård, (1969) Biochem. J. 114, 725-734; Pick & Bray (1969) Biochem. J. 114, 735-742]. Xanthine forms two complexes with the enzyme that are believed to correspond to different orientations of the substrate molecule in the active site. Only one complex appears to undergo the catalytic reaction. Non-productive complexes, analogous to theone with xanthine, are not formed by 1-methylxanthine or purine. Uric acid forms more than one e.p.r.-detectable complex, one of which is analogous to the non-productive xanthine complex. The computer program used for handing the e.p.r. data is described briefly.

Animals↗
PubMed1991

Influence of disodium aurothiomalate on the activities of xanthine dehydrogenase and xanthine oxidase in endothelial cells.

The effect of aurothiomalate in modulating the conversion of xanthine dehydrogenase to its superoxide producing oxidase form in rat and human liver cytosolic preparations has been investigated. Low concentrations (10(-8)-10(-5) mol.dm-3) of this second-line agent were found to inhibit the conversion of the dehydrogenase to its corresponding oxidase form. High concentrations (10(-4) mol.dm-3), however, accelerated this conversion. It is possible that the influence of aurothiomalate on the relative proportions of xanthine dehydrogenase and xanthine oxidase is a reflection of the gold(I) blockage of critical thiol(ate) or sulphido ligands present in this enzymatic system. These effects may form the basis of aurothiomalate's anti-proliferative action on endothelial cells.

Animals↗
PubMed1991

Relaxant effects of adenosine analogs on guinea pig trachea in vitro: xanthine-sensitive and xanthine-insensitive mechanisms.

Adenosine analogs were tested for their ability to relax carbachol-contracted trachea in vitro. The rank order of potency was: 5'-N-ethylcarboxamidoadenosine (NECA) greater than 2-chloroadenosine (2-CIADO) greater than 5'-chloroadenosine = N6-R-1-phenyl-2-propyladenosine (R-PIA) greater than N6-cyclohexyladenosine greater than 2-phenylaminoadenosine (CV1808) greater than 5'-methylthioadenosine (MTA). The rank order of potency for NECA, 2-CIADO and R-PIA is characteristic of an A2 subtype of adenosine receptor. 8-Para-sulfophenyltheophylline (8-p-ST) and 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX), were used to antagonize tracheal relaxation elicited by adenosine analogs. 8-p-ST antagonized the 2-CIADO, N6-cyclohexyladenosine, R-PIA and 5'-chloroadenosine responses, but had little or no effect on the CV1808 and MTA responses. 8-p-ST antagonized responses to NECA at concentrations of NECA up to approximately 30 microM, but had no effect on responses to higher concentrations of NECA. The differences in antagonist potency of 8-p-ST and the clear biphasic response of NECA are indicative of at least two mechanisms of adenosine analog action leading to tracheal relaxation. One mechanism is mediated through a xanthine-sensitive site, at which NECA acted in a potent manner, whereas the other mechanism or mechanisms are insensitive to blockade by xanthines and account for the effects of action of MTA and CV1808, as well as for NECA at high concentrations. The low potency of the A1-selective antagonist DPCPX indicates that the xanthine-sensitive site is an A2 type receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1975

Nutritional control of xanthine dehydrogenase. II. Effects on xanthine dehydrogenase and aldehyde oxidase of culturing wild-type and mutant Drosophila on different levels of molybdenum.

Two new mutants, deficient in aldehyde oxidase and xanthine dehydrogenase, have been isolated from a wild-type stock of Drosophila melanogaster and have been provisionally termed lxd-c and lxd-d, respectively, as both mutants appear to be allelic with lxd (low xanthine dehydrogenase). An analysis has been made of the effects of dietary molybdenum on lxd, lxd-c, lxd-d, lao (low aldehyde oxidase), mal (maroon-like eye color), and pac (Pacific) wild-type flies. On the lower dietary levels of 10(-3) M and 10(-2) M molybdenum, increases in specific activity of both enzymes were observed only in lxd. Furthermore, two- to three-fold increases in specific activity of both enzymes occurred in all strains, except mal, when cultured on 5 x 10(-2) M molybdenum. The lxd and lxd-c strains failed to survive on this high concentration of the ion. Similar concentrations of molybdenum had no effect in vitro. An extra electrophoretic band of xanthine dehydrogenase was observed on polyacrylamide gel from extracts of wild-type flies cultured on certain levels of molybdenum, but its appearance was not always correlated with the increases in specific activity.

Aldehyde Oxidoreductases↗
PubMed1991

Kinetic comparison of reduction and intramolecular electron transfer in milk xanthine oxidase and chicken liver xanthine dehydrogenase by laser flash photolysis.

A comparative study using laser flash photolysis of the kinetics of reduction and intramolecular electron transfer among the redox centers of chicken liver xanthine dehydrogenase and of bovine milk xanthine oxidase is described. The photogenerated reductant, 5-deazariboflavin semiquinone, reacts with the dehydrogenase (presumably at the Mo center) in a second-order manner, with a rate constant (k = 6 x 10(7) M-1 s-1) similar to that observed with the oxidase [k = 3 x 10(7) M-1 s-1; Bhattacharyya et al. (1983) Biochemistry 22, 5270-5279]. In the case of the dehydrogenase, neutral FAD radical formation is found to occur by intramolecular electron transfer (kobs = 1600 s-1), presumably from the Mo center, whereas with the oxidase the flavin radical forms via a bimolecular process involving direct reduction by the deazaflavin semiquinone (k = 2 x 10(8) M-1 s-1). Biphasic rates of Fe/S center reduction are observed with both enzymes, which are due to intramolecular electron transfer (kobs approximately 100 s-1 and kobs = 8-11 s-1). Intramolecular oxidation of the FAD radical in each enzyme occurs with a rate constant comparable to that of the rapid phase of Fe/S center reduction. The methylviologen radical, generated by the reaction of the oxidized viologen with 5-deazariboflavin semiquinone, reacts with both the dehydrogenase and the oxidase in a second-order manner (k = 7 x 10(5) M-1 s-1 and 4 x 10(6) M-1 s-1, respectively). Alkylation of the FAD centers results in substantial alterations in the kinetics of the reaction of the viologen radical with the oxidase but not with the dehydrogenase. These results suggest that the viologen radical reacts directly with the FAD center in the oxidase but not in the dehydrogenase, as is the case with the deazaflavin radical. The data support the conclusion that the environments of the FAD centers differ in the two enzymes, which is in accord with other studies addressing this problem from a different perspective [Massey et al. (1989) J. Biol. Chem. 264, 10567-10573]. In contrast, the rate constants for intramolecular electron transfer among the Mo, FAD, and Fe/S centers in the two enzymes (where they can be determined) are quite similar.

