[Importance of binding of 2,3-diphosphoglycerate and ATP to hemoglobin for erythrocyte glycolysis: activation by 2,3-diphosphoglycerate of hexokinase at intracellular conditions].
In a theoretical study the influence of hemoglobin and Mg-ions as binding partners of red cell 2,3-diphosphoglycerate and ATP was investigated. Free hemoglobin may be an efficient competitor of Mg2+ for the ligand ATP. At conditions which favour hemoglobin as binding partner (i.e. desoxygenation, low medium pH and incubation temperature, as in blood preservation) up to 95% of the whole cellular ATP (ca. 2mM in cell water) may be bound to hemoglobin (ca. 7 mM). This binding is largely prevented in the presence of physiological amounts of diphosphoglycerate (ca. 7 mM) which is in excess and has a higher binding affinity to hemoglobin. Therefore, diphosphoglycerate keeps ATP (MgATP) in cell water solution at conditions in which Hb would trop it in the presence of Mg2+ (ca. 3mM). It can be calculated that, by lack of free MgATP, the activity of hexokinase within the cell drops by a factor of greater than 10 when diphosphoglycerate is metabolized. This indirect activation by diphosphoglycerate of hexokinase is operative at free concentrations of DPG far below those which exert the well known excess inhibitory effect on hexokinase and phosphofructokinase. In a model study, the activation by diphosphoglycerate of the initial two-kinase stage was introduced into a simplified kinetic model of glycolysis. A pronounced hysteresis loop of the stationary concentrations of ATP and diphosphoglycerate was produced indicating the existence of several stationary states, one with high ATP and high diphosphoglycerate, the other one with low values. It is demonstrated that diphosphoglycerate, being a protector of glycolysis at physiological concentrations, triggers an autocatalytic breakdown of the energy state when permitted to drop to low values.
D000255:Adenosine Triphosphate / Q000097:blood*; D004163:Diphosphoglyceric Acids / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006019:Glycolysis; D006454:Hemoglobins / Q000378:metabolism*; D006593:Hexokinase / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008433:Mathematics
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D000255:Adenosine Triphosphate; D006593:Hexokinase; D008274:Magnesium
Bedeutung der Bindung von 2,3-Diphosphoglyzerat und ATP an Hämoglobin für die Glykolyse in Erythrozyten: Aktivierung der Hexokinase durch 2,3-Diphosphoglyzerat unter intrazellulären Bedingungen.