Application Notes:
Ceramide trihexoside (CTH) is a glycosphingolipid found mostly in mammalian cell membranes. It is involved in cellular
signaling and has been identified as a receptor for various toxins including shiga toxins and shiga-like toxins.1 Some toxins,
such as veratoxins from Escherichia coli, require specific fatty acids on the ceramide portion of CTH to show affinity in
binding. An accumulation of CTH in the cellular membranes due to a lack of alpha-galactosidase to convert it into lactosyl
ceramide results in Fabry disease.2 This product can be used as an excellent standard for the identification of CTH in Fabry
disease by HPLC3 and mass spectrometry.4 An inability to convert CTH to globoside due to mutations in the gene sequence
leads to the Pk blood group phenotype. It appears that under certain conditions CTH can enhance anticoagulant activity. CTH
has also been studied as a tool to investigate lymphocyte activation.5 Neutral glycolipids may help to cause resistance to
natural killer cells in some types of cells. Interferon appears to slightly increase the resistance of cells towards natural killer
cells and also increases the amounts of non-hydroxylated fatty acids on various glycolipids, suggesting that there may be a
connection between the hydroxylated fatty acids and natural killer cell resistance.
References:
1. S. Ashkenazi and T. G. Cleary, “Rapid method to detect shiga toxin and shiga-like toxin I based on binding to globotriosyl ceramide (Gb3), their natural
receptor.” J Clin Microbio. June; 27(6): 1145-1150, 1989
2. S. Bekri, O. Lidove, R. Jaussaud, B. Knebelmann, F. Barbey. "The role of ceramide trihexoside (globotriaosylceramide) in the diagnosis and follow-up of
the efficacy of treatment of Fabry disease: a review of the literature". Cardiovasc Hematol Agents Med Chem 4 (4): 289–97, October 2006
3. J. E. Groener, B. J. Poorthuis, S. Kuiper, M. T. Helmond, C. E. Hollak, J. M. Aerts. “HPLC for simultaneous quantification of total ceramide,
glucosylceramide, and ceramide trihexoside concentrations in plasma.” Clin Chem., Apr;53(4):742-7, 2007. Epub Mar 1 2007
4. K. Mills, A. Johnson, B. Winchester. “Synthesis of novel internal standards for the quantitative determination of plasma ceramide trihexoside in Fabry
disease by tandem mass spectrometry.” FEBS Lett., Mar 27;515(1-3):171-6, 2002
5. C. Menge, I. Stamm, M. Wuhrer, R. Geyer, L. H. Wieler, G. Baljer. “Globotriaosylceramide (Gb(3)/CD77) is synthesized and surface expressed by
bovine lymphocytes upon activation in vitro.” Vet Immunol Immunopathol., Nov;83(1-2):19-36, 2001