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Metabolism of stored human and macaque RBC
genetic, pharmacological, dietary, or surgical interven- tions, which are difficult, and sometimes impossible, to achieve with humans. Given their phylogenetic similarity to humans, RM may provide a particularly relevant RBC storage and transfusion model. For example, RM demon-
A
strate similar pathobiology and metabolic derangements common to human trauma patients.2
By combining state-of-the-art targeted and untargeted metabolomics and lipidomics, as well as tracing experi- ments with [1,2,3-13C3]glucose, the present study shows
BCD
EF
Figure 7. Validation experiments on red blood cells and supernatants. (A) Validation via targeted quantitative mass spectrometry-based measurements against sta- ble isotope-labeled internal standards. (B, C) There was a substantial overlap of relative and absolute quantitative measurements for both metabolites showing sim- ilar interspecies concentrations (e.g., glutathione – GSH (B) and significantly different interspecies levels (e.g., arginine) (C). This is further exemplified in (D), in which red dots in the heat map show metabolites from different pathways (including amino acids, glutathione homeostasis, purines, and fatty acids), whose measurements by either method correlated significantly (r2 >0.75). (E) Notably, significant metabolic changes during storage, illustrated in the heat map, recapitulate the relative quantification measurements in Figure 1 and related supplements. For example, quantitative measurements of urate, carnosine, and arginine are consistent with respective measurements from the exploratory analysis. All measurements are provided in tabular form in Online Supplementary Table S2 and in vectorial form in Online Supplementary Figure S7.
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