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UGP2  -  UDP-glucose pyrophosphorylase 2

Homo sapiens

Synonyms: UDP-glucose pyrophosphorylase, UDPG, UDPGP, UDPGP2, UGP1, ...
 
 
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Disease relevance of UGP2

  • Biochemical and autoradiographic evidence show both glycogen synthesis and the presence of glycogen synthase (UDP glucose [UDPG]: glycogen 4-alpha-D-glucosyltransferase; EC 2.4.1.11) in isolated nuclei of Ehrlich-Lettré mouse ascites tumor cells of the mutant subline HD33 [1].
  • We speculate that increased expression of hUGP2 in humans could alleviate poor outcomes in humans with classic galactosemia [2].
 

High impact information on UGP2

  • The Km value for (a + b) glycogen synthase is 1 x 10(-3) M UDPG, the activation constant is 5 x 10(-3) M glucose-6-phosphate (Glc-6-P) [1].
  • In intact cells, synthesis of UDPG for nuclear glycogen synthesis depends on the activity of the exclusively cytoplasmic UDPG pyrophosphorylase (UTP: alpha-D-glucose-1-phosphate uridylyltransferase; EC 2.7.7.9) [1].
  • The methodologic variables of the UDPG pyrophosphorylase method for analysis of inorganic pyrophosphate (PPi) levels in biologic fluids are described [3].
  • During the first two thirds of gestation, the concentrations of UDPG, ATP, ADP, and Mg++ in human fetal liver remain constant, whereas the concentration of Pi decreases twofold and the G-6-P and AMP concentrations increase [4].
  • The first enzyme-catalyzed reaction leading from indole-3-acetic acid (IAA) to the myo-inositol esters of IAA is the synthesis of indole-3-acetyl-1-O-beta-D-glucose from uridine-5'-diphosphoglucose (UDPG) and IAA [5].
 

Biological context of UGP2

 

Anatomical context of UGP2

  • Therefore we conclude that HA synthesis during chondrocyte differentiation is regulated at the level of the substrate-provider gene, UDPG-PPase, as well as the HAS genes [7].
  • In three human fetuses, the apparent Km UDPG was 0.54 x 10(-4) M [10].
  • In both pooled human liver microsomes and expressed UGT2B7, UDPG and UDPGA competitively inhibited their counterpart conjugations with K(i) values close to their K(m) values, indicating a comparable affinity of the enzyme toward these two nucleotide sugars [11].
  • The activity (mean +/- SD) of galactose-1-phosphate uridyl transferase in two long-term lymphoid cell lines from Caucasian patients with transferase deficiency galactosaemia, a heterozygote, and eight normal subjects was 0, 78 and 168 +/- 55 nmol UDPG consumed (mg protein)-1h-1, respectively [12].
  • The results suggest that pollen and anther FK may play a role in the regulation of pollen germination, possibly by providing fructose-6-phosphate for glycolysis, or through conversion to UDP-glucose (UDPG) to support the biosynthesis of cell wall material for pollen tube growth [13].
 

Associations of UGP2 with chemical compounds

  • Localization of the human UGP2 gene encoding the muscle isoform of UDPglucose pyrophosphorylase to 2p13-p14 by fluorescence in situ hybridization [14].
  • The solution conformations of UDPG, UDPGN, UDPGal, UDPM, UDPGluc, UDPGalc, ADPG, ADPM, GDPG, GDPM, and CDPG and their components Glu-1-P, Gal-1-P, Man-1-P, Gluc-1-P, Galc-1-P, ADP, GDP, UDP, and CDP are studied by high resolution fast Fourier transform nuclear magnetic resonance spectroscopy with iterative computer line shape simulation [15].
  • From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP [16].
  • We found that 2.5 mM Gal-1-P increased the apparent KM of purified hUGP2 for glucose-1-phosphate from 19.7 microM to 169 microM, without changes in apparent Vmax [17].
  • Product-inhibition studies showed competitive inhibition between UDPG and UDP (KiQ 20 microM) and non-competitive inhibition between the flavonol substrate and its glucoside (KiP 1 mM) [18].
 

Other interactions of UGP2

  • Our data suggest that an increase in both activities, UDPG-PPase and HAS-2, is required for non-hypertrophic chondrocytes to synthesize an amount of HA comparable with that in hypertrophic chondrocytes [7].
  • When we transfected the GALT-deficient cells with either the hUGP2 or GALT gene, their UDP-glucose content increased to 305+/-28 micromoles/100 g protein (hUGP2-transfected) and 210+/-13 micromoles/100 g protein (GALT-transfected), respectively [17].

