Sanne de Bruin

127 Metabolic changes in erythrocytes in vivo, during storage and after transfusion tose-6-phosphate into fructose-1,6-biphosphate is significantly influenced by aging of the erythrocyte. It has been observed that PFK activity is significantly lower in the oldest erythrocyte fraction compared to the youngest fraction 23 . Changes in enzyme activity are not limited to PFK, several other enzymes are also influenced by the aging process. Phosphohexokinase and aldolase activity progressively decrease during the aging of erythrocytes 21,23 . Pyruvate kinase activity, which is responsible for the penultimate step in the glycolysis, is also significantly decreased in the oldest erythrocyte fraction 24 . And finally, it is seen that some isoenzymes of lactate dehydrogenase (LDH), the enzyme responsible for converting pyruvic acid into lactate, are destroyed or inactivated over time 25 . Consequently, aged erythrocytes can utilize less glucose than younger cells 21 . Furthermore, it is hypothesized that in younger cells relatively more glucose is entering other pathways than the glycolysis, because relatively less glucose is converted into lactate 21 . Luebering-Rapoport shunt A second important metabolic pathway parallel to the glycolysis is the Lueber- ing-Rapoport shunt. In this pathway 1,3-bisphosphoglycerate is converted into 2,3-DPG (see figure 1). 2,3-DPG is important in the oxygen delivery capacity of the erythrocytes and the concentration of 2,3-DPG in erythrocytes is therefore relatively high compared to other cells in the human body 6 . When 2,3-DPG is produced, one step of the glycolysis is bypassed and thereby this process indirectly costs ATP. Similar to the glycolysis, also the Luebering-Rapoport shunt activity decreases as erythrocytes age. Multiple studies have shown an age dependent decrease of 2,3-DPG levels in the range of 13-42% 21,22,26 . However, the activity of 2,3-diphosphoglycerate mutase, the enzyme responsible for the conversion of 1,3-diphosphoglycerate into 2,3-DPG, remains constant over time 23 . This suggests that the decreased 2,3-DPG levels are caused by diminished glycolytic activity resulting in less substrate for this shunt. 5