Glycobiology Advance Access originally published online on January 12, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Glycobiology vol 14 no 5 pp. 443-450, 2004
Glycobiology vol. 14 no. 5 © Oxford University Press 2004; all rights reserved.
Glycosaminoglycan degradation fragments in mucopolysaccharidosis I
Lysosomal Diseases Research Unit, Department of Genetic Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia, 5006; and Department of Paediatrics, University of Adelaide, South Australia, 5005
Received on October 15, 2003; revised on December 1, 2003; accepted on December 15, 2003
The catabolism of glycosaminoglycans begins with endohydrolysis of polysaccharides to oligosaccharides followed by the sequential action of an array of exoenzymes to reduce these oligosaccharides to monosaccharides and inorganic sulfate. In a lysosomal storage disorder known as mucopolysaccharidosis I, caused by a deficiency of the exohydrolase 
-L-iduronidase, fragments of two different glycosaminoglycans, dermatan sulfate and heparan sulfate, have been shown to accumulate. Oligosaccharides isolated from the urine of a mucopolysaccharidosis I patient using anion exchange and gel filtration chromatography were identified as di-, tri-, tetra-, penta-, and hexasaccharides using electrospray ionization–tandem mass spectrometry and shown to have nonreducing terminal -L-iduronate residues, susceptible to digestion with -L-iduronidase. The presence of odd and even oligosaccharides suggests both endo-ß-glucuronidase and endo-N-acetylhexosaminidase activities toward both glycosaminoglycans. Cultured skin fibroblasts from mucopolysaccharidosis I patients accumulate the same dermatan sulfate–and heparan sulfate–derived di- and trisaccharides as identified in urine, and supplementation of culture medium with recombinant -L-iduronidase reduced their level to that of unaffected control fibroblasts. A dermatan-derived tetrasaccharide not elevated in mucopolysaccharidosis I fibroblasts transiently increased in these fibroblasts in the presence of recombinant -L-iduronidase, indicating it is an intermediate product of catabolism. These oligosaccharides were elevated in urine samples from mucopolysaccharidosis I patients, and we suggest that these glycosaminoglycan-derived oligosaccharides may be useful biochemical markers for the identification and the clinical management of mucopolysaccharidosis I patients.
1 To whom correspondence should be addressed; e-mail: maria.fuller{at}adelaide.edu.au
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. C Nielsen, P. J Meikle, J. J Hopwood, and M. Fuller Minimum substrate requirements of endoglycosidase activities toward dermatan sulfate by electrospray ionization-tandem mass spectrometry Glycobiology, December 1, 2008; 18(12): 1119 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fuller, A. Chau, R. C. Nowak, J. J. Hopwood, and P. J. Meikle A defect in exodegradative pathways provides insight into endodegradation of heparan and dermatan sulfates Glycobiology, April 1, 2006; 16(4): 318 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Nandini, T. Mikami, M. Ohta, N. Itoh, F. Akiyama-Nambu, and K. Sugahara Structural and Functional Characterization of Oversulfated Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from the Notochord of Hagfish: NEURITOGENIC AND BINDING ACTIVITIES FOR GROWTH FACTORS AND NEUROTROPHIC FACTORS J. Biol. Chem., December 3, 2004; 279(49): 50799 - 50809. [Abstract] [Full Text] [PDF]
|
|