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Showing papers on "Xanthine published in 2008"


Journal ArticleDOI
TL;DR: The regulation of ureide levels by Atxdh1 has general implications for optimal plant survival during nutrient remobilization, such as occurs during normal growth, dark stress and senescence, and point to the dual functionality of Ureides as efficient stores of nitrogen and as cellular protectants.
Abstract: The remobilization of metabolites during stress and senescence plays an important role in optimal plant adaptation to the environment. The plant molybdenum co-factor (MoCo) and flavin-containing enzyme xanthine dehydrogenase (XDH; EC 1.2.1.37) are pivotal for purine remobilization, and catalyze the conversion of the purine catabolic products hypoxanthine and xanthine to uric acid, which is subsequently degraded to the ureides allantoin and allantoate. We observed that in wild-type plants conditions of extended darkness or increasing leaf age caused induction of transcripts related to purine catabolism, resulting in marked accumulation of the purine catabolic products allantoin and allantoate. In contrast, Arabidopsis mutants of XDH, Atxdh1, accumulated xanthine and showed premature senescence symptoms, as exemplified by enhanced chlorophyll degradation, extensive cell death and upregulation of senescence-related transcripts. When dark-treated mutant lines were re-exposed to light, they showed elevated levels of reactive oxygen species (ROS) and a higher mortality rate compared with wild-type plants. Interestingly, the level of ROS and mortality could be attenuated by the addition of allantoin and allantoate, suggesting that these metabolites can act as scavengers of ROS. The results highlight a crucial need for the controlled maintenance of ureide levels mediated by AtXDH1 activity during dark stress and ageing, and point to the dual functionality of ureides as efficient stores of nitrogen and as cellular protectants. Thus, the regulation of ureide levels by Atxdh1 has general implications for optimal plant survival during nutrient remobilization, such as occurs during normal growth, dark stress and senescence.

170 citations


Journal ArticleDOI
TL;DR: The crystal structure of reduced bovine milk xanthine oxidoreductase complexed with oxipurinol was determined and clear electron density was observed between the N2 nitrogen of oxipirinol and themolybdenum atom of the molybdopterin cofactor, indicating that oxipURinol coordinated directly to molyb denum.
Abstract: Inhibitors of xanthine oxidoreductase block conversion of xanthine to uric acid and are therefore potentially useful for treatment of hyperuricemia or gout. We determined the crystal structure of reduced bovine milk xanthine oxidoreductase complexed with oxipurinol at 2.0 A resolution. Clear electron density was observed between the N2 nitrogen of oxipurinol and the molybdenum atom of the molybdopterin cofactor, indicating that oxipurinol coordinated directly to molybdenum. Oxipurinol forms hydrogen bonds with glutamate 802, arginine 880, and glutamate 1261, which have previously been shown to be essential for the enzyme reaction. We discuss possible differences in the hypouricemic effect of inhibitors, including allopurinol and newly developed inhibitors, based on their mode of binding in the crystal structures.

97 citations


Journal ArticleDOI
TL;DR: This is the first crystal structure of a reaction intermediate with a purine substrate that is hydroxylated at its C8 position as is xanthine and confirms the structure predicted to occur in the course of the presently favored reaction mechanism.

79 citations


Journal ArticleDOI
TL;DR: The results suggested that LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro, and presents hypouricemic and anti-inflammatory actions in vivo.

