Effect of Fructose, Dihydroxyacetone, Glycerol, and Glucose on Metabolites and Related Compounds in Liver and Kidney

Abstract

The effects of large intraperitoneal doses of fructose and dihydroxyacetone on the levels of many metabolites of carbohydrate metabolism are reported for liver, kidney cortex, and medulla of the rat. Levels were also measured in liver after glycerol and glucose administration, and in kidney cortex and medulla, after glycerol. In both liver and kidney there were large accumulations of fructose-1-P from fructose and of glycero-P from glycerol. The accumulations were associated with marked depletion of ATP, UTP, and total adenylate, and, in liver at least, of Pi. The increases in glycero-P were not associated with comparable changes in dihydroxyacetone-P, and the ratio between the two rose from 18:1 to as high as 1000:1, with relatively minor changes in lactate to pyruvate ratios. Riboflavin deficiency, which drastically lowers glycero-P oxidase activity, caused an increased accumulation of glycero-P. These results suggest that the newly formed glycero-P is chiefly oxidized by glycero-P oxidase rather than by glycero-P dehydrogenase. The disproportionate increase in glycero-P seen after glycerol was also observed after fructose administration in kidney cortex but not in liver. In the case of each of the four nutrients, fructose, dihydroxyacetone, glycerol, and glucose, UDP-glucose decreased in liver. Concomitantly, metabolites of the Embden-Meyerhof pathway increased. The increases tended to be smaller for fructose 1,6-diphosphate and dihydroxyacetone-P than for members above and below them on the pathway. The increases were generally greatest after fructose and least after glucose. Fructose caused rapid large increases in glucose but there was little glycogen formation during the first hour.