SEARCH · PubMed Health

Results for “Tungsten Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1998

A new polyoxometalate complex inhibits retrovirus encoded reverse transcriptase activity in vitro and in vivo.

We examined the recently synthesized and characterized polyoxometalate compound (NH4)10[Co2Sb2W20 O70(H2O)6] (POM1). The inhibitory potency of POM1 was studied in tissue culture experiments with uninfected and Rous sarcoma virus (RSV)-infected chicken embryo fibroblasts (CEF) in vivo. We measured a considerable decrease in total cellular phosphotyrosine content in treated infected cells in vivo. POM1 treatment of SR-RSV-A infected CEF in vivo resulted in decreased pp60v-src activity, possibly due to a reduced rate of v-src translation caused by the inhibitory effect of POM1 on the RSV encoded reverse transcriptase activity (RT) activity. In further studies we were able to demonstrate the inhibitory effect of this complex on the RT activity of RSV in vitro and in vivo.

Animals↗

PubMed2000

Oxo/sulfidotungstate(VI) as precursors to W(VI)O2, W(VI)OS, and W(VI)S2 complexes and W(IV)-dithiolene chelate rings.

Synthetic models leading to oxosulfidotungsten(VI) groups and dithiolene chelate rings have been investigated. The heterogeneous reaction systems [WO4-nSn]2-/2Ph3SiCl/Me4phen (n = 0-2) in acetonitrile afford the complexes [WQ2(OSiPh3)2(Me4phen)] (1-3) in the indicated yields containing the groups W(VI)O2 (1; 86%), W(VI)O2 (2; 45%), and W(VI)S2 (3; 83%). In the crystalline state these complexes have imposed C2 symmetry, with cis-oxo/sulfido and trans-silyloxide ligands. 1H NMR spectra indicate that this stereochemistry is retained in solution. The colors of 2 (yellow, 367 nm) and 3 (orange, 451 nm) arise from LMCT absorptions at the indicated wavelengths. These results demonstrate that the silylation procedure previously introduced for the preparation of molecules with the Mo(VI)OS group (Thapper, et al. Inorg. Chem. 1999, 38, 4104) extends to tungsten. Methods for the formation of dithiolene chelate rings MS2C2R2 in reactions with sulfide-bound M = Mo or W precursors are summarized. In a known reaction type, 3 and activated acetylenes rapidly form [W(IV)(OSiPh3)2(Me4phen)(S2C2R2)] (R = CO2Me, 4, 83%, and Ph, 5, 98%). In a new reaction type not requiring the isolation of an intermediate, the systems [MO2S2]2-/2Ph3SiCl/Me4phen/PhC=CPh in acetonitrile afford 5 (68%) and [Mo(IV)(OSiPh3)2(Me4phen)(S2C2Ph2)] (6; 61%). Complexes 5 and 6 are isostructural, maintain the trans-silyloxide stereochemistry, and exhibit chelate ring dimensions indicative of ene- 1,2-dithiolate coordination. Reductions in the -1.4 to -1.7 V range are described as metal-centered. It remains to be seen whether the oxo/sulfidotungsten(VI) groups in 1-3 eventuate in the active sites of tungstoenzymes. (Me4phen = 3,4,7,8-tetramethyl-1,10-phenanthroline.)

Chelating Agents↗

PubMed1997

Antilipolytic actions of vanadate and insulin in rat adipocytes mediated by distinctly different mechanisms.

