Depletion of Liver Adenosine Phosphates and Metabolic Effects of Intravenous Infusion of Fructose or Sorbitol in Man and in the Rat*,**

Abstract

Summary. 1. The effect of parenteral administration of fructose and sorbitol on hepatic adenosine phosphates (AP) and intermediates of carbohydrate metabolism was examined in man and rat.—2. Intravenous injection of fructose rapidly decreases ATP, total adenosine phosphates (AP), and inorganic phosphate in the liver of fed male and female rats. The depletion in hepatic ATP and total AP is also observed in the regenerating rat liver following partial hepatectomy. Equimolar administration of sorbitol has the same effect on liver AP has that observed following fructose, while glucose administration produces no significant changes.—3. In man i.v. infusion of 0.6–0.8 g/kg body weight of fructose or sorbitol reduces hepatic ATP to about 50 %, and total AP to about 65 % of initial values. Glucose has no effect. Blood AP content is not affected by intravenous infusion of 500 ml of 10 % fructose in man.—‐4. Fructose distinctly increases the content of various hexose phosphates and triose phosphates in the liver of man. Fructose‐1‐phosphate accumulates 4‐to 5‐fold and α‐glycerophosphate 3‐fold during infusion of 0.6–0.8 g/kg body weight of fructose within 30 minutes.—5. RNA‐synthesis in the regenerating rat liver following partial hepatectomy as neasured by incorporation of 6‐14 C‐orotic acid is distinctly inhibited by i. v. injection of 1.6 g of fructose kg. The incorporation rate of 1‐14 C‐D, L‐leucine into rat liver protein drops to 35 % of initial levels within 10 minutes after the same amount of fructose, whereas glucose has no inhibitory effect.—6. Both ATP and Pi are important inhibitors of AMP degradation. Thus the drop in total AP content can be explained by the increased breakdown of the latter. This assumption is supported by the observation that injection of fructose plus equimolar amounts of Pi reduces the decrease in total AP, but not in ATP content. The concentration of the final product of AMP degradation, uric acid, increases distinctly following i. v. fructose administration in man.—7. These results indicate that in clinical medicine infusion of large doses of fructose or sorbitol have more disadvantages than advantages compared to glucose.