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Gangliosides pp 97-141 | Cite as

Ganglioside Metabolism and Its Inherited Diseases

  • Bernadette Breiden
  • Konrad SandhoffEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1804)

Abstract

Gangliosides are sialic acid containing glycosphingolipids, which are abundant in mammalian brain tissue. Several fatal human diseases are caused by defects in glycolipid metabolism. Defects in their degradation lead to an accumulation of metabolites upstream of the defective reactions, whereas defects in their biosynthesis lead to diverse problems in a large number of organs.

Gangliosides are primarily positioned with their ceramide anchor in the neuronal plasma membrane and the glycan head group exposed on the cell surface. Their biosynthesis starts in the endoplasmic reticulum with the formation of the ceramide anchor, followed by sequential glycosylation reactions, mainly at the luminal surface of Golgi and TGN membranes, a combinatorial process, which is catalyzed by often promiscuous membrane-bound glycosyltransferases.

Thereafter, the gangliosides are transported to the plasma membrane by exocytotic membrane flow. After endocytosis, they are degraded within the endolysosomal compartments by a complex machinery of degrading enzymes, lipid-binding activator proteins, and negatively charged lipids.

Keywords

Glycosphingolipids Biosynthesis Catabolism Bis(monoacylglycero)phosphate Sialic acid Membranes Luminal vesicles Ceramide Gangliosidosis 

Notes

Acknowledgments

We thank Roger Sandhoff and Christina Schuette for helpful corrections and discussions. This work was supported by German Research Foundation Grants SFB 645 and TRR83.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.LIMES Institute, Membrane Biology & Lipid Biochemistry Unit, Kekulé-Institut für Organische Chemie und BiochemieUniversität BonnBonnGermany

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