Vanadate, which mimics the biological effects of insulin, also inhibits lipolysis in rat adipocytes. Here we demonstrate that the antilipolytic effect of vanadate differs from that of insulin at least by the five following criteria: 1) vanadate inhibits lipolysis mediated by high (supraphysiological) concentrations of catecholamines; 2) vanadate antagonizes (Bu)2cAMP-mediated lipolysis; 3) vanadate antagonizes isobutylmethylxanthine-dependent lipolysis, 4) vanadate inhibits lipolysis mediated by okadaic acid; and 5) wortmannin, which blocks the antilipolytic effect of insulin, fails to block vanadate-mediated antilipolysis. Vanadate does activate phosphoinositol 3-kinase, and wortmannin blocks this activation. Our working hypothesis assumes that all of the insulin-like effects of vanadate, including antilipolysis, are initiated by the inhibition of protein phosphotyrosine phosphatases (PTPases). Among documented PTPase inhibitors we found that VOSO4 (oxidation state +4), several organic vanadyl compounds (+4), zinc (Zn2+), tungstate (W), and molybdate (Mo) also had antilipolytic activity. The order of potency was vanadyl acetylacetonate > or = VOSO4 > or = NaVO3 > or = vanadyl-dipicolinate > Zn2+ >> W > Mo, and it correlated better with the inhibition of adipose membranal-PTPases in cell-free experiments. We have concluded that the antilipolytic effect of vanadate is 1) mechanistically distinct from that of insulin, 2) independent of phosphoinositol 3-kinase activation, and 3) independent of the lipolytic cascade. We also strongly suggest that the antilipolytic effect of vanadate emanates from inhibiting adipose membranal, rather than cytosolic PTPases, and present preliminary data showing distinct differences in catalysis between these two PTPase categories. Overall, the study indicates that antilipolysis can be manifested via alternative, insulin-independent, signal-transducing pathways.

Adipocytes↗

PubMed1992

Physicochemical properties of the novel heteropolyanion antiviral hexapotassium-alpha-vanado-11-tungstoborate (DuP 925).

Hexapotassium-alpha-vanado-11-tungstoborate (DuP 925) is a yellow irregular-shaped crystalline powder. The DSC thermogram indicates that decomposition begins to occur above 250 degrees C. The compound exhibits a volatile loss of 3.7% by thermogravimetric analysis. The drug substance adsorbs water reaching a 7.1% volatile loss after 3 weeks at 85% relative humidity. The solubility of DuP 925 in water is high (1.6 g/ml at pH 4.8). Changes in pH have a negligible effect on the solubility with values of 1.3 g/ml in 0.1 N HCl and 1.4 g/ml in 0.1 N NaOH. The solubility is minimally affected by changes in sodium ion concentration. The compound ion pairs with tetrabutyl-ammonium ions at 1:2 and 1:6 ratios, with the 1:6 ion pair having an affinity over six orders of magnitude greater than that of the 1:2 ion pair. The degradation of DuP 925 in solution follows apparent first-order kinetics over the pH range of 0.6 to 12.6 at 80 degrees C. Citrate, EDTA, and phosphate buffers are catalytic at the pH minimum, with citrate and EDTA being stronger catalysts than phosphate. Acetate buffers appear to have negligible catalytic effects at pH 4 to 5. The degradation proceeds through the formation of the symmetrical dodecatungstoborate [BW12O40]-5. In acid, the dodecatungstoborate is stable, while in base it degrades further. Increasing the ionic strength has a catalytic effect on the degradation of DuP 925, while changes in the initial concentration of DuP 925 have a negligible effect on the stability. The pH-rate profile indicates a pH minimum of approximately 3.

Calorimetry, Differential Scanning↗

PubMed2006

Synthesis and two-dimensional correlation infrared spectroscopy study of an organic-inorganic hybrid compound constructed by [Mo(5)P(2)O(23)] and Cu-imidazole components.

A novel compound, (Himi)(H(3)O) [Cu(imi)(2)](2)[P(2)Mo(5)O(23)].H(2)O 1 (imi=imidazole), was synthesized by hydrothermal method and characterized by X-ray single analysis, ESR spectrum, one-dimensional (1D) infrared spectroscopy and two-dimensional (2D) correlation infrared spectroscopy under thermal and magnetism perturbation. Crystal data for the compound 1: orthorhombic system, space group Pnma, a = 14.580(3)A, b = 21.073(4)A, c = 16.664(3)A, Z = 4. It consists of the Mo-Cu building-blocks [Cu(imi)(4)](2)[P(2)Mo(5)O(23)](2-), protonated imidazole cations and water molecules. In the Mo-Cu building-blocks, [Mo(5)P(2)O(23)](6-) clusters are linked by {Cu(imi)(4)}(2+) group to form a two-dimension parallelogram griddling structure. From the 2D IR correlation spectroscopy analyses, it is discovered that the intensity changes of Mo=O and P-O band are sensitive to the temperature variation, whereas the Mo-O bond linking to Cu(2+) can be remarkably affected by the magnetism variation. Furthermore, the intensity changes of P-O bands occur prior to that of the Mo=O band during the temperature elevation.

