A Low Km Phosphoenolpyruvate Mutant in the Amish with Red Cell Pyruvate Kinase Deficiency

Summary. The biochemical heterogeneity of red cell pyruvate kinase (PK)‐deficiency was demonstrated in a study of six patients with this abnormality. Three siblings of an Amish kindred were found to possess a mutant enzyme with a decreased Km phosphoenolpyruvate. In this kindred the Km PEP ranged from 0.018 to 0.024 mM (normal 0.055–0.067 mm). Two deficient patients were found to have an enzyme with a normal Km PEP, while in the sixth patient the Km PEP was increased to 0.120 mM. In all patients the red cells possessed increased quantities of the glycolytic intermediates proximal to the PK step, reduced levels of ATP and reduced glycolysis for cell age. When reconstituted haemolysates from these patients were supplemented with PK, a correction of