A defect in exodegradative pathways provides insight into endodegradation of heparan and dermatan sulfates

Maria Fuller, Ally Chau, Rachael C. Nowak, John J. Hopwood, Peter J. Meikle

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Within cells, dermatan sulfate (DS) and heparan sulfate (HS) are degraded in two steps. The initial endohydrolysis of these polysaccharides is followed by the sequential action of lysosomal exoenzymes to reduce the resulting oligosaccharides to monosaccharides and inorganic sulfate. Mucopolysaccharidosis (MPS) type II is a lysosomal storage disorder caused by a deficiency of the exoenzyme iduronate-2-sulfatase (I2S). Consequently, partially degraded fragments of DS and HS have been shown to accumulate in the lysosomes of affected cells and are excreted in the urine. Di- to hexadecasaccharides, isolated from the urine of a MPS II patient using anion exchange and gel filtration chromatography, were identified using electrospray ionization-tandem mass spectrometry (ESI-MS/MS). These oligosaccharides were shown to have non-reducing terminal iduronate-2-sulfate residues by digestion with recombinant I2S. A pattern of growing oligosaccharide chains composed of alternating uronic acid and T=N-acetylhexosamine residues was identified and suggested to originate from DS. A series of oligosaccharides consisting of hexosamine/T=N-acetylhexosamine alternating with uronic acid residues was also identified and on the basis of the presence of unacetylated hexosamine; these oligosaccharides are proposed to derive from HS. The presence of both odd and even-length oligosaccharides suggests both endo-β-glucuronidase and endo-T=N-acetylhexosaminidase activities toward both glycosaminoglycans. Furthermore, the putative HS oligosaccharide structures identified indicate that heparanase activities are directed toward regions of both low and high sulfation, while the N-acetylhexosaminidase activity acted only in regions of low sulfation in this polysaccharide.

LanguageEnglish
Pages318-325
Number of pages8
JournalGlycobiology
Volume16
Issue number4
DOIs
Publication statusPublished - 1 Apr 2006
Externally publishedYes

Keywords

  • Dermatan sulfate
  • Endohydrolase
  • Glycosaminoglycans
  • Heparan sulfate
  • Mucopolysaccharidosis II

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fuller, Maria ; Chau, Ally ; Nowak, Rachael C. ; Hopwood, John J. ; Meikle, Peter J. / A defect in exodegradative pathways provides insight into endodegradation of heparan and dermatan sulfates. In: Glycobiology. 2006 ; Vol. 16, No. 4. pp. 318-325.
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abstract = "Within cells, dermatan sulfate (DS) and heparan sulfate (HS) are degraded in two steps. The initial endohydrolysis of these polysaccharides is followed by the sequential action of lysosomal exoenzymes to reduce the resulting oligosaccharides to monosaccharides and inorganic sulfate. Mucopolysaccharidosis (MPS) type II is a lysosomal storage disorder caused by a deficiency of the exoenzyme iduronate-2-sulfatase (I2S). Consequently, partially degraded fragments of DS and HS have been shown to accumulate in the lysosomes of affected cells and are excreted in the urine. Di- to hexadecasaccharides, isolated from the urine of a MPS II patient using anion exchange and gel filtration chromatography, were identified using electrospray ionization-tandem mass spectrometry (ESI-MS/MS). These oligosaccharides were shown to have non-reducing terminal iduronate-2-sulfate residues by digestion with recombinant I2S. A pattern of growing oligosaccharide chains composed of alternating uronic acid and T=N-acetylhexosamine residues was identified and suggested to originate from DS. A series of oligosaccharides consisting of hexosamine/T=N-acetylhexosamine alternating with uronic acid residues was also identified and on the basis of the presence of unacetylated hexosamine; these oligosaccharides are proposed to derive from HS. The presence of both odd and even-length oligosaccharides suggests both endo-β-glucuronidase and endo-T=N-acetylhexosaminidase activities toward both glycosaminoglycans. Furthermore, the putative HS oligosaccharide structures identified indicate that heparanase activities are directed toward regions of both low and high sulfation, while the N-acetylhexosaminidase activity acted only in regions of low sulfation in this polysaccharide.",
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A defect in exodegradative pathways provides insight into endodegradation of heparan and dermatan sulfates. / Fuller, Maria; Chau, Ally; Nowak, Rachael C.; Hopwood, John J.; Meikle, Peter J.

In: Glycobiology, Vol. 16, No. 4, 01.04.2006, p. 318-325.

Research output: Contribution to journalArticle

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