Biology:Globotriaosylceramide
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
- ↑ globotriaosylceramide at the US National Library of Medicine Medical Subject Headings (MeSH)
- ↑ "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. doi:10.2174/187152506778520718. PMID 17073606. http://www.bentham-direct.org/pages/content.php?CHAMC/2006/00000004/00000004/002AE.SGM.
- ↑ 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.
- ↑ 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. e6813.
- ↑ Geyer, Philipp Emanuel; Maak, Matthias; Nitsche, Ulrich; Perl, Markus; Novotny, Alexander; Slotta-Huspenina, Julia; Dransart, Estelle; Holtorf, Anne et al. (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.
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