Chemistry, Inorganic↗

PubMed1999

Simultaneous determination of seven penicillins in muscle, liver and kidney tissues from cattle and pigs by a multiresidue high-performance liquid chromatographic method.

A high-performance liquid chromatographic (HPLC) method based on solid-phase extraction (SPE) was developed for determination of amoxicillin, penicillin G (benzylpenicillin), ampicillin, oxacillin, cloxacillin, nafcillin and dicloxacillin in muscle, liver and kidney tissues of pigs and cattle. The compounds were extracted in aqueous solution by precipitation of organic materials with a mixture of sulphuric acid and sodium tungstate. The extract was cleaned up by SPE on a divinylbenzene-co-N-vinylpyrrolidone polymeric sorbent. Further clean-up was performed by liquid-liquid partition with diethyl ether. The extract was derivatised with benzoic anhydride and 1,2,4-triazole mercury (II) reagent. Chromatography was performed by reversed-phase gradient HPLC on a C18 column with ultraviolet detection at 323 nm. The limits of detection estimated by a conservative model were in the range 8.9-11.1 microg/kg for amoxicillin, penicillin G, ampicillin, oxacillin, cloxacillin and nafcillin and 18.3-20.9 microg/kg for dicloxacillin. The mean recovery range was 66-77% for amoxicillin, 73-75% for penicillin G, 81-82% for ampicillin, 73-76% for oxacillin, 74-75% for cloxacillin, 66-72% for nafcillin and 58-65% for dicloxacillin.

Amoxicillin↗

PubMed2002

Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate.

Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like, and cytoplasmic enzymes, which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Together with protein tyrosine kinases (PTKs), PTPs are critically involved in regulating many cellular signaling processes. In this study, diverse compounds were screened for PTP inhibition and selectively screened for inhibitors with the end product inhibition properties. Among phosphate analogues and their derivatives for PTP inhibition, Keggin compounds phosphomolybdate (PM) and phosphotungstate (PT) strongly inhibited both PTP-1B and SHP-1, with K(i) values of 0.06-1.2 micromM in the presence of EDTA. Unlike the vanadium compounds, inhibition potencies of PM and PT were not significantly affected by EDTA. PM and PT were potent, competitive inhibitors for PTPs, but relatively poor inhibitors of Ser/Thr phosphatase. Interestingly, PM and PT did not inhibit alkaline phosphatase at all. The crystal structure of PTP-1B in complex with PM, at 2.0 A resolution, reveals that MoO(3), derived from PM by hydrolysis, binds at the active site. The molybdenium atom of the inhibitor is coordinated with six ligands: three oxo-ligands, two apical water molecules and a S atom of the catalytic cysteine residue. In support of the crystallographic finding, we observed that molybdenium oxides (MoO(3), MoO(2), and MoO(2)Cl(2)) inhibited PTP-1B with IC(50) in the range 5-15 micromM.

Binding, Competitive↗

PubMed2006

Determination of total content of phenolic compounds and their antioxidant activity in vegetables--evaluation of spectrophotometric methods.

This research studies in detail the contents of phenolic compounds determined by the Folin-Ciocalteu reagent and the antioxidant activities determined by the TEAC (Trolox equivalent antioxidant capacity), DPPH (using diphenyl-p-picrylhydrazyl radical), and FRAP (ferric reducing antioxidant power) methods, and their correlations for used standards with these methods (catechine, gallic acid, caffeic acid, ferulic acid, Trolox, ascorbic acid, and ferrous sulfate) and extracts from several species of commonly consumed vegetables were studied in detail. The comparison of absolute values of absorption coefficients for used standards and for individual methods allows one to choose optimal common standards for methods to be compared. The procedures applied for the same sets of the extracts using identical calibration procedures and common standards allowed better comparison of the results obtained by the TEAC, DPPH, and FRAP methods. The values of content of phenolic substances and total antioxidant activity of the sets of samples correlate very well for all used methods. The very high values of antioxidant activity were found in intensely colored vegetables (red cabbage, red onion, etc.), and the values were very low in watery vegetables such as potato, marrow, and cucumber.

