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Heparan Sulfate Synthases and Related Genes

  • Shuji Mizumoto
  • Hiroshi Kitagawa

Abstract

Heparan sulfate (HS) and heparin (HP) are linear polysaccharides composed of repeating disaccharide units, [-4GlcAβ1(IdoAα1)-4GlcNAcα1-]n, where GlcA, IdoA, and GlcNAc represent glucuronic acid, iduronic acid, and N-acetylglucosamine, respectively, which are covalently linked to specific core proteins through the glycosaminoglycan (GAG)-protein linkage region tetrasaccharide, GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O-Ser (where Gal, Xyl, and Ser stand for galactose, xylose, and serine, respectively) forming proteoglycans (PGs). HS and HP backbones are synthesized by five glycosyltransferases, human exostosin (EXT) family members, which are associated with hereditary multiple exostoses (HME). Subsequently, HS and HP are modified by GlcNAc N-deacetylase/Nsulfotransferase, GlcA C5-epimerase, and O-sulfotransferases, resulting in the formation of functional domains and/or sequences (Mizumoto et al. 2005).

Keywords

Heparan Sulfate Hereditary Multiple Exostosis Heparan Sulfate Chain Iduronic Acid Repeat Disaccharide Unit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Izumikawa T, Egusa N, Taniguchi F, Sugahara, K, Kitagawa H (2006) Heparan sulfate polymerization in Drosophila. J Biol Chem 281:1929–1934PubMedCrossRefGoogle Scholar
  2. Kitagawa H, Izumikawa T, Mizuguchi S, Dejima K, Nomura KH, Egusa N, Taniguchi F, Tamura J, Gengyo-Ando K, Mitani S, Nomura K, Sugahara K (2007) Expression of rib-1, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes is indispensable for heparan sulfate synthesis and embryonic morphogenesis. J Biol Chem 282:8533–8544PubMedCrossRefGoogle Scholar
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  4. Mizumoto S, Kitagawa H, Sugahara K (2005) Biosynthesis of heparin and heparan sulfate. In: Garg HG, Linhardt RJ, Hales CA (eds) Chemistry and biology of heparin and heparan sulfate. Elsevier, Oxford, pp 203–243CrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Shuji Mizumoto
    • 1
  • Hiroshi Kitagawa
    • 2
  1. 1.Laboratory of Proteoglycan Signaling and Therapeutics, Faculty of Advanced Life SciencesHokkaido University, Frontier Research Center for Post-Genomic Science and TechnologySapporoJapan
  2. 2.Department of BiochemistryKobe Pharmaceutical UniversityKobeJapan

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