Showing papers on "Xanthine published in 1969"
TL;DR: The hypothesis is formulated that most of the xanthine oxidase of rat liver supernatant is a dehydrogenase (Type D), and may be converted (activated) into an oxid enzyme (Type O).
694 citations
TL;DR: Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro.
Abstract: 1 Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro 2 The extent of the inhibition of DNA synthesis is markedly increased by preincubation of the cells with mycophenolic acid before the addition of [(14)C]thymidine 3 The inhibition of DNA synthesis by mycophenolic acid in L cells in vitro is reversed by guanine in a non-competitive manner, but not by hypoxanthine, xanthine or adenine 4 The reversal of inhibition by guanine can be suppressed by hypoxanthine, 6-mercaptopurine and adenine 5 Mycophenolic acid does not inhibit the incorporation of [(14)C]thymidine into DNA in suspensions of Landschutz and Yoshida ascites cells in vitro 6 Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into cold-acid-soluble and -insoluble guanine nucleotides in Landschutz and Yoshida ascites cells and also in L cells in vitro There is some increase in the radioactivity of the adenine fraction in the presence of the antibiotic 7 Mycophenolic acid inhibits the conversion of [(14)C]hypoxanthine into xanthine and guanine fractions in a cell-free system from Landschutz cells capable of converting hypoxanthine into IMP, XMP and GMP 8 Preparations of IMP dehydrogenase from Landschutz ascites cells, calf thymus and LS cells are strongly inhibited by mycophenolic acid The inhibition showed mixed type kinetics with K(i) values of between 303x10(-8) and 45x10(-8)m 9 Evidence was also obtained for a partial, possibly indirect, inhibition by mycophenolic acid of an early stage of biosynthesis of purine nucleotides as indicated by a decrease in the accumulation of formylglycine amide ribonucleotide induced by the antibiotic azaserine in suspensions of Landschutz and Yoshida ascites cells and L cells in vitro
358 citations
TL;DR: The deflavoenzyme is catalytically active in the oxidation of xanthine with acceptors such as ferricyanide and cytochrome c.
233 citations
TL;DR: Although the formation of urinary xanthine stones has been anticipated as a possible complication of allopurinol therapy, to date this occurrence has not been documented in the clinical use.
Abstract: SINCE its clinical introduction in 1964, allopurinol (4-hydroxypyrazolo-[3,4-d]-pyrimidine) has been increasingly used for the treatment of hyperuricemia of gout,1 , 2 many neoplastic diseases and other metabolic disorders. Allopurinol and its principal metabolic product, oxipurinol (alloxanthine, oxoallopurinol), inhibit the enzyme, xanthine oxidase, that normally converts hypoxanthine to xanthine, and xanthine to uric acid. The concentration of these oxypurine precursors of uric acid in blood and urine thus increases in patients treated with allopurinol. Although the formation of urinary xanthine stones has been anticipated as a possible complication of allopurinol therapy, to date this occurrence has not been documented in the clinical use . . .
139 citations
TL;DR: The formation of a free radical species, having the characteristics of the superoxide anion radical, (O2−), during aerobic catalysis involving milk xanthine oxidase is confirmed, and on reoxidation of a number of flavin-free iron-sulfur proteins of the plant ferredoxin type no O2− radicals were detected.
95 citations
TL;DR: It was concluded that a low concentrations the limiting step to adenine incorporation into nucleotides was its entrance into the cell, and within the cellAdenine was metabolized to adenosine nucleotide and xanthine to uric acid, and both products accumulated within thecell.
90 citations
TL;DR: The reduction of cy tochromes mediated by p-benzoquinone and molecular oxygen in the xanthine oxidase system is explained on the basis of an one-electron transfer mechanism, in which free-radical intermediates such as semiquinone and perhydroxyl radical are direct reductants for the cytochromes.
73 citations
TL;DR: Further electron-paramagnetic-resonance studies relating to the role of molybdenum in the enzymic mechanisms of xanthine oxidase were carried out, and the origin of the protons is discussed in the light of the direct hydrogen-transfer mechanism implicated earlier for the enzyme.
