Alterations in metabolic energetics and cation transport during aging of red cells.

With the total life span of the human red cell averaging 120 days, about 0.8 per cent of the circulating erythrocytes disintegrate daily. Normal red cell destruction has been attributed to extraand intracorpuscular factors (1, 2); until recently, little attention has been paid to the intrinsic processes of impaired function in normal red cells that may lead to possible disintegration. The metabolic energy of the red cell is predominantly derived from glycolytic mechanisms and is utilized to maintain transport and membrane functions and to prevent the auto-oxidation of hemoglobin (3). This investigation was designed to ascertain whether alterations in glycolysis and the activity of certain crucial enzymes concerned in the Embden-Meyerhof path occur with the in vivo aging of circulating red cells. Centrifugation of blood aggregates young red cells (including reticulocytes) in the top layers of the packed red cell column (4, 5). Examination of layers of centrifuged red cells after Fe59 administration reveals that, five to 15 days later, high radioactivity is incorporated in the top fraction, while at subsequent stages in the life span, the greatest radioactivity is present in the bottom layer (6, 7). Fractionation of red cell samples on the basis of increasing density of the erythrocyte population with age has revealed decreases in content of water, solids and cations (4, 8), lipids (7) and enzyme activity (5) with age. Some chemical and enzyme activities of normal cells are lower than erythrocyte values from subjects during a reticulocyte response (9-12). Examination of the rate of glucose disappearance, the activity of phosphohexose isomerase, aldolase and lactic apodehydrogenase and the concentration of phosphorylated intermediates of the Embden-Meyerhof path for red cell populations fractionated by differential centrifugation indicates a decrease in glycolytic and enzyme activity for old cell fractions. Energy-dependent cation transport systems also show some diminution.