AUTHOR=Bertolone Lorenzo , Shin Hye K. , Stefanoni Davide , Baek Jin Hyen , Gao Yamei , Morrison Evan J. , Nemkov Travis , Thomas Tiffany , Francis Richard O. , Hod Eldad A. , Zimring James C. , Yoshida Tatsuro , Karafin Matthew , Schwartz Joseph , Hudson Krystalyn E. , Spitalnik Steven L. , Buehler Paul W. , D’Alessandro Angelo 

TITLE=ZOOMICS: Comparative Metabolomics of Red Blood Cells From Old World Monkeys and Humans

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.593841

DOI=10.3389/fphys.2020.593841

ISSN=1664-042X

ABSTRACT=<p>As part of the ZOOMICS project, we set out to investigate common and diverging metabolic traits in the blood metabolome across various species by taking advantage of recent developments in high-throughput metabolomics. Here we provide the first comparative metabolomics analysis of fresh and stored human (<italic>n</italic> = 21, 10 males, 11 females), olive baboon (<italic>n</italic> = 20), and rhesus macaque (<italic>n</italic> = 20) red blood cells at baseline and upon 42 days of storage under blood bank conditions. The results indicated similarities and differences across species, which ultimately resulted in a differential propensity to undergo morphological alterations and lyse as a function of the duration of refrigerated storage. Focusing on purine oxidation, carboxylic acid, fatty acid, and arginine metabolism further highlighted species-specific metabolic wiring. For example, through a combination of steady state measurements and <sup>13</sup>C<sub>6</sub><sup>15</sup>N<sub>4</sub>-arginine tracing experiments, we report an increase in arginine catabolism into ornithine in humans, suggestive of species-specific arginase 1 activity and nitric oxide synthesis—an observation that may impact the translatability of cardiovascular disease studies carried out in non-human primates (NHPs). Finally, we correlated metabolic measurements to storage-induced morphological alterations via scanning electron microscopy and hemolysis, which were significantly lower in human red cells compared to both NHPs.</p>