Sanne de Bruin

126 Chapter 5 metabolome or proteome analyses, identifying a metabolic fingerprint on a specific time point under specific conditions. The big limitation of most studies is that these metabolic changes are only studied during normal aging and during in vitro storage of RCCs. Studies of themetabolic recov- ery of stored RCCs after transfusion are limited, while this information could determine how storage techniques should be adjusted to further improve RCC quality. Superiority of fresh RCCs above stored RCCs still remains questionable for at least two reasons. First, contradictory results have been published about clearance in comparing fresh with stored RCCs 8,9 . And secondly, no effect onmortality is seen inmultiple randomized controlled trials comparing fresh blood with longer stored RCCs 10–13 . A review summarizing studies focusing onmetabolic changes in erythrocytes and RCCs during aging in vivo , in vitro and after transfusion is still lacking. This review aims to summarize all current knowledge on the metabolic changes in these three different conditions. Metabolism of aging erythrocytes The life cycle of erythrocytes starts in the bone marrow. After the differentiation from hematopoietic stemcells to reticulocytes in the bonemarrow, reticulocytes are released into the circulation 14 . Reticulocytes have already lost their nucleus, but still contain some residual RNA 15 . In two to three days, after being released into the circulation, the reticulocytes mature into erythrocytes 16 . This phase of maturation is characterized by the elimination of all internal membrane bound organelles includingmitochondria 17 . The most relevant metabolic change of this phase for the red blood cells is that reticulocytes still have a citric acid cycle 18 , while after maturation the erythrocytes are dependent on the energy production by the glycolysis to fulfil their function. Glycolysis During glycolysis glucose is converted into lactate via multiple enzymatic reactions, which leads to a net production of two molecules ATP per molecule glucose (see figure 1). In in vivo aged erythrocytes ATP levels decrease with 20-32% 19–22 while lactate is accumulating 21 . The current opinion is that glycolytic activity decreases when eryth- rocytes age. This hypothesis is supported by the fact that ATP levels decrease and the activity of different enzymes of the glycolysis is altered during aging 21,23–25 . The rate limiting enzyme in the glycolysis, phosphofructokinase (PFK), which converts fruc-