Generation and Export of Red Blood Cell ATP in Health and Disease

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...

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Autores principales:	Timothy J. McMahon, Cole C. Darrow, Brooke A. Hoehn, Hongmei Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	transfusion blood flow sepsis hypoxia endothelial cells Physiology QP1-981
Acceso en línea:	https://doaj.org/article/67fa7c62e8d74728b42454c90f430fd9
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spelling	oai:doaj.org-article:67fa7c62e8d74728b42454c90f430fd92021-11-05T10:14:02ZGeneration and Export of Red Blood Cell ATP in Health and Disease1664-042X10.3389/fphys.2021.754638https://doaj.org/article/67fa7c62e8d74728b42454c90f430fd92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.754638/fullhttps://doaj.org/toc/1664-042XMetabolic 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.Timothy J. McMahonCole C. DarrowBrooke A. HoehnHongmei ZhuFrontiers Media S.A.articletransfusionblood flowsepsishypoxiaendothelial cellsPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transfusion blood flow sepsis hypoxia endothelial cells Physiology QP1-981
spellingShingle	transfusion blood flow sepsis hypoxia endothelial cells Physiology QP1-981 Timothy J. McMahon Cole C. Darrow Brooke A. Hoehn Hongmei Zhu Generation and Export of Red Blood Cell ATP in Health and Disease
description	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.
format	article
author	Timothy J. McMahon Cole C. Darrow Brooke A. Hoehn Hongmei Zhu
author_facet	Timothy J. McMahon Cole C. Darrow Brooke A. Hoehn Hongmei Zhu
author_sort	Timothy J. McMahon
title	Generation and Export of Red Blood Cell ATP in Health and Disease
title_short	Generation and Export of Red Blood Cell ATP in Health and Disease
title_full	Generation and Export of Red Blood Cell ATP in Health and Disease
title_fullStr	Generation and Export of Red Blood Cell ATP in Health and Disease
title_full_unstemmed	Generation and Export of Red Blood Cell ATP in Health and Disease
title_sort	generation and export of red blood cell atp in health and disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/67fa7c62e8d74728b42454c90f430fd9
work_keys_str_mv	AT timothyjmcmahon generationandexportofredbloodcellatpinhealthanddisease AT colecdarrow generationandexportofredbloodcellatpinhealthanddisease AT brookeahoehn generationandexportofredbloodcellatpinhealthanddisease AT hongmeizhu generationandexportofredbloodcellatpinhealthanddisease
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Generation and Export of Red Blood Cell ATP in Health and Disease

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