Application Notes:
Glucosylsphingosine is the lyso-derivative of the common glycolipid glucocerebroside. This product is a stable isotope
labeled standard containing six carbon-13 units on the glucose moiety. Glucosylceramide and glucosylsphingosine are
important biological species that are the precursors for many complex glycosphingolipids. These lipids are involved in
critical cellular functions such as cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions,
tumorigenesis, and metastasis. One of the most important roles of glucosylsphingosine is as a biomarker for the lysosomal
storage disorder Gaucher disease.
Gaucher disease is characterized by an accumulation of glucocerebroside due to a deficiency in the enzyme
glucocerebrosidase and it has now been found that glucosylsphingosine also accumulates in this disease.1 This accumulation
of glucosylsphingosine contributes to neuronal dysfunction and destruction in patients with neuronopathic Gaucher disease2
and it has been found to be a potent inhibitor of glucocerebrosidase. At least some instances of Gaucher disease also have a
deficiency in the activity of glucopsychosine beta-glucosidase, the enzyme responsible for cleaving off the glucose of
glucopsychosine and glucocerebroside. Like glucocerebroside and galactocerebroside, glucosylsphingosine can increase Ca2
+
mobilization from intracellular stores although it uses a different mechanism.3 Conduritol B epoxide (CBE), an inhibitor of
beta-glucosidase, and l-phenyl-2-decanoylamino-3-morpholino-l-propanol (PDMP), an inhibitor of glucosylceramide
synthase, can be used to create a model of Gaucher disease and consequently an accumulation of glucosylsphingosine.4
References:
1. E. Orvisky et al. “Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype” Molecular
genetics and metabolism, Vol. 76(4) pp. 262-270, 2002
2. R. Brady et al. “Toxicity of glucosylsphingosine (glucopsychosine) to cultured neuronal cells: a model system for assessing neuronal damage in Gaucher
disease type 2 and 3” Neurobiology of Disease, Vol. 14(3) pp. 595-601, 2003
3. E. Loyd-Evans et al. “Glucosylceramide and Glucosylsphingosine Modulate Calcium Mobilization from Brain Microsomes via Different Mechanisms”
The Journal of Biological Chemistry, Vol. 278 pp. 23594-23599, 2003
4. D. Sillance et al. “Glucosylceramide modulates membrane traffic along the endocytic pathway” Journal of Lipid Research, Vol. 43 pp. 1837-1845, 2002