UDP-glucose 6-dehydrogenase

UDP-glucose 6-dehydrogenase

Rendering based on PDB 2Q3E.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsUGDH ; GDH; UDP-GlcDH; UDPGDH; UGD
External IDsOMIM: 603370 MGI: 1306785 HomoloGene: 2520 GeneCards: UGDH Gene
EC number1.1.1.22
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez735822235
EnsemblENSG00000109814ENSMUSG00000029201
UniProtO60701O70475
RefSeq (mRNA)NM_001184700NM_009466
RefSeq (protein)NP_001171629NP_033492
Location (UCSC)Chr 4:
39.5 – 39.53 Mb
Chr 5:
65.41 – 65.44 Mb
PubMed search

UDP-glucose 6-dehydrogenase is a cytosolic enzyme that in humans is encoded by the UGDH gene.[1][2][3]

The protein encoded by this gene converts UDP-glucose to UDP-glucuronate and thereby participates in the biosynthesis of glycosaminoglycans such as hyaluronan, chondroitin sulfate, and heparan sulfate. These glycosylated compounds are common components of the extracellular matrix and likely play roles in signal transduction, cell migration, and cancer growth and metastasis. The expression of this gene is up-regulated by transforming growth factor beta and down-regulated by hypoxia.[3]

This enzyme participates in 4 metabolic pathways: pentose and glucuronate interconversions, ascorbate and aldarate metabolism, starch and sucrose metabolism, and nucleotide sugars metabolism.

Nomenclature

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is UDP-glucose:NAD+ 6-oxidoreductase.

Other names in common use include:

Biochemistry

UDP-glucose 6-dehydrogenase
Identifiers
EC number 1.1.1.22
CAS number 9028-26-6
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

In enzymology, a UDP-glucose 6-dehydrogenase (EC 1.1.1.22) is an enzyme that catalyzes the chemical reaction

UDP-glucose + 2 NAD+ + H2O \rightleftharpoons UDP-glucuronate + 2 NADH + 2 H+

The 3 substrates of this enzyme are UDP-glucose, NAD+, and H2O, whereas its 3 products are UDP-glucuronate, NADH, and H+


References: [4] [5] [6] [7]

References

  1. Spicer AP, Kaback LA, Smith TJ, Seldin MF (Oct 1998). "Molecular cloning and characterization of the human and mouse UDP-glucose dehydrogenase genes". J Biol Chem 273 (39): 25117–24. doi:10.1074/jbc.273.39.25117. PMID 9737970.
  2. Marcu O, Stathakis DG, Marsh JL (Jan 2000). "Assignment of the UGDH locus encoding UDP-glucose dehydrogenase to human chromosome band 4p15.1 by radiation hybrid mapping". Cytogenet Cell Genet 86 (3–4): 244–5. doi:10.1159/000015350. PMID 10575217.
  3. 3.0 3.1 "Entrez Gene: UGDH UDP-glucose dehydrogenase".
  4. Bauer S; Kusov, YY; Shibaev, VN; Kochetkov, NK; Bielý, P; Kucár, S; Bauer, S (1975). "Uridine diphosphate 2-deoxyglucose. Chemical synthesis, enzymic oxidation and epimerization". Biochim. Biophys. Acta 381 (2): 3017. doi:10.1016/0304-4165(75)90236-6. PMID 1091296.
  5. Kalckar HM, Maxwell ES, Strominger JL (MON 1956). "Some properties of uridine diphosphoglucose dehydrogenase". Arch. Biochem. Biophys. 65 (1): 210. doi:10.1016/0003-9861(56)90171-0. PMID 13373402. Check date values in: |date= (help)
  6. Strominger JL, Mapson LW (1957). "Uridine diphosphoglucose dehydrogenase of pea seedlings". Biochem. J. 66 (4): 56772. PMC 1200063. PMID 13459898.
  7. Axelrod J, Kalckar HM, Maxwell ES, Strominger JL (1957). "Enzymatic formation of uridine diphosphoglucuronic acid". J. Biol. Chem. 224 (1): 7990. PMID 13398389.

Further reading

  • Peng HL, Lou MD, Chang ML, Chang HY (1999). "cDNA cloning and expression analysis of the human UDPglucose dehydrogenase". Proc. Natl. Sci. Counc. Repub. China B 22 (4): 166–72. PMID 9850599.
  • Bontemps Y, Maquart FX, Wegrowski Y (2000). "Human UDP-glucose dehydrogenase gene: complete cloning and transcription start mapping". Biochem. Biophys. Res. Commun. 275 (3): 981–5. doi:10.1006/bbrc.2000.3389. PMID 10973831.
  • Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Bontemps Y; Vuillermoz B; Antonicelli F et al. (2003). "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". J. Biol. Chem. 278 (24): 21566–75. doi:10.1074/jbc.M209366200. PMID 12682078.
  • Ota T; Suzuki Y; Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
  • Sommer BJ, Barycki JJ, Simpson MA (2004). "Characterization of human UDP-glucose dehydrogenase. CYS-276 is required for the second of two successive oxidations". J. Biol. Chem. 279 (22): 23590–6. doi:10.1074/jbc.M401928200. PMID 15044486.
  • Brandenberger R; Wei H; Zhang S et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
  • Huh JW; Yoon HY; Lee HJ et al. (2004). "Importance of Gly-13 for the coenzyme binding of human UDP-glucose dehydrogenase". J. Biol. Chem. 279 (36): 37491–8. doi:10.1074/jbc.M404234200. PMID 15247292.
  • Gerhard DS; Wagner L; Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
  • Huh JW; Lee HJ; Choi MM et al. (2005). "Identification of a UDP-glucose-binding site of human UDP-glucose dehydrogenase by photoaffinity labeling and cassette mutagenesis". Bioconjug. Chem. 16 (3): 710–6. doi:10.1021/bc0500387. PMID 15898741.
  • Vatsyayan J, Peng HL, Chang HY (2005). "Analysis of human UDP-glucose dehydrogenase gene promoter: identification of an Sp1 binding site crucial for the expression of the large transcript". J. Biochem. 137 (6): 703–9. doi:10.1093/jb/mvi082. PMID 16002992.
  • Wang L; Zhu YF; Guo XJ et al. (2006). "A two-dimensional electrophoresis reference map of human ovary". J. Mol. Med. 83 (10): 812–21. doi:10.1007/s00109-005-0676-y. PMID 16021519.
  • Vatsyayan J, Lin CT, Peng HL, Chang HY (2006). "Identification of a cis-acting element responsible for negative regulation of the human UDP-glucose dehydrogenase gene expression". Biosci. Biotechnol. Biochem. 70 (2): 401–10. doi:10.1271/bbb.70.401. PMID 16495656.
  • Huh JW; Robinson RC; Lee HS et al. (2006). "Expression, purification, crystallization, and preliminary X-Ray analysis of the human UDP-glucose dehydrogenase". Protein Pept. Lett. 13 (8): 859–62. doi:10.2174/092986606777841253. PMID 17073734.
  • Easley KE; Sommer BJ; Boanca G et al. (2007). "Characterization of human UDP-glucose dehydrogenase reveals critical catalytic roles for lysine 220 and aspartate 280". Biochemistry 46 (2): 369–78. doi:10.1021/bi061537d. PMID 17209547.