Showing papers on "Xanthine published in 1970"
TL;DR: It was shown that at any given pH and oxygen tension, the amount of univalently reduced oxygen, which was detectable in terms of the reduction of cytochrome c, rose as the turnover rate of the enzyme was decreased by decreasing the concentration of xanthine.
1,012 citations
TL;DR: The results have led to the conclusion that xanthine oxidase generates O2- and H2O2 as the primary products of the reduction of oxygen and generates ·OH as a secondary consequence of the interaction of O1- with H1O2 and that it is the hydroxyl radical rather than the superoxide anion radical which reacts with methional to generate ethylene.
632 citations
Journal Article•
TL;DR: Close correlation between these two activities strongly indicates that the lipolytic activity of the xanthine derivatives is a result of inhibition of cyclic AMP phosphodiesterase.
Abstract: The lipolytic potencies of 64 compounds, mostly xanthine derivatives, were determined in epididymal fat cells. Nine of the compounds of widely varying lipolytic potency were examined as inhibitors of cyclic AMP phosphodiesterase activity. Substantial lipolytic effects were seen at concentrations producing less than 20% inhibition of phosphodiesterase activity. The most active compound, 1-methyl-3-isobutylxanthine, was about 15 times more potent than theophylline in both systems. Over a 20-fold range of concentrations, there was close agreement between the lipolytic activities of the compounds and their activities as inhibitors of phosphodiesterase. The close correlation between these two activities strongly indicates that the lipolytic activity of the xanthine derivatives is a result of inhibition of cyclic AMP phosphodiesterase.
471 citations
TL;DR: The data suggest that Neurospora nitrate reductase and the xanthine oxidizing system and aldehyde oxidase of animals, all of which are molybdenum-containing enzymes catalyzing the reduction of nitrate to nitrite, share a highly similar protein subunit.
Abstract: In vitro assembly or complementation of a hybrid assimilatory nitrate reductase was attained by mixing a preparation of nitrate-induced N. crassa mutant nit-1 specifically with acid-treated (pH 2.5) bovine milk or intestinal xanthine oxidase, rabbit liver aldehyde oxidase, or chicken liver xanthine dehydrogenase. The complementation reaction specifically required induced nit-1, the only nitrate reductase mutant of Neurospora that lacked xanthine dehydrogenase and was unable to use hypoxathine or nitrate as a sole nitrogen source. The complementing activities of the above acid-treated enzymes correspond to their xanthine or aldehyde oxidizing activity profiles on sucrose density gradients. The resulting soluble, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductases are the same as the Neurospora wild type enzyme in sucrose density gradient profile, molecular weight, substrate affinities, and sensitivity to inhibitors and temperature. By analogy to a similar in vitro complementation of nitrate reductase in mixtures of induced nit-1 and individual nonalleic Neurospora mutants, or uninduced wild type, the complemented nitrate apparently consists of an inducible protein subunit (possessing inducible NADPH-cytochrome c reductase) furnished by nit-1 and a subunit from the acid-treated xanthine or aldehyde oxidizing system which can substitute for the constitutive component furnished by the other mutants or uninduced wild type. The data suggest that Neurospora nitrate reductase and the xanthine oxidizing system and aldehyde oxidase of animals, all of which are molybdenum-containing enzymes catalyzing the reduction of nitrate to nitrite, share a highly similar protein subunit.
118 citations
TL;DR: Four patients in a kindred who have had hyperuricemia, uric acid crystalluria and stones, were found to have partial deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity, and the pattern of inheritance is consistent with the observation that the activity of HGPRT is determined by a gene on the X chromosome.
75 citations
TL;DR: The data indicate that excessive uric acid in HG-PRTase deficiency is derived from hypoxanthine which is insufficiently reutilized and, as a consequence thereof, catabolized inordinately to uric Acid.
