Zinc inhibition of hepatic fructose metabolism in rats

The ability of Zn to modulate key metabolic processes was investigated in a study of gluconeogenesis in isolated hepatocytes from fasted rats. Zn (100 microM) inhibited glucose production from fructose by 41%, sorbitol by 28%; glycerol by 17%, and glyceraldehyde by 26%. Maximum inhibition of gluconeogenesis from fructose occurred at 25 microM Zn. Zn inhibited the rate of lactate production from fructose by 24% but not from sorbitol, glycerol, or glyceraldehyde. Fructose uptake by hepatocytes was not affected by Zn. A positive linear relationship (r=0.994) was obtained between inhibition by Zn of glucose and lactate production, indicating that a common step in both pathways is inhibited by Zn. The effect of Zn on fructokinase, aldolase-B, and triokinase activities was determined on semipurified rat liver enzyme preparations. Zn had no affect on triokinase activity but inhibited the two other enzymes in a dose-dependent manner, with the inhibition of aldolase-B being much greater than of fructokinase for concentrations of Zn between 2.5 and 20 microM. Zn increased the intracellular concentration of fructose-1-P in hepatocytes incubated with fructose, indicating a more potent Zn inhibition of aldolase-B than fructokinase. In addition, hepatocytes treated with Zn had decreased ATP and ADP concentrations, but had normal energy charge, suggesting an effect of Zn on adenine nucleotide degradation or synthesis. The demonstration that Zn inhibits two enzymes in fructose metabolism adds to the growing list of metabolic pathways that are catalyzed by enzymes that are sensitive to Zn.