Overview and biosynthetic pathway of the four most prominent ganglioside series.

<p>The glycan parts of important members are shown for each series. The downstream biosynthetic steps are identical for all members of a row, although they may vary in linkage orientation. The six-membered pyranose rings are numbered counterclockwise, starting from the bottom (C1, except for C2 in Neu5Ac), and the ring oxygen is symbolized with a black dot. Neu5Ac moieties are rearranged for clarity, and all linkages are mediated by O2 or O8. Most of the gangliosides (e.g. LM1) can be further modified, e.g. by fucosylation. Linkages involving Neu5Ac are present in the α conformation, all other linkages are in the β conformation. Boxes represent three distinguishable sialoglycotopes that contain linkages found in GT1a (blue, representative for [α-2,8]), GD1a (green, [α-2,3]), and 3’-6’-iso-LD1 (also referred to as DSLNT, orange, [α-2,6]). The naming is according to the corresponding gangliosides; if possible, the Svennerholm shorthand is used [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref064" target="_blank">64</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref066" target="_blank">66</a>] All biosynthetic routes were verified using the KEGG metabolic pathway database [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref067" target="_blank">67</a>]. A prototype glycan that exemplifies the different positions of Gal and Neu5Ac moieties is depicted on the lower right. The glycan portions investigated in this study are highlighted by purple boxes.