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Gne  -  glucosamine (UDP-N-acetyl)-2-epimerase/N...

Rattus norvegicus

Synonyms: Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, Glcne, UDP-GlcNAc-2-epimerase/ManAc kinase
 
 
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Disease relevance of Gne

 

Psychiatry related information on Gne

 

High impact information on Gne

 

Chemical compound and disease context of Gne

 

Biological context of Gne

  • However, cDNAs encoding the known epimerase-deficient mutation H132A or the new Lec3 G135E Gne mutation did not rescue the Lec3 phenotype [14].
  • The G135E Gne missense mutation is a novel mechanism for inactivating UDP-GlcNAc 2-epimerase activity [14].
  • The postmitochondrial supernatants showed defective incorporation only when obtained from cells incubated in the absence of glucose or in the presence of monolodoacetate; inhibition of glycolysis by glucosamine and NADH did not seem to affect the subcellular basis for protein synthesis [15].
  • This study provides a causal link between apoptosis in beta cells and glucose metabolism through glucosamine to O-GlcNAc, implicating this pathway of glucose metabolism with beta cell glucose toxicity [16].
  • Based on an earlier observation that growth factor gene transcription can be regulated by glucose and glucosamine in vascular smooth muscle cells, we determined whether Sp1 glycosylation could be regulated and if this modification altered Sp1 function [17].
 

Anatomical context of Gne

 

Associations of Gne with chemical compounds

 

Physical interactions of Gne

  • The increase in the binding of alpha 2-macroglobulin-protease complex parallelled an increase in the incorporation of glucosamine, although the latter did not increase to the same extent [25].
  • In order to better understand its mechanism of action, we determined if glucosamine could prevent the binding of IL-1 beta to its cellular receptors or could interfere with its signaling pathway at a post-receptor level [26].
 

Enzymatic interactions of Gne

 

Regulatory relationships of Gne

 

Other interactions of Gne

 

Analytical, diagnostic and therapeutic context of Gne

  • Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats [36].
  • When rats were subjected to partial hepatectomy, glucosamine 6-phosphate synthase (EC 5.3.1.19) of the remaining liver underwent alterations both in activity and in molecular form [37].
  • To study the molecular alterations, glucosamine 6-phosphate synthase was purified from regenerating as well as control liver and was analyzed by isoelectric focusing [37].
  • Male SD rats were infused with glucosamine at 0.1 mg x kg(-1) x min(-1) (low-GlcN group), 6.5 mg x kg(-1) x min(-1) (high-GlcN group), or saline (control group) for 6.5 h and exercised on a treadmill for 30 min (17 m/min) at the end of the infusion period [38].
  • Quantitation of hybrid content by immunoblotting revealed that their abundance was 1.9-fold higher in glucosamine-treated rats [39].