64 citations


Journal ArticleDOI
TL;DR: The dual role of resveratrol in directly scavenging superoxide and inhibiting its generation via xanthine oxidase reported in this study may explain, at least in part, the protective role of this compound against oxidative injury in various disease processes.
Abstract: Resveratrol (3,4',5-trihydroxystilbene), a polyphenolic compound found in mulberries, grapes, and red wine, has received considerable attention because of its apparent protective effects against various degenerative diseases due to its potential antioxidant activities. However, direct evidence for the superoxide-scavenging capacity of resveratrol is lacking in literature. In this study, electron paramagnetic resonance spectroscopy in combination with 5-(diethoxyphosphoryl)-5-methylpyrroline-N-oxide (DEPMPO)-spin trapping technique was utilized to determine the ability of resveratrol in scavenging superoxide anions generated from both potassium superoxide and the xanthine oxidase/xanthine system. We have demonstrated here for the first time that the presence of resveratrol resulted in decreased formation of DEPMPO-superoxide adduct (DEPMPO-OOH) in both the potassium superoxide and xanthine oxidase/xanthine systems, indicating that resveratrol could directly scavenge superoxide anions. The inhibition of DEPMPO-OOH in the xanthine oxidase/xanthine system, however, was found to be much potent as compared to that observed in potassium superoxide system. It was further shown that resveratrol could also directly inhibit xanthine oxidase activity as assessed by oxygen consumption and formation of uric acid. Taken together, the dual role of resveratrol in directly scavenging superoxide and inhibiting its generation via xanthine oxidase reported in this study may explain, at least in part, the protective role of this compound against oxidative injury in various disease processes.

62 citations


Journal ArticleDOI
TL;DR: Spectroscopic evidence showed that the complexation of caffeine and theophylline with DNA occurred via G-C and A-T and PO2 group with overall binding constants of K(caffeine–DNA) = 9.7 × 103 M−1 and K(theophyllines–DNA), and the affinity of ligand–DNA binding is in the order of theophyLLine > caffeine.

54 citations


Journal ArticleDOI
TL;DR: A unique heterotrimeric caffeine dehydrogenase was purified from Pseudomonas sp.
Abstract: A unique heterotrimeric caffeine dehydrogenase was purified from Pseudomonas sp. strain CBB1. This enzyme oxidized caffeine to trimethyluric acid stoichiometrically and hydrolytically, without producing hydrogen peroxide. The enzyme was not NAD(P)+ dependent; coenzyme Q0 was the preferred electron acceptor. The enzyme was specific for caffeine and theobromine and showed no activity with xanthine.

49 citations


Journal ArticleDOI
TL;DR: Evidence is provided that epidermal XO contributes to H2O2‐mediated oxidative stress in vitiligo via H2 O2‐production and allantoin formation in the epidersmal compartment through the activity of XDH/XO.
Abstract: Xanthine dehydrogenase/xanthine oxidase (XDH/XO) catalyses the hydroxylation of hypoxanthine to xanthine and finally to uric acid in purine degradation. These reactions generate H(2)O(2) yielding allantoin from uric acid when reactive oxygen species accumulates. The presence of XO in the human epidermis has not been shown so far. As patients with vitiligo accumulate H(2)O(2) up to mm levels in their epidermis, it was tempting to examine whether this enzyme and consequently allantoin contribute to the oxidative stress theory in this disease. To address this question, reverse transcription-polymerase chain reaction, immunoreactivity, western blot, enzyme kinetics, computer modelling and high performance liquid chromatography/mass spectrometry analysis were carried out. Our results identified the presence of XDH/XO in epidermal keratinocytes and melanocytes. The enzyme is regulated by H(2)O(2) in a concentration-dependent manner, where concentrations of 10(-6 )m upregulates the activity. Moreover, we demonstrate the presence of epidermal allantoin in acute vitiligo, while this metabolite is absent in healthy controls. H(2)O(2)-mediated oxidation of Trp and Met in XO yields only subtle alterations in the enzyme active site, which is in agreement with the enzyme kinetics in the presence of 10(-3 )m H(2)O(2). Systemic XO activities are not affected. Taken together, our results provide evidence that epidermal XO contributes to H(2)O(2)-mediated oxidative stress in vitiligo via H(2)O(2)-production and allantoin formation in the epidermal compartment.

