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Emerging concepts of ganglioside metabolism
Author(s) -
Sandhoff Roger,
Sandhoff Konrad
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13114
Subject(s) - ganglioside , metabolism , chemistry , biochemistry , computational biology , biology
Gangliosides ( GG s) are sialic acid‐containing glycosphingolipids ( GSL s) and major membrane components enriched on cellular surfaces. Biosynthesis of mammalian GG s starts at the cytosolic leaflet of endoplasmic reticulum ( ER ) membranes with the formation of their hydrophobic ceramide anchors. After intracellular ceramide transfer to Golgi and trans‐Golgi network ( TGN ) membranes, anabolism of GG s, as well as of other GSL s, is catalyzed by membrane‐spanning glycosyltransferases ( GT s) along the secretory pathway. Combined activity of only a few promiscuous GT s allows for the formation of cell‐type‐specific glycolipid patterns. Following an exocytotic vesicle flow to the cellular plasma membranes, GG s can be modified by metabolic reactions at or near the cellular surface. For degradation, GG s are endocytosed to reach late endosomes and lysosomes. Whereas membrane‐spanning enzymes of the secretory pathway catalyze GSL and GG formation, a cooperation of soluble glycosidases, lipases and lipid‐binding cofactors, namely the sphingolipid activator proteins ( SAP s), act as the main players of GG and GSL catabolism at intralysosomal luminal vesicles ( ILV s).