Abstract: Further electron-paramagnetic-resonance studies relating to the role of molybdenum in the enzymic mechanisms of xanthine oxidase were carried out. The classification of the various molybdenum signals obtained on reducing the enzyme is briefly discussed. The group of ;Rapidly appearing' signals, which are obtained with all substrates within the turnover time and which show interaction with exchangeable protons, were studied in detail. Signals with salicylaldehyde, purine and xanthine in H(2)O and in 95% D(2)O were examined at 9 and 35GHz and interpreted with the help of computer simulation. Molybdenum atoms in a number of different chemical environments are involved, each substrate giving rise to two superimposed spectra with slightly different parameters; g values and proton splittings were determined. The spectrum with salicylaldehyde is believed to represent the reduced enzyme alone not in the form of a complex with substrate and its two constituents are believed to represent the two molybdenum atoms bonded slightly differently within the enzyme molecule. With purine and xanthine the spectra are thought to represent complexes of reduced enzyme with substrate molecules. With xanthine one signal-giving species shows coupling to two equivalent protons, whereas in all the other species observed two non-equivalent protons are involved. The origin of the protons is discussed in the light of the direct hydrogen-transfer mechanism implicated earlier for the enzyme. It is concluded that the proton derived from the substrate is located at least 3a from the molybdenum atom with which it interacts.
67 citations
TL;DR: The method is suitable for determining the xanthine oxidase activity of serum in liver patients or of small tissue specimens, however, the interpretation of the results of tissue activity is rendered difficult by a spontaneous increase of activity during storage either at 4 ° C. or −25 °C.
48 citations
TL;DR: The reaction of 6-chloropurine with t-butyl α-benzyloxycarbonylamido-γ-bromobutyrate (6b) gave high yields of the corresponding N 6 -alkylated products as discussed by the authors.
45 citations
TL;DR: In this article, the sign relationship S(hkl)S(h′k′l′)∼S (h+h′,k+k′,l+l′), from (hk 0) intensity data and refined by three-dimensional least-squares methods.
Abstract: The crystals of sodium salt of xanthine, C5H3N4O2Na·4H2O, are monoclinic with four molecules in a unit cell of dimensions; a=7.31, b=19.52, c=7.17 A, β=100.0°, space group P21⁄c. The structure has been determined by application of the sign relationship S(hkl)S(h′k′l′)∼S(h+h′,k+k′,l+l′) from (hk0) intensity data and refined by three-dimensional least-squares methods. The positions of the hydrogen atoms were determined by a three-dimensional difference Fourier analysis, and it was confirmed that deprotonation took place at the position of the imino N(3)H of the xanthine molecule. Each Na+ cation is surrounded by six water molecules and each xanthine anion participates in ten hydrogen bonds, forming a close-packed system.
TL;DR: It was found that xanthine accumulates in the reaction mixture with hypoxanthine as the substrate and that hyp oxanthine does not accumulate in detectable quantities during xanthin oxidation, suggesting that a dismutation reaction occurs in the chicken liver system.
Abstract: Handler and coworkers [1,2] have studied the non-linearity of xanthine oxidase reciprocal plots for the chicken liver and the Micrococcus lactilyticus systems. In the latter case it was suggested that the non-linearity was due to a dismutation reaction observed at high xanthine concentrations. The studies reported here were undertaken in an effort to demonstrate the presence of such a reaction in the chicken liver system. On the basis of ultraviolet spectra taken during the course of xanthine and hypoxanthine oxidations, it was found that xanthine accumulates in the reaction mixture with hypoxanthine as the substrate and that hypoxanthine does not accumulate in detectable quantities during xanthine oxidation. Conditions were used such that hypoxanthine should have been detectable as a transient if the dismutation reaction occurred. Hypoxanthine which has not been reported to undergo a dismutation reaction shows the same type of non-linearity in reciprocal plots as does xanthine. Relatively high rates of xanthine conversion to uric acid under anaerobic conditions (due to vigorous sweeping with nitrogen) were explained on the basis of residual oxygen. Similar results were obtained for hypoxanthine oxidation. On the basis of these results it seems highly unlikely that a dismutation reaction occurs in this system. Random and multi-site mechanisms can be used to explain the non-linearity.
TL;DR: A patient with congenital deficiency of xanthine oxidase (xanthinuria) excreted the xanthinesomer 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (oxipurinol) in his urine when the hypoxanthine isomer 4-hydroxypYrazolo (allopur inol) was given by mouth.
Abstract: 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.
