Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Procarbazine, a 1,2-disubstituted hydrazine, is employed therapeutically in the treatment of Hodgkin's disease and a limited number of other neoplasias. The isomeric azoxy metabolites of procarbazine have recently been identified as the precursors of species responsible for both the anti-cancer efficacy and toxic effects mediated by this drug. This study demonstrates that cytosolic enzymes are involved in the metabolism of the azoxy metabolites of procarbazine. Two azoxy procarbazine oxidase activities were resolved by diethylaminoethyl (DEAE)-cellulose chromatography. The activity which did not bind to this column was purified to homogeneity and was identified as a phenobarbital-inducible form of cytosolic aldehyde dehydrogenase. This protein fraction was shown to metabolize only the azoxy 2 procarbazine isomer to yield N-isopropy-p-formylbenzamide (ALD) in a reaction which did not require NAD+ as cofactor. The ALD product formed was also a substrate for a subsequent NAD(+)-dependent reduction reaction catalyzed by that purified protein. The azoxy 2 procarbazine isomer and ALD were shown to be potent inhibitors of both the dehydrogenase and esterase activities of aldehyde dehydrogenase. The second azoxy procarbazine oxidase activity which was retained by the DEAE-cellulose column co-eluted with xanthine oxidase activity. Both the xanthine dehydrogenase/oxidase and azoxy procarbazine oxidase activities of this protein fraction were inhibited by allopurinol, a specific inhibitor of xanthine dehydrogenase. Xanthine dehydrogenase/oxidase was partially purified by an alternative procedure and was shown to metabolize both the azoxy 2 procarbazine isomer and ALD, ultimately producing N-isopropylterephthalamic acid. The ability of xanthine oxidase to metabolize azoxy 2 procarbazine and ALD was confirmed using commercial, purified milk xanthine oxidase.
...
PMID:Metabolism of azoxy derivatives of procarbazine by aldehyde dehydrogenase and xanthine oxidase. 168 Jun 57

Molybdenum is an essential trace element taking part in the active site of three human enzymes: xanthine oxidase, aldehyde oxidase and sulfite oxidase, playing a role in the detoxification of the organism and/or the production of important intermediary products. The perturbation of the first two enzymes has no established clinical consequence, but a decrease in activity of the third one is harmful for the organism, particularly the nervous system during pre- or post-natal development. The anomalies in the function of these enzymes are generally inherited and linked to the impaired production of the molybdenum cofactor, an organic molecule complexed to the element in the active site. However, several pathological cases in animals and one case in man have been clearly attributed to molybdenum deficiency. It is the reason why molybdenum supplementation has been recommended in long term total parenteral nutrition in infants and adults.
...
PMID:[The nutritional importance and physiopathology of molybdenum in man]. 175 80

NAD(P)-linked aldehyde dehydrogenases catalyze the oxidation of a wide variety of aldehydes. Thirteen of these enzymes have been identified in mouse tissues; eleven are found in the liver. Some are substrate-nonspecific; others are relatively substrate-specific. The present investigation sought to determine which of these enzymes are operative in catalyzing the oxidation of retinaldehyde to retinoic acid, a metabolite of vitamin A that promotes the differentiation of epithelial and other cells. Spectrophotometric and HPLC assays were used for this purpose. Enzyme-catalyzed oxidation of retinaldehyde (25 microM) was restricted to the cytosol (105,000 g supernatant fraction) and occurred at a rate of 211 nmol/min/g liver; oxidation of acetaldehyde (4 mM) by this fraction proceeds about ten times faster. At least 90% of this activity was NAD dependent. Of the approximately 10% that was apparently NAD independent, two-thirds was inhibited by 1 mM pyridoxal, a known inhibitor of aldehyde oxidase. Of the six cytosolic aldehyde dehydrogenases, only two, viz. AHD-2 and AHD-7, catalyzed the oxidation of retinaldehyde to retinoic acid. An additional NAD-dependent enzyme, viz. xanthine oxidase (dehydrogenase form), also catalyzed the reaction. Catalysis by AHD-2 accounted for more than 90% of the total NAD-dependent activity. Km values were 0.7, 0.6 and 0.9 microM, respectively, for the AHD-2-, AHD-7- and xanthine oxidase (dehydrogenase form)-catalyzed reaction. AHD-4, an aldehyde dehydrogenase found in the cytosol of mouse stomach epithelium and cornea, did not catalyze the reaction.
...
PMID:Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. 188 36