References

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  2. Role of the glucosamine pathway in fat-induced insulin resistance. Hawkins, M., Barzilai, N., Liu, R., Hu, M., Chen, W., Rossetti, L. J. Clin. Invest. (1997) [Pubmed]
  3. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity. Baron, A.D., Zhu, J.S., Zhu, J.H., Weldon, H., Maianu, L., Garvey, W.T. J. Clin. Invest. (1995) [Pubmed]
  4. Glucosamine in osteoarthritis. Russell, A.I., McCarty, M.F. Lancet (1999) [Pubmed]
  5. Structure and properties of an under-sulfated heparan sulfate proteoglycan synthesized by a rat hepatoma cell line. Robinson, J., Viti, M., Höök, M. J. Cell Biol. (1984) [Pubmed]
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  7. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Wang, J., Liu, R., Hawkins, M., Barzilai, N., Rossetti, L. Nature (1998) [Pubmed]
  8. In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. Rossetti, L., Hawkins, M., Chen, W., Gindi, J., Barzilai, N. J. Clin. Invest. (1995) [Pubmed]
  9. Mechanism of expression of Thomsen-Friedenreich (T) antigen at the cell surface of a mammary adenocarcinoma. Hull, S.R., Carraway, K.L. FASEB J. (1988) [Pubmed]
  10. Biosynthesis of a nonphysiological sialic acid in different rat organs, using N-propanoyl-D-hexosamines as precursors. Kayser, H., Zeitler, R., Kannicht, C., Grunow, D., Nuck, R., Reutter, W. J. Biol. Chem. (1992) [Pubmed]
  11. Hexosamine pathway is responsible for inhibition by diabetes of phenylephrine-induced inotropy. Pang, Y., Bounelis, P., Chatham, J.C., Marchase, R.B. Diabetes (2004) [Pubmed]
  12. Glucosamine-induced inhibition of liver glucokinase impairs the ability of hyperglycemia to suppress endogenous glucose production. Barzilai, N., Hawkins, M., Angelov, I., Hu, M., Rossetti, L. Diabetes (1996) [Pubmed]
  13. Differential regulation of thyrotropin subunit apoprotein and carbohydrate biosynthesis by thyroid hormone. Taylor, T., Weintraub, B.D. Endocrinology (1985) [Pubmed]
  14. Lec3 Chinese hamster ovary mutants lack UDP-N-acetylglucosamine 2-epimerase activity because of mutations in the epimerase domain of the Gne gene. Hong, Y., Stanley, P. J. Biol. Chem. (2003) [Pubmed]
  15. Inhibition of glycolysis and interference with protein synthesis in hepatoma cells. Ferrero, M.E., Ferrero, E., Bernelli-Zazzera, A. J. Natl. Cancer Inst. (1977) [Pubmed]
  16. Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells: linkage of O-linked GlcNAc to beta cell death. Liu, K., Paterson, A.J., Chin, E., Kudlow, J.E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  17. Reduced O glycosylation of Sp1 is associated with increased proteasome susceptibility. Han, I., Kudlow, J.E. Mol. Cell. Biol. (1997) [Pubmed]
  18. Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells. McClain, D.A., Paterson, A.J., Roos, M.D., Wei, X., Kudlow, J.E. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  19. Role of hexosamine biosynthesis in glucose-mediated up-regulation of lipogenic enzyme mRNA levels: effects of glucose, glutamine, and glucosamine on glycerophosphate dehydrogenase, fatty acid synthase, and acetyl-CoA carboxylase mRNA levels. Rumberger, J.M., Wu, T., Hering, M.A., Marshall, S. J. Biol. Chem. (2003) [Pubmed]
  20. Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Gouze, J.N., Bordji, K., Gulberti, S., Terlain, B., Netter, P., Magdalou, J., Fournel-Gigleux, S., Ouzzine, M. Arthritis Rheum. (2001) [Pubmed]
  21. Galactosamine-induced cell death in primary cultures of rat hepatocytes. Schanne, F.A., Pfau, R.G., Farber, J.L. Am. J. Pathol. (1980) [Pubmed]
  22. Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells. Goldberg, H.J., Scholey, J., Fantus, I.G. Diabetes (2000) [Pubmed]
  23. A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Molecular cloning and functional expression of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase. Stäsche, R., Hinderlich, S., Weise, C., Effertz, K., Lucka, L., Moormann, P., Reutter, W. J. Biol. Chem. (1997) [Pubmed]
  24. Purification and characterization of a major human Pneumocystis carinii surface antigen. Lundgren, B., Lipschik, G.Y., Kovacs, J.A. J. Clin. Invest. (1991) [Pubmed]
  25. In vivo inflammatory stimulation induces a transient change in the binding of thrombin to rat peritoneal macrophages. Fisker, S., Kudahl, K., Sonne, O. Exp. Cell Res. (1992) [Pubmed]
  26. Glucosamine modulates IL-1-induced activation of rat chondrocytes at a receptor level, and by inhibiting the NF-kappa B pathway. Gouze, J.N., Bianchi, A., Bécuwe, P., Dauça, M., Netter, P., Magdalou, J., Terlain, B., Bordji, K. FEBS Lett. (2002) [Pubmed]
  27. Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase. Hashimoto, Y., Orellana, A., Gil, G., Hirschberg, C.B. J. Biol. Chem. (1992) [Pubmed]
  28. Phosphorylation of D-glucosamine by rat liver glucokinase. Oguchi, M., Miyatake, Y., Ayabe, J., Akamatsu, N. J. Biochem. (1975) [Pubmed]
  29. Glucosamine enhances platelet-derived growth factor-induced DNA synthesis via phosphatidylinositol 3-kinase pathway in rat aortic smooth muscle cells. Sato, A., Sasaoka, T., Yamazaki, K., Nakamura, N., Temaru, R., Ishiki, M., Takata, M., Kishida, M., Wada, T., Ishihara, H., Usui, I., Urakaze, M., Kobayashi, M. Atherosclerosis (2001) [Pubmed]
  30. High glucose-induced upregulation of osteopontin is mediated via Rho/Rho kinase pathway in cultured rat aortic smooth muscle cells. Kawamura, H., Yokote, K., Asaumi, S., Kobayashi, K., Fujimoto, M., Maezawa, Y., Saito, Y., Mori, S. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  31. Regulation of insulin-stimulated glycogen synthase activity by overexpression of glutamine: fructose-6-phosphate amidotransferase in rat-1 fibroblasts. Crook, E.D., Daniels, M.C., Smith, T.M., McClain, D.A. Diabetes (1993) [Pubmed]
  32. Glucosamine-induced insulin resistance in L6 muscle cells. Bailey, C.J., Turner, S.L. Diabetes, obesity & metabolism. (2004) [Pubmed]
  33. Rats that are made insulin resistant by glucosamine treatment have impaired skeletal muscle insulin receptor phosphorylation. Spampinato, D., Giaccari, A., Trischitta, V., Costanzo, B.V., Morviducci, L., Buongiorno, A., Di Mario, U., Vigneri, R., Frittitta, L. Metab. Clin. Exp. (2003) [Pubmed]
  34. The hexosamine pathway regulates the plasminogen activator inhibitor-1 gene promoter and Sp1 transcriptional activation through protein kinase C-beta I and -delta. Goldberg, H.J., Whiteside, C.I., Fantus, I.G. J. Biol. Chem. (2002) [Pubmed]
  35. Glucosamine infusion in rats rapidly impairs insulin stimulation of phosphoinositide 3-kinase but does not alter activation of Akt/protein kinase B in skeletal muscle. Kim, Y.B., Zhu, J.S., Zierath, J.R., Shen, H.Q., Baron, A.D., Kahn, B.B. Diabetes (1999) [Pubmed]
  36. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat. Sorrell, M.F., Nauss, J.M., Donohue, T.M., Tuma, D.J. Gastroenterology (1983) [Pubmed]
  37. Glucosamine 6-phosphate synthase of regenerating rat liver. Miyagi, T., Tsuiki, S. Cancer Res. (1979) [Pubmed]
  38. Exercise-stimulated glucose turnover in the rat is impaired by glucosamine infusion. Miles, P.D., Higo, K., Olefsky, J.M. Diabetes (2001) [Pubmed]
  39. Evidence for glucose/hexosamine in vivo regulation of insulin/IGF-I hybrid receptor assembly. Federici, M., Giaccari, A., Hribal, M.L., Giovannone, B., Lauro, D., Morviducci, L., Pastore, L., Tamburrano, G., Lauro, R., Sesti, G. Diabetes (1999) [Pubmed]
 
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