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FEBS Lett. 2016 Mar;590(6):716-25. doi: 10.1002/1873-3468.12104. Epub 2016 Mar 3.

Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases.

Author information

1
Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
2
Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, The Netherlands.
3
Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, The Netherlands.

Abstract

Glycosphingoid bases are elevated in inherited lysosomal storage disorders with deficient activity of glycosphingolipid catabolizing glycosidases. We investigated the molecular basis of the formation of glucosylsphingosine and globotriaosylsphingosine during deficiency of glucocerebrosidase (Gaucher disease) and α-galactosidase A (Fabry disease). Independent genetic and pharmacological evidence is presented pointing to an active role of acid ceramidase in both processes through deacylation of lysosomal glycosphingolipids. The potential pathophysiological relevance of elevated glycosphingoid bases generated through this alternative metabolism in patients suffering from lysosomal glycosidase defects is discussed.

KEYWORDS:

Fabry disease; Gaucher disease; acid ceramidase; globotriaosylsphingosine; glucosylsphingosine; glycosphingolipids

PMID:
26898341
DOI:
10.1002/1873-3468.12104
[Indexed for MEDLINE]
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