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 μg/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 glucokinase 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.