References

  1. Role of nuclear glycogen synthase and cytoplasmic UDP glucose pyrophosphorylase in the biosynthesis of nuclear glycogen in HD33 Ehrlich-Lettré ascites tumor cells. Granzow, C., Kopun, M., Zimmermann, H.P. J. Cell Biol. (1981) [Pubmed]
  2. Overexpression of human UDP-glucose pyrophosphorylase rescues galactose-1-phosphate uridyltransferase-deficient yeast. Lai, K., Elsas, L.J. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  3. Quantification of human plasma inorganic pyrophosphate. I. Normal values in osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease. Ryan, L.M., Kozin, F., McCarty, D.J. Arthritis Rheum. (1979) [Pubmed]
  4. Hormonal regulation of glycogen metabolism in human fetal liver. II. Regulation of glycogen synthase activity. Schwartz, A.L., Rall, T.W. Diabetes (1975) [Pubmed]
  5. Enzymic synthesis of indole-3-acetyl-1-O-beta-d-glucose. I. Partial purification and characterization of the enzyme from Zea mays. Leznicki, A.J., Bandurski, R.S. Plant Physiol. (1988) [Pubmed]
  6. Isolation and assignment of the UDP-glucose pyrophosphorylase gene (UGP2) to porcine chromosome 3q21-->q22 by FISH and by analysis of somatic cell and radiation hybrid panels. Looft, C., Paul, S., Thomsen, P.D., Yerle, M., Brenig, B., Kalm, E. Cytogenet. Cell Genet. (2000) [Pubmed]
  7. UDP-glucose pyrophosphorylase: up-regulation in hypertrophic cartilage and role in hyaluronan synthesis. Magee, C., Nurminskaya, M., Linsenmayer, T.F. Biochem. J. (2001) [Pubmed]
  8. Enzymic measurement of urinary pyrophosphate with a centrifugal analyzer. Roullet, J.B., Lacour, B., Ulmann, A., Bailly, M. Clin. Chem. (1982) [Pubmed]
  9. Cloning, expression and characterization of a mammalian Nudix hydrolase-like enzyme that cleaves the pyrophosphate bond of UDP-glucose. Yagi, T., Baroja-Fernández, E., Yamamoto, R., Muñoz, F.J., Akazawa, T., Hong, K.S., Pozueta-Romero, J. Biochem. J. (2003) [Pubmed]
  10. Reduced hepatic bilirubin uridine diphosphate glucuronyl transferase and uridine diphosphate glucose dehydrogenase activity in the human fetus. Felsher, B.F., Maidman, J.E., Carpio, N.M., VanCouvering, K., Woolley, M.M. Pediatr. Res. (1978) [Pubmed]
  11. Acyl glucuronidation and glucosidation of a new and selective endothelin ET(A) receptor antagonist in human liver microsomes. Tang, C., Hochman, J.H., Ma, B., Subramanian, R., Vyas, K.P. Drug Metab. Dispos. (2003) [Pubmed]
  12. Galactose metabolism in transferase-deficient galactosaemic and normal long-term lymphoid cell lines. Beratis, N.G., Wilbur, L. J. Inherit. Metab. Dis. (1987) [Pubmed]
  13. Fructokinase and hexokinase from pollen grains of bell pepper (Capsicum annuum L.): possible role in pollen germination under conditions of high temperature and CO2 enrichment. Karni, L., Aloni, B. Ann. Bot. (2002) [Pubmed]
  14. Localization of the human UGP2 gene encoding the muscle isoform of UDPglucose pyrophosphorylase to 2p13-p14 by fluorescence in situ hybridization. Cheng, S.D., Peng, H.L., Chang, H.Y. Genomics (1997) [Pubmed]
  15. Nuclear magnetic resonance studies of the solution conformation of nucleoside diphosphohexoses and their components. Lee, C.H., Sarma, R.H. Biochemistry (1976) [Pubmed]
  16. Hepatic UDP-glucose (13)C isotopomers from [U-(13)C]glucose: A simple analysis by (13)C NMR of urinary menthol glucuronide. Mendes, A.C., Caldeira, M.M., Silva, C., Burgess, S.C., Merritt, M.E., Gomes, F., Barosa, C., Delgado, T.C., Franco, F., Monteiro, P., Providencia, L., Jones, J.G. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. (2006) [Pubmed]
  17. GALT deficiency causes UDP-hexose deficit in human galactosemic cells. Lai, K., Langley, S.D., Khwaja, F.W., Schmitt, E.W., Elsas, L.J. Glycobiology (2003) [Pubmed]
  18. Kinetic mechanism of a flavonol-ring-B O-glucosyltransferase from Chrysosplenium americanum. Khouri, H., Ibrahim, R.K. Eur. J. Biochem. (1984) [Pubmed]
 
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