A fresh view of glycolysis and glucokinase regulation: history and current status

Abstract

This minireview looks back at a century of glycolysis research with a focus on the mechanisms of flux regulation. Traditionally, glycolysis is regarded as a feeder pathway that prepares glucose for further catabolism and energy production. However, glycolysis is much more than that, in particular in those tissues that express the low affinity glucose-phosphorylating enzyme glucokinase. This enzyme equips the glycolytic pathway with a special steering function for the regulation of intermediary metabolism. In beta cells, glycolysis acts as a transducer for triggering and amplifying physiological glucose-induced insulin secretion. On the basis of these considerations, I have defined a glycolytic flux regulatory unit composed of the two fructose ester steps of this pathway with various enzymes and metabolites that regulate glycolysis.

Keywords: Beta Cell; Glucokinase; Glycolysis; Liver; Metabolic Regulation; Phosphofructokinase.

FIGURE 1.

The regulatory unit of the glycolytic pathway composed of the fructose steps at the interface between the initial step of glucose trapping in the cell through phosphorylation and the conditioning of the glucose molecule for catabolism. Several molecules in these fructose steps are regulatory in nature and determine the glycolytic flux rate. Regulatory proteins that inhibit glucokinase (GK) in pancreatic beta cells and the liver are encircled in green (midnolin and parkin) and blue (GRP), respectively. FBPase-2, which activates glucokinase in pancreatic beta cells and the liver, is encircled in red. Regulatory small molecules that are expressed only in the liver but not in pancreatic beta cells are printed in blue. +, activation; −, inhibition; −−, strong inhibition of target structures. HK, hexokinase; PP, pentose phosphate.