Differential activities of glycolipid glycosyltransferases in Tay-Sachs disease: studies in cultured cells from cerebrum.
Four different glycolipid:glycosyltransferase activities involved in the biosynthesis in vitro of gangliosides and blood group-related glycosphingolipids have been tested in a simian virus 40-transformed glial cell culture derived from the cerebrum of a fetus with Tay-Sachs disease (TSD). The TSD cultured brain cells contained little activity of either UDP-Gal:GM2(beta 1-3)galactosyltransferase (GalT-3; EC 2.4.1.62), which catalyzes the formation of GM1a from GM2 (tay-Sachs) ganglioside, or GDP-Fuc:nLcOse4Cer (alpha 1-2)fucosyltransferase (FucT-2; EC 2.4.1.89), which catalyzes the formation of H1 glycolipid from nLcOse4Cer. These cells contained a potent inhibitor of the second reaction (catalyzed by a Golgi-rich membrane fraction from bovine spleen), whereas no inhibition of the first reaction (catalyzed by a membrane fraction from 14-day-old embryonic chicken brain) was observed. The activity of UDP-Gal:LcOse3Cer(beta 1-4)galactosyltransferase (GalT-4; EC 2.4.1.86) was 30- to 80-fold higher than the activity of GalT-3. The presence of CMP-AcNeu:nLcOse4Cer sialyltransferase activity and the absence of either GalT-3 or FucT-2 suggested a probable pathway for the synthesis of sialylneolactotetraosylceramide [GM1b(GlcNAc)] in addition to a specific blockage of GM1a ganglioside synthesis from GM2 in these TSD transformed cells.
D000017:ABO Blood-Group System; D001921:Brain / Q000201:enzymology*; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors; D005677:G(M1) Ganglioside / Q000096:biosynthesis*; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005732:Gangliosides / Q000096:biosynthesis*; D006028:Glycosphingolipids / Q000096:biosynthesis*; D006801:Humans; D009457:Neuroglia / Q000201:enzymology; D012799:Sialyltransferases / Q000378:metabolism; D013661:Tay-Sachs Disease / Q000201:enzymology*
D000017:ABO Blood-Group System; D005732:Gangliosides; D006028:Glycosphingolipids; D005677:G(M1) Ganglioside; D005647:Fucosyltransferases; D005700:Galactosyltransferases; D012799:Sialyltransferases