METABOLISM OF FRUCTOSE IN LIVER

Abstract. For liver a metabolic pathway for fructose has been described in which the ketosugar is phosphorylated by ketohexokinase to fructose‐1‐phosphate, which is then converted by liver aldolase to D‐glyceraldehyde and dihydroxyacetone phosphate, an intermediate of the glycolytic pathway. D‐glyceraldehyde could be oxidized to glycerate. By phosphorylation glycerate becomes an intermediate of the Embden‐Meyerhof pathway, like D‐glyceraldehyde if phosphorylated directly by triokinase. The reduction of D‐glyceraldehyde forming glycerol, which could be phosphorylated to L‐glycerol 3‐phosphate is in variance with isotope studies with fructose‐6‐14C. This special metabolic pathway is limited to warmblooded animals and man, because only in the liver of these species ketohexokinase could be detected. An adaption of enzymes was found in rats, which have had a high fructose diet over three weeks. The activity of ketohexokinase estimated under optimal conditions and 37°C agrees well with fructose extraction rates found in liver perfusion for rat and in in vivo experiments for human liver. The fast catabolism of fructose in human liver, in contrast to glucose, is due to higher enzyme levels of ketohexokinase, in contrast to hexokinase and glucokinase. By this high phosphorylation capacity and the low activity of aldolase together with the action of metabolic inhibitors on this enzyme and the equilibrium far at the side of fructose‐1‐phosphate, fructose‐1‐phosphate will accumulate if high fructose concentrations were offered. But even under these conditions, the levels of metabolites following fructose‐1‐phosphate were enlarged. Enzyme regulations based on the high fructose‐1‐phosphate and low ATP levels were discussed.