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Chemical Compound Review

TUNGSTEN     tungsten

Synonyms: Tunsten, Wolfram, tungstene, tungsteno, volframio, ...
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Disease relevance of tungsten


Psychiatry related information on tungsten


High impact information on tungsten

  • A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome) [10].
  • Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4 [1].
  • Based on a linkage analysis of 11 families segregating for this syndrome using microsatellite repeat polymorphisms throughout the human genome, we found the Wolfram syndrome gene to be linked to markers on the short arm of human chromosome 4, with Zmax = 6.46 at theta = 0.02 for marker D4S431 [1].
  • The crystal structure of the tungsten-containing aldehyde ferredoxin oxidoreductase (AOR) from Pyrococcus furiosus, a hyperthermophilic archaeon (formerly archaebacterium) that grows optimally at 100 degrees C, has been determined at 2.3 angstrom resolution by means of multiple isomorphous replacement and multiple crystal form averaging [11].
  • A nonreverting strain, which is respiratory deficient because of a deletion in the mitochondrial oxi3 gene, was bombarded with tungsten microprojectiles coated with DNA bearing sequences that could correct the oxi3 deletion [12].

Chemical compound and disease context of tungsten


Biological context of tungsten

  • We propose a dual genome defect model for Wolfram syndrome in which nuclear genetic defects or mitochondrial genetic defects can independently lead to the disease [18].
  • This model suggests that besides a mitochondrial gene defect alone, a nuclear gene defect, which interferes with the normal function of mitochondria (probably with a normal mitochondrial genome), can also be the underlying explanation for the pleiotropic features of Wolfram syndrome [18].
  • Molybdenum and tungsten are found in biological systems in a mononuclear form in the active site of a diverse group of enzymes that generally catalyze oxygen-atom-transfer reactions [19].
  • Plastid transformation was obtained after bombardment of leaves with tungsten particles coated with pZS148 plasmid DNA [20].
  • These patients, who have the Wolfram syndrome phenotype, also have additional features that have not previously been reported [21].

Anatomical context of tungsten


Associations of tungsten with other chemical compounds


Gene context of tungsten

  • The CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1 gene, in which mutations also cause low frequency sensorineural hearing loss (LFSNHL) [29].
  • Direct DNA sequencing was done to screen the entire coding region of the WFS1 gene in 30 patients from 19 British kindreds with Wolfram syndrome [30].
  • MATERIALS AND METHODS: To study the role of the Wolfram gene (Wfs1) in beta cells, we developed a mouse model with conditional deletion of Wfs1 in beta cells by crossing floxed Wfs1 exon 8 animals with mice expressing Cre recombinase under the control of a rat insulin promoter (RIP2-Cre) [31].
  • In hemorrhaged mice depleted of xanthine oxidase (XO) by a tungsten-enriched diet, pulmonary mononuclear cell mRNA levels for IL-1 beta and TNF-alpha were significantly decreased (P < 0.01 and 0.05, respectively), compared with cells from hemorrhaged control mice fed a normal diet [32].
  • Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes [33].

