Erythrocyte metabolism and function: Hexokinase inhibition by 2,3-diphosphoglycerate and interaction with ATP and Mg2+

Abstract

Recent findings have suggested an important role for variation in levels of 2,3-diphosphoglycerate and ATP in the regulation of oxygen transport by the human erythrocyte, and in making homeostatic adjustments to hypoxia. For this reason, the erythrocytic glycolytic mechanisms which control or bring about changes in levels of 2,3-diphosphoglycerate and ATP are of vital importance in understanding respiratory homeostasis. Hexokinase is the first step in glycolysis, and available evidence suggests that it is an important rate-limiting step in the erythrocyte. In this paper we have examined a possible mechanism for feedback control of glycolysis through 2,3-diphosphoglycerate inhibition of hexokinase activity. We have found that 2,3-diphosphoglycerate does inhibit hexokinase and have shown that the inhibition is relieved by increasing concentrations of ATP and Mg2+. It is our conclusion that inhibition of erythrocyte hexokinase by 2,3-diphosphoglycerate, with modulation by ATP and/or Mg2+, is well suited for feedback control of glycolysis, and hence for the control of levels of 2,3-diphosphoglycerate and ATP, which in turn regulate hemoglobin function.