Evidence For a Functional Role of Pyruvate Kinase in Decreasing Gluconeogenesis in the Perfused Rat Liver 1

Abstract

Summary

The inverse relationship between the rate of gluconeogenesis from lactate and the pyruvate kinase/phosphoe-nolpyruvate carboxykinase ratio in the perfused livers from rats fed a 65% glucose diet, a 65% fructose diet, and a 90% casein diet suggested that phosphoenolpyruvate synthesized from oxaloacetate was available to pyruvate kinase for conversion to pyruvate. The intermediate or intermediates of gluconeogenesis and glycolysis which may intermix are not clear, but the earliest intermediate in gluconeogenesis at which intermixing could occur is phosphoenolpyruvate. This implied the absence of functional compartmentation between the metabolic intermediates of gluconeogenesis and glycolysis at the level of phosphoenolpyruvate and that control of pyruvate kinase activity serves to regulate the rate of gluconeogenesis. Thus, the observed decrease in pyruvate kinase activity reported for liver during gluconeogenic conditions is probably of considerable physiological significance in permitting a greater rate of glucose production to occur from amino acids, lactate and pyruvate.

The authors acknowledge the technical assistance of Mr. E. H. Avery.