DEPLETION OF LIVER ADENINE NUCLEOTIDES INDUCED BY D-FRUCTOSE - DOSE-DEPENDENCE AND SPECIFICITY OF FRUCTOSE EFFECT

The effect of d-fructose on adenine nucleotide metabolism was studied in rats in vivo by analyzing liver metabolite levels after intravenous fructose injections, and in vitro by measuring allantoin production by the isolated perfused liver after the addition of fructose to the perfusion medium. Significant depression of liver ATP and inorganic phosphate levels was demonstrated after fructose administration. Minimum effective dose was 0.25 m-mole, and maximum depression was observed after 5 min. Analogous, but quantitatively less impressive alterations were produced by l-sorbose and d-sorbitol, whereas d-glucose, d-galactose, d-mannose, d-ribose and 2-deoxy-d-glucose were without effect. In the perfusion studies, marked increase in allantoin production was observed after the addition of d-fructose to the perfusion medium. The minimum effective dose was 0.25 m-mole, corresponding to a mean initial concentration of 4.5 mM in the medium. Allopurinol prevented both the basal allantoin production and the fructose-induced increase. d-galactose, d-ribose, d-sorbitol, sodium-dl-lactate or ethanol did not influence the basal rate of allantoin release. The loss of liver adenine nucleotides in the in vivo experiments was of a similar order of magnitude as the amount of allantoin produced in the perfusion experiments, when calculated per total liver after equal doses of fructose. Therefore, accelerated degradation of preformed purines, rather than increased de novo synthesis, appears to be the main mechanism of fructose-induced increase in uric acid and allantoin production. © 1969.