Abstract
Quantitative and qualitative genetic defects of erythrocyte pyruvate kinase (PK) were characterized by electrophoresis, kinetics, stability test and immunologic study.
In quantitative defect, erythrocyte PK isozyme (PK-R1 and PK-R2) was not detectable but PK-M2was present by compensatory mechanism. Severe hemolytic anemia may be caused by the low activity and instability of PK-M2 and the loss of PK production in the mature erythrocyte and splenectomy revealed significant benefit with marked reticulocytosis although the patient has still hemolytic anemia. Cyanide which is toxic to the mitochondria, inhibited ATP production of PK deficient red cells with high reticulocyte count. It is suggested that there may be selective sequestration of reticulocytes by loosing the mitochondria which has an alternate ATP production (TCA cycle) in the spleen.
In qualitative defect, PK-Tokyo I, PK-Nagasaki and PK-Maebashi had high Km for phosphoenolpyruvate (PEP), low Vmax, urea instability and moderate hemolytic anemia but different electrophoretic mobilities in each other. PK-Sapporo and PK-Tsukiji had abnormal nucleotide specificity, high Km for PEP, high Vmax, urea instability and moderate to mild hemolytic anemia. PK-Tsukiji showed low affinity to ADP as well as PEP. The double defects may cause moderate hemolytic anemia despite of high Vmax. After splenectomy, the patient had normal red cell counts with reticulocytosis. Two cases of PK-Tokyo II in different family had low Km (PEP), low Vmax, fast moving bands on electrophoresis, stable enzyme and mild hemolytic anemia. Hemolytic anemia may be mild because of high affinity to PEP and stable enzyme although low Vmax. PK-Ube detected in a search for genetic polymorphism in healthy persons, had abnormal electrophoretic mobility but functionally normal, and no anemia. PK-Ube is considered to be heterozygous and there may be no defect of enzyme reacting site on the PK molecule.
In addition, there were three PK deficiencies in two acute granulocytic leukemias and an erythroleukemia, which showed normal function and electrophoresis and no hemolytic anemia or genetic evidence of PK deficiency. These cases may have secondary PK deficiency because of low enzyme production during erythroblast maturation in myeloproliferative disorders.
