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The Effect of the Progression of Vitamin A Deficiency on Glucose, Galactose and Mannose Incorporation into Sugar Phosphates and Sugar Nucleotides in Hamster Liver

Differentiation Control Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892

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.

KEY WORDS: • hamster • liver • vitamin A deficiency • sugar phosphates • sugar nucleotides

¹ Present address: Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892.

² Present address: Department of Chemistry, University of South Carolina, Columbia, SC 29208.

³ To whom correspondence should be addressed at Building 37, Room 3A-17.

Manuscript received 9 January 1989. Revision accepted 28 September 1989.