Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of inhibitors and activators on the azo- and nitro-reductases of Ascaris lumbricoides var suum have been investigated. Both types of reduction were inhibited by FAD, FMN, riboflavin, allopurinol, dicoumarol, 5-nitro-2-furaldehyde, azide and cyanide at concentrations of 1 mM. Neither reaction was inhibited by menadione, nitrofurantoin, SKF 525-A or fluoride. Both reactions were stimulated by addition of hypoxanthine. 2. The enzyme preparation contained no detectable aldehyde oxidase or xanthine oxidase activity. 3. The differences in the effects of flavins and inhibitors on mammalian and nematode azo- and nitro-reductases might have practical significance in the development of anthelmintic synergists.
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PMID:The effect of flavins and enzyme inhibitors on 4-nitrobenzoic acid reductase and azo reductase of Ascaris lumbricoides var suum. 5 46

NADH-FMN oxidoreductase has been proposed as an enzyme involved in the release of iron from ferritin. The effects of riboflavin and/or iron deficiencies and of dietary allopurinol on the activities of this enzyme and on the iron contents of liver, kidney and duodenum were investigated. Allopurinol, a xanthine oxidase inhibitor, did not affect organ enzyme activities nor iron contents. Riboflavin-deficient rats and iron-deficient rats both had significantly lower organ enzyme activities and iron contrnts than controls. Organ enzyme activities and iron contents of rats fed a diet deficient in both iron and riboflavin were significantly lower than those of controls. After dietary iron and/or riboflavin repletion, organ enzyme activities and iron contents increased. Rats fed an irons-overload diet had enzyme activities similar to that of controls, but organ iron contents were significantly increased over those of controls. Effects of riboflavin and/or deficiencies in rats on NADH-FMN oxidoreductase activities and iron contents of liver, kidney and duodenum appeared to be reversible by riboflavin and/or iron supplementation. The data support the view that NADH-FMN oxidoreductase may be a controlling enxyme in iron release from ferritin.
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PMID:NADH-FMN oxidoreductase activity and iron content of organs from riboflavin and iron-deficient rats. 85 41

Xanthine oxidase from milk was reconstituted with the photoreactive flavin, 6-azido-FAD. While irradiation of the reconstituted enzyme under anaerobic conditions yielded 6-amino-FAD as a light product, aerobic irradiation resulted in formation of an unknown product, which gave the enzyme almost the same activity as that of the native enzyme. The light product could be extracted from the enzyme without breakdown and was found to be highly fluorescent. Upon treatment with phosphodiesterase, this light product was converted to the FMN form. The absorption spectrum of the FMN form has a peak at 464 nm, a shoulder at 450 nm in the visible region, and two peaks at 260 and 298 nm in the UV. Irradiation of free 6-azido-3-methyllumiflavin in the presence of a saturating concentration of oxygen yielded a light product whose absorbance and fluorescence spectra were very similar to those of the light product extracted from the enzyme, suggesting that the two had undergone some common photochemical change at the same place in the isoalloxazine ring. Analysis of the light product of 6-azido-3-methyllumiflavin with 1H NMR and FAB mass spectrometry suggested its possible structure with a new five-membered ring, C(6) = N-O-CH = C(7), adjacent to the benzene ring of the flavin.
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PMID:Light product of photoreactive 6-azido-FAD bound to deflavo-milk xanthine oxidase. 162 69

The rates of NADH oxidation in presence of xanthine oxidase increase to a small and variable extent on addition of high concentrations of lactate dehydrogenase and other dehydrogenases. This heat stable activity is similar to polyvanadate-stimulation with respect to pH profile and SOD sensitivity. Isocitric dehydrogenase (NADP-specific) showed heat labile, SOD-sensitive polyvanadate-stimulated NADH oxidation activity. Polyvanadate-stimulated SOD-sensitive NADH oxidation was also found to occur with riboflavin, FMN and FAD in presence of a non-specific protein, BSA, suggesting that some flavoproteins may possess this activity.
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PMID:Stimulation of NADH oxidation by xanthine oxidase and polyvanadate in presence of some dehydrogenases and flavin compounds. 178 72

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.
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PMID:The kinetics of 1-nitropyrene and 3-nitrofluoranthene metabolism using bovine liver xanthine oxidase. 220 87