Analytical, diagnostic and therapeutic context of tungsten


  1. Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4. Polymeropoulos, M.H., Swift, R.G., Swift, M. Nat. Genet. (1994) [Pubmed]
  2. Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). Rötig, A., Cormier, V., Chatelain, P., Francois, R., Saudubray, J.M., Rustin, P., Munnich, A. J. Clin. Invest. (1993) [Pubmed]
  3. A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome. Barrientos, A., Volpini, V., Casademont, J., Genís, D., Manzanares, J.M., Ferrer, I., Corral, J., Cardellach, F., Urbano-Márquez, A., Estivill, X., Nunes, V. J. Clin. Invest. (1996) [Pubmed]
  4. Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts. Brown, J.M., Terada, L.S., Grosso, M.A., Whitmann, G.J., Velasco, S.E., Patt, A., Harken, A.H., Repine, J.E. J. Clin. Invest. (1988) [Pubmed]
  5. Mutation screening of the Wolfram syndrome gene in psychiatric patients. Torres, R., Leroy, E., Hu, X., Katrivanou, A., Gourzis, P., Papachatzopoulou, A., Athanassiadou, A., Beratis, S., Collier, D., Polymeropoulos, M.H. Mol. Psychiatry (2001) [Pubmed]
  6. Activity patterns of cerebellar cortical neurones and climbing fibre afferents in the awake cat. Armstrong, D.M., Rawson, J.A. J. Physiol. (Lond.) (1979) [Pubmed]
  7. Delay lines and amplitude selectivity are created in subthalamic auditory nuclei: the brachium of the inferior colliculus of the mustached bat. Kuwabara, N., Suga, N. J. Neurophysiol. (1993) [Pubmed]
  8. Mutational analysis of the Wolfram syndrome gene in two families with chromosome 4p-linked bipolar affective disorder. Evans, K.L., Lawson, D., Meitinger, T., Blackwood, D.H., Porteous, D.J. Am. J. Med. Genet. (2000) [Pubmed]
  9. Bipolar disorder and variation at a common polymorphism (A1832G) within exon 8 of the Wolfram gene. Middle, F., Jones, I., McCandless, F., Barrett, T., Khanim, F., Owen, M.J., Lendon, C., Craddock, N. Am. J. Med. Genet. (2000) [Pubmed]
  10. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Mueckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M.A. Nat. Genet. (1998) [Pubmed]
  11. Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase. Chan, M.K., Mukund, S., Kletzin, A., Adams, M.W., Rees, D.C. Science (1995) [Pubmed]
  12. Mitochondrial transformation in yeast by bombardment with microprojectiles. Johnston, S.A., Anziano, P.Q., Shark, K., Sanford, J.C., Butow, R.A. Science (1988) [Pubmed]
  13. Role of xanthine oxidase in passive Heymann nephritis in rats. Gwinner, W., Plasger, J., Brandes, R.P., Kubat, B., Schulze, M., Regele, H., Kerjaschki, D., Olbricht, C.J., Koch, K.M. J. Am. Soc. Nephrol. (1999) [Pubmed]
  14. Purification and characterization of a tungsten-containing formate dehydrogenase from Desulfovibrio gigas. Almendra, M.J., Brondino, C.D., Gavel, O., Pereira, A.S., Tavares, P., Bursakov, S., Duarte, R., Caldeira, J., Moura, J.J., Moura, I. Biochemistry (1999) [Pubmed]
  15. Multiple formate dehydrogenase enzymes in the facultative methylotroph Methylobacterium extorquens AM1 are dispensable for growth on methanol. Chistoserdova, L., Laukel, M., Portais, J.C., Vorholt, J.A., Lidstrom, M.E. J. Bacteriol. (2004) [Pubmed]
  16. Purification and characterization of a benzylviologen-linked, tungsten-containing aldehyde oxidoreductase from Desulfovibrio gigas. Hensgens, C.M., Hagen, W.R., Hansen, T.A. J. Bacteriol. (1995) [Pubmed]
  17. WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum. Takei, D., Ishihara, H., Yamaguchi, S., Yamada, T., Tamura, A., Katagiri, H., Maruyama, Y., Oka, Y. FEBS Lett. (2006) [Pubmed]
  18. Wolfram syndrome: a mitochondrial-mediated disorder? Bu, X., Rotter, J.I. Lancet (1993) [Pubmed]