Reductive metabolism of the hair dye constituent, nitro-p-phenylenediamine (2-nitro-1,4-diaminobenzene, NPDA), and its acetylated metabolite, NPDA N4-acetate, was investigated with rat liver subcellular fractions, microsomes and cytosol. Under anaerobic conditions, these compounds were reduced to their corresponding amines by these fractions. The microsomal nitro-reducing activity was retarded completely by air and strongly by carbon monoxide. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) functioned more effectively than reduced nicotinamide adenine dinucleotide (NADH) as an electron donor in the microsomal reduction of the nitro compounds, and flavin mononucleotide (FMN) gave rise to a marked enhancement in the microsomal activity, especially when added to an anaerobic incubation mixture containing both NADH and NADPH. The cytosolic nitro-reducing activity was attributed to xanthine oxidase, aldehyde oxidase and other unknown enzyme(s), based on the results of cofactor requirements and inhibition experiments.
...
PMID:Reductive metabolism of nitro-p-phenylenediamine by rat liver. 204 1

This study evaluated the effect of ischemia-reperfusion (I-R) on pulmonary capillary permeability in isolated rabbit lungs and the roles of xanthine oxidase (XO), aldehyde oxidase (AO), and neutrophils (PMN) in producing this lung injury. Effects of XO and AO were studied by inactivation with a tungsten-enriched diet (0.7 g/kg) and inhibition of XO by allopurinol (100 microM) or AO by menadione (3.5 microM). PMN effects were studied by preventing endothelial adhesion with the monoclonal antibody IB4 (10 microM). Vascular permeability was evaluated by determining the capillary filtration coefficient (Kf,c) measured before and after I-R in all experimental conditions. Reperfusion after 2 h of ischemia significantly increased pulmonary capillary permeability (Kf,c changed from 0.096 +/- 0.014 to 0.213 +/- 0.025 ml.min-1. cmH2O-1.100 g-1), and this increase was blocked by the addition of catalase (50,000 U) at reperfusion (baseline Kf,c was 0.125 +/- 0.023 and 0.116 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). XO inactivation with the tungsten-supplemented diet and XO inhibition with allopurinol prevented the Kf,c increase observed after I-R (0.183 +/- 0.030 to 0.185 +/- 0.033 and 0.126 +/- 0.018 to 0.103 +/- 0.005 ml.min-1.cmH2O-1.100 g-1). Inhibition of AO had no effect on I-R injury (Kf,c 0.108 +/- 0.011 to 0.167 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). Preventing PMN adhesion resulted in significant attenuation of the change in Kf,c associated with I-R (0.112 +/- 0.032 to 0.090 +/- 0.065 ml.min-1.cmH2O-1.100 g-1). We conclude that XO and PMN adherence, but not AO, are involved in the increased capillary permeability associated with I-R.
...
PMID:Role of xanthine oxidase and neutrophils in ischemia-reperfusion injury in rabbit lung. 207 95

The cytosolic molybdoflavoprotein xanthine oxidase has been shown to catalyze the reduction of exocyclic nitro groups to the corresponding nitroso, hydroxylamino and amino derivatives for a wide variety of xenobiotics including the nitrated polycyclic aromatic hydrocarbons 1-nitropyrene and 3-nitrofluoranthene. Using commercially available bovine liver xanthine oxidase, we have studied the kinetics of the metabolism of 1-nitropyrene and 3-nitrofluoranthene. The nitroreduction of these nitro compounds in the presence of xanthine oxidase is dependent on the presence of hypoxanthine or xanthine and the absence of oxygen. This nitroreduction is independent of added flavins (FMN and FAD), unlike the related molybdoflavoprotein aldehyde oxidase. Xanthine oxidase has a Km of 0.7 microM and Vmax of 0.06 nmol/min per unit enzyme for 1-nitropyrene and a Km of 8.6 microM and Vmax of 0.7 nmol/min per unit enzyme for 3-nitrofluoranthene. The importance of these kinetic constants in evaluating the cytosolic metabolism of 1-nitropyrene and 3-nitrofluoranthene are discussed.
...
PMID:The kinetics of 1-nitropyrene and 3-nitrofluoranthene metabolism using bovine liver xanthine oxidase. 220 87

The aim of this paper is to apply inverse regression as a method for treating experimental data obtained from gel filtration chromatography in order to obtain estimates of hydrodynamic parameters of globular proteins with true confidence intervals. The method is illustrated with the determination, using inverse regression, of molecular mass and Stokes radius for four test proteins (aldolase, chymotrypsinogen A, aldehyde oxidase and xanthine oxidase), from experimental data obtained with a Sephacryl S-300 column. A simple personal computer (PC) program written in standard basic, that is useful for this purpose, is included.
...
PMID:Application of inverse regression for estimating molecular masses and Stokes radii of globular proteins by gel filtration chromatography. 231 34

