Generation and Export of Red Blood Cell ATP in Health and Disease.
Generation and Export of Red Blood Cell ATP in Health and Disease.
复制标题
DOI：
10.3389/fphys.2021.754638
复制
发表时间：
2021
影响因子：
4
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
McMahon TJ;Darrow CC;Hoehn BA;Zhu H
动物的代谢稳态在很大程度上取决于红细胞 (RBC) 血红蛋白 (Hb) 感知氧气 (O2) 需求并做出相应反应的进化机制。红细胞内 ATP 生成和抗氧化系统的相互交织的调节也利用基于 Hb 的 O2 敏感性来响应各种生理和病理生理应激。例如，O2 卸载可促进糖酵解，从而产生 2,3-DPG（Hb O2 结合的负变构效应子）和 ATP。或者，在 O2 丰度的氧化条件下，有利于生成对还原系统至关重要的烟酰胺腺嘌呤二核苷酸磷酸 (NADPH)。 ATP 的动态控制不仅确保了离子泵的功能活动和细胞灵活性，而且还有助于在必要时（例如缺氧或微血管红细胞变形时）输出血管调节 ATP 的可用性。红细胞 ATP 输出响应缺氧或变形而扩张血管，以促进有效的 O2 输送。面对酶病[丙酮酸激酶缺乏；葡萄糖-6-磷酸脱氢酶 (G6PD) 缺乏症]、血库、糖尿病、COVID-19 或败血症以及镰状细胞病。能够增强红细胞 ATP 的疗法的出现，包括新建立的变构效应器和红细胞输注代谢物特异性添加剂解决方案的使用，提出了通过这些代谢物输送机制进行临床干预以优化或纠正红细胞功能的前景。
Metabolic homeostasis in animals depends critically on evolved mechanisms by which red blood cell (RBC) hemoglobin (Hb) senses oxygen (O2) need and responds accordingly. The entwined regulation of ATP production and antioxidant systems within the RBC also exploits Hb-based O2-sensitivity to respond to various physiologic and pathophysiologic stresses. O2 offloading, for example, promotes glycolysis in order to generate both 2,3-DPG (a negative allosteric effector of Hb O2 binding) and ATP. Alternatively, generation of the nicotinamide adenine dinucleotide phosphate (NADPH) critical for reducing systems is favored under the oxidizing conditions of O2 abundance. Dynamic control of ATP not only ensures the functional activity of ion pumps and cellular flexibility, but also contributes to the availability of vasoregulatory ATP that can be exported when necessary, for example in hypoxia or upon RBC deformation in microvessels. RBC ATP export in response to hypoxia or deformation dilates blood vessels in order to promote efficient O2 delivery. The ability of RBCs to adapt to the metabolic environment via differential control of these metabolites is impaired in the face of enzymopathies [pyruvate kinase deficiency; glucose-6-phosphate dehydrogenase (G6PD) deficiency], blood banking, diabetes mellitus, COVID-19 or sepsis, and sickle cell disease. The emerging availability of therapies capable of augmenting RBC ATP, including newly established uses of allosteric effectors and metabolite-specific additive solutions for RBC transfusates, raises the prospect of clinical interventions to optimize or correct RBC function via these metabolite delivery mechanisms.
登录
查看更多内容
影响因子：
2.9
作者：
Gehrke, Sarah;Shah, Nirmish;D'Alessandro, Angelo
通讯作者：
D'Alessandro, Angelo
影响因子：
8.8
作者：
Corwin, HL;Gettinger, A;Shapiro, MJ
通讯作者：
Shapiro, MJ
影响因子：
20.1
作者：
Billaud M;Lohman AW;Straub AC;Looft-Wilson R;Johnstone SR;Araj CA;Best AK;Chekeni FB;Ravichandran KS;Penuela S;Laird DW;Isakson BE
通讯作者：
Isakson BE
影响因子：
5.5
作者：
FORRESTER, T;LIND, AR
通讯作者：
LIND, AR
影响因子：
11.4
作者：
Chen, Yan-Mei;Zheng, Yuanting;Zhang, Yong-Zhen
通讯作者：
Zhang, Yong-Zhen