We have established that 2,3-diphosphoglycerate (2,3-DPG) content and intracellular pH exert separate, but interdependent, effects on the equilibrium solubility (csat) of deoxyhemoglobin S (deoxy-Hb S) that act in concert to modulate intraerythrocytic polymer formation. In a nonphysiologic csat assay system, a steep dependence of csat on pH in the physiologic range 7.0 to 7.6 was shown for both stripped (Hb) and DPG-saturated deoxy-Hb S (Hb-DPG). The solubility-pH profile for Hb under near-physiologic buffer conditions also showed that csat increased steeply in the same pH range (6.8 to 7.6). The effect of 2,3-DPG on csat under near-physiologic conditions was evaluated separately. At pH 7.20, the pH of the human red blood cell, csat values for Hb and Hb-DPG were 19.56 +/- 0.14 and 17.95 +/- 0.45 g/dL, respectively, indicating that the solubility of Hb-DPG is lower than that of Hb by 8.2% +/- 2.3%. Thus, binding of 2,3-DPG in the beta-cleft promotes the polymerization of deoxy-Hb S, the ultimate determinant of cell sickling. Furthermore, because of the abnormal Bohr effect of sickle blood (approximately double that of normal blood), the intracellular pH of deoxygenated sickle erythrocytes should be approximately 0.28 pH unit higher than that of oxygenated cells (ie, 7.41 v 7.13). At the higher pH, the corresponding csat for Hb-DPG is 20.22 g/dL, which is the best estimate of the intrinsic solubility of T-state Hb S under conditions that approximate closely those of pH, temperature, ionic strength, and 2,3-DPG saturation in the fully desaturated sickle erythrocyte.

译文

:我们已经确定2,3-二磷酸甘油酸(2,3-DPG)的含量和细胞内pH值对脱氧血红蛋白S(deoxy-Hb S)的平衡溶解度(csat)发挥了独立但相互依存的影响,这些作用共同调节红细胞内聚合物的形成。在非生理性csat分析系统中,对于汽提(Hb)和DPG饱和的脱氧Hb S(Hb-DPG),csat对pH值在7.0到7.6的生理范围内具有很强的依赖性。在接近生理缓冲液的条件下,Hb的溶解度-pH谱也显示csat在相同pH范围(6.8至7.6)下急剧增加。分别评估了2,3-DPG在近生理条件下对csat的影响。在pH 7.20时,人红细胞的pH,Hb和Hb-DPG的csat值分别为19.56 /-0.14和17.95 /-0.45 g / dL,表明Hb-DPG的溶解度低于Hb-DPG的溶解度。血红蛋白增加8.2%/-2.3%。因此,β-裂隙中2,3-DPG的结合促进了脱氧Hb S的聚合,脱氧Hb S是细胞镰刀的最终决定因素。此外,由于镰刀血具有异常的玻尔效应(大约是正常血液的两倍),脱氧的镰刀红细胞的细胞内pH值应比含氧细胞的细胞内pH值高约0.28 pH单位(即7.41 v 7.13)。在较高的pH值下,Hb-DPG的对应csat为20.22 g / dL,这是在接近pH,温度,离子强度和2的条件下,T型Hb S固有溶解度的最佳估计。完全去饱和的镰状红细胞中的3-DPG饱和。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录