Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1986 Feb 1;233(3):749–754. doi: 10.1042/bj2330749

UDP-glucosamine as a substrate for dolichyl monophosphate glucosamine synthesis.

W McDowell, G Weckbecker, D O Keppler, R T Schwarz
PMCID: PMC1153095  PMID: 3707523

Abstract

The sugar nucleotide analogue UDP-glucosamine was found to function as a sugar donor in microsomal preparations of both chick-embryo cells and rat liver, yielding dolichyl monophosphate glucosamine (Dol-P-GlcN). This was characterized by t.l.c. and retention by DEAE-cellulose. Glucosamine was the only water-soluble product released on mild acid hydrolysis. Dol-P-GlcN did not serve as substrate by transferring its glucosamine moiety to dolichol-linked oligosaccharide. Competition experiments between UDP-[3H]glucose and UDP-glucosamine showed Dol-P-[3H]glucose synthesis to be depressed by 56 or 73% in microsomes from chick-embryo cells and rat liver respectively. The concentrations of the UDP-sugars in this experiment were comparable with those occurring in galactosamine-metabolizing liver. These findings suggest that Dol-P-GlcN, formed as a metabolite of D-galactosamine, may interfere with Dol-P-dependent reactions.

Full text

PDF
749

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauer C. H., Lukaschek R., Reutter W. G. Studies on the golgi apparatus. Cumulative inhibition of protein and glycoprotein secretion by D-galactosamine. Biochem J. 1974 Aug;142(2):221–230. doi: 10.1042/bj1420221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  3. Datema R., Schwarz R. T. Interference with glycosylation of glycoproteins. Inhibition of formation of lipid-linked oligosaccharides in vivo. Biochem J. 1979 Oct 15;184(1):113–123. doi: 10.1042/bj1840113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Datema R., Schwarz R. T., Jankowski A. W. Fluoroglucose-inhibition of protein glycosylation in vivo. Inhibition of mannose and glucose incorporation into lipid-linked oligosaccharides. Eur J Biochem. 1980 Aug;109(2):331–341. doi: 10.1111/j.1432-1033.1980.tb04799.x. [DOI] [PubMed] [Google Scholar]
  5. Decker K., Keppler D. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol. 1974;(71):77–106. doi: 10.1007/BFb0027661. [DOI] [PubMed] [Google Scholar]
  6. Decker K., Keppler D. Galactosamine induced liver injury. Prog Liver Dis. 1972;4:183–199. [PubMed] [Google Scholar]
  7. Hemming F. W. Dolichol phosphate, a coenzyme in the glycosylation of animal membrane-bound glycoproteins. Biochem Soc Trans. 1977;5(4):1223–1231. doi: 10.1042/bst0051223. [DOI] [PubMed] [Google Scholar]
  8. Holstege A., Schulz-Holstege C., Henninger H., Reiffen K. A., Schneider F., Keppler D. O. Uridylate trapping induced by the C-2-modified D-glucose analogs glucosone, fluoroglucose, and glucosamine. Eur J Biochem. 1982 Jan;121(2):469–474. doi: 10.1111/j.1432-1033.1982.tb05811.x. [DOI] [PubMed] [Google Scholar]
  9. Hubbard S. C., Ivatt R. J. Synthesis and processing of asparagine-linked oligosaccharides. Annu Rev Biochem. 1981;50:555–583. doi: 10.1146/annurev.bi.50.070181.003011. [DOI] [PubMed] [Google Scholar]
  10. Keppler D. O., Rudigier J. F., Bischoff E., Decker K. F. The trapping of uridine phosphates by D-galactosamine. D-glucosamine, and 2-deoxy-D-galactose. A study on the mechanism of galactosamine hepatitis. Eur J Biochem. 1970 Dec;17(2):246–253. doi: 10.1111/j.1432-1033.1970.tb01160.x. [DOI] [PubMed] [Google Scholar]
  11. Keppler D., Lesch R., Reutter W., Decker K. Experimental hepatitis induced by D-galactosamine. Exp Mol Pathol. 1968 Oct;9(2):279–290. doi: 10.1016/0014-4800(68)90042-7. [DOI] [PubMed] [Google Scholar]