49 citations


Journal ArticleDOI
TL;DR: An episomally complemented pfnt1Delta knockout parasite strain is used to confirm genetically the functional role of PfNT1 in P. falciparum purine uptake and utilization and demonstrate that, in addition to hypoxanthine, inosine and adenosine, PfNT 1 is essential for the transport and utilization of xanthine , guanine and guanosine.

48 citations


Journal ArticleDOI
TL;DR: That caffeine and perhaps other xanthinoids have a protective effect against cataract formation induced by UV has hence been demonstrated for the first time.
Abstract: Ultraviolet (UV) irradiation is one of the significant risk factors in the genesis of cataracts. Pathogenetically, the process can be triggered by the intraocular generation of various reactive species of oxygen that are well known to be initiated by the penetration of light, especially of the UV frequencies. The contribution of UV exposure in the etiology of this disease is likely to increase further due to ozone depletion in the upper atmosphere. The present studies were undertaken to examine if the UV effects can be attenuated with the xanthine-based alkaloids primarily present in tea and coffee. We have examined this possibility by in vitro lens culture studies with caffeine. As expected, mice lenses incubated in Tyrode solution exposed to UV at 302 nm are physiologically damaged, as evidenced by the inhibition of the active transport of (86)Rb(+), an ion acting as a surrogate of the K(+). There was a simultaneous decrease in the levels of adenosine triphosphate and glutathione. The addition of caffeine to the medium prevented such deleterious effects. That caffeine and perhaps other xanthinoids have a protective effect against cataract formation induced by UV has hence been demonstrated for the first time.

45 citations


Journal ArticleDOI
TL;DR: The compound L-valine-3-{8-[(E)-2-[3-methoxyphenyl)ethenyl]7-methyl-1-propargylxanthine- 3-yl}propyl ester hydrochloride (MSX-4) was synthesized as an amino acid ester prodrug of the adenosine A2A receptor antagonist MSX-2.
Abstract: The compound L -valine-3-{8-[( E )-2-[3-methoxyphenyl)ethenyl]-7-methyl-1-propargylxanthine-3-yl}propyl ester hydrochloride (MSX-4) was synthesized as an amino acid ester prodrug of the adenosine A 2A receptor antagonist MSX-2. It was found to be stable in artificial gastric acid, but readily cleaved by pig liver esterase. Keywords: Prodrug; adenosine receptor antagonist; MSX-4; water-solubility; Parkinson’s disease; esterase. Introduction Adenosine A 2A receptor antagonists, such as istradefylline ( 1 ) and privadenant ( 2 ) are currently in clinical trials as novel therapeutics for the treatment of Parkinson’s disease [1]. Such compounds have also been proposed to possess activity as cognition enhancers, neuroprotectives, antidepressant agents, and against neuropathic pain [1, 2, 3]. Different chemical classes of A 2A antagonists have been developed, including xanthine derivatives derived from the alkaloid caffeine, and adenine derivatives and analogs [1, 5, 6]. MSX-2 ( 3 , 3-(3-hydroxypropyl)-8-(

Journal ArticleDOI
TL;DR: It is concluded that the effect of H2O2 results from an impairment of protein synthesis, which is accompanied by the “superinduction” of c‐fos, c‐jun, or NGF genes.
Abstract: Newborn rat brain astrocytes, cultured in a serum-free medium, were exposed for 30 min to two types of reactive oxygen species. Cells were either treated with the xanthine/xanthine oxidase (X/XOD) system, which generates both H2O2 and the O2.- radical, or to H2O2 alone. Both treatments induced a dose-dependent accumulation of nerve growth factor (NGF) transcripts, 6 h after the exposure. Maximal effect was obtained with 6 mU/ml XOD, or 10(-4) M H2O2. A rapid expression of protooncogenes of the jun and fos families was also noticed in X/XOD- or H2O2-treated cells. This phenomenon was transient in cells exposed to X/XOD. However, in the case of H2O2-treated cells, the accumulation of c-fos or c-jun mRNAs was still pronounced 6 h after the end of the treatment and the levels of cell-secreted NGF appeared relatively reduced, when compared with those obtained after a shock with the X/XOD system. This raised the possibility that H2O2 at 10(-4) M could depress protein synthesis. Measurements of the incorporation of radiolabeled amino acids into trichloroacetic acid-precipitable material supported this assumption. Level of radioactivity associated with cellular material was dramatically reduced in H2O2-treated cells, when it was compared with control or X/XOD-treated cells. Furthermore, treatment of cells with the protein synthesis inhibitor anisomycin had an effect similar to that of H2O2 because it caused an accumulation of c-fos, c-jun, and NGF transcripts after 6 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: It is observed that 430nm irradiation of A2E in the presence of the spin trap DMPO, led to the appearance of a superoxide dismutase-inhibitable electron paramagnetic resonance (EPR) spectrum characteristic of D MPO-OH; this finding was indicative of hydroxyl radical (OH) formation following initial spin trapping of superoxide anion by DMPo.

