Fluoroglucose-inhibition of protein glycosylation in vivo. Inhibition of mannose and glucose incorporation into lipid-linked oligosaccharides.
The effects of the glycosylation inhibitor 2-deoxy-2-fluoro-D-glucose on the formation of the lipid-linked oligosaccharides and monosaccharides that are involved in protein glycosylation were investigated. In chick embryo cells treated with fluoroglucose the formation of lipid-linked oligosaccharides cannot go to completion and oligosaccharides with decreased amounts of glucose and mannose can be detected. These oligosaccharides are probably biosynthetic intermediates and serve as acceptors of sugar residues while reversing fluoroglucose-inhibition by the addition of mannose and glucose to the culture medium. In contrast to deoxyglucose, fluoroglucose was not incorporated into lipid-linked oligosaccharides. Fluoroglucose inhibits the formation in vivo of dolichyl phosphate glucose and dolichyl phosphate mannose, but not the transfer of those sugar residues from the lipid monophosphate derivative to the lipid-linked oligosaccharides. The pool size of UDP-glucose, but not of GDP-mannose and UDP-N-acetylglucosamine, was decreased. Also, the formation of lipid-linked N-acetylglucosamine was not affected by fluoroglucose. Fluoroglucose was applied to deplete cellular membranes of endogenous lipid-linked mannose and glucose, and can possibly be used to discern different pathways of glycosylation.
D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18; D006017:Glycolipids / Q000096:biosynthesis*; D006023:Glycoproteins / Q000096:biosynthesis*; D006155:Guanosine Diphosphate Mannose / Q000378:metabolism*; D009980:Influenza A virus / Q000378:metabolism; D007700:Kinetics; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D014532:Uridine Diphosphate Glucose / Q000378:metabolism*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism; D014539:Uridine Diphosphate Sugars / Q000378:metabolism*
D003837:Deoxy Sugars; D006017:Glycolipids; D006023:Glycoproteins; D009702:Nucleoside Diphosphate Sugars; D009844:Oligosaccharides; D014539:Uridine Diphosphate Sugars; D019788:Fluorodeoxyglucose F18; D006155:Guanosine Diphosphate Mannose; D014537:Uridine Diphosphate N-Acetylglucosamine; D003847:Deoxyglucose; D014532:Uridine Diphosphate Glucose