TL;DR: A spectrometric procedure has been devised which permits measurement of the enzymatic reduction of N-oxides or other compounds by monitoring the disappearance of the dithionite absorption and theenzymatic synthesis of 8-hydroxyguanine 3-oxide is described.
TL;DR: The origin of the Rapid molybdenum electron-paramagnetic-resonance signals, which are obtained on reducing xanthine oxidase with purine or withxanthine, and whose parameters were measured by Bray & Vänngård (1969), were studied and it was concluded that they represent complexes of reduced enzyme with substrate molecules.
Abstract: The origin of the Rapid molybdenum electron-paramagnetic-resonance signals, which are obtained on reducing xanthine oxidase with purine or with xanthine, and whose parameters were measured by Bray & Vanngard (1969), was studied. It is concluded that these signals represent complexes of reduced enzyme with substrate molecules. Xanthine forms one complex at high concentrations and a different one at low concentrations. Purine forms a complex indistinguishable from the low-concentration xanthine complex. There are indications that some other substrates also form complexes, but uric acid, a reaction product, does not appear to do so. The possible significance of the complexes in the catalytic cycle of the enzyme is discussed and it is suggested that they represent substrate molecules bound at the reduced active site, waiting their turn to react there, when the enzyme has been reoxidized. Support for this role for the complexes was deduced from experiments in which frozen samples of enzyme–xanthine mixtures, prepared by the rapid-freezing method, were warmed until the signals began to change. Under these conditions an increase in amplitude of the Very Rapid signal took place. Data bearing on the origin of the Slow molybdenum signal are also discussed. This signal disappears only slowly in the presence of oxygen, and its appearance rate is unaffected by change in the concentration of dithionite. It is concluded that, like other signals from the enzyme, it is due to Mov but that a slow change of ligand takes place before it is seen. The Slow species, like the Rapid, seems capable of forming complexes with purines.
TL;DR: Data obtained by comparing the radioactivity incorporated into bacterial guanine, xanthine, and riboflavine indicate that guansine or a close derivative of Guanine is the purine precursor of rib oflavine.
Abstract: Corynebacterium species lacks the ability to convert either xanthine or guanine to adenine. This defect and the use of the purine nucleoside antibiotic decoyinine, which blocks the conversion of xanthosine monophosphate → guanosine monophosphate, permit an experimental design in which the interconversion of purines is largely prevented. Cultures of this organism were grown in the presence of decoyinine and various purine supplements. Data obtained by comparing the radioactivity incorporated from guanine-2-14C or xanthine-2-14C into bacterial guanine, xanthine, and riboflavine indicate that guanine or a close derivative of guanine is the purine precursor of riboflavine.
TL;DR: DNA labelled with ( 14)C in the purine residues was prepared by treating newborn rats with [(14)C]formate and killing them for preparation of nucleic acids at 11-17 months, and, after preliminary denaturation of the DNA, 1-methyladenine was detected.
Abstract: 1. DNA labelled with 14C in the purine residues was prepared by treating newborn rats with [14C]formate and killing them for preparation of nucleic acids at 11–17 months. This DNA was incubated with N-methyl-N′-nitro-N-nitrosoguanidine, and then analysed for products of methylation and deamination reactions. 2. Evidence was found for the formation of 7-methylguanine and a smaller amount of 3-methyladenine, and, after preliminary denaturation of the DNA, 1-methyladenine was detected. The presence of cysteine increased the extent of methylation. No evidence was found for the formation of xanthine or hypoxanthine, even at pH5·5.
TL;DR: The anomalous acceptor requirements support the possibility that the xanthine oxidase-catalyzed reaction occurs by direct electron transfer to an external acceptor, by-passing the internal electrontransport chain of the enzyme.
TL;DR: The occurrence of crystalline material resembling xanthine and hypoxanthine in the striped muscle of two xanthinuric patients is reported.
Abstract: XANTHINE oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2) catalyses the oxidation of hypoxanthine to xanthine and of xanthine to uric acid. The increased excretion of hypoxanthine and xanthine, and the very low concentrations of uric acid in blood and urine which are characteristic of xanthinuria, were first reported by Dent and Philpot1 and by Dickinson and Smellie2. Gross deficiency of jejunal and hepatic xanthine oxidase was reported by Watts et al.3 and by Engelman et al.4. We report here the occurrence of crystalline material resembling xanthine and hypoxanthine in the striped muscle of two xanthinuric patients.
