Regulation of the Level of Key Enzymes of Glycolysis and Gluconeogenesis in Liver

TLDR: The results of a nutritional approach involving diets rich in fructose and/or showed that pyruvate carboxykinase levels were high, consistent with the hypothesis of induction by insulin of the enzymes that catalyze these two irreversible steps of glycolysis in liver.

Abstract: pyruvate carboxykinase were low. A metabolic bifurcation to glycolysis and gluconeogenesis, below and above the trioscphosphates level respectively, has then been shown to be easily maintained in liver. It is suggested that the induction of glucokinase and pyruvate kinase in diabetic animals after insulin administration is a sequential process that involves hormonal induction of glucokinase by insulin and secondary metabolite induction of the L isoenzyme of pyruvate kinase by some glycolytic intermediate. The occurrence of independent mechanisms for the regulation in liver of the activity of enzymes which catalyze irreversible steps of glycolysis and gluconeogenesis affords a valuable metabolic plasticity. Changes in the apparent concentration of a number of enzymes in liver have been observed in relation to the nutritional and hormonal conditions of the animal. Some of these changes could be of considerable significance in the regulation of major metabolic pathways. Glucose-6-phosphatase [l], fructosediphosphatase [a], phosphoenolpyruvate carboxykinase [3] and pyruvate carboxylase [4] had been reported to be increased in gluconeogenic conditions, like fasting, diabetes, or corticosteroids administration. In 1963, an insulin-dependent glucokinase was identified [5-71. After the finding of the induction of glucokinase in rat liver by insulin, Weber et al. [S] postulated the hypothesis that the key steps of glycolysis and gluconeogenesis could depend on two functional genic units, with insulin as inducer of the glycolytic unit and repressor of the gluconeogenic one. Shortly afterwards a number of observations were reported on the behaviour of pyruvate kinase [9- 111 and phosphofructokinase [12], consistent with the hypothesis of induction by insulin of the enzymes that catalyze these two irreversible steps of glycolysis in liver. This paper presents the results of a nutritional approach involving diets rich in fructose and/or