Causal mechanisms of multiple acquired red cell enzyme defects in a patient with acquired dyserythropoiesis.
A patient with an unclassified form of acquired dyserythropoiesis was found to have multiple defects in erythrocyte enzyme activity, involving especially pyruvate kinase (PK), glucose phosphate isomerase (GPI), and phosphofructokinase (PFK). The PK activity defect was associated with a normal concentration of PK-related antigen, and the enzyme could be reactivated during the procedure of partial purification of the enzyme. The concentration of GPI-related antigen was as reduced as the GPI enzymatic activity, and the defect was not improved by any treatment (cross-incubation of red cells or treatment of the hemolysate by SH reagents); the residual enzyme had a normal stability to heat, and a normal electrophoretic and electrofocusing pattern. The PFK activity defect was not improved either by cross-incubation of red cells or by treatment with SH reagents. Immunologic data with antimuscle and antileukocyte antisera seemed to indicate that the defect involved especially the muscle-type subunit of erythrocyte PFK. In agreement with this assumption was the fact that deficient PFK was markedly more inhibited by ATP than normal enzyme. Changes similar to those of deficient PFK herein studied were noted for PFK of unfractionated erythrocytes from premature newborns or of "old" erythrocytes from full-term infants. It appeared that each of the three enzyme defects detected in the patient could be due to a different mechanism, involving post-translational changes, decreased synthesis, and possible reversion of the genetic regulation mechanisms of the abnormal erythroid precursors toward a fetal type. The possible relationships between these various phenomena and the nature of a hypothetical common underlying cause are discussed.
D000746:Anemia, Hemolytic, Congenital Nonspherocytic; D004912:Erythrocytes / Q000201:enzymology*; D004920:Erythropoiesis; D005260:Female; D005312:Fetal Blood / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D008875:Middle Aged; D010732:Phosphofructokinase-1 / Q000172:deficiency; D011770:Pyruvate Kinase / Q000172:deficiency
D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase