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The Quaternary Structure of Tetrameric Hemoglobin Regulates the Oxygen Affinity of Polymerized Hemoglobin

机译:四聚体血红蛋白的季结构调节聚合血红蛋白的氧亲和力。

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This study focuses on the effect of the initial quaternary structure of bovine hemoglobin (Hb) on the physical properties of glutaraldehyde polymerized Hb (PolyHb) solutions. Tense (T) state PolyHb was synthesized by maintaining the pO2 of Hb before and after polymerization at 0 mm Hg. In contrast, relaxed (R) state PolyHb was generated by maintaining the pO2 of Hb before and after polymerization to >749 mm Hg. PolyHb solutions were characterized by measuring the pO2, methemoglobin (metHb) level, molecular weight distribution, O2 affinity and cooperativity coefficient. The metHb level of all PolyHb solutions was low (<2%). Analysis of the molecular weight distribution of PolyHb solutions indicates that in general, the molecular weight of PolyHb solutions increased with increasing cross-link density. T-state PolyHb solutions exhibited lower O2 affinity compared to unmodified Hb, whereas R-state PolyHb solutions exhibited higher O2 affinity compared to unmodified Hb. In addition, the polymerization reaction resulted in a significant decrease in cooperativity that was more pronounced at higher cross-link densities. All of these results were explained in terms of the quaternary structure of Hb. Taken together, our results yield more insight into the importance Hb's quaternary structure plays in defining the physical properties of glutaraldehyde PolyHb solutions. This information will be useful in designing optimized glutaraldehyde PolyHb oxygen carriers for various applications in transfusion medicine.
机译:这项研究的重点是牛血红蛋白(Hb)的初始四级结构对戊二醛聚合Hb(PolyHb)溶液的物理性能的影响。通过在聚合之前和之后将Hb的pO2保持在0 mm Hg来合成时态(T)状态的PolyHb。相反,通过在聚合之前和之后将Hb的pO2保持在> 74​​9 mm Hg,可以生成松弛(R)状态的PolyHb。通过测量pO2,高铁血红蛋白(metHb)含量,分子量分布,O2亲和力和协同系数来表征PolyHb溶液。所有PolyHb溶液的metHb含量均较低(<2%)。对PolyHb溶液的分子量分布的分析表明,通常,PolyHb溶液的分子量随交联密度的增加而增加。与未修饰的Hb相比,T态PolyHb溶液表现出较低的O2亲和力,而与未修饰的Hb相比,R态PolyHb溶液表现出更高的O2亲和力。另外,聚合反应导致协同性显着降低,这在较高的交联密度下更为明显。所有这些结果都是根据Hb的四​​级结构解释的。综上所述,我们的结果使人们更深入地了解了Hb的四级结构在定义戊二醛PolyHb溶液的物理性质方面的重要性。该信息将有助于设计优化的戊二醛PolyHb氧载体,用于输血医学中的各种应用。

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