Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2017
Erindi/veggspjald / Talk/poster E51
Höfundar / Authors: Freyr Jóhannsson, Steinn Guðmundsson, Giuseppe Paglia, Sveinn Guðmundsson, Bernhard Palsson, Ólafur E. Sigurjónsson and Óttar Rolfsson
Starfsvettvangur / Affiliations: Háskóli Íslands, kerfisslífræðisetur
Kynnir / Presenter: Freyr Jóhannsson
Platelets deteriorate over time during their storage within blood banks through a biological process known as platelet storage lesion (PSL). Here we describe the refinement of biochemical network of platelet metabolism iAT-PLT-636 and its application to describe and investigate changes in metabolism during platelet storage. Changes to extracellular acetate and citrate were measured in buffy coat and aphaeresis platelet units over 10 days of storage in the platelet additive solution T-Sol. Metabolic network analysis of these data was performed alongside our prior metabolomics data to describe the metabolism of fresh (days 1-3), intermediate (days 4-6), and old (days 7-10) platelets. Changes to metabolism was studied by comparing metabolic model flux predictions of iAT-PLT-636 between stages and between collection methods. Extracellular acetate and glucose contribute most to central carbon metabolism in platelets. The anticoagulant citrate is metabolized in aphaeresis stored platelets and is converted to malate. The consumption of nutrients changes during storage and reflects altered platelet activation profiles following their collection. Irrespective of collection method, a slowdown in oxidative phosphorylation takes place, consistent with mitochondrial dysfunction during PSL. Metabolic enzymes influenced by PSL were identified using and are primarily involved in glycolysis and respiration. Finally, the main contributors to intracellular ammonium and NADPH are highlighted. Future optimization of flux through these pathways provides opportunities to address intracellular pH changes and reactive oxygen species which are both of importance to PSL. The metabolic models provide descriptions of platelet metabolism at steady state and represent a platform for future platelet metabolic research.