Geier T, Glende M, Reich J G
Acta Biol Med Ger. 1978;37(1):59-72.
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.
在一项理论研究中，研究了血红蛋白和镁离子作为红细胞2,3 - 二磷酸甘油酸和ATP结合伙伴的影响。游离血红蛋白可能是镁离子与配体ATP的有效竞争者。在有利于血红蛋白作为结合伙伴的条件下（即脱氧、低介质pH值和孵育温度，如在血液保存中），高达95%的全细胞ATP（细胞内水中约2mM）可能与血红蛋白（约7mM）结合。在存在生理量的二磷酸甘油酸（约7mM）时，这种结合在很大程度上受到抑制，二磷酸甘油酸过量且对血红蛋白具有更高的结合亲和力。因此，在存在镁离子（约3mM）时血红蛋白会使其释放的条件下，二磷酸甘油酸将ATP（MgATP）保持在细胞水溶液中。可以计算出，当二磷酸甘油酸被代谢时，由于缺乏游离MgATP，细胞内己糖激酶的活性下降超过10倍。二磷酸甘油酸对己糖激酶的这种间接激活作用在远低于对己糖激酶和磷酸果糖激酶产生众所周知的过量抑制作用的二磷酸甘油酸游离浓度下即可发挥作用。在一项模型研究中，将二磷酸甘油酸对初始双激酶阶段的激活引入到糖酵解的简化动力学模型中。产生了ATP和二磷酸甘油酸稳态浓度的明显滞后环，表明存在几种稳态，一种具有高ATP和高二磷酸甘油酸，另一种具有低值。结果表明，二磷酸甘油酸在生理浓度下是糖酵解的保护剂，当允许其降至低值时会引发能量状态的自催化分解。