Abstract: Certain gouty subjects with excessive de novo purine synthesis are deficient in hypoxanthineguanine phosphoribosyltransferase (HG-PRTase [EC 2.4.2.8]). The mechanism of accelerated uric acid formation in these patients was explored by measuring the incorporation of glycine-(14)C into various urinary purine bases of normal and enzyme-deficient subjects during treatment with the xanthine oxidase inhibitor, allopurinol. In the presence of normal HG-PRTase activity, allopurinol reduced purine biosynthesis as demonstrated by diminished excretion of total urinary purine or by reduction of glycine-(14)C incorporation into hypoxanthine, xanthine, and uric acid to less than one-half of control values. A boy with the Lesch-Nyhan syndrome was resistant to this effect of allopurinol while a patient with 12.5% of normal enzyme activity had an equivocal response. Three patients with normal HG-PRTase activity had a mean molar ratio of hypoxanthine to xanthine in the urine of 0.28, whereas two subjects who were deficient in HG-PRTase had reversal of this ratio (1.01 and 1.04). The patterns of (14)C-labeling observed in HG-PRTase deficiency reflected the role of hypoxanthine as precursor of xanthine. The data indicate that excessive uric acid in HG-PRTase deficiency is derived from hypoxanthine which is insufficiently reutilized and, as a consequence thereof, catabolized inordinately to uric acid. The data provide evidence for cyclic interconversion of adenine and hypoxanthine derivatives. Cleavage of inosinic acid to hypoxanthine via inosine does not contribute significantly to the formation of uric acid in either normal man or in patients with HG-PRTase deficiency.HG-PRTase was not completely absent in red blood cells from a boy with the Lesch-Nyhan syndrome; with hypoxanthine as substrate, the activity in erythrocyte hemolysates was 0.64% of normal values.
68 citations
TL;DR: In extracts of both L. casei and E. coli, the activity toward adenine was distinct from the activities toward hypoxanthine, guanine, and xanthine.
61 citations
Journal Article•
TL;DR: Although the assay response to adenine 1- N -oxide has been variable, a sufficient incidence of tumors has been observed to indicate that it is at least a moderately oncogenic purine N-oxide, which indicates that the oncogenicity of purines and of a few other purine derivatives is influenced both by the position of theN -oxide and by other substituents.
Abstract: Assays of the oncogenic N -oxide derivatives of xanthine and guanine, which have now been proven to be 3-hydroxyxanthine and guanine 3- N -oxide, continue to show about equal activities. Parallel titrations at 1.0, 0.5, and 0.1 mg/week for 26 weeks, administered subcutaneously, in female Wistar rats show that, for these conditions, the 50% tumor incidence doses lie between the two lower dose levels, or between a total of 2 and 10 mg of the free bases.
The isomeric 1-hydroxyxanthine elicits a different response. While being administered it induces a severe inflammatory and granulomatous condition, but it leads to only a small incidence of tumors. This, coupled with the confirmed low incidence of tumors from 6-mercaptopurine 3- N -oxide, indicates that the oncogenicity of purine N -oxide derivatives is influenced both by the position of the N -oxide and by other substituents.
Although the assay response to adenine 1- N -oxide has been variable, a sufficient incidence of tumors has been observed to indicate that it is at least a moderately oncogenic purine N -oxide.
The inactivities of the parent purines and of a few other purine derivatives are recorded.
42 citations
TL;DR: The results provide final confirmation that one-electron reduction of oxygen can occur in biological systems.
Abstract: The electron paramagnetic resonance spectrum of 17O in O2− generated by reduction of O2 by two related systems has been observed using the rapid freezing method. The systems were: (a) during re-oxidation of xanthine oxidase following reduction with dithionite and (b) during steady-state oxidation of xanthine catalysed by xanthine oxidase. The spectrum was similar to that reported for O2− adsorbed on MgO. Both the 11-line spectrum from 17O17O− and the six-line spectrum from 17O16O− were detected. The results provide final confirmation that one-electron reduction of oxygen can occur in biological systems.
36 citations
TL;DR: The inhibition of cream and liver xanthine oxidase by several drugs was studied in a spectrophotometric assay of uric acid formation and tetrazolium reduction.
Abstract: 1
Xanthine oxidase has been partially purified from mammalian liver by a simple procedure.
2
The inhibition of cream and liver xanthine oxidase by several drugs was studied in (a) spectrophotometric assay of uric acid formation and (b) tetrazolium reduction.
