An inhibitor of mannosylation of retinyl-phosphate.
The guanosine diphosphate and uridine diphosphate esters of the antiviral sugar analog 2-deoxy-2-fluoro-D-glucose (GDP-FGlc and UDP-FGlc) were synthesized and tested as inhibitors of formation of lipid-linked sugars in cell-free extracts. Formation of dolichol-phosphate mannose and of dolichol-diphosphate di-N-acetyl-chitobiose were not inhibited by either sugar nucleotide. Formation of dolichol-phosphate glucose was inhibited by UDP-FGlc, not by GDP-FGlc. Although GDP-FGlc did not inhibit formation of dolichol-phosphate mannose, it did inhibit formation of retinol-phosphate mannose from retinol-phosphate and GDP-Man. This inhibition was not reversed by exogenous retinol-phosphate, nor was FGlc from GDP-FGlc incorporated into retinol-phosphate-linked derivatives. As FGLc inhibits formation of dolichol-phosphate mannose in intact cells, but does not decrease pool sizes of GDP-Man and dolichol-phosphate (Datema et al., 1980, Eur. J. Biochem. 109, 331-341), we discuss that inhibition of formation of retinol-phosphate mannose by one of the metabolites of FGlc, namely GDP-FGlc, may lead to decreased synthesis of dolichol-phosphate mannose in FGlc-treated cells. This implies a role for vitamin A in the dolichol cycle of protein glycosylation.
D000818:Animals; D002250:Carbon Radioisotopes; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000494:pharmacology*; D004224:Diterpenes; D006155:Guanosine Diphosphate Mannose / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism; D009975:Orthomyxoviridae; D011103:Polyisoprenyl Phosphate Monosaccharides / Q000096:biosynthesis*; D011105:Polyisoprenyl Phosphate Sugars / Q000096:biosynthesis*; D051381:Rats; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000378:metabolism
D002250:Carbon Radioisotopes; D003837:Deoxy Sugars; D004224:Diterpenes; D011103:Polyisoprenyl Phosphate Monosaccharides; D011105:Polyisoprenyl Phosphate Sugars; D014801:Vitamin A; D006155:Guanosine Diphosphate Mannose; C012532:retinol phosphate; C013101:mannosylretinylphosphate; C041530:uridine-2-deoxy-2-fluoro-D-glucose diphosphate ester; C041529:guanosine-2-deoxy-2-fluoro-D-glucose diphosphate ester; D003847:Deoxyglucose