Application Notes:
Glucosylsphingosine is the lyso-derivative of the common glycolipid glucocerebroside. 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 glucosylsphingosine
beta-glucosidase, the enzyme responsible for cleaving off the glucose of glucosylsphingosine 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 glucopsychosine.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