Antioxidants↗

PubMed1983

Chemical excitation of Limulus photoreceptors. I. Phosphatase inhibitors induce discrete-wave production in the dark.

Molybdate, tungstate, fluoride, vanadate, and GTP-gamma-S [guanosine-5'-0-(3-thiotriphosphate)] were injected into Limulus ventral photoreceptors by ionophoresis from microelectrodes. All of these drugs induce discrete waves of depolarization similar in waveform to, but smaller in amplitude than, those normally elicited by dim light. As for light-evoked waves, the amplitude of drug-induced waves decreases with light adaptation. For the compounds examined so far (fluoride, vanadate, GTP-gamma-S), the drug-induced waves share a reversal potential with light-induced discrete waves at about +15 mV. The induction of discrete waves by fluoride, vanadate, and molybdate was found to be reversible, whereas the induction of waves by GTP-gamma-S was not. Unlike fluoride and vanadate, which induce waves when added to the bath, molybdate appears to be ineffective when applied extracellularly. Because of the similarity of the drug-induced waves to light-induced discrete waves, we conclude that the drug-induced waves arise from a process similar or perhaps identical to visual excitation of the photoreceptor. However, the smaller size of drug-induced waves suggests that they arise at a stage of phototransduction subsequent to the isomerization of rhodopsin. On the basis of the chemical properties and action of the drugs, we suggest that discrete waves may arise through the activation of a GTP-binding protein.

Animals↗

PubMed2006

One-electron redox processes during polyoxometalate-mediated photocatalytic reactions of TiO(2) studied by two-color two-laser flash photolysis.

The one-electron redox processes of several compounds during polyoxometalate (POM)-mediated photocatalytic reactions of TiO(2) were investigated using the two-color two-laser flash-photolysis technique. The efficiency of the one-electron oxidation of aromatic sulfides by the trapped hole (h(tr) (+)) or the surface-bound OH radical (OH(s) (.)) is found to be significantly enhanced due to electron transfer from the conduction band (CB) of TiO(2) to the POM. The efficiency of the electron transfer from the CB of TiO(2) to the POM decreases in the order H(2)W(12)O(40) (6-) < SiW(12)O(40) (4-) < PW(12)O(40) (3-), that is, it depends on the reduction potential (E(red)) of the POMs. Electron injection from PW(12)O(40) (4-) in the excited state (PW(12)O(40) (4-*)) to the CB of TiO(2) was clearly observed using the two-color two-laser flash-photolysis technique. Storage of electrons in the TiO(2)/PW(12)O(40) (3-)/methyl viologen (MV(2+)) ternary system was also achieved upon two-color two-laser irradiation.

Catalysis↗

PubMed2004

Stable and functional regeneration of pancreatic beta-cell population in nSTZ-rats treated with tungstate.

AIMS/HYPOTHESIS: Sodium tungstate has recently emerged as an effective oral treatment for diabetes. We examined the effects of tungstate administration in the beta-cell mass of the pancreas as well as its therapeutic potential. METHODS: Sodium tungstate was administered via drinking water to healthy and neonatal streptozotocin (nSTZ)-diabetic rats for one month. The pancreas from each rat was removed and morphometric and immunocytochemical studies were carried out. The molecular mechanism of tungstate's action was also studied. RESULTS: In nSTZ rats administration of this compound normalised glycaemia, and increased insulinaemia and islet insulin content. Blood glucose concentrations were normalised as early as on day 4 of treatment, and tungstate treatment produced a partial recovery of beta-cell mass. The rats remained normoglycaemic after tungstate withdrawal. Morphometric studies showed that the increase in beta-cell mass was not due to beta-cell hypertrophy but to hyperplasia, with an increase in islet density in treated diabetic rats. Tungstate treatment increased extra-islet beta-cell replication without modifying intra-islet beta-cell replication rates. Moreover, the treatment induced increases in insulin-positive cells located close to ducts; and in PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. In islets from treated diabetic rats, tungstate is able to increase the phosphorylation state of PDX-1 through the activation of p38. CONCLUSION/INTERPRETATION: These observations indicate that tungstate treatment is able to regenerate a stable, functional pancreatic beta-cell population which leads to and maintains normoglycaemia.