The interaction of a series of 1-substituted phthalazine derivatives with partially purified aldehyde oxidase from rabbit, guinea-pig and baboon liver, and with bovine milk xanthine oxidase, has been investigated. Of the 18 compounds examined, rabbit liver aldehyde oxidase metabolized 10, whereas guinea-pig and baboon liver enzyme oxidized 13 and 14, respectively. Where metabolites were characterized, oxidation was shown to occur at position four of the phthalazine ring. Km values ranged from 0.003 to 1.8 mM. In contrast, most compounds were competitive inhibitors of bovine milk xanthine oxidase with Ki values ranging from 0.015 to 1.3 mM; the cationic derivative 2-methylphthalazinium iodide was oxidized to 2-methyl-1-phthalazinone by both aldehyde oxidase and, with a much reduced affinity, by xanthine oxidase. In terms of structure-metabolism relationships, Vmax values were relatively insensitive to the electronic effects of substituents, but a trend for the more lipophilic derivatives to show increased affinities (Km and Vmax/Km) towards aldehyde oxidase could be seen. However, calculations of molecular size revealed a species-dependent cut-off threshold above which compounds were not metabolized. Results suggest that the relative size of the active site for hepatic aldehyde oxidase is in the order baboon greater than guinea-pig greater than rabbit, and that in spatial terms the active site of bovine milk xanthine oxidase is similar to that of baboon liver aldehyde oxidase. Thus, the binding site of rabbit liver aldehyde oxidase, a widely used source of the oxidase, is apparently more restricted than in some other species.
...
PMID:1-substituted phthalazines as probes of the substrate-binding site of mammalian molybdenum hydroxylases. 232 6

Genetic heterogeneity has been suggested in xanthinuria from the hitherto unexplained ability of some patients with this hereditary disorder to convert allopurinol to its active metabolite oxipurinol--an activity generally attributed to xanthine oxidase. This study provides evidence that the enzyme aldehyde oxidase is also deficient in xanthinuric patients not converting allopurinol to oxipurinol, whereas a xanthinuric patient with normal formation of oxipurinol had normal aldehyde oxidase activity. It is concluded that the enzyme aldehyde oxidase is the principal enzyme responsible for the formation of oxipurinol in man.
...
PMID:Demonstration of a combined deficiency of xanthine oxidase and aldehyde oxidase in xanthinuric patients not forming oxipurinol. 232 62

SR 4233 (3-amino-1,2,4-benzotriazine-1,4-dioxide) is a novel benzotriazine di-N-oxide which shows unusually high selective toxicity towards hypoxic cells, probably as a result of reductive bioactivation. Using an HPLC assay for the parent drug and its 2- and 4-electron reduction products (SR 4317 and SR 4330, respectively), we have examined the enzymology of SR 4233 reductive metabolism in vitro using a variety of different enzyme preparations. SR 4233 was converted extremely rapidly to SR 4317 under N2 by mouse liver microsomes, and showed a marked preference for NADPH over NADH as a reduced cofactor. The reaction was inhibited completely in air and boiled preparations. It was also inhibited by 78-86% in carbon monoxide (CO), implicating cytochrome P-450 as the major microsomal SR 4233 reductase. The kinetics of reductive metabolism of SR 4233 to SR 4317 by mouse liver microsomes conformed to Michaelis-Menten kinetics, with a Km of 1.4 mM and a Vmax of 950 nmol/min/mg protein. SR 4233 reduction was also catalysed by mouse liver cytosol under N2. However, rates were markedly slower than for microsomes and showed an equal dependency on NADH and NADPH. The cytosolic enzymes aldehyde oxidase and xanthine oxidase both catalysed SR 4233 reduction to SR 4317 under N2. Purified buttermilk xanthine oxidase also catalysed this reaction. In contrast to other enzyme preparations, DT-diaphorase from Walker 256 tumour cells reduced SR 4233 predominantly to SR 4330, and this reaction occurred under aerobic conditions. These data illustrate that SR 4233 is reduced rapidly by a wide variety of reductases. We propose that the therapeutic selectivity of SR 4233 will be controlled by the relative expression of reductases in tumour versus normal tissues, and in particular by the differential participation of putative activating versus detoxifying enzymes.
...
PMID:Enzymology of the reductive bioactivation of SR 4233. A novel benzotriazine di-N-oxide hypoxic cell cytotoxin. 234 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---