AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

Angelo d’Alessandro, Travis Nemkov, Kaiqi Sun, Hong Liu, Anren Song, Andrew A. Monte, Andrew W. Subudhi, Andrew T. Lovering, Daniel Dvorkin, Colleen G. Julian, Christopher G. Kevil, Gopi K. Kolluru, Sruti Shiva, Mark T. Gladwin, Yang Xia, Kirk C. Hansen, Robert C. Roach

Research output: Contribution to journalArticlepeer-review


Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia  through  the so-called  oxygen-dependent  metabolic  regulation,  which  involves  the competitive  binding  of  deoxyhemoglobin  and  glycolytic  enzymes  to  the  N-terminal  cytosolic domain  of  band  3.  This  mechanism  promotes  the  accumulation  of  2,3-DPG,  stabilizing  the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the  Bohr  effect.  Despite  in  vitro  studies,  in  vivo adaptations  to  hypoxia  have  not  yet  been completely elucidated.

Within  the  framework  of  the AltitudeOmics  study,  erythrocytes  were  collected  from  21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following  reascent  after  7days  at 1525m.  UHPLC-MS  metabolomics  results  were  correlated  to physiological and athletic performance parameters.

Immediate  metabolic  adaptations  were  noted as early as a few hours from ascending  to >5000m, and maintained for 16 days at high altitude.  Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism.

Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic


Original languageEnglish
Pages (from-to)3883-3895
Number of pages13
JournalJournal of Proteome Research
Issue number10
Early online date20 Sept 2016
Publication statusPublished - 7 Oct 2016

Bibliographical note

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see


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