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Gene Review

Ugcg  -  UDP-glucose ceramide glucosyltransferase

Rattus norvegicus

Synonyms: Ceramide glucosyltransferase, GCS, GLCT-1, Glucosylceramide synthase, UDP-glucose:N-acylsphingosine D-glucosyltransferase
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Disease relevance of Ugcg


High impact information on Ugcg

  • To determine whether the alteration in glucosylceramide content per se played a functional role in the decrease in Na-Pi cotransport, control rats were treated with the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1-propanol (PDMP) [5].
  • D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.HCl (PDMP), a glucosylceramide synthase and LacCer synthase (GalT-2) inhibitor, inhibited astrocyte proliferation and GFAP expression, which were reversed by exogenous supplementation of LacCer but not by other glycosphingolipids [6].
  • TNF-alpha stimulated the colocalization of GD3 with early and late endosomal markers, Rab 5 and Rab 7, whereas perturbation of plasma membrane cholesterol or actin cytoskeleton or inhibition of glucosylceramide synthase prevented the trafficking of GD3 to mitochondria [7].
  • Identification of active site residues in glucosylceramide synthase. A nucleotide-binding catalytic motif conserved with processive beta-glycosyltransferases [8].
  • The amino acid sequence of GCS was reported to be dissimilar from other proteins, with no identifiable functional domains [8].

Chemical compound and disease context of Ugcg


Biological context of Ugcg


Anatomical context of Ugcg

  • After 24-hour middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats, brain ceramide level increased from baseline reached 595% (ischemic core) and 460% (perifocal/penumbral areas); brain glucosylceramide synthase (GCS) activities in these areas simultaneously decreased by 70% and 50%, respectively [1].
  • The results show that the flux through GCS is sensitive to concentrations of calcium which would be achieved in the cytoplasm of hepatocytes stimulated by calcium-mobilizing hormones [13].
  • Flux through GCS in isolated mitochondria was exquisitely sensitive to free Ca2+ in the medium; half-maximal stimulation occurred at about 0.4 microM free Ca2+ and maximal stimulation (7-fold) was reached when the free Ca2+ in the medium was 1 microM [13].
  • Trypsinization and immunoprecipitation studies with Golgi membranes showed that both the C terminus and a hydrophilic loop near the N terminus of GCS are accessible from the cytosolic face of the Golgi membrane [14].
  • Glucosylceramide synthase inhibitor inhibits the action of nerve growth factor in PC12 cells [15].

Associations of Ugcg with chemical compounds

  • In ischemic tolerance, GCS appears to modulate otherwise high levels of brain ceramide [1].
  • These results indicate that His193 is the primary target of DEPC and is at, or near, the UDP-Glc-binding site of GCS [10].
  • Mutant proteins were expressed in which the eight histidine residues in GCS were individually replaced by other amino acids [10].
  • Glucosylceramide synthase (GCS) catalyses the transfer of glucose from UDP-glucose (UDP-Glc) to ceramide to form glucosylceramide, the common precursor of most higher-order glycosphingolipids [10].
  • The possibility that the stimulation of flux by adrenergic agonists and vasopressin is mediated by increases in cytoplasmic Ca2+ which in turn could regulate mitochondrial glycine catabolism was examined by measuring flux through GCS in isolated mitochondria in the presence of 0.04-2.88 microM free Ca2+ [13].