  12. Koch H. U., Schwarz R. T., Scholtissek C. Glucosamine itself mediates reversible inhibition of protein glycosylation. A study of glucosamine metabolism at inhibitory concentrations in influenza-virus-infected cells. Eur J Biochem. 1979 Mar;94(2):515–522. doi: 10.1111/j.1432-1033.1979.tb12920.x. [DOI] [PubMed] [Google Scholar]
  13. Krag S. S., Robbins P. W. Sindbis envelope proteins as endogenous acceptors in reactions of guanosine diphosphate-[14C]Mannose with preparations of infected chicken embryo fibroblasts. J Biol Chem. 1977 Apr 25;252(8):2621–2629. [PubMed] [Google Scholar]
  14. Krug E., Zweibaum A., Schulz-Holstege C., Keppler D. D-glucosamine-induced changes in nucleotide metabolism and growth of colon-carcinoma cells in culture. Biochem J. 1984 Feb 1;217(3):701–708. doi: 10.1042/bj2170701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Maley F., McGarrahan J. F., DelGiacco R. Galactosamine: a precursor of glycogen glucosamine. Biochem Biophys Res Commun. 1966 Apr 6;23(1):85–91. doi: 10.1016/0006-291x(66)90273-7. [DOI] [PubMed] [Google Scholar]
  16. Maley F., Tarentino A. L., McGarrahan J. F., Delgiacco R. The metabolism of d-galactosamine and N-acetyl-d-galactosamine in rat liver. Biochem J. 1968 May;107(5):637–644. doi: 10.1042/bj1070637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reynolds R. D., Reutter W. Inhibition of induction of rat liver tyrosine aminotransferase by D-galactosamine. J Biol Chem. 1973 Mar 10;248(5):1562–1567. [PubMed] [Google Scholar]
  18. Scholtissek C., Rott R., Klenk H. D. Two different mechanisms of the inhibition of the multiplication of enveloped viruses by glucosamine. Virology. 1975 Jan;63(1):191–200. doi: 10.1016/0042-6822(75)90384-0. [DOI] [PubMed] [Google Scholar]
  19. Schwarz R. T., Datema R. Inhibition of the dolichol pathway of protein glycosylation. Methods Enzymol. 1982;83:432–443. doi: 10.1016/0076-6879(82)83041-3. [DOI] [PubMed] [Google Scholar]
  20. Schwarz R. T., Datema R. The lipid pathway of protein glycosylation and its inhibitors: the biological significance of protein-bound carbohydrates. Adv Carbohydr Chem Biochem. 1982;40:287–379. doi: 10.1016/s0065-2318(08)60111-0. [DOI] [PubMed] [Google Scholar]
  21. Schwarz R. T., Schmidt M. F., Datema R. Inhibition of glycosylation of viral glycoproteins. Biochem Soc Trans. 1979 Apr;7(2):322–326. doi: 10.1042/bst0070322. [DOI] [PubMed] [Google Scholar]
  22. Sharma C. B., Babczinski P., Lehle L., Tanner W. The role of dolicholmonophosphate in glycoprotein biosynthesis in Saccharomyces cerevisiae. Eur J Biochem. 1974 Jul 1;46(1):35–41. doi: 10.1111/j.1432-1033.1974.tb03594.x. [DOI] [PubMed] [Google Scholar]
  23. Shidoji Y., De Luca L. M. Rat liver microsomes catalyse mannosyl transfer from GDP-D-mannose to retinyl phosphate with high efficiency in the absence of detergents. Biochem J. 1981 Dec 15;200(3):529–538. doi: 10.1042/bj2000529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tarentino A. L., Maley F. Direct evidence that D-galactosamine incorporation into glycogen occurs via UDP-glucosamine. FEBS Lett. 1976 Oct 15;69(1):175–178. doi: 10.1016/0014-5793(76)80680-1. [DOI] [PubMed] [Google Scholar]
  25. Weckbecker G., Keppler D. O. Dual role of hexose-1-phosphate uridylyltransferase in galactosamine metabolism. Eur J Biochem. 1982 Nov;128(1):163–168. doi: 10.1111/j.1432-1033.1982.tb06947.x. [DOI] [PubMed] [Google Scholar]
  26. Weckbecker G., Keppler D. O. Separation and analysis of 4'-epimeric UDP-sugars by borate high-performance liquid chromatography. Anal Biochem. 1983 Jul 15;132(2):405–412. doi: 10.1016/0003-2697(83)90027-1. [DOI] [PubMed] [Google Scholar]
  27. Weckbecker G., Keppler D. O. Substrate properties of 5-fluorouridine diphospho sugars detected in hepatoma cells. Biochem Pharmacol. 1984 Jul 15;33(14):2291–2298. doi: 10.1016/0006-2952(84)90669-5. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES