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UGDH  -  UDP-glucose 6-dehydrogenase

Homo sapiens

Synonyms: GDH, UDP-Glc dehydrogenase, UDP-GlcDH, UDPGDH, UGD
 
 
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Disease relevance of UGDH

  • The expression of UGDH was up- and down-regulated by transforming growth factor (TGF)-beta and hypoxia, respectively [1].
  • For this work, we have chemically synthesized a 1509-base pair gene encoding human UGDH and expressed it in Escherichia coli as a soluble protein [2].
  • We used crystal coordinates for Streptococcus pyogenes UGDH in complex with NAD+ cofactor and UDP-glucose substrate to generate a model of the enzyme active site [3].
  • This question was tested by treating the human hepatoma cells HepG2 with several medicinal compounds and the UGDH gene expression analyzed by using real-time PCR [4].
  • A UGDH siRNA plasmid was constructed using a pRNA-U6.1/Neo vector and transfected into breast cancer cells, ZR-75-1, with an efficiency of up to 50% [5].
 

High impact information on UGDH

  • The anomalous sex ratio of CV deaths in UGDP placebo-treated subjects dictates the conclusion that the CV death rate in placebo-treated subjects was spuriously low, giving the false impression of increased death rates in the other treatment groups, thereby accounting for all of the controversial observations reported by UGDP investigators [6].
  • Tolbutamide pharmacogenetics and the UGDP controversy [7].
  • The Michaelis constant (Km) of normal human fibroblast GDH for [2,3,4-3H]glutaryl-CoA was 5.9 microM, and activity was severely inhibited by (methylenecyclopropyl)acetyl-CoA at low concentrations [8].
  • RESULTS: The UGDP compared the effects of a fixed-dose standard insulin regimen, a variable-dose insulin regimen, and a diet plus oral placebo regimen in over 600 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were followed for up to 13 years (1962 to 1975) [9].
  • It appears that placental GDH is controlled by five codominant autosomal alleles producing 15 possible phenotypes [10].
 

Chemical compound and disease context of UGDH

  • As UDPGDH is required for the production of uridine 5'-diphosphoglucuronic acid, a substrate for the steroid-conjugating uridine diphospho-glucuronosyltransferase enzymes, up-regulation of UDPGDH expression by androgens might play an important role in the control of sex steroid inactivation via glucuronidation in breast cancer cells [11].
  • A photoinduced hydrogen production system that couples sucrose degradation with invertase and glucose dehydrogenase (GDH) and hydrogen production with colloidal platinum as a catalyst using visible light-induced photosensitization of artificial Zn chlorophyll-a (Zn Chl-a) has been developed [12].
  • Periplasmic glucose oxidation (by way of a pyrrolo-quinoline-quinone [PQQ]-linked glucose dehydrogenase [GDH]) was observed in continuous cultures of Gluconacetobacter diazotrophicus regardless of the carbon source (glucose or gluconate) and the nitrogen source (N(2) or NH(3)) [13].
  • Glucose dehydrogenase (GDH), one of the recently discovered NAD(P)+-independent 'quinoprotein' class of oxidoreductase enzymes, was purified from Acinetobacter calcoaceticus LMD 79.41 and immobilised on a 1,1'-dimethylferrocene-modified graphite foil electrode [14].
  • A gene fragment encoding a putative pyrroloquinoline quinone glucose dehydrogenase (PQQ GDH) was cloned from a bacterial cellulose (BC)-forming acetic acid bacterium, Gluconacetobacter xylinus (=Acetobacter xylinum) strain BPR 2001, which was isolated as a high BC producer when using fructose as the carbon source [15].
 

Biological context of UGDH

  • These results indicate that numerous Sp1 cis-acting sequences of the UGDH core promoter are responsible for up- and down-regulation of the gene after TGF-beta stimulation and in hypoxic conditions, respectively [1].
  • Using the bacterial artificial chromosome approach, we have cloned and characterized the human UGDH promoter [1].
  • Our results thus identify an alternative transcription start site on the UGDH promoter, and locate the cis-element that greatly enhances the basal transcriptional activity of UGDH gene [16].
  • To delineate the regions in the UGDH promoter required for regulating the expression of the gene, in particular the synthesis of the large transcript, serial deletions of the 2.1-kb UGDH promoter region were constructed and their activities determined by the firefly luciferase reporter gene assay [16].
  • Through interspecific backcross analyses, we localized the Ugdh gene to mouse chromosome 5 at approximately 39 centimorgans, suggesting that the human UGDH gene is localized to chromosome 4p13-15 [17].
 