TL;DR: The presence of hypoxanthine and xanthine in the skeletal muscle of two patients with congenitalxanthine oxidase deficiency (xanthinuria) was demonstrated by high-resolution mass spectrometry.
Abstract: 1. The presence of hypoxanthine and xanthine in the skeletal muscle of two patients with congenital xanthine oxidase deficiency (xanthinuria) was demonstrated by high-resolution mass spectrometry. 2. Evidence was obtained for the presence of a trace of hypoxanthine only in normal muscle. 3. Dry pulverized tissue was introduced directly into the mass spectrometer and preliminary chemical processing of the tissue was therefore unnecessary. 4. The criteria for the mass-spectrometric identification of hypoxanthine and xanthine in the tissue and the significance of the observations are discussed.
TL;DR: The order of susceptibility of the aminopteridines (2- > 4-) to oxidation by xanthine oxidase was found to be different from that previously reported by Bergmann and Kwietny 9 for the analogous hydroxypteridine (4- > 2-).
TL;DR: Penicillium chrysogenum utilized the purines hypoxanthine, xanthine and uric acid and adenine as sole nitrogen sources but not the methylated purines caffeine and theobromine.
Abstract: SUMMARY: Penicillium chrysogenum utilized the purines hypoxanthine, xanthine, uric acid and adenine as sole nitrogen sources but not the methylated purines caffeine and theobromine. Cell-free extracts of this organism contained the enzymes xanthine dehydrogenase, uricase, allantoinase, allantoicase and urease. Uric acid was degraded to allantoic acid by way of allantoin; allantoin was degraded to glyoxylic acid by way of allantoic acid. Xanthine dehydrogenase, uricase, allantoinase and urease were constitutive whereas allantoicase was inducible by xanthine or allantoin.
TL;DR: The enzymatic spectrophotometric determination of oxypurines (hypoxanthine plus xanthine) in urine and blood plasma has been extended by the use of differential spectrophOTometry at 280 and 292 nm to enable the separate determination of hypoxanthines and xanthines to be carried out.
Abstract: The enzymatic spectrophotometric determination of oxypurines (hypoxanthine plus xanthine) in urine and blood plasma has been extended by the use of differential spectrophotometry at 280 and 292 nm to enable the separate determination of hypoxanthine and xanthine to be carried out. The method retains the high degree of accuracy and specificity of the determination of total oxypurines, and has shown good recoveries and reproducibility when applied to aqueous solutions and to urine. Although less precise when applied to plasma, the method is the only simple method at present available that enables the determination of hypoxanthine and xanthine to be carried out on this material.
TL;DR: The magnitude of this patient's defect in xanthine oxidase activity is similar to that of the three previously described patients but none of their associated abnormalities (xanthine renal stones, pheochromocytoma, hemochromatosis).
TL;DR: The major metabolites found in the urine after administration of 3-Hydroxyxanthine-8-14C to rats are 3-hydroxyuric acid, uric Acid, xanthine, allantoin, and unchanged starting material.
Journal Article•
TL;DR: The pattern of metabolism of soluble purines infiltrated into pea seedlings has been investigated, providing strong evidence for the presence of xanthine oxidase (xanthine: O 2 oxido-reductase, EC 1.2.3.2) in these seedlings.
Patent•
27 Feb 1969TL;DR: MUTANTS OF BACILLUS SUBTILIS as mentioned in this paper as mentioned in this paper can be made resistant to 8-AZ guanine, and SUCH MODIFIED MUTANS PRODUCE USEFUL AMOUNTS OF GUANOSINE with only MINOR AMOUNts OF INOSINE.
Abstract: MUTANTS OF BACILLUS SUBTILIS WHICH REQUIRE ADENINE, DO NOT REQUIRE XANTHINE NOR GUANINE, AND PRODUCE INOSINE TOGETHER WITH MINOR AMOUNTS OF GUANOSINE, IF ANY, CAN BE MADE RESISTANT TO 8-AZGUANINE, AND SUCH MODIFIED MUTANTS PRODUCE USEFUL AMOUNTS OF GUANOSINE WITH ONLY MINOR AMOUNTS OF INOSINE