The chemical reactivity of 8-chloroflavins and 8-mercaptoflavins has been exploited in order to examine the orientation of protein-bound flavins relative to solvent. The apoprotein form of a series of flavoproteins was prepared and the native flavin was replaced by either 8-Cl-flavin or 8-mercaptoflavin (FAD, FMN, or riboflavin form as was appropriate). The reconstituted proteins were exposed to reagents capable of reacting with the group at position 8. The 8-Cl-proteins were challenged with sodium sulfide and thiophenol, while the 8-mercaptoproteins were faced with iodoacetamide and iodoacetic acid. The kinetics of the ensuing reactions served as a measure of the solvent availability of position 8 for the protein-bound flavin. These studies indicated that position 8 of flavin bound to melilotate hydroxylase, D-amino acid oxidase, old yellow enzyme, p-OH-benzoate hydroxylase, and flavodoxin is accessible to solvent, while position 8 on L-lactate oxidase, glucose oxidase, putrescine oxidase, and riboflavin-binding protein appears to be inaccessible. For luciferase, D-lactate dehydrogenase, and xanthine oxidase, the data suggest that position 8 is exposed but the results are inconclusive. The effect of ligand binding on the accessibility of position 8 was also studied. NADPH binding to 8-mercapto old yellow enzyme and benzoate binding to 8-Cl-D-amino acid oxidase results in complete blockage of previously available position 8. On the other hand, p-OH-benzoate hydroxylase and melilotate hydroxylase bind their respective substrates (p-OH-benzoate and melilotate) without significantly altering the reactivity of position 8.
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PMID:Active site probes of flavoproteins. Determination of the solvent accessibility of the flavin position 8 for a series of flavoproteins. 689 55

Iodonium inhibition of the flavoenzymes neutrophil NADPH oxidase and cytochrome P450 reductase has been suggested to require reductive metabolism of the inhibitor to a phenyl radical. Inhibition would ultimately result from covalent attachment of phenyl radicals to either the flavin cofactor or adjacent amino acid side chains important in catalysis. In this paper we provide evidence, using EPR techniques, that phenyl radicals are formed during reaction of iodonium diphenyl with reduced free flavin (FMN) and protein-bound (cytochrome P450 reductase or xanthine oxidase) flavin. Kinetic analysis indicated iodonium diphenyl to be an uncompetitive inhibitor of xanthine oxidase, suggesting the need for reduced enzyme for inhibition. A study of the catalytic and structural properties of different flavoenzymes suggested that only enzymes containing flavins that function in one-electron transfer are targets for iodonium inhibition.
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PMID:Involvement of phenyl radicals in iodonium inhibition of flavoenzymes. 796 60

The characterization of the enzymatic step(s) involved in the reduction of 3'-azido-3'-deoxythymidine (zidovudine)(ZDV) to 3'-amino-3'-deoxythymidine (AMT) was pursued. AMT formation by human liver microsomes was NADPH dependent, enhanced under anaerobic conditions, and increased by flavin adenine dinucleotide (FAD) and FMN. Carbon monoxide inhibited AMT formation by up to 80%. The effect of theophylline (CYP1A substrate), tolbutamide (CYP2C substrate), chlorzoxazone, thiobenzamide, p-nitrophenol, mercaptoethanol, isoniazid (CYP2E substrates), cortisol (CYP3A substrate), ketoconazole, itraconazole, fluconazole, cimetidine, micronazole (CYP inhibitors), methimazole (flavin-containing mono-oxygenase inhibitor), chloramphenicol (undergoes nitroreduction), allopurinol (xanthine oxidase inhibitor) and dicoumarol (DT-diaphorase inhibitor) on AMT formation were studied to see if the reduction reaction was mediated by a particular isozyme. The greatest inhibition was observed with ketoconazole (concentration producing 50% inhibition = 78.0 microM). At this concentration ketoconazole acted as a non-selective inhibitor of several CYP isozymes. Overall, these data suggested that ZDV reduction was probably mediated by both cytochrome P450 isozymes and NADPH-cytochrome P450 reductase. Formation of AMT, as measured by intrinsic clearance (Clint), was significantly increased in microsomes from rats pre-treated with phenobarbitone, dexamethasone and clofibrate (inducers of CYP2B, CYP3A and CYP4A, respectively). Pre-treatment of rats with beta-naphthoflavone and ethanol (CYP1A and CYP2E1 inducers, respectively) had no effect on AMT formation.
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PMID:The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. 805 24