The effect of the progression of vitamin A deficiency on glucose, galactose and mannose incorporation into sugar phosphates and sugar nucleotides in hamster liver.
The incorporation of [2-3H]mannose into dolichyl phosphate mannose and glycoproteins is markedly reduced in livers of vitamin A-deficient hamsters. To determine whether vitamin A deficiency selectively alters the level of mannose incorporation into sugar phosphates and sugar nucleotides, we studied the in vivo incorporation of [2-3H]mannose, [5-3H]glucose, and [4,5-3H]galactose into sugar phosphates and sugar nucleotides. Male hamsters fed either a vitamin A-depleted or a retinoic acid-supplemented (3 micrograms/g) diet were used at 4, 6 and 8 wk of age; the animals were killed at various time points after an intraperitoneal injection of the radiolabeled sugar. A two- to threefold increase in the amount of [2-3H]mannose was found in liver of hamsters fed a vitamin A-depleted diet for 4 wk, resulting in enhanced incorporation into mannosyl-phosphate and guanosine diphosphate (GDP) mannose. As deficiency progressed, there was a smaller increase in [2-3H]mannose and a significant decrease in [3H]mannose-phosphate and GDP-[3H]mannose, suggesting a decreased mannose kinase activity. [5-3H]Glucose-labeled livers showed no difference in the total uptake of the label or its incorporation into uridine diphosphate glucose and galactose-phosphate during the 8-wk study. However, the synthesis of glucosyl-phosphate was reduced by 50 to 90% at 6 and 8 wk of deficiency, suggesting an impaired gluco-kinase activity. In hamsters injected with [4,5-3H]galactose only [3H]glucose was found within 5 min in the free sugar fraction. In contrast, as much as 70% of the label in the sugar phosphate and sugar nucleotide fraction remained as [3H]galactose even at 60 min. These effects on sugar, sugar phosphate and sugar nucleotide formation in part may explain the effects of vitamin A deficiency on glycoconjugate biosynthesis.
Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892.
S
S
Shankar
K E
KE
Creek
L M
LM
De Luca
D000818:Animals; D006224:Cricetinae; D004032:Diet; D005690:Galactose / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D006155:Guanosine Diphosphate Mannose / Q000096:biosynthesis; D008099:Liver / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008358:Mannose / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D008647:Mesocricetus; D008954:Models, Biological; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D013403:Sugar Phosphates / Q000096:biosynthesis*; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage / Q000032:analysis; D014532:Uridine Diphosphate Glucose / Q000096:biosynthesis; D014802:Vitamin A Deficiency / Q000378:metabolism*
D009702:Nucleoside Diphosphate Sugars; D013403:Sugar Phosphates; D006155:Guanosine Diphosphate Mannose; D014212:Tretinoin; D005947:Glucose; D008358:Mannose; D014532:Uridine Diphosphate Glucose; D005690:Galactose