Journal ArticleDOI
TL;DR: In this article, the authors present resonant two-photon ionization and IR-UV double resonance spectra of methylated xanthine derivatives including 7-methylxanthine, theophylline and theobromine monomer, seeded in a supersonic jet by laser desorption.
Abstract: We present resonant two-photon ionization and IR–UV double resonance spectra of methylated xanthine derivatives including 7-methylxanthine dimer and theobromine dimer seeded in a supersonic jet by laser desorption. For 7-methylxanthine, theophylline and theobromine monomer we assign the lowest energy tautomer based on comparison with IR–UV double resonance spectra and calculated IR frequencies. For the 7-methylxanthine dimer, we observe hydrogen bonding on the N3H position suggesting 3 possible combinations, one that is reverse Watson–Crick type and two that are reverse Hoogsteen type. For the theobromine dimer, we observe a stacked structure. For trimethylxanthine dimers we infer a stacked structure as well.

Journal ArticleDOI
TL;DR: The characterization of the G·iG and D·X base-pairing system in DNA is reported, and 7-deazaxanthine was deemed a more-suitable complement to diaminopurine than xanthine because the lack of a 7-nitrogen atom leads to reduced susceptibility to depurination and an increased pKa.
Abstract: Non-natural nucleic acid frameworks have exhibited functional behavior as independent, expanded, and potentially prebiotic genetic systems. While success has been achieved in these areas by replacing the native chemical functionality that is found in the sugar-phosphate backbone or bases with nonnative groups, less-divergent structural alternatives to nucleic acids still remain to be fully explored. To date, nonstandard base pairs rely on alternate hydrogen-bonded motifs, complementary hydrophobic surfaces, dimensional homologues, and metal coordination. One minimally divergent alternative that is yet to be fully explored is an all-purine genetic system. Crick proposed that a genetic system that incorporates only adenine and hypoxanthine might have preceded the modern genetic code. In this connection, a wide array of helical structures have been reported for all-purine nucleic acids, including those that contain three, four, and five strands. Doublestranded purine–purine structures are known in the context of both nonstandard 11] and natural 13, 14] nucleic acids; however, only two reports describe all-purine duplexes of DNA that display Watson–Crick or reverse Watson–Crick pairing for association. Whereas model systems have so far failed to demonstrate nonenzymatic oligomerization by purine–purine pairs, insufficient information exists to date concerning the fitness of an all-purine double helix to assess its suitability as a precursor or independent genetic material. In an extension of our earlier work on iG self-pairing, 10] we report the characterization of the G·iG and D·X base-pairing system in DNA (Scheme 1). Several considerations guided purine nucleobase selection. To minimize potential mispairs (e.g. , A·G 17] or H·iG), diaminopurine and xanthine motifs were utilized in place of adenine and hypoxanthine. Further, 7-deazaxanthine was deemed a more-suitable complement to diaminopurine than xanthine because the lack of a 7-nitrogen atom leads to reduced susceptibility to depurination and an increased pKa. [18] Additionally, the nitrogen substitution in 7-deazaxanthine removes a HoogACHTUNGTRENNUNGsteen-face hydrogen-bond acceptor, thereby inhibiting alternative modes of strand association. Isoguanine, via its N3-H tautomer, was chosen to complement guanine in analogy with homo-DNA pairing. It is notable that both D·X and iG·G base pairs benefit from the potential to form three hydrogen bonds via their Watson–Crick faces. The oligonucleotides displayed in Scheme 1 were synthesized from commercially available phosphoramidites on an Expedite 8909 DNA synthesizer. To assess the association of complementary strands, UV-monitored thermal denaturation experiments were performed on each of two strands individually, and then combined. Because the optimal wavelength at which to observe hyperchromicity is expected to be unique for a given nucleic acid complex, multiple wavelengths were monitored simultaneously during initial experiments. A clear melting transition was observed with maximal hyperchromicity at 250 nm for 1·2 (Figure 1 A). It can also be seen from Figure 1 that profiles for 1 and 2 alone do not sum to the denaturation profile of 1 and 2 combined. These results are consistent with duplex formation between 1 and 2. Similarly, clear melting transitions are seen for 5·6 and 9·10 (Figure 1 C, E). Thermodynamic values for strand association were obtained by nonlinear regression of the melting curve traces and a van’t Hoff plot (Table 1). Whereas clear evidence is seen for association between oligomers 1 and 2, thermal denaturation of the individual strands revealed that oligomer 2 self associates in the absence of its Scheme 1. A) Purine–purine and purine–pyrimidine base-pair structures ; B) oligonucleotide sequences.

