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The Involvement of Liver Fructokinase in the Metabolism of D-Xylulose and Xylitol in Isolated Rat Hepatocytes¹

Division of Nutritional Sciences and Section of Biochemistry, Cell and Molecular Biology, Division of Biological Sciences, Cornell University, Ithaca, NY 14853

Hepatocytes isolated from fed, male, Sprague-Dawley rats accumulate xylulose-1-phosphate and glycolaldehyde as well as xylulose-5-phosphate when incubated with 2–20 mM D-xylulose. Fructokinase inhibitors (fructose and 1-deoxyfructose) decreased xylulose-1-phosphate and glycolaldehyde (but not xylulose-5-phosphate) levels in xylulose-treated hepatocytes, demonstrating the role of fructokinase in xylulose-1-phosphate and glycoaldehyde formation. As the fructokinase inhibitors had no overall effects on the conversion of D-xylulose to glucose, the overall flux through the pathway involving fructokinase was less than 27% of the total D-xylulose utilized. In hepatocytes from fed or fasted rats there was no detectable accumulation of either xylulose-1-phosphate or glycolaldehyde after treatment with 20 mM xylitol. Other differences between xylitol and D-xylulose metabolism in rat hepatocytes included a slower rate of xylitol metabolism in all preparations and a difference in the relative conversion of xylitol to glucose in hepatocytes from fasted rats. Rats adapted to 20% xylitol (diarrhea-free) had a lower water consumption than those fed a control cornstarch diet; there were no differences in weight gain, food consumption or in rates or metabolite patterns of xylitol metabolism in hepatocytes isolated from these rats. Despite the minor role of fructokinase in the overall metabolism of xylitol and of D-xylulose as shown by these results, it is not possible to exclude the possibility of some flux through the pathway involving xylulose-1-phosphate and glycolaldehyde formation as a possible route for oxalate formation.

KEY WORDS: • xylitol • xylulose-1-phosphate • oxalate • fructokinase inhibitors • isolated hepatocytes

¹ Supported in part by Grants No. HD-10967, AM-20882 and CA-26755 from the National Institutes of Health, U.S. Public Health Service, Bethesda, MD 20814. Portions of this study were presented at the 65th Annual Meeting of the Federation of American Societies for Experimental Biology, Atlanta, GA, 12–17 April 1981: Barngrover, D. A., and Dills, W. L., Jr. (1981) D-Xylulose-I-phosphate production in xylitol-treated rat hepatocytes. Fed. Proc. 40, 843 (abs.).

² Current address: Department of Nutrition and Food Science E18-666, Massachusetts Institute of Technology, Cambridge, MA 02139.

³ To whom reprint requests should be sent. Current address, Department of Chemistry, Southeastern Massachusetts University, North Dartmouth, MA 02747.

Manuscript received 17 June 1982.