THE REGULATION OF GLYCOLYSIS IN HUMAN-ERYTHROCYTES - THE DEPENDENCE OF THE GLYCOLYTIC FLUX ON THE ATP CONCENTRATION

According to the mathematical model, the dependence of the rate of glycolysis on the ATP concentration can be represented by the bell-shaped curve with the descending part at the concentration of ATP close to physiological values. The existence of the descending part is a result of the strong inhibition of phosphofructokinase by ATP and hexokinase by G-6-P and provides stabilization of the intracellular concentration of ATP. Using arsenate as an uncoupler of the oxidation of glucose and ATP synthesis, the dependence of the rate of glycolysis on the ATP concentration in erythrocytes was measured. This dependence (glycolysis characteristic) is represented by a bell-shape curve. The normalized glycolysis characteristics are the same for all the donors investigated. The increase of permeability of the erythrocyte membrane to monovalent cations by the polyene antibiotic levorin leads to an increase of glycolytic rate in erythrocytes (40-70%) and to a decrease in the ATP concentration (15%) and G-6-P (25-60%). The data obtained with levorin, and also other results on Na, K-ATPase activation are in a good agreement with the characteristic obtained using arsenate. In all cases, inhibition of Na+, K+-ATPase of erythrocytes by ouabain leads to the decrease of the rate of lactate production (10-20%) and increase of the concentration of G-6-P (14-40%). The ATP concentrations remains almost unchanged or is only slightly increased. The rate of glucose utilization in erythrocytes from different donors show 2 types of behavior. In the 1st type of erythrocyte it drops proportionally to the decrease in the lactate production rate; in the 2nd type of erythrocyte it remains unchanged. The experimental results presented are in qualitative agreement with the predictions of the mathematical model.