Journal ArticleDOI
TL;DR: In this article, a sample of Euphorbia heterophylla leaves was extracted with n-hexane, chloroform, ethylacetate and methanol and the precipitates from the fractions were subjected to chromatographic and re-crystallization procedures.
Abstract: Euphorbia heterophylla Linn (Euphorbiaceae) is a medicinal plant used by traditional herbal practitioners in Nigeria and some parts of West Africa for the treatment of constipation, bacterial and inflammatory disease conditions (arthritis and rheumatism). Powdered plant material was subjected to phytochemical screening using standard experimental procedures. The crude powdered sample of Euphorbia heterophylla leaves was extracted with n-hexane, chloroform, ethylacetate and methanol. The precipitates from the fractions were subjected to chromatographic and re-crystallization procedures. The structures of isolated compounds were characterized and elucidated with chemical and spectroscopic techniques such as IR, NMR and MS experiments. The in vitro biological activity of the isolated and characterized compounds were evaluated by superoxide scavenging assay using xanthine – xanthine oxidase system to generate superoxides. The result of the study showed that the crude plant material contained some secondary metabolites such as saponins, flavonoids and tannins. The phytochemical investigation led to the isolation of four known compounds stigmasterol, β-stigmasterol glucoside, benzoic acid and 4 – hydroxyl benzoic acid. The four compounds exhibited good activity against the xanthine oxidase enzymes while the 4-hydroxybenzoic acid showed a marked activity. The isolation of the compounds from the leaves of E. heterophylla, which inhibited the xanthine oxidase enzyme, has justified the claims for which the plant is known and used. Key words: Euphorbia heterophylla, euphorbiaceae, xanthine oxidase activity, superoxide scavenging, steriods.

Journal ArticleDOI
TL;DR: In this article, the effect of multi-walled carbon nanotube (MWCNT) and single-wall carbon nanotsube (SWCNT)-based carbon paste electrode (CPE) electrochemical response was examined by introducing various portions of CNT into the CPE.
Abstract: The effect of multi-walled carbon nanotube (MWCNT) and single-wall carbon nanotube (SWCNT) on carbon paste electrode (CPE) electrochemical response was examined by introducing various portions of CNT into the CPE. The optimum electrode structure was determined by comparing the prepared electrodes' electroanalytical performance towards ferricyanide. Then these optimum compositions were modified with xanthine oxidase (XO) enzyme for obtaining a xanthine biosensor. After the optimization of biosensor working conditions, the developed systems were characterized for xanthine. Linearity was obtained in the concentration range between 1 and 100 μM xanthine with an RSD value of 3.35% for MWCNT-CPE, while with SWCNT-CPE these values were 1-20 μM and 3.5%, respectively. The developed biosensors were also applied for the detection of xanthine in denatured plasma samples (MWCNT-CPE) and canned tuna fish samples (SWCNT-CPE), and very good recoveries were obtained.

