Reduced mannose incorporation into GDP-mannose and dolichol-linked intermediates of N-glycosylation in hamster liver during vitamin A deficiency.
The molecular mechanism of reduced incorporation of radioactively labeled mannose into hamster liver glycoconjugates during the progression of vitamin A deficiency was investigated. In particular the in vivo incorporation of [2-3H]mannose into GDP-mannose, dolichyl phosphate mannose (Dol-P-Man), lipid-linked oligosaccharides, and glycopeptides of hamster liver was examined. Hamsters maintained on a vitamin A-free diet showed a reduction in the incorporation of mannose into GDP-mannose about 10 days before clinical signs of vitamin A deficiency could be observed. The decrease in [2-3H]mannose incorporated into GDP-mannose was accompanied by a reduction in label incorporated into Dol-P-Man, lipid linked oligosaccharides and glycopeptides, which became more severe with the progression of vitamin A deficiency. By the time they reached a plateau stage of growth, hamsters fed the vitamin A-free diet showed a 50% reduction in the amount of [2-3H]mannose converted to GDP-mannose, and the radioactivity associated with Dol-P-Man and glycopeptides was reduced by approximately 60% as compared to retinoic acid-supplemented controls. These results strongly indicate that the reduced incorporation of mannose into lipidic intermediates and glycoproteins observed during vitamin A deficiency is due to impaired GDP-mannose synthesis.
Differentiation Control Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
D
D
Rimoldi
K E
KE
Creek
L M
LM
De Luca
D000818:Animals; D006224:Cricetinae; D004286:Dolichols / Q000378:metabolism*; D005215:Fasting; D006031:Glycosylation; D006155:Guanosine Diphosphate Mannose / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008358:Mannose / Q000378:metabolism*; D008647:Mesocricetus; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D014802:Vitamin A Deficiency / Q000378:metabolism*
D004286:Dolichols; D009702:Nucleoside Diphosphate Sugars; D006155:Guanosine Diphosphate Mannose; D008358:Mannose