Abstract
Temperature plays a fundamental role in biology, influencing cellular function, chemical reaction rates, molecular structures, and interactions. While the temperature dependence of many biochemical reactions is well defined in vitro, the effect of temperature on metabolic function at the network level is poorly understood, and it remains an important challenge in optimizing the storage of cells and tissues at lower temperatures. Here, we used time-course metabolomic data and systems biology approaches to characterize the effects of storage temperature on human platelets (PLTs) in a platelet additive solution. We observed that changes to the metabolome with storage time do not simply scale with temperature but instead display complex temperature dependence, with only a small subset of metabolites following an Arrhenius-type relationship. Investigation of PLT energy metabolism through integration with computational modeling revealed that oxidative metabolism is more sensitive to temperature changes than glycolysis. The increased contribution of glycolysis to ATP turnover at lower temperatures indicates a stronger glycolytic phenotype with decreasing storage temperature. More broadly, these results demonstrate that the temperature dependence of the PLT metabolic network is not uniform, suggesting that efforts to improve the health of stored PLTs could be targeted at specific pathways.