Animals↗

PubMed2004

Effect of NO3- transport and reduction on intracellular pH: an in vivo NMR study in maize roots.

The effect of NO3- uptake on cellular pH was studied in maize roots by an in vivo 31P-NMR technique. In order to separate the effects on cytoplasmic pH due to NO3- uptake from those due to NO3- reduction, tungstate was used to inhibit nitrate reductase (NR). The results confirm that in maize roots tungstate inhibited NR activity. 15N-NMR in vivo experiments demonstrated the cessation of nitrogen flux from nitrate to organic compounds. Tungstate affected neither NO3- uptake nor the levels of the main phosphorylated compounds. Slight changes in cytoplasmic pH were observed during NO3- uptake and reduction (i.e. control). By contrast, in the presence of tungstate, a consistent decrease in cytoplasmic pH occurred. The vacuolar pH did not change in any of the conditions tested. These data show that NO3- uptake is an acidifying process and suggest a possible involvement of NO3- reduction in pH homeostasis. In the presence of NO3-, a transient depolarization of transmembrane electric potential difference (Em) was observed in all the conditions analysed. However, in tungstate-treated roots, a lesser depolarization accompanied by a greater ability to recover Em was found. This was related to a higher activity of the plasma membrane (PM) H+-ATPase. When NO3- was administered as potassium salt, its uptake increased and a greater depolarization of Em took place, whilst the changes in cytoplasmic pH were remarkably reduced, according to the central role played by K+ in the control of plasma membrane activities and cell pH homeostasis. A possible involvement of cytoplasmic pH in the control of PM H+-ATPase expression during nitrate exposure is suggested.

Biological Transport↗

PubMed2006

Cathodic electrodeposition of mixed molybdenum tungsten oxides from peroxo-polymolybdotungstate solutions.

Mixed molybdenum tungsten trioxide films of varying stoichiometry (MoxW1 - xO3, 0 < x < 1) were prepared by cathodic electrodeposition on indium tin oxide (ITO)-coated glass substrates from aqueous peroxo-polymolybdotungstate solutions. Electrochemical quartz crystal microbalance (EQCM), cyclic voltammetry, and chronocoulometry were used to gain insight into the electrodeposition mechanism. The compositional and structural properties were characterized for MoxW1 - xO3 films deposited at intermediate potentials (-0.35 V vs Ag/AgCl) and sintered at 250 degrees C using energy-dispersive spectroscopy, X-ray diffraction, and Raman spectroscopy. These studies reveal that films consist of homogeneously mixed MoxW1 - xO3, with an enriched Mo content ranging in composition from 0.4 < x < 0.7 depending upon the mol % Mo present in the deposition solution. Chronoamperometry and spectroelectrochemical measurements were conducted to estimate lithium ion diffusion coefficients and coloration efficiencies for the mixed metal oxide films in 1 M LiClO4/propylene carbonate. The subtle interplay between structural and compositional properties due to the uniform mixing of Mo and W oxide components shows that electrochromic and lithium ion transport properties are moderately enhanced relative to those of single-component WO3 and MoO3 and demonstrate improved structural stability over pure MoO3 polymorphs during electrochemical cycling.

Cations↗

PubMed2002

Influence of food and diabetes on pharmacokinetics of sodium tungstate in rat.

