The Role of Red Cell Aging in the Diagnosis of Glycolytic Enzyme Defects
During the development from stem cell to mature erythrocyte, the human red cell loses several of its metabolic and synthetic capacities. The mature red cell is devoid of DNA and RNA and therefore lacks the possibility of protein synthesis. With respect to metabolism, the disappearance of mitochondria and ribosomes deprives the erythroid cell from obtaining energy through oxydative phosphorylation and from renewed enzyme required in metabolic processes. As a consequence the mature red cell is almost completely dependent upon anaerobic glycolysis as a source of energy supply during its 120 day mean life span. Despite the limited metabolic capacity of the glycolytic pathway in the mature erythrocyte sufficient ATP is available for processes involved in its optimal functioning i.e. keeping the haem iron in the reduced state, synthesis of glutathione, maintaining the electrochemical gradients over the plasma membrane, salvage of purine nucleotides and protection of hemoglobin against methemoglobin formation and oxidative denaturation. In reticulocytes the energy consumption pattern is completely different. First of all the production of ATP is about 100 times higher than in mature erythrocytes, partly by increased glycolytic enzyme activities and further by a still intact oxidative phosphorylation. The increased activities of glycolytic enzymes in young red cell fractions predominantly concern those of hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase. The increased enzyme activities are linearly correlated with the reticulocyte counts in these fractions. This finding suggests that the presumed age dependency of these enzymes is mainly related to reticulocyte maturation. In patients with hemolytic anemia the diagnosis of a deficiency of one of these enzymes may be masked by an increased reticulocyte number. On the other hand in patients with severe transfusiondependent hemolytic anemia, the diagnosis of an erythrocyte enzymopathy is often troubled by the presence of relatively large amounts of donor erythrocytes with normal enzyme activities. In this paper we present a few examples, mainly concerning abnormal pyruvate kinase, illustrating the above mentioned problems, in the diagnosis of an enzymopathy.
KeywordsHemolytic Anemia Pyruvate Kinase Reticulocyte Count Pyruvate Kinase Activity Lower Density Fraction
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