Anatomical context of UGDH

  • In human smooth muscle cells the overexpression of xUGDH or endogenous abrogation of UGDH modulated hyaluronan synthesis specifically [18].
  • Plant UDP-glucose dehydrogenase (UGDH) is an important enzyme in the formation of hemicellulose and pectin, the components of primary cell walls [19].
  • Furthermore, no direct correlation between GDH and fetal hemoglobin (HbF) was obtained in cord and thalassemic erythrocytes [20].
  • After fractionation into young and old erythrocyte populations, clearly higher GDH activity was found in the younger cells; however, there was no significant correlation with the reticulocyte count [20].
  • We have cloned and characterized two human glutamate dehydrogenases (GDH), one of which is nerve tissue specific [21].
 

Associations of UGDH with chemical compounds

  • Mithramycin A, an inhibitor of transcription factor Sp1, abrogates the promoter activity, suggesting the involvement of this specific protein in UGDH expression [16].
  • Pathological overproduction of extracellular matrix components may be linked to the availability of UDP-glucuronic acid; therefore UGDH is an intriguing therapeutic target [3].
  • The unidentified residue, X, can be designated as a photolabeled Gly-13 because the sequences including the glycine residue in question have a complete identity with those of other UGDH species known [2].
  • In this report, we have identified an NAD(+)-binding site within human UGDH by photoaffinity labeling with a specific probe, [(32)P]nicotinamide 2-azidoadenosine dinucleotide (2N(3) NAD(+)), and cassette mutagenesis [2].
  • The unidentified residue, X, can be designated as a photolabeled C276 because the sequences including the cysteine residue in question have a complete identity with those of other UGDH species known [22].
 

Physical interactions of UGDH

 

Regulatory relationships of UGDH

 

Other interactions of UGDH

 

