Abstract
Although intraerythrocytic ATP and 2,3-bisphophoglycerate (2,3-BPG) are known as direct indicators of the viability of preserved red blood cells and the efficiency of post-transfusion oxygen delivery, no current blood storage method in practical use has succeeded in maintaining both these metabolites at high levels for long periods. In this study, we constructed a mathematical kinetic model of comprehensive metabolism in red blood cells stored in a recently developed blood storage solution containing adenine and guanosine, which can maintain both ATP and 2,3-BPG. The predicted dynamics of metabolic intermediates in glycolysis, the pentose phosphate pathway, and purine salvage pathway were consistent with time-series metabolome data measured with capillary electrophoresis time-of-flight mass spectrometry over 5 weeks of storage. From the analysis of the simulation model, the metabolic roles and fates of the 2 major additives were illustrated: (1) adenine could enlarge the adenylate pool, which maintains constant ATP levels throughout the storage period and leads to production of metabolic waste, including hypoxanthine; (2) adenine also induces the consumption of ribose phosphates, which results in 2,3-BPG reduction, while (3) guanosine is converted to ribose phosphates, which can boost the activity of upper glycolysis and result in the efficient production of ATP and 2,3-BPG. This is the first attempt to clarify the underlying metabolic mechanism for maintaining levels of both ATP and 2,3-BPG in stored red blood cells with in silico analysis, as well as to analyze the trade-off and the interlock phenomena between the benefits and possible side effects of the storage-solution additives.
Highlights
In the last 3 decades, various additive solutions for blood storage have been developed to prevent storage lesions, including metabolic or physiologic changes
A PAGGGM-stored red blood cells (RBCs) model was developed by refinement of our previous model of coldstored RBC metabolism in MAP-solution [9] to meet the difference in environmental or intracellular conditions
The model was validated by comparison with timeseries metabolomics data from CE-TOFMS experiments during long-term cold storage of RBCs
Summary
In the last 3 decades, various additive solutions for blood storage have been developed to prevent storage lesions, including metabolic or physiologic changes. The principal indicators of metabolic deterioration are the decrease in adenosine-59-triphosphate (ATP) and 2,3-bisphosphoglycerate (2,3-BPG) levels. Irreversible change in cell shape and loss of membrane plasticity are strongly associated with ATP depletion during storage [4]. Under these circumstances, efforts to improve RBC storage methods have focused on optimizing energy-producing ATP and 2,3-BPG [4]. Current additive solutions do not maintain constant levels of ATP and 2,3-BPG in RBCs, leading to the rapid decrease in 2,3-BPG and a 30–50% decrease in ATP content over a storage period of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