In this paper, the influence of food and diabetes on the pharmacokinetics of sodium tungstate in rat was investigated. The compound was administered intravenously (9 mg/kg) and orally in the form of solution (36 mg/kg). An empirical Bayes methodology was used to compute individual pharmacokinetic parameters. Sodium tungstate followed first-order kinetics, and plasma concentration versus time data were described by a two-compartment model. A significant relationship was found between the bioavailability and the status of the animals. Total plasma clearance and elimination half-life averaged 3.1 ml/min/kg and 1.6 h, respectively. Food had some effects on the extent of sodium tungstate absorption. After oral administration, the bioavailability (0.67 versus 0.85), C(max) (6.10 versus 15.2 microg/ml) and AUC (70.7 versus 105 mgh/l) were 20, 60 and 32% lower in fed than in fasted rats, respectively. The presence of cellulose and sulphate anions in rat chow could partially explain the fed state-associated reduction of tungstate bioavailability. In streptozotocin-induced diabetic fed rats, a 25% decrease occurred in AUC and F, and a 14% increase occurred in the elimination rate constant compared with healthy fed rats. These changes could be explain on the one hand, by the increase of liquid consumption and food intake, and on the other hand, by a gastroparesis in the early diabetic rats.

Animals↗

PubMed1998

Characterization of Aquamicrobium defluvii gen. nov. sp. nov., a thiophene-2-carboxylate-metabolizing bacterium from activated sludge.

A gram-negative bacterium was isolated from activated sewage sludge with thiophene-2-carboxylate as the sole source of carbon and with nitrate as an electron acceptor. The isolate, strain NKK, was a motile, oxidase- and catalase-positive, rod-like bacterium with a G+C content of 61.7 mol%. Besides nitrate, oxygen could serve as a terminal electron acceptor. Among many carbon sources tested, only a few sugars, fatty acids, and thiophene-2-carboxylate supported growth. Other heterocyclic compounds were not used. The sulfur atom of thiophene-2-carboxylate was oxidized to thiosulfate when cells were grown aerobically, or to elemental sulfur when cells were grown anaerobically with nitrate. Nitrate was reduced to nitrite. Growth on thiophene-2-carboxylate was dependent on the addition of molybdate to the medium. Tungstate, a specific antagonist of molybdate, inhibited growth on thiophene-2-carboxylate at concentrations > 10(-7) M. Three inducible enzymes involved in the metabolism of thiophene-2-carboxylate were detected: an ATP-, CoA-, thiophene-2-carboxylate- and Mg2+-dependent thiophene-2-carboxyl-CoA ligase (AMP-forming), a molybdenum-containing thiophene-2-carboxyl-CoA dehydrogenase, and a thiophene-2-carboxyl-CoA thioesterase. The sequence of the 16S rRNA gene suggested a classification of strain NKK within the alpha-subgroup of the Proteobacteria as a new genus and species, Aquamicrobium defluvii gen. nov. sp. nov. (DSM 11603), closely related to Mesorhizobium sp. and Phyllobacterium sp., but representing a distinct lineage equal in depth to those of the two mentioned genera. Aquamicrobium defluvii can be distinguished from both genera by a distinct spectrum of substrates, the maximal growth temperature, and a different salt tolerance.

Carboxylic Acids↗

PubMed1993

Microbial metabolism of quinoline and related compounds. XVIII. Purification and some properties of the molybdenum- and iron-containing quinaldic acid 4-oxidoreductase from Serratia marcescens 2CC-1.

Serratia marcecens 2CC-1 utilizes quinaldic acid (quinoline 2-carboxylic acid) as sole source of carbon, nitrogen and energy. Growth of strain 2CC-1 on quinaldic acid as well as on nicotinic acid and hypoxanthine was inhibited completely by the molybdate antagonist tungstate, whereas growth on kynurenic acid and 6-hydroxynicotinic acid was not affected by tungstate. The synthesis of the molybdenum-containing hydroxylases quinaldic acid 4-oxidoreductase and nicotinic acid 6-oxidoreductase was found to be inducible. In addition, Serratia marcescens 2CC-1 produced a constitutively expressed xanthine oxidoreductase. Quinaldic acid 4-oxidoreductase was purified 1075-fold with a recovery of 5%. For catalytic activity, artificial electron acceptors were necessary. The 95-100-kDa enzyme was a heterodimer with subunit molecular masses of 75-80 kDa and 18-19 kDa. Quinaldic acid 4-oxidoreductase contained 2.3-3.7 g atom of iron and 0.5-0.6 g atom of molybdenum per mol of enzyme. The absorption spectrum exhibited maxima at 280 nm, 334 nm, 480 nm and a shoulder at 550 nm, with A280/A334 = 4.8, A280/A450 = 10.0, A280/A480 = 9.4, and A450/A550 = 1.6, suggesting the absence of a flavin cofactor. Acridine, quinacrine, ethylenediaminetetraacetate, 2,2'-dipyridyl, 1,10-phenanthroline and iodoacetate did not affect enzyme activity. p-Hydroxymercuribenzoate, m-arsenite, cyanide and methanol were effective inhibitors of quinaldic acid 4-oxidoreductase. Cyanide-inhibited enzyme was reactivated by treatment with S2-, indicating the presence of a pterin molybdenum cofactor with a monooxo-monosulfidotype molybdenum center. Quinaldic acid 4-oxidoreductase showed a very high substrate specificity, quinaldic acid being the only substrate found to be transformed significantly.

