Glycolipids modulate glycosyl transfer to endogenous protein acceptors.
Regulation by gangliosides of glycosylation of endogenous membrane glycoproteins is indicated from in vitro studies in which incorporation of radioactive sugars into endogenous protein acceptors was measured and from in vitro studies where transferase activities of membranes were correlated with ganglioside content during hepatic tumorigenesis. Galactosyl transfer from UDP galactose exhibited a complex response pattern and was stimulated by lactosyl ceramide and the ganglioside N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GM2) but was inhibited by higher gangliosides. Except for N-acetylneuraminylgalactosylglucosylceramide (GM3), which had no effect, inhibition was proportional to ganglioside complexity. Inhibition of glycosylation of the exogenous acceptor, ovomucoid, by ganglioside was slight by comparison. While marked structure-linked latency was observed with the high molecular weight exogenous acceptor, no latency was observed for incorporation into endogenous acceptors suggesting that the membranes were permeable to sugar nucleotides. Membrane disruption with detergents lessened rather than enhanced inhibition by gangliosides. Sialyl transfer from CMPsialic acid, on the other hand, was unaffected or stimulated by gangliosides. Stimulation by galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GM1) was proportional to concentration and reached 2-fold at 240 micrograms/mg protein. The results suggest that the ganglioside content of membrane may affect glycosylation of membrane glycoproteins.
D000818:Animals; D005700:Galactosyltransferases / Q000378:metabolism*; D005732:Gangliosides / Q000494:pharmacology*; D006017:Glycolipids / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D051381:Rats; D012799:Sialyltransferases / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*
D005732:Gangliosides; D006017:Glycolipids; D006023:Glycoproteins; D014166:Transferases; D005700:Galactosyltransferases; D012799:Sialyltransferases