Journal ArticleDOI
TL;DR: The probable pathways leading to xanthine synthesis in Arabidopsis plants during senescence and the role that purine metabolites play as an ongoing source of nitrogen in plant growth are discussed.
Abstract: In our recent paper in The Plant Journal,1 we described the remobilization of purine metabolites during natural and dark induced senescence in wild type and Atxdh1 mutant lines impaired in xanthine dehydrogenase (XDH), a pivotal enzyme in the purine catabolism pathway. In the light of these observations and additional evidence shown here, we discuss the probable pathways leading to xanthine synthesis in Arabidopsis plants during senescence and the role that purine metabolites play as an ongoing source of nitrogen in plant growth.

Journal ArticleDOI
20 May 2008-Analyst
TL;DR: In this article, high selectivity and sensitivity were reported in the measurements of xanthine in urine by fast scan cyclic voltammetry (FSV) with a nanostructured carbon fiber sensor of 3.5 ± 0.4 μm radius.
Abstract: High selectivity and sensitivity is reported in the measurements of xanthine in urine by fast scan cyclic voltammetry (FSV) with a nanostructured carbon fiber sensor of 3.5 ± 0.4 μm radius. Fabrication of the sensors for the measurements is described. Fabrication of the nanostructure at the carbon fiber sensor surface exposes surface pores. SEM images confirm the formation of the nanostructure. The results indicate that the nanostructure improves the sensitivity and limit of detection (LOD) in the measurements of xanthine and uric acid. The sensors allow rapid direct measurements of xanthine in 2000-fold diluted xanthinuric urine and of uric acid in 2000-fold diluted normal urine. The sensitivity and the LOD of xanthine is 0.40 ± 0.02 nA μM−1 (0.995) and 1 μM, respectively, and 0.99 ± 0.01 nA μM−1 (0.998) and 500 nM for uric acid. The concentration of xanthine in 2000-fold diluted xanthinuric urine is 1.6 ± 0.2 μM from FSV and from HPLC. The concentration of xanthine and uric acid in urine can be determined by pre- or post-calibration of the sensor in buffer or by the method of standard addition.

Journal ArticleDOI
TL;DR: In Sertoli cells, ROH treatment increased xanthine oxidase activity and inhibition of the enzyme with allopurinol attenuated ROH-induced ROS production, protein damage and cytotoxicity, and data show that xanthin oxidase may play a role on vitamin A pro-oxidant effects.
Abstract: Several studies have suggested that vitamin A (retinol, ROH) presents pro-oxidant properties in biological systems. Recent studies point out that xantine oxidase, a ROS-generating enzyme, catalyses ROH oxidation to RA in vitro. These works stimulated the authors to investigate whether xanthine oxidase could be involved on the ROH pro-oxidative effects reported in cultured Sertoli cells. In vitro, it was demonstrate that xanthine oxidase generates superoxide in the presence of ROH as assessed by superoxide mediated-NBT reduction. Superoxide production is potentiated in the presence of NADH and inhibited by allopurinol. In Sertoli cells, ROH treatment increased xanthine oxidase activity and inhibition of the enzyme with allopurinol attenuated ROH-induced ROS production, protein damage and cytotoxicity. Moreover, inhibition of ROH oxidation to RA by retinaldehyde dehydrogenase inhibitor potentiated both xanthine oxidase-dependent ROS production and cell damage in ROH-treated cells. The data show that xanthine oxidase may play a role on vitamin A pro-oxidant effects.

