Biosynthesis of heparan sulfate on β-D-xylosides depends on aglycone structure

Timothy A. Fritz, Fulgentius Nelson Lugemwa, Arun K. Sarkar, Jeffrey D. Esko

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Abstract

We have reported that 3-estradiol-β-D-xyloside primes heparan sulfate synthesis in Chinese hamster ovary cells and that the proportion of heparan sulfate made rises with increasing concentration of xyloside (Lugemwa, F. N. and Esko, J. D. (1991) J. Biol. Chem. 266, 6674-6677). Using estradiol as a guide, we varied the structure of the aglycone and showed that β-D- xylosides containing two fused aromatic rings efficiently prime heparan sulfate. Thus, 2-naphthol-β-D-xyloside primed heparan sulfate at low dose (≤10 μM) and the proportion of heparan sulfate increased with concentration (up to 50% of total glycosaminoglycan). Various ring additions and heterocyclic ring substitutions altered the efficiency of heparan sulfate priming, but had no effect on the overall level of glycosaminoglycan synthesis. Replacement of the bridging oxygen with sulfur (2- naphthalenethiol-β-D-xyloside) increased the efficiency of heparan sulfate priming. Priming of heparan sulfate correlated with hydrophobicity of the xyloside, but several exceptions suggested that the chemical structure of the aglycone played an equally important role. Interestingly, the heparan sulfate chains generated on 2-naphthol-β-D-xyloside showed a 2-fold decrease in the proportion of disaccharides containing 6-O-sulfate groups and a striking diminution in non-sulfated iduronic acid containing disaccharides compared to the chains attached to cellular proteoglycans. Thus, both the type of glycosaminoglycan made on a xyloside and its fine structure depends on the aglycone.

Original languageEnglish (US)
Pages (from-to)300-307
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number1
StatePublished - Jan 7 1994

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Heparitin Sulfate
Biosynthesis
Glycosaminoglycans
Disaccharides
Estradiol
Iduronic Acid
xylosides
Proteoglycans
Hydrophobicity
Cricetulus
Hydrophobic and Hydrophilic Interactions
Sulfur
Sulfates
Ovary
Substitution reactions
Cells
Oxygen

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fritz, Timothy A. ; Lugemwa, Fulgentius Nelson ; Sarkar, Arun K. ; Esko, Jeffrey D. / Biosynthesis of heparan sulfate on β-D-xylosides depends on aglycone structure. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 1. pp. 300-307.
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Biosynthesis of heparan sulfate on β-D-xylosides depends on aglycone structure. / Fritz, Timothy A.; Lugemwa, Fulgentius Nelson; Sarkar, Arun K.; Esko, Jeffrey D.

In: Journal of Biological Chemistry, Vol. 269, No. 1, 07.01.1994, p. 300-307.

Research output: Contribution to journalArticle

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