Marschner J P, Seidlitz T, Rietbrock N
Department of Clinical Pharmacology, University Hospital, Frankfurt/Main.
Int J Clin Pharmacol Ther. 1994 Mar;32(3):116-21.
Studies under equilibrium conditions have shown that the oxygen affinity of hemoglobin (Hb) is lowered by 2,3-diphosphoglycerate (2,3-DPG), the physiological allosteric effector in erythrocytes, and enhanced by glycosylation of Hb. The kinetics of oxygen release, as a function of 2,3-DPG and the degree of glycosylation have been determined using the stopped flow method and a new in vitro glycosylation procedure allowing adequate amounts of functionally intact hemoglobin to be obtained. The rate constant k of O2-dissociation in glycosylated Hb (8% HbA1c) was approximately 10% lower than in native Hb (4% HbA1c). The addition of 2,3-DPG in concentrations up to 20 mmol/l resulted in a progressive increase of k from 61.5 +/- 3.3 s-1 to 65.3 ae 4.1 s-1 for native Hb and from 56.8 +/- 5.2 s-1 to 59.4 +/- 4.1 s-1 for glycosylated Hb. We conclude that (a) the degree of glycosylation similar to that found in diabetic patients is responsible for a significant decrease of the oxygen dissociation velocity and (b) 2,3-DPG concentration similar to those occurring in vivo have only a weak effect on the oxygen dissociation velocity.
平衡条件下的研究表明，血红蛋白（Hb）的氧亲和力会被红细胞中的生理性变构效应物2,3-二磷酸甘油酸（2,3-DPG）降低，而被Hb的糖基化增强。利用停流法和一种新的体外糖基化程序，已测定了作为2,3-DPG和糖基化程度函数的氧释放动力学，该程序能获得足够量的功能完整的血红蛋白。糖基化血红蛋白（HbA1c为8%）中O2解离的速率常数k比天然血红蛋白（HbA1c为4%）低约10%。添加浓度高达20 mmol/l的2,3-DPG会使天然Hb的k从61.5±3.3 s-1逐渐增加到65.3±4.1 s-1，使糖基化Hb的k从56.8±5.2 s-1逐渐增加到59.4±4.1 s-1。我们得出结论：（a）与糖尿病患者中发现的糖基化程度相似，会导致氧解离速度显著降低；（b）与体内发生的浓度相似的2,3-DPG浓度，对氧解离速度的影响较弱。