Journal ArticleDOI
TL;DR: It is found that pentoxifylline, rac-M1, R- M1, S-M 1 and M4 significantly inhibit ADP induced platelet aggregation in whole blood in vitro in a concentration-dependent manner.

Journal ArticleDOI
TL;DR: The result showed both the F1 and F2 flavones as antigout and therefore supports the development of novel drugs for the treatment of gout.
Abstract: Xanthine dehydrogenase (XDH) is responsible for the pathological condition called Gout. In the present study different flavones synthesized from chalcone were evaluated in vitro for their inhibitory activity. Inhibitory activity of flavones on XDH was determined in terms of inhibition of uric acid synthesis from Xanthine. The enzymatic activity was found maximum at pH 7.5 and temperature 40°C. The flavones 6-chloro-2-[3-(4–hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F1) and 6-chloro-7methyl-2-[3-(4-chloro-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one(F2),were noncompetitive and competitive inhibitor with Ki values 1.1 and 0.22 respectively. The flavones (F1), (F2), 6-chloro-2-[3-(4-chloro-phenyl)-1phenyl-1-H-pyrazol-4-yl]-chromen-4-one(F3), 8-bromo-6-chloro-2-[3-(4-chloro-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F4), 2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F5) and 6-methyl-2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F6) were also sc...

Journal ArticleDOI
TL;DR: A highly sensitive fluorescent multienzymatic biosensor built by the simultaneous encapsulation of three enzymes, xanthine oxidase, superoxide dismutase and peroxidase, in a single sol-gel matrix coupled to the Amplex Red probe is reported.

Journal ArticleDOI
TL;DR: An assay has been developed to study the enzymatic conversion of caffeine to subsequent methylxanthines by cell free extracts of Pseudomonas sp.
Abstract: Previously isolated strain of Pseudomonas sp. has the capability of utilizing caffeine as the sole source of carbon and nitrogen and degrading caffeine at higher concentrations (>10 g l–1). In this study, an assay has been developed to study the enzymatic conversion of caffeine to subsequent methylxanthines by cell free extracts of Pseudomonas sp., the activity of which has been stabilized by use of stabilizers in the lysis buffer. Growth of the strain in various methylxanthines and later enzyme assay demonstrated that the enzyme(s) involved in degradation of caffeine and other methylxanthines were inducible in nature. The results also indicated that more than one enzyme are involved in degradation of caffeine to xanthine, which constitute the primary steps in bacterial caffeine catabolism. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Journal ArticleDOI
TL;DR: Crystal structures of XOR bound with various inhibitors reveal that inhibitors can be categorized into three types, i.e. mechanism- based, structure-based, and hybrid types.
Abstract: Xanthine oxidoreductase (XOR) catalyzes the reaction of hypoxanthine to xanthine and of xanthine to uric acid. Inhibitors of XOR can thus decrease the concentration of uric acid in serum. Crystal structures of XOR bound with various inhibitors reveal that inhibitors can be categorized into three types, i.e. mechanism-based, structure-based, and hybrid types.

Journal ArticleDOI
TL;DR: In this paper, three genes encoding putative purine transporters have been identified in silico in the genome of Aspergillus fumigatus by their very close similarity of their translation products to well-studied homologues in A. nidulans.

