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Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells

Nature Chemical Biology volume 2, pages 195–196 (2006)Cite this article

Abstract

Biosynthesis of heparin, a mast cell–derived glycosaminoglycan with widespread importance in medicine, has not been fully elucidated. In biosynthesis of heparan sulfate (HS), a structurally related polysaccharide, HS glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) residues. We have generated Hsepi-null mouse mutant mast cells, and we show that the same enzyme catalyzes the generation of IdoA in heparin and that 'heparin' lacking IdoA shows a distorted O-sulfation pattern.

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Figure 1: Structural analysis of heparin from mast cells.

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Acknowledgements

We thank A. Tietz and E. Gottfridsson for expert technical assistance and H.J. Fehling for discussions. This work was supported by the Swedish Research Council (32X-15023), the Swedish Cancer Society (4708-B02-01XAA), the European Commission (QLK3-CT-2002-02049), Polysackaridforskning AB (Uppsala, Sweden) (UL, JPL) and the Deutsche Forschungsgemeinschaft (DFG-RO754/2-2) (THF, HRR).

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Author notes

  1. Thorsten B Feyerabend and Jin-Ping Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, University of Ulm, Ulm, D-89070, Germany

    Thorsten B Feyerabend & Hans-Reimer Rodewald

  2. Department of Medical Biochemistry and Microbiology, University of Uppsala, The Biomedical Center, Box 582, Uppsala, SE-751 23, Sweden

    Jin-Ping Li & Ulf Lindahl

Authors
  1. Thorsten B Feyerabend
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  2. Jin-Ping Li
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  3. Ulf Lindahl
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  4. Hans-Reimer Rodewald
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Corresponding authors

Correspondence to Jin-Ping Li or Hans-Reimer Rodewald.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Generation of Hsepi-deficient mast cells. (PDF 1442 kb)

Supplementary Table 1

Disaccharide composition of heparin isolated from Hsepi+/+ or Hsepi−/− mast cells. (PDF 67 kb)

Supplementary Methods (PDF 88 kb)

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Feyerabend, T., Li, JP., Lindahl, U. et al. Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells. Nat Chem Biol 2, 195–196 (2006). https://doi.org/10.1038/nchembio777

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