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

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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)

The toxic effect and anti-tumor activity of B-3839, a new molecular combination of pyrimidine antimetabolite 5-fluorouracil (5-FU) with the alkylating agent N-Chloroethyl-N-nitrosourea (BCNU), was compared to that of BCNU and 5-FU given alone and in physical combination. The tumor inhibitory effect of B-3839 was similar to that of BCNU given alone or combined with a low dose of 5-FU in the i.m. Walker tumor model. Furthermore, the bone marrow toxicity of BCNU was not significantly altered by either form of combination with 5-FU. The intestinal side effects, evaluated by measuring the decrease of marker enzyme (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) activities in isolated enterocytes, were dose-dependent and moderate. A significant, more than 30%, decrease occurred only if BCNU and 5-FU were given simultaneously or as B-3839. The molecular combination of the two drugs does not provide any additional advantage over their physical combination.
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PMID:Comparison of tumor growth inhibitory and toxic effects of a new fluorouracil--nitrosourea derivative (B-3839). 297 32

A simple method is presented for the determination of pyrimidine-5'-nucleotidase activity using a continuous spectrophotometric assay system. Activity is determined by measuring inorganic phosphate generation using a linked indicator system that produces uric acid in the presence of inosine, purine nucleoside phosphorylase, and xanthine oxidase. This method has several advantages over any of the methods currently in use.
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PMID:A continuous spectrophotometric assay for pyrimidine-5'-nucleotidase. 300 35

Nitrated polycyclic aromatic compounds, 1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-diNP), are environmental mutagens and carcinogens. Nitroreductases purified from an anaerobic bacterium, Bacteroides fragilis, catalyzed the metabolic activation of these compounds to produce DNA- and tRNA-bound adducts in vitro. Formation of the adducts was inhibited by p-chloromercuribenzoic acid, which is an inhibitor of nitroreductases from B. fragilis. The enzyme and coenzyme (NADPH) were essential for the adduct formation. These results suggest that nitroreduction is a necessary step in the metabolic activation of nitropyrenes. 1-NP bound specifically to poly(G) and poly(dG), and 1,6-diNP bound to poly(G), poly(dG), and poly(X). The other purine polynucleotides were weak acceptors. However, the reactive products of nitropyrenes formed by nitroreductases could not bind to pyrimidine polynucleotides. Enzymatic hydrolysis of 1-NP-bound DNA and subsequent analysis by high-performance liquid chromatography showed one major and two minor adducts in the hydrolysate. The peak of the major adduct corresponded to that of N-(deoxyguanosin-8-y1)-1-aminopyrene, which is the same as an adduct formed by xanthine oxidase, a mammalian nitroreductase. Nitroreductase activity in the various organs and intestinal contents of Sprague-Dawley rats was assayed in the presence of NADPH or NADH under nitrogen gas. Nitroreductase activity was widely distributed in the organs of the rats; in particular, that of the liver and of the small intestine was relatively high, but that of the respiratory organs such as lung and alveolar macrophages was very low. Intestinal contents had high nitroreductase activity, which was proportional to the number of bacteria, especially anaerobic bacteria, in the intestine. These results suggest that the nitroreductase activity of the normal bacterial flora is very high in rats and that the intestinal bacteria play a major role in the metabolism of nitropyrenes in vivo.
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PMID:Metabolic activation of 1-nitropyrene and 1,6-dinitropyrene by nitroreductases from Bacteroides fragilis and distribution of nitroreductase activity in rats. 379 18

1. Allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) selectively inhibits the apotryptophan pyrrolase activity in homogenates of rat liver in vitro and after intraperitoneal administration. The inhibition is abolished by an excess of haematin. The allopurinol metabolite alloxanthine has no effect on the pyrrolase activity in vitro or after administration. Allopurinol also inhibits the activation of the enzyme in vitro by ascorbate, ethanol plus NAD(+), NADH, hypoxanthine or xanthine. It is suggested that these agents cause the conversion of a latent form of the pyrrolase into the apoenzyme, and that xanthine oxidase is not involved in this process. 2. The raised total pyrrolase activity observed after the administration of cortisol, cyclic AMP, tryptophan, salicylate or ethanol is lowered by allopurinol in vitro to the corresponding holoenzyme values. A similar effect is observed when allopurinol is administered shortly before cortisol or cyclic AMP. Pretreatment of rats with allopurinol completely prevents the enhancement of the pyrrolase activities by tryptophan, salicylate or ethanol. 3. It is suggested that allopurinol inhibits rat liver tryptophan pyrrolase activity in vitro and after administration by preventing the conjugation of the apoenzyme with its haem activator. The possible usefulness of combined allopurinol-tryptophan therapy of affective disorders is discussed.
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PMID:The mechanism of inhibition of rat liver tryptophan pyrrolase activity by 4-hydroxypyrazolo(3,4-d)pyrimidine (Allopurinol). 435 41

1. A patient with congenital deficiency of xanthine oxidase (EC 1.2.3.2) (xanthinuria) excreted the xanthine isomer 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (oxipurinol) in his urine when the hypoxanthine isomer 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) was given by mouth. 2. The identity of the oxipurinol that the patient excreted was established by mass spectrometry. 3. The mass spectra and infrared spectra of allopurinol, oxipurinol, hypoxanthine and xanthine are compared. 4. A mechanism for the fragmentation of these compounds that occurs during their mass-spectrometric investigation is proposed. 5. A possible metabolic pathway for the oxidation of allopurinol to oxipurinol in the absence of xanthine oxidase is discussed.
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PMID:The conversion of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) into 4,6-dihroxypyrazolo[3,4-d]pyrimidine (Oxipurinol) in vivo in the absence of xanthine-oxen oxidoreductase. 580 74

Allopurinol (4-hydroxypyrazolo (3,4-d)-pyrimidine) is a potent xanthine oxidase inhibitor which inhibits the oxidation of naturally occurring oxypurines, thus decreasing uric acid formation. The clinical and metabolic effects of this agent were studied in 80 subjects with primary and secondary gout and other disorders of uric acid metabolism. Allopurinol has been universally successful in lowering the serum uric acid concentration and uric acid excretion to normal levels, while not significantly affecting the clearance of urate or other aspects of renal function. Oxypurine excretion increased concomitantly with the fall in urine uric acid. The agent is particularly valuable in the management of problems of gout with azotemia, acute uric acid nephropathy and uric acid urolithiasis. The minor side effects, clinical indications and theoretical complications are discussed.
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PMID:The treatment of gout and disorders of uric acid metabolism with allopurinol. 592 71

The purine metabolism of four cases with marked hypouricemia (serum uric acid concentration of less than 0.018 mmol/l) from three Japanese families was investigated. Erythrocyte adenosine deaminase (EC 3.5.4.4) and purine-nucleoside phosphorylase (EC 2.4.2.1) activities of the patients were within the normal ranges. Urinary hypoxanthine and xanthine concentrations were 0.096-0.397 mmol/l and 0.743-1.717 mmol/l, respectively. Xanthine oxidase (EC 1.2.3.2) activities in the jejunal mucosa of the two normal controls were 0.257 and 0.283 units/g protein, while those of three of the patients were extremely low and could not be determined. The findings of these biochemical features may indicate that the four patients have hereditary xanthinuria. In order to study the purine metabolism in the hypouricemic condition of this disorder, a single oral dose of allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) was administered in one case. The excretion pattern of allopurinol and oxypurinol (4,6-dihydroxypyrazolo[3,4-d]pyrimidine) in the urine of the patient was similar to that of a normal control male. These data suggest that some residual enzyme activity may be functioning in vivo, although the presence of xanthine oxidase could not be detected.
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PMID:Biochemical studies on the purine metabolism of four cases with hereditary xanthinuria. 642 23

The rate of purine de novo synthesis from sodium formate in developing rat brain falls in the late gestational stages to birth, rises again in the 1st week of life and then decreases rapidly to the 3rd week, and continues declining up to 8 weeks of life (adulthood). The changes in the overall purine biosynthetic rate with respect to time are similar to those in the activity of the rate-limiting enzyme [amidophosphoribosyltransferase (phosphoribosyl diphosphate amidotransferase; EC 2.4.2.14)]. Azaserine [O-diazoacetyl-L-serine], a known inhibitor of glutamine requiring metabolic steps, inhibits purine de novo synthesis by more than 90%. This confirms that the method used to assess purine de novo synthesis in fact does so. The effects of virazole [1-beta-ribofuranosyl-1-H,1,2,4-triazole-3-carboxamide], an inhibitor of IMP dehydrogenase (EC 1.2.1.14), and of alanosine [L-2-amino-3-(hydroxynitrosamino)propanoic acid] an inhibitor of adenylosuccinate synthetase (EC 6.3.4.4), on the rate of purine de novo synthesis were investigated in liver and brain tissue. The effect of the xanthine oxidase inhibitor allopurinol [4-hydroxypyrazolo(3,4-d)pyrimidine] was also investigated in liver tissue. The biosynthesis of the purines which were extruded into the incubation medium as well as those which remained in the tissue was studied. Only inhibitory effects were observed, and these were confined to the purines remaining in the tissue. Allopurinol was completely inert from this viewpoint. The results are compared with those of other workers using lymphoid cells, and emphasize the differences in the control of de novo purine synthesis in different tissues and under different conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Purine de novo synthesis in liver and developing rat brain, and the effect of some inhibitors of purine nucleotide interconversion. 662 51

Biochemical studies have demonstrated that dihydroorotate dehydrogenase (DHOdehase; EC 1.3.3.1 or 1.3.99.11) is the sole enzyme of de novo pyrimidine synthesis in mitochondria, whereas the rest of the pathway takes place in the cytosol. The dehydrogenation of dihydroorotate to orotate is linked to the respiratory chain via ubiquinone. In this study, we show for the first time the ultrastructural localization of DHOdehase. Since the purified enzyme was found to act both as dehydrogenase and as oxidase, the cerium capture technique for detecting enzymatically generated hydrogen peroxide could be applied to pin-point the in situ activity of DHOdehase oxidase in mitochondria of rat heart and kidney cortex. Cerium perhydroxide as the final reaction product was detected predominantly in the matrix with some focal condensation along the inner membrane, but not in the intermembrane space. From this pattern of localization, it is concluded that the active site of the membrane-bound enzyme could face the mitochondrial matrix similar to succinate dehydrogenase. The reliability of the applied method for the demonstration of DHOdehase oxidase was demonstrated by the addition of Brequinar sodium to the incubation medium. This quinoline-carboxylic acid derivative is a potent inhibitor of DHOdehase and has proven anti-proliferative activity. The present observations do not ascertain whether the oxidase is permanently active as a constant portion of the enzyme in vivo, similar to xanthine oxidase/dehydrogenase. However, DHOdehase should be considered as a source of radical oxygen species under pathophysiological conditions.
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PMID:Localization of dihydroorotate oxidase in myocardium and kidney cortex of the rat. An electron microscopic study using the cerium technique. 764 4

A sensitive peroxyoxalate chemiluminescent (PO-CL) assay for activities of oxidases (uricase, choline oxidase, cholesterol oxidase and xanthine oxidase) which catalyse a formation of hydrogen peroxide was developed using 4,4'-oxalyl- bis[(trifluoromethyl-sulphonyl)imino]trimethylene-bis(4- methylmorpholinium)trifluoromethanesulphonate as a chemiluminogenic reagent and 2,4,6,8-tetramorpholinopyrimido[5,4- d]pyrimidine as fluorophore. The standard curve for hydrogen peroxide was linear over the range 1 x 10(-7)-1 x 10(-4) mol/L. Relative standard deviations for oxidase assays were 5.1-12.7% (n = 10). Detection limits were 1 x 10(-3) U/mL for uricase, 5 x 10(-4) U/mL for choline oxidase, 5 x 10(-3) U/mL for cholesterol oxidase and 5 x 10(-4) U/mL xanthine oxidase (sample to blank ratio, 3).
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PMID:Peroxyoxalate chemiluminescent assay for oxidase activities based on detecting enzymatically formed hydrogen peroxide. 767 61


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