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Metabolites 2014, 4(4), 1088-1100; doi:10.3390/metabo4041088

Distribution of Heparan Sulfate Oligosaccharides in Murine Mucopolysaccharidosis Type IIIA

1
Forensic Science South Australia, 21 Divett Place, Adelaide, South Australia 5000, Australia
2
Baker ID Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3006, Australia
3
SAHMRI, North Terrace, Adelaide, South Australia, 5000 Australia
4
SA Pathology at Women's and Children's Hospital, 72 King William Road, North Adelaide 5006, Australia
*
Author to whom correspondence should be addressed.
Received: 22 September 2014 / Revised: 27 November 2014 / Accepted: 3 December 2014 / Published: 11 December 2014
(This article belongs to the Special Issue Inborn Errors of Metabolism)
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Abstract

Heparan sulfate (HS) catabolism begins with endo-degradation of the polysaccharide to smaller HS oligosaccharides, followed by the sequential action of exo-enzymes to reduce these oligosaccharides to monosaccharides and inorganic sulfate. In mucopolysaccharidosis type IIIA (MPS IIIA) the exo-enzyme, N-sulfoglucosamine sulfohydrolase, is deficient resulting in an inability to hydrolyze non-reducing end glucosamine N-sulfate esters. Consequently, partially degraded HS oligosaccharides with non-reducing end glucosamine sulfate esters accumulate. We investigated the distribution of these HS oligosaccharides in tissues of a mouse model of MPS IIIA using high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Oligosaccharide levels were compared to total uronic acid (UA), which was used as a measure of total glycosaminoglycan. Ten oligosaccharides, ranging in size from di- to hexasaccharides, were present in all the tissues examined including brain, spleen, lung, heart, liver, kidney and urine. However, the relative levels varied up to 10-fold, suggesting different levels of HS turnover and storage. The relationship between the di- and tetrasaccharides and total UA was tissue specific with spleen and kidney showing a different disaccharide:total UA ratio than the other tissues. The hexasaccharides showed a stronger correlation with total UA in all tissue types suggesting that hexasaccharides may more accurately reflect the storage burden in these tissues. View Full-Text
Keywords: lysosomal storage disorder; mouse model; mucopolysaccharidosis type IIIA; heparan sulfate; oligosaccharides; reverse phase high performance liquid chromatography; electrospray ionization-tandem mass spectrometry lysosomal storage disorder; mouse model; mucopolysaccharidosis type IIIA; heparan sulfate; oligosaccharides; reverse phase high performance liquid chromatography; electrospray ionization-tandem mass spectrometry
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mason, K.; Meikle, P.; Hopwood, J.; Fuller, M. Distribution of Heparan Sulfate Oligosaccharides in Murine Mucopolysaccharidosis Type IIIA. Metabolites 2014, 4, 1088-1100.

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