Globotriaosylceramide

Globotriaosylceramide (R is a carbon chain)

Globotriaosylceramide is a globoside.^[1] It is also known as CD77, Gb3, GL3, and ceramide trihexoside.^[2] It is one of the few clusters of differentiation that is not a protein.

It is formed by the alpha linkage of galactose to lactosylceramide catalyzed by A4GALT.

It is metabolized by alpha-galactosidase, which hydrolyzes the terminal alpha linkage.

Clinical significance

Defects in the enzyme alpha-galactosidase lead to the buildup of globotriaosylceramide, causing Fabry's disease.^[3] The pharmaceutical drug migalastat enhances the function of alpha-galactosidase and is used to treat Fabry's.

Globotriaosylceramide is also one of the targets of Shiga toxin, which is responsible for pathogenicity of enterohemorrhagic Escherichia coli (EHEC).^{[citation needed]}

The bacterial Shiga toxin can be used for targeted therapy of certain gastrointestinal cancers that express the receptor of the Shiga toxin.^[4] For this purpose a non-specific chemotherapeutic agent is conjugated to the B-subunit to make it specific. In this way only the tumor cells, but not healthy cells, should be destroyed during therapy.^[5]

References

1. globotriaosylceramide at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
2. Bekri S, Lidove O, Jaussaud R, Knebelmann B, Barbey F (October 2006). "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. doi:10.2174/187152506778520718. PMID 17073606. Archived from the original on 2013-04-14.
3. Desnick RJ, Ioannou YA, Eng CM. a-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic & molecular bases of inherited disease. 8th ed. Vol. 3. New York: McGraw-Hill, 2001:3733-74.
4. Distler, Ute; Souady, Jamal; Hülsewig, Marcel; Drmić-Hofman, Irena; Haier, Jörg; Friedrich, Alexander W.; et al. (2009). "Shiga toxin receptor Gb3Cer/CD77: Tumor-association and promising therapeutic target in pancreas and colon cancers". PLoS One. 4 (8). doi:10.1371/journal.pone.0006813. PMC 2730034. e6813.
5. Geyer, Philipp Emanuel; Maak, Matthias; Nitsche, Ulrich; Perl, Markus; Novotny, Alexander; Slotta-Huspenina, Julia; Dransart, Estelle; Holtorf, Anne; Johannes, Ludger; Janssen, Klaus-Peter (2016). "Gastric adenocarcinomas express the glycosphingolipid Gb₃/CD77: Targeting of gastric cancer cells with Shiga toxin B-subunit". Molecular Cancer Therapeutics. 15 (5): 1008–1017. doi:10.1158/1535-7163.MCT-15-0633.