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. 2020 Sep 19;21(18):6881. doi: 10.3390/ijms21186881

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Pathways of glycosphingolipid (GSL) biosynthesis. (A). Lacto series GSLs. Lactosylceramide (LacCer) is the common intermediate for lacto, globo and ganglio series GSLs. The lacto series GSLs can have numerous different extensions and can carry glycan epitopes and antigens. Addition of GlcNAc to LacCer produces the precursor to all neo-lacto series GSLs, known as lactotriaosylceramide (Lc3). Lc3 is extended by the substitution of GlcNAc by a Galβ1-4 residue. The names of enzymes involved are indicated near the arrows. (B). Gal-ceramide series GSLs. Gal is added to ceramide by Cer-β-Gal-transferase UGT8 and reaction product GalCer can then undergo at least three different substitutions. (C). Globo series GSLs. The globosides are first produced by substitution of the Gal residue of LacCer with a Galα1-4 residue to yield globotriaosylceramide (Gb3). Addition of GalNAc in β1-3 linkage to Gb3 forms globotetraosylceramide (Gb4). The iso-globo series contains Galα1-3 instead of Galα1-4. (D). Ganglioseries-α GSLs. LacCer is the precursor for neutral GSLs, GA2 and GA1, and for all gangliosides. The addition of sialic acid in α2-6 linkage to GalNAc forms the α series of compounds. Here we show the synthesis of GD1α from GM1b. (E). Ganglio series a, b and c GSLs. The GM3 synthase ST3GAL V adds a sialic acid in α2-3 linkage to the Gal residue of LacCer to form GM3. The series that carries one sialic acid on Galβ1-4 is named ganglio a-series. Gangliosides having sialylα2-8sialylα2-3 substitutions are name ganglio b-series. The c-series have sialylα2-8sialylα2-8sialylα2-3 substitutions.