Advertisement

Chondroitin Sulfate Biosynthesis and Related Genes

  • Hideto Watanabe
  • Koji Kimata

Abstract

Chondroitin sulfate (CS) comprises repeating disaccharide units of N-acetylgalactosamine (GalNAc) and glucuronic acid (GlcA) residues with sulfate residues at different positions. CS biosynthesis (Fig. 1) is initiated by the transfer of a GalNAc residue to the linkage region of a GlcA-β1, 3-galactose (Gal)-β1, 3-Gal-β1,4-Xyl tetrasaccharide primer that is attached to a serine residue of the core protein. Then, chain elongation occurs by the alternate addition of GalNAc and GlcA residues. Enzyme activities that catalyze the initiation and elongation processes are termed as glycosyltransferase-I and II activities, respectively. To date, six glycosyltransferases involved in CS synthesis have been identified (Fig. 2): chondroitin sulfate synthase-1 (CSS-1)/chondroitin synthase (CSy) (Kitagawa et al. 2001), chondroitin sulfate synthase-2 (CSS-2)/chondroitin polymerizing factor (ChPF) (Yada et al. 2003), chondroitin sulfate synthase-3 (CSS-3), chondroitin sulfate glucuronyltransferase (CSGlcAT) (Gotoh et al. 2002a), chondroitin sulfate N-acetylgalactosaminyltransferase-1 (Gotoh et al. 2002b), and 2 (Sato et al. 2003) (CSGalNAcT-1, 2). All these enzymes have an N-terminal transmembrane domain and are localized to the Golgi apparatus where CS biosynthesis takes place. CSS-1, CSS-2, CSS-3, and CSGlcAT form a family of glycosyltransferase enzymes. CSS-1, CSS-2, and CSS-3 contain two glycosyltransferase domains and exhibit both N-acetylgalactosaminyltransferase (GalNAcT) and glucuronyltransferase (GlcAT) activities in chain elongation. Thus, they have glycosyltransferase-II (both GalNAcT-II and GlcAT-II) activity. CSGlcAT has an inactive GalNAcT domain and exhibits only GlcAT-II activity.

Keywords

Chondroitin Sulfate Glucuronic Acid Chain Elongation Elongation Process Sulfate Residue 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kitagawa H, Uyama T, Sugahara K (2001) Molecular cloning and expression of human chondroitin synthase. J Biol Chem 276:38721–38726PubMedCrossRefGoogle Scholar
  2. Gotoh M, Yada T, Sato T, Akashima T, Iwasaki H, Mochizuki H, Inaba N, Togayachi A, Kudo T, Watanabe H, Kimata K, Narimatsu H (2002a) Molecular cloning and characterization of a novel chondroitin sulfate glucuronyltransferase that transfers glucuronic acid to N-acetylgalactosamine. J Biol Chem 277:38179–38188PubMedCrossRefGoogle Scholar
  3. Gotoh M, Sato T, Akashima T, Iwasaki H, Kameyama A, Mochizuki H, Yada T, Inaba N, Zhang Y, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Nishihara S, Watanabe H, Kimata K, Narimatsu H (2002b) Enzymatic synthesis of chondroitin with a novel chondroitin sulfate N-acetylgalactosaminyltransferase that transfers N-acetylgalactosamine to glucuronic acid in initiation and elongation of chondroitin sulfate synthesis. J Biol Chem 277:38189–38196PubMedCrossRefGoogle Scholar
  4. Sato T, Gotoh M, Kiyohara K, Akashima T, Iwasaki H, Kameyama A, Mochizuki H, Yada T, Inaba N, Togayachi A, Kudo T, Asada M, Watanabe H, Imamura T, Kimata K, Narimatsu H (2003) Differential roles of two N-acetylgalactosaminyltransferases, CSGalNAcT-1, and a novel enzyme, CSGalNAcT-2. Initiation and elongation in synthesis of chondroitin sulfate. J Biol Chem 278:3063–3071PubMedCrossRefGoogle Scholar
  5. Yada T, Gotoh M, Sato T, Shionyu M, Go M, Kaseyama H, Iwasaki H, Kikuchi N, Kwon Y D, Togayachi A, Kudo T, Watanabe H, Narimatsu H, Kimata K (2003) Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities. J Biol Chem 278:30235–30247PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Hideto Watanabe
    • 1
  • Koji Kimata
    • 1
  1. 1.Institute for Molecular Science of MedicineAichi Medical UniversityNagakute, AichiJapan

Personalised recommendations