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Open AccessArticle

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