title: Metabolic fate of adenine in red blood cells during storage in SAGM solution.
abstract: BACKGROUND
  Red blood cells (RBCs) are routinely stored and transfused worldwide. Recently, metabolomics have shown that RBCs experience a three-phase metabolic decay process during storage, resulting in the definition of three distinct metabolic phenotypes, occurring between Days 1 and 10, 11 and 17, and 18 and 46. Here we use metabolomics and stable isotope labeling analysis to study adenine metabolism in RBCs.
  
  
  METHODS
  A total of 6 units were prepared in SAGM or modified additive solutions (ASs) containing15N5-adenine. Three of them were spiked with15N5-adenine on Days 10, 14, and 17 during storage. Each unit was sampled 10 times spanning Day 1 to Day 32. At each time point metabolic profiling was performed.
  
  
  RESULTS
  We increased adenine concentration in the AS and we pulsed the adenine concentration during storage and found that in both cases the RBCs' main metabolic pathways were not affected. Our data clearly show that RBCs cannot consume adenine after 18 days of storage, even if it is still present in the storage solution. However, increased levels of adenine influenced S-adenosylmethionine metabolism.
  
  
  CONCLUSIONS
  In this work, we have studied in detail the metabolic fate of adenine during RBC storage in SAGM. Adenine is one of the main substrates used by RBCs, but the metabolic shift observed during storage is not caused by an absence of adenine later in storage. The rate of adenine consumption strongly correlated with duration of storage but not with the amount of adenine present in the AS.
authors: Center for Biomedicine, European Academy of Bolzano/Bozen, Bolzano, Italy. giuseppe.paglia@eurac.edu.|Center for Systems Biology, University of Iceland, Reykjavik, Iceland;. giuseppe.paglia@eurac.edu.
authors: Giuseppe
authors: G
authors: Paglia
authors: The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland.|School of Science and Engineering, Reykjavik University, Reykjavik, Iceland; and.
authors: Ólafur E
authors: ÓE
authors: Sigurjónsson
authors: Sinopia Biosciences, San Diego, California.
authors: Aarash
authors: A
authors: Bordbar
authors: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors: Óttar
authors: Ó
authors: Rolfsson
authors: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors: Manuela
authors: M
authors: Magnusdottir
authors: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.|Sinopia Biosciences, San Diego, California.
authors: Sirus
authors: S
authors: Palsson
authors: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors: Kristine
authors: K
authors: Wichuk
authors: The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland.
authors: Sveinn
authors: S
authors: Gudmundsson
authors: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors: Bernhard O
authors: BO
authors: Palsson
mesh_terms: D000225:Adenine / Q000378:metabolism*; D001793:Blood Preservation / Q000379:methods*; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose; D006801:Humans; D007553:Isotope Labeling; D008353:Mannitol; D055432:Metabolomics; D012965:Sodium Chloride; D013997:Time Factors
chemical_list: C037839:ADSOL; D008353:Mannitol; D012965:Sodium Chloride; D005947:Glucose; D000225:Adenine