Animals↗
PubMed1978

pH-jump studies at subzero temperatures on an intermediate in the reaction of xanthine oxidase with xanthine.

Xanthine oxidase is stable and active in aqueous dimethyl sulphoxide solutions of up to at least 57% (w/w). Simple techniques are described for mixing the enzyme in this solvent at--82 degrees C, with its substrate, xanthine. When working at high pH values under such conditions, no reaction occurred, as judged by the absence of e.p.r. signals. On warming to--60 degrees C, for 10 min, however, the Very Rapid molybdenum(V) e.p.r. signal was obtained. This signal did not change on decreasing the pH, while maintaining the sample in liquid nitrate reductase, caused its molybdenum(V) e.p.r. signal to change from the high-pH to the low-pH form. These findings are not compatible with the conclusions of Edmondson, Ballou, Van Heuvelen, Palmer & Massey [J. Biol. Chem. (1973) 248, 6135-6144], that the Very Rapid signal is in prototropic equilibrium with the Rapid signal, and should be important in understanding the mechanism of action of the enzyme. They emphasize the unique nature of the intermediate represented by the Very Rapid e.p.r. signal. The possible value of the pK for loss of an exchangeable proton from the Rapid signal is discussed.

Chemical Phenomena↗
PubMed1977

Distribution of xanthine oxidase and xanthine dehydrogenase specificity types among bacteria.

A diverse collection of xanthine-metabolizing bacteria was examined for xanthine-, 1-methylxanthine-, and 3-methylxanthine-oxidizing activity. Both particulate and soluble fractions of extracts from aerobically grown gram-negative bacteria exhibited oxidation of all three substrates; however, when facultative gram-negative bacteria were grown anaerobically, low particulate and 3-methylxanthine activities were detected. Gram-positive and obligately anaerobic bacteria showed no particulate activity or 3-methylxanthine oxidation. Substrate specificity studies indicate two types of enzyme distributed among the bacteria along taxonomic lines, although other features indicate diversity of the enzyme within these two major groups. The soluble and particulate enzymes from Pseudomonas putida and the enzyme from Arthrobacter S-2 were examined as type examples with a series of purine and analogues differing in the number and position of oxygen groups. Each preparation was active with a variety of compounds, but the compounds and position attacked by each enzyme was different, both from the other enzymes examined and from previously investigated enzymes. The soluble enzyme from Pseudomonas was inhibited in a competitive manner by uric acid, whereas the Arthrobacter enzyme was not. This was correlated with the ability of Pseudomonas, but not Arthrobacter, to incorporate radioactivity from [2-14C]uric acid into cellular material.

Actinomycetales↗
PubMed1992

Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells.

The central importance of xanthine dehydrogenase (XDH) and xanthine oxidase (XO) in the pathobiochemistry of a number of clinical disorders underscores the need for a comprehensive understanding of the regulation of their expression. This study was undertaken to examine the effects of cytokines on XDH/XO activity and gene expression in pulmonary endothelial cells. The results indicate that IFN-gamma is a potent inducer of XDH/XO activity in rat lung endothelial cells derived from both the microvasculature (LMVC) and the pulmonary artery. In contrast, interferon-alpha/beta, tumor necrosis factor-alpha, interleukin-1 or -6, lipopolysaccharide and phorbol myristate acetate have no demonstrable effect. The increase in XDH/XO activity requires new protein synthesis. By Northern analysis, IFN-gamma markedly increases the level of the 5.0-kb XDH/XO mRNA in LMVC. The increase is due, in part, to increased transcription rate of the XDH/XO gene. Transcriptional activation does not require new protein synthesis. The physiologic relevance of these observations was evaluated by administering IFN-gamma to rats. Intraperitoneal administration leads to an increased XDH/XO activity and XDH/XO mRNA level in rat lungs. In sum, IFN-gamma is a potent and biologically relevant inducer of XDH/XO expression; the major site of upregulation occurs at the transcriptional level.

Animals↗
PubMed1992

Effects of copper and selenium on electric parameters of cultured myocardial cells damaged by xanthine-xanthine oxidase.

Addition of xanthine 0.42 mmol.L-1 and xanthine oxidase 5.3 nmol.L-1 (X-XO) to the culture medium increased the amplitude of ESR spectra of myocardial cells, demonstrating an increase in free radical contents; diminished the action potential parameters significantly and reduced the input impedances from 0.34 +/- 0.11 to 0.24 +/- 0.1 M omega, expressing a typical electrical appearance of membrane damage. Supplying Cu 62.5 ng.ml-1 and/or Se 173 ng.ml-1 to the medium brought all of the electric parameters and the free radical content of myocardial cells back to normal. The results indicate that both the two trace elements are able to scavenge free radicals, thus antagonizing X-XO, which induces damage to myocardial cells.

Action Potentials↗