Analytical, diagnostic and therapeutic context of UGDH

References

  1. Specific protein-1 is a universal regulator of UDP-glucose dehydrogenase expression: its positive involvement in transforming growth factor-beta signaling and inhibition in hypoxia. Bontemps, Y., Vuillermoz, B., Antonicelli, F., Perreau, C., Danan, J.L., Maquart, F.X., Wegrowski, Y. J. Biol. Chem. (2003) [Pubmed]
  2. Importance of Gly-13 for the coenzyme binding of human UDP-glucose dehydrogenase. Huh, J.W., Yoon, H.Y., Lee, H.J., Choi, W.B., Yang, S.J., Cho, S.W. J. Biol. Chem. (2004) [Pubmed]
  3. Characterization of human UDP-glucose dehydrogenase. CYS-276 is required for the second of two successive oxidations. Sommer, B.J., Barycki, J.J., Simpson, M.A. J. Biol. Chem. (2004) [Pubmed]
  4. Effects of xenobiotics and peroxisome proliferator-activated receptor-alpha on the human UDPglucose dehydrogenase gene expression. Vatsyayan, J., Lee, S.J., Chang, H.Y. J. Biochem. Mol. Toxicol. (2005) [Pubmed]
  5. Inhibition of human UDP-glucose dehydrogenase expression using siRNA expression vector in breast cancer cells. Huh, J.W., Choi, M.M., Yang, S.J., Yoon, S.Y., Choi, S.Y., Cho, S.W. Biotechnol. Lett. (2005) [Pubmed]
  6. The Achilles heel of the University Group Diabetes Program. Kilo, C., Miller, J.P., Williamson, J.R. JAMA (1980) [Pubmed]
  7. Tolbutamide pharmacogenetics and the UGDP controversy. Scott, J., Poffenbarger, P.L. JAMA (1979) [Pubmed]
  8. Specific glutaryl-CoA dehydrogenating activity is deficient in cultured fibroblasts from glutaric aciduria patients. Hyman, D.B., Tanaka, K. J. Clin. Invest. (1984) [Pubmed]
  9. Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus. Genuth, S. Ann. Intern. Med. (1996) [Pubmed]
  10. Glucose dehydrogenase polymorphism among ethnic groups of Singapore--with report of two additional alleles (GDH4 and GDH5). Saha, N., Bhattacharyya, S.P., Yeoh, S.C., Chua, S.P., Ratnam, S.S. Am. J. Hum. Genet. (1987) [Pubmed]
  11. Identification and cloning of a novel androgen-responsive gene, uridine diphosphoglucose dehydrogenase, in human breast cancer cells. Lapointe, J., Labrie, C. Endocrinology (1999) [Pubmed]
  12. Biohydrogen production from sucrose using the visible light sensitization of artificial Zn chlorophyll-a. Takeuchi, Y., Amao, Y. Bioconjug. Chem. (2003) [Pubmed]
  13. Glucose metabolism in batch and continuous cultures of Gluconacetobacter diazotrophicus PAL 3. Luna, M.F., Bernardelli, C.E., Galar, M.L., Boiardi, J.L. Curr. Microbiol. (2006) [Pubmed]
  14. Quinoprotein glucose dehydrogenase and its application in an amperometric glucose sensor. D'Costa, E.J., Higgins, I.J., Turner, A.P. Biosensors. (1986) [Pubmed]
  15. Cellulose production from glucose using a glucose dehydrogenase gene (gdh)-deficient mutant of Gluconacetobacter xylinus and its use for bioconversion of sweet potato pulp. Shigematsu, T., Takamine, K., Kitazato, M., Morita, T., Naritomi, T., Morimura, S., Kida, K. J. Biosci. Bioeng. (2005) [Pubmed]
  16. Analysis of human UDP-glucose dehydrogenase gene promoter: identification of an Sp1 binding site crucial for the expression of the large transcript. Vatsyayan, J., Peng, H.L., Chang, H.Y. J. Biochem. (2005) [Pubmed]
  17. Molecular cloning and characterization of the human and mouse UDP-glucose dehydrogenase genes. Spicer, A.P., Kaback, L.A., Smith, T.J., Seldin, M.F. J. Biol. Chem. (1998) [Pubmed]
  18. Molecular cloning and characterization of UDP-glucose dehydrogenase from the amphibian Xenopus laevis and its involvement in hyaluronan synthesis. Vigetti, D., Ori, M., Viola, M., Genasetti, A., Karousou, E., Rizzi, M., Pallotti, F., Nardi, I., Hascall, V.C., De Luca, G., Passi, A. J. Biol. Chem. (2006) [Pubmed]
  19. Cloning and expression studies of the Dunaliella salina UDP-glucose dehydrogenase cDNA. Qinghua, H., Dairong, Q., Qinglian, Z., Shunji, H., Yin, L., Linhan, B., Zhirong, Y., Yi, C. DNA Seq. (2005) [Pubmed]
  20. Glycerol-3-phosphate dehydrogenase activity in the red cells of patients with thalassemia. Fessas, P., Anagnou, N.P., Loukopoulos, D. Blood (1980) [Pubmed]
  21. Glutamate transport and metabolism in dopaminergic neurons of substantia nigra: implications for the pathogenesis of Parkinson's disease. Plaitakis, A., Shashidharan, P. J. Neurol. (2000) [Pubmed]
  22. Identification of a UDP-glucose-binding site of human UDP-glucose dehydrogenase by photoaffinity labeling and cassette mutagenesis. Huh, J.W., Lee, H.J., Choi, M.M., Yang, S.J., Yoon, S.Y., Kim, D.W., Kim, S.Y., Choi, S.Y., Cho, S.W. Bioconjug. Chem. (2005) [Pubmed]
  23. Investigation of the UDP-glucose dehydrogenase reaction for a coupled assay of UDP-glucose pyrophosphorylase activities. Elling, L., Kula, M.R. Biotechnol. Appl. Biochem. (1991) [Pubmed]
  24. Regulatory mechanisms of UDP-glucuronic acid biosynthesis in cultured human skin fibroblasts. Castellani, A.A., De Luca, G., Rindi, S., Salvini, R., Tira, M.E. Ital. J. Biochem. (1986) [Pubmed]
  25. A new mass screening method for determining UDP-galactose in blood. Fujimura, Y., Kawamura, M., Naruse, H. Tohoku J. Exp. Med. (1983) [Pubmed]
  26. Enzymes of glucose metabolism in palmar fascia and Dupuytren's contracture. Hoopes, J.E., Jabaley, M.E., Su, C.T., Wilgis, S., Im, M.J. The Journal of hand surgery. (1977) [Pubmed]
  27. Assignment of the UGDH locus encoding UDP-glucose dehydrogenase to human chromosome band 4p15.1 by radiation hybrid mapping. Marcu, O., Stathakis, D.G., Marsh, J.L. Cytogenet. Cell Genet. (1999) [Pubmed]
  28. Molecular cloning and characterization of a cDNA encoding poplar UDP-glucose dehydrogenase, a key gene of hemicellulose/pectin formation. Johansson, H., Sterky, F., Amini, B., Lundeberg, J., Kleczkowski, L.A. Biochim. Biophys. Acta (2002) [Pubmed]
 
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