  19. Structural and Electron Paramagnetic Resonance (EPR) Studies of Mononuclear Molybdenum Enzymes from Sulfate-Reducing Bacteria. Brondino, C.D., Rivas, M.G., Rom??o, M.J., Moura, J.J., Moura, I. Acc. Chem. Res. (2006) [Pubmed]
  20. Stable transformation of plastids in higher plants. Svab, Z., Hajdukiewicz, P., Maliga, P. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  21. Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. El-Shanti, H., Lidral, A.C., Jarrah, N., Druhan, L., Ajlouni, K. Am. J. Hum. Genet. (2000) [Pubmed]
  22. Single bacteriorhodopsin molecules revealed on both surfaces of freeze-dried and heavy metal-decorated purple membranes. Studer, D., Moor, H., Gross, H. J. Cell Biol. (1981) [Pubmed]
  23. Autosomal recessive Wolfram syndrome associated with an 8.5-kb mtDNA single deletion. Barrientos, A., Casademont, J., Saiz, A., Cardellach, F., Volpini, V., Solans, A., Tolosa, E., Urbano-Marquez, A., Estivill, X., Nunes, V. Am. J. Hum. Genet. (1996) [Pubmed]
  24. Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. Terada, L.S., Guidot, D.M., Leff, J.A., Willingham, I.R., Hanley, M.E., Piermattei, D., Repine, J.E. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  25. WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic {beta}-cells. Yamada, T., Ishihara, H., Tamura, A., Takahashi, R., Yamaguchi, S., Takei, D., Tokita, A., Satake, C., Tashiro, F., Katagiri, H., Aburatani, H., Miyazaki, J., Oka, Y. Hum. Mol. Genet. (2006) [Pubmed]
  26. Tungsten in biological systems. Kletzin, A., Adams, M.W. FEMS Microbiol. Rev. (1996) [Pubmed]
  27. A structural comparison of molybdenum cofactor-containing enzymes. Kisker, C., Schindelin, H., Baas, D., Rétey, J., Meckenstock, R.U., Kroneck, P.M. FEMS Microbiol. Rev. (1998) [Pubmed]
  28. Roles of protein-tyrosine phosphatases in Stat1 alpha-mediated cell signaling. Haque, S.J., Flati, V., Deb, A., Williams, B.R. J. Biol. Chem. (1995) [Pubmed]
  29. Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes. Sivakumaran, T.A., Lesperance, M.M. Int. J. Mol. Med. (2004) [Pubmed]
  30. Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. Hardy, C., Khanim, F., Torres, R., Scott-Brown, M., Seller, A., Poulton, J., Collier, D., Kirk, J., Polymeropoulos, M., Latif, F., Barrett, T. Am. J. Hum. Genet. (1999) [Pubmed]
  31. Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis. Riggs, A.C., Bernal-Mizrachi, E., Ohsugi, M., Wasson, J., Fatrai, S., Welling, C., Murray, J., Schmidt, R.E., Herrera, P.L., Permutt, M.A. Diabetologia (2005) [Pubmed]
  32. Xanthine oxidase-derived oxygen radicals increase lung cytokine expression in mice subjected to hemorrhagic shock. Schwartz, M.D., Repine, J.E., Abraham, E. Am. J. Respir. Cell Mol. Biol. (1995) [Pubmed]
  33. Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes. Hofmann, S., Bezold, R., Jaksch, M., Obermaier-Kusser, B., Mertens, S., Kaufhold, P., Rabl, W., Hecker, W., Gerbitz, K.D. Genomics (1997) [Pubmed]
  34. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Barrett, T.G., Bundey, S.E., Macleod, A.F. Lancet (1995) [Pubmed]
  35. Shadow-cast electron microscopy of fibrinogen with antibody fragments bound to specific regions. Price, T.M., Strong, D.D., Rudee, M.L., Doolittle, R.F. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  36. Extent of intracortical arborization of thalamocortical axons as a determinant of representational plasticity in monkey somatic sensory cortex. Rausell, E., Jones, E.G. J. Neurosci. (1995) [Pubmed]
  37. The active sites of molybdenum- and tungsten-containing enzymes. McMaster, J., Enemark, J.H. Current opinion in chemical biology. (1998) [Pubmed]
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