Amino Acid Sequence↗

PubMed2005

Identification of aldehyde oxidase 1 and aldehyde oxidase homologue 1 as dioxin-inducible genes.

Aldehyde oxidases are a family of highly related molybdo-flavoenzymes acting upon a variety of compounds of industrial and medical importance. We have identified aldehyde oxidase 1 (AOX1) as a 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) inducible gene in the mouse hepatoma cell line Hepa-1. AOX1 mRNA levels were not increased by dioxin in mutant derivatives of the Hepa-1 cell line lacking either functional aryl hydrocarbon receptor (AHR) or aryl hydrocarbon receptor nuclear translocator (ARNT) proteins, thus demonstrating that transcriptional induction of AOX1 in response to dioxin occurs through the AHR pathway. Dioxin induction of AOX1 mRNA was also observed in mouse liver. In addition, levels of AOX1 protein as well as those of aldehyde oxidase homologue 1 (AOH1), a recently identified homolog of AOX1, were elevated in mouse liver in response to dioxin. Employing an aldehyde oxidase specific substrate, AOX1/AOH1 activity was shown to be induced by dioxin in mouse liver. This activity was inhibited by a known inhibitor of aldehyde oxidases, and eliminated by including tungstate in the mouse diet, which is known to lead to inactivation of molybdoflavoenzymes, thus confirming that the enzymatic activity was attributable to AOX1/AOH1. Our observations thus identify two additional xenobiotic metabolizing enzymes induced by dioxin.

Aldehyde Oxidoreductases↗

PubMed1996

Mechanism of polyoxometalate-mediated inactivation of DNA polymerases: an analysis with HIV-1 reverse transcriptase indicates specificity for the DNA-binding cleft.

The anti-DNA polymerase activity of a structural family of polyoxometalates has been determined. Two representative compounds of this family, possessing a saddle-like structure [(O3POPO3)4W12O36]16- (polyoxometalate I) and [(O3PCH2PO3)4W12O36]16- (polyoxometalate II) were found to inhibit all the DNA polymerases tested, with IC50 values ranging from 2 to 10 microM. A comparative study with HIV-1 reverse transcriptase (RT) and Klenow polymerase as representative DNA polymerases indicated that protection from inactivation was achieved by inclusion of DNA but not by deoxynucleotide triphosphates (dNTPs). Kinetic analysis revealed that the mode of HIV-1 RT inhibition is competitive with respect to DNA, and non-competitive with respect to dNTP binding. Cross-linking experiments confirmed that the inhibitors interfere with the DNA-binding function of HIV-1 reverse transcriptase. Interestingly, a number of drug-resistant mutants of HIV-1 RT exhibit a sensitivity to polyoxometalate comparable to the wild-type HIV-1 RT, suggesting that these polyoxometalates interact at a novel site. Because different polymerases contain DNA-binding clefts of various dimensions, it should be possible to modify polyoxometalates or to add a link to an enzyme-specific drug so that more effective inhibitors could be developed. Using a computer model of HIV-1 RT we performed docking studies in a binary complex (enzyme-polyoxometalate I) to propose tentatively a possible interacting site in HIV-1 RT consistent with the available biochemical results as well as with the geometric and charge constraints of the two molecules.

Binding Sites↗