Journal ArticleDOI
TL;DR: It is indicated that the number of carbons at R1 and R3 is important for the antitumor-promoting activity of the trialkylxanthines and xanthine 70 might be a promising anticancer agent.
Abstract: Some xanthine analogues, including 1,3,7-trimethylxanthine (caffeine) and 1,3-dimethylxanthine (theophylline), have been shown to exert anticancer activities in both cell culture and animal models. The present study focused on the relationship of structure and activity of 50 different caffeine analogues in preventing epidermal growth factor (EGF)-induced malignant transformation of mouse epidermal JB6 promotion-sensitive (P+) Cl41 (JB6 P+) cells. Results indicated that the inhibition of cell transformation by the 1,3,7-trialkylxanthines depends on the number of carbons at the alkyl groups R1 and R3, but not R7. Notably, 1-ethyl-3-hexylxanthine (xanthine 70) was the most effective compound for inhibiting EGF-induced neoplastic transformation among the 50 xanthine analogues tested. The 50% inhibition of cell transformation (ICT(50)) value for xanthine 70 was 48- or 75-fold less than the ICT(50) value of caffeine or theophylline, respectively. Further study revealed that xanthine 70 (5-40 muM) dose dependently inhibited EGF-induced transactivation of activator protein 1 (AP-1), whereas theophylline or caffeine (up to 500 muM) had no effect on AP-1 activity. In addition, xanthine 70 (10 muM) inhibited 12-O-tetradecanoylphorbol-13-acetate- or H-Ras-induced neoplastic transformation in JB6 P+ cells by 78.2 or 62.0%, respectively. Collectively, these results indicated that the number of carbons at R1 and R3 is important for the antitumor-promoting activity of the trialkylxanthines and xanthine 70 might be a promising anticancer agent.

DOI
01 Jun 2008
TL;DR: It is found that serum UA has been found to be not only a weak predictor of cardiovascular disease in general asymptomatic population but a significant independent predictor among subjects who are at high risk.
Abstract: Uric acid (UA) is converted from xanthine, the degradation product of purine nucleotides, by the enzyme xanthine oxidase (XO). Because hyperuricemia can be induced not only by inflammatory risk factors but is also associated with the generation of new acute and chronic inflammation, therefore, elevation of uric acid in blood (hyperuricemia) is considered as a sensitive marker of underlying inflammation taking place at various site of the body. In addition, anti-inflammatory medications have been shown to reduce the level of serum uric acid. As expected, hyperuricemia are detectable in almost all inflammatory diseases. It should be noted that hyperuricemia is not a risk factor but rather a risk marker signaling the presence of risk for the development of severe clinical complications. It is because that most damages found with hyperuricemia are not caused directly by UA but by superoxide free radical produced at the same time with UA by the enzyme XO. It should also be noted that serum UA has been found to be only a weak predictor of cardiovascular disease in general asymptomatic population but a significant independent predictor among subjects who are at high risk.

Journal ArticleDOI
TL;DR: It is hypothesized that ENT2 also mediates the cellular release of hypoxanthine, which would limit the amount of intracellular hypox anthine available for metabolism by xanthine oxidase and enhance the intrACEllular production of ROS.

Journal ArticleDOI
TL;DR: Despite the substantial advantages of using defined media for the culture of human pathogens, the factor(s) in urine that is responsible for promoting growth of Leishmania has not been identified.
Abstract: The leishmaniases are parasitic diseases that affect large populations in vast areas of the world (Desjeux, 2001). The causative agents of these diseases, protozoan parasites belonging to the genus Leishmania (Kinetoplastida: Trypanosomatidae), are transmitted by phlebotomine sand flies (Killick-Kendrick, 1999). In culture media (at 26–28 uC, pH ~7.2), Leishmania parasites develop as motile promastigotes similar to those found in the sand fly midgut. A number of reports have shown that the addition of 1– 5 % human urine stimulates growth, leading to more rapid multiplication and a higher concentration of parasites at the stationary phase (Ali et al., 1998; Armstrong & Patterson, 1994; Howard et al., 1991; Iqbal et al., 2006; Shamsuzzaman et al., 1999; Singh et al., 2000). Preliminary studies have indicated that the factor responsible for this enhancement is a small molecule which is not destroyed by autoclaving (Ali et al., 1998). However, despite the substantial advantages of using defined media for the culture of human pathogens (Schuster & Sullivan, 2002), the factor(s) in urine that is responsible for promoting growth of Leishmania has not been identified.