Other interactions of Ugcg


Analytical, diagnostic and therapeutic context of Ugcg


  1. Glucosylceramide synthase activity and ceramide levels are modulated during cerebral ischemia after ischemic preconditioning. Takahashi, K., Ginis, I., Nishioka, R., Klimanis, D., Barone, F.C., White, R.F., Chen, Y., Hallenbeck, J.M. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  2. Retrograde labeling, enrichment, and characterization of retinal ganglion cells from the neonatal rat. Sarthy, P.V., Curtis, B.M., Catterall, W.A. J. Neurosci. (1983) [Pubmed]
  3. Glycine cleavage system in neurogenic regions. Ichinohe, A., Kure, S., Mikawa, S., Ueki, T., Kojima, K., Fujiwara, K., Iinuma, K., Matsubara, Y., Sato, K. Eur. J. Neurosci. (2004) [Pubmed]
  4. Anoxia and reoxygenation of human endothelial cells decrease ceramide glucosyltransferase expression and activates caspases. Zhao, H., Miller, M., Pfeiffer, K., Buras, J.A., Stahl, G.L. FASEB J. (2003) [Pubmed]
  5. Dexamethasone modulates rat renal brush border membrane phosphate transporter mRNA and protein abundance and glycosphingolipid composition. Levi, M., Shayman, J.A., Abe, A., Gross, S.K., McCluer, R.H., Biber, J., Murer, H., Lötscher, M., Cronin, R.E. J. Clin. Invest. (1995) [Pubmed]
  6. A novel role of lactosylceramide in the regulation of tumor necrosis factor alpha-mediated proliferation of rat primary astrocytes. Implications for astrogliosis following neurotrauma. Pannu, R., Singh, A.K., Singh, I. J. Biol. Chem. (2005) [Pubmed]
  7. Trafficking of ganglioside GD3 to mitochondria by tumor necrosis factor-alpha. García-Ruiz, C., Colell, A., Morales, A., Calvo, M., Enrich, C., Fernández-Checa, J.C. J. Biol. Chem. (2002) [Pubmed]
  8. Identification of active site residues in glucosylceramide synthase. A nucleotide-binding catalytic motif conserved with processive beta-glycosyltransferases. Marks, D.L., Dominguez, M., Wu, K., Pagano, R.E. J. Biol. Chem. (2001) [Pubmed]
  9. Structure and expression of the glycine cleavage system in rat central nervous system. Sakata, Y., Owada, Y., Sato, K., Kojima, K., Hisanaga, K., Shinka, T., Suzuki, Y., Aoki, Y., Satoh, J., Kondo, H., Matsubara, Y., Kure, S. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  10. Histidine-193 of rat glucosylceramide synthase resides in a UDP-glucose- and inhibitor (D-threo-1-phenyl-2-decanoylamino-3-morpholinopropan-1-ol)-binding region: a biochemical and mutational study. Wu, K., Marks, D.L., Watanabe, R., Paul, P., Rajan, N., Pagano, R.E. Biochem. J. (1999) [Pubmed]
  11. Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells. Shi, M.M., Kugelman, A., Iwamoto, T., Tian, L., Forman, H.J. J. Biol. Chem. (1994) [Pubmed]
  12. Regulation of gamma-glutamylcysteine synthetase by protein phosphorylation. Sun, W.M., Huang, Z.Z., Lu, S.C. Biochem. J. (1996) [Pubmed]
  13. Stimulation of glycine catabolism in isolated perfused rat liver by calcium mobilizing hormones and in isolated rat liver mitochondria by submicromolar concentrations of calcium. Jois, M., Hall, B., Brosnan, J.T. J. Biol. Chem. (1990) [Pubmed]
  14. Oligomerization and topology of the Golgi membrane protein glucosylceramide synthase. Marks, D.L., Wu, K., Paul, P., Kamisaka, Y., Watanabe, R., Pagano, R.E. J. Biol. Chem. (1999) [Pubmed]
  15. Glucosylceramide synthase inhibitor inhibits the action of nerve growth factor in PC12 cells. Mutoh, T., Tokuda, A., Inokuchi, J., Kuriyama, M. J. Biol. Chem. (1998) [Pubmed]
  16. The mitochondria-associated endoplasmic-reticulum subcompartment (MAM fraction) of rat liver contains highly active sphingolipid-specific glycosyltransferases. Ardail, D., Popa, I., Bodennec, J., Louisot, P., Schmitt, D., Portoukalian, J. Biochem. J. (2003) [Pubmed]
  17. Depletion of cerebral D-serine in non-ketotic hyperglycinemia: possible involvement of glycine cleavage system in control of endogenous D-serine. Iwama, H., Takahashi, K., Kure, S., Hayashi, F., Narisawa, K., Tada, K., Mizoguchi, M., Takashima, S., Tomita, U., Nishikawa, T. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  18. Rationales for cancer chemotherapy with PDMP, a specific inhibitor of glucosylceramide synthase. Radin, N.S. Mol. Chem. Neuropathol. (1994) [Pubmed]
  19. Preparation, quality control and application of 99mTc-gluco-ene-diolate for renal scanning. Shafiq, Y.F., Al-Janabi, M.A. Nuklearmedizin. (1985) [Pubmed]
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