3
Inhibitors tested caused different response, which depended on the assay type.
4
A protein was isolated from normal mammalian liver, which selectively inhibited tetrazolium reduction; the effect was observed with the xanthine/xanthine oxidase and ethanol/alcohol dehydrogenase systems.
5
Oxygen consumption by xanthine oxidase was prevented by tetrazolium salt; this effect was blocked by the inhibitor.
6
Some properties of the inhibitor are described.
33 citations
TL;DR: In this paper, purine restriction is associated with decreased excretion of a number of uv-absorbing compounds, including uric acid, hypoxanthine, xanthine and adenine.
Abstract: We demonstrate that purine restriction is associated with a decreased excretion of a number of uv-absorbing compounds—including uric acid, hypoxanthine, xanthine, adenine, pseudouridine, and 5-acetylamino-6-amino-3-methyluracil—indicating that these compounds originate, at least partly, exogenously. Administration of allopurinol and oxipurinol is associated with a decreased excretion of uric acid and an increased excretion of hypoxanthine and xanthine, as well as the excretion of the previously identified products of allopurinol and oxipurinol metabolism. Moreover, these drugs further decrease excretion of 5-acetylamino-6-amino-3-methyluracil, increase uracil excretion slightly, and strikingly increase orotic acid and orotidine excretion. No change in pseudouridine excretion was observed. The ultraviolet-analyzer is a valuable tool for detecting qualitative changes in the excretion of ultraviolet-absorbing compounds in the urine; with it, identified peaks can be semiquantitated.
TL;DR: The enzyme mediates the "heme-splitting" reaction by the generation of peroxides which, in turn, oxidize the alpha-methene bridge of the heme ring releasing iron and forming biliverdin.
TL;DR: Under anaerobic conditions, xanthine oxidase was found to be readily reduced by allopurinol and there was only a small secondary decrease in absorbance that was complete in 2–3 min.
Abstract: Publisher Summary This chapter discusses experimental study analyzing the existence of nonfunctional active sites in milk xanthine oxidase. In this study, milk xanthine oxidase was prepared, and xanthine–oxygen reductase activity was measured spectrophotometrically at 295 nm and at a temperature of 25°. Following the original work of Avis, such catalytic activity is also expressed as AFR 25° values. This value is obtained by dividing the change in absorbancy per minute at 295 nm by the absorbancy at 450 nm of the xanthine oxidase employed in the assay. Under anaerobic conditions, xanthine oxidase was found to be readily reduced by allopurinol. On the addition of allopurinol anaerobically, there was an immediate reduction of the enzyme to the same level as that found in the rapid phase of reduction with xanthine. However, with xanthine further reduction occurred over several hours to a level close to that given by dithionite, whereas with allopurinol, there was only a small secondary decrease in absorbance that was complete in 2–3 min. No further changes occurred even on incubation for as long as 24 h.
TL;DR: Inosine enhances iron absorption in in vivo (rat, Wistar strain) and in isolated small intestine (same animal) and these metabolites, separately administered, positively affect intestinal iron absorption.
TL;DR: A method has been devised utilizing 14C-labeled oxypurines to measure the blood plasma levels of hypoxanthine, xanthine and uric acid using an anion-exchange column, and values were determined spectrophotometrically after treatment withxanthine oxidase.
TL;DR: Treatment with allopurinol results in an induced xanthinuria, and inhibition of xanthine oxidase results in inhibition of hypoxanthine toxanthine and of xAnthine to uric acid.
Abstract: Treatment with allopurinol results in an induced xanthinuria. Allopurinol inhibits xanthine oxidase, the enzyme that catalyzes oxidation of hypoxanthine to xanthine and of xanthine to uric acid,1 a...
TL;DR: Fusarium moniliforme utilized the purines hypoxanthine, xanthine and uric acid as sole nitrogen sources and allantoin and urea supported relatively more growth.
Abstract: SUMMARY: Fusarium moniliforme utilized the purines hypoxanthine, xanthine and uric acid as sole nitrogen sources. Allantoin and urea supported relatively more growth. The methylated purines caffeine and theobromine were not utilized. Uric acid, allantoic acid, glyoxylic acid and ammonia were detected in culture filtrates. Xanthine dehydrogenase, uricase, allantoinase, allantoicase and urease were present in cell homogenates and cell-free extracts. Uric acid was degraded to allantoic acid via allantoin.
Patent•
11 Jun 1970TL;DR: In this article, N-ALKYLATION OF CORRESPONDING COMPOUNDS at EITHER the 1-POSITION OR the 7-position are provided. The COMPOUNTS are CEREBRAL STIMULANTS of the CAFFEINE type.
Abstract: 1,3-DIALKYL-7-MEHTYL-8-STYRYLXANTHINES (I) 1-R1,2,6-(O=),3-R2,7-(CH3-),8-(AR-CH=CH-)-1,2,3,6-TETRA HYDROPURINE ARE PROVIDED BY N-ALKYLATION OF CORRESPONDING COMPOUNDS AT EITHER THE 1-POSITION OR THE 7-POSITION; WHERE R1 AND R2 ARE METHYL OR ETHYL AND AR IS PHENYL OR 3,4,5-TRIMETHOXYPHENYL. THE COMPOUNDS ARE CEREBRAL STIMULANTS OF THE CAFFEINE TYPE.
TL;DR: Intermolecular complexation between a mixture of the comparatively water-insoluble alkaloids comprising 9,10-dihydroergotoxine and several xanthines was investigated and seemed to evidence some “driving force” pulling the drug into solution.
TL;DR: In this article, reaction of 6-amino-5-nitrosouracil derivatives with various substituted hydrazones of aldehydes led to the formation of the corresponding xanthine derivatives.
Abstract: Reaction of 6-amino-5-nitrosouracil derivatives with various substituted hydrazones of aldehydes led to the formation of the corresponding xanthine derivatives.
TL;DR: Investigations on the identity of the enzyme(s) produced by the induced wild type and the constitutive apl r mutants are reported are reported and it is shown that the apI r mutants when grown under non-inducing conditions produce a different enzyme from the one made by theinduced wild type chain.
TL;DR: Previous detailed studies of the transport of hypoxanthine and uric acid indicate that these two oxypurines are handled by rather different processes.
Abstract: Previous detailed studies of the transport of hypoxanthine and uric acid indicate that these two oxypurines are handled by rather different processes. This report gives information on another importan
TL;DR: The colorless water-soluble alkali sulfomercurates behave in an alkaline milieu as sulfide-donors with simultaneous deposition of black mercury(II) sulfide.
TL;DR: Uric acid appears to be the principal purine excretory product of the majority of insect species so far studied, and purines other than uric acid have not often been found.
Abstract: Uric acid appears to be the principal purine excretory product of the majority of insect species so far studied (Wigglesworth 1953). Purines other than uric acid have not often been found. Hypoxanthine has been reported to be a minor component of the excreta of the larvae and adults of the greater wax moth, Galleria mellonella (L.) (Nation and Patton 1961). Uric acid, which was the major purine component, was accompanied by a 2nd minor component subsequently identified as xanthine (Nation 1963). Hypoxanthine, xanthine, and uric acid have been detected in the excreta of the sheep ked, Melophagus ovinus (L.) (Nelson 1958). Hypoxanthine also has been reported to be present in the excreta of a mutant of Drosophila melanogaster (Meigen) (Mitchell et al. 1959). Guanine has been detected in the feces of the boll weevil, Anthonomus grandis Boheman (Mitlin and Vickers 1964).
TL;DR: When tritiated dihydroergocristine was given orally to humans along with 7-β-hydroxy-propyl-theophylline, blood levels went higher and stayed higher than when the alkaloid was administered alone and the same situation was true of total urinary excretion of tritium.
TL;DR: Studying of the effect of xanthines on the solubility of molecules related to the proteinaceous ergot alkaloids indicate the indole moiety to be a primary site for complexation.
TL;DR: Molecular orbital calculations show that C-6 in 2,4-dihydroxy-pteridine carries a smaller positive charge and exhibits a lower superdelocalizability for nucleophilic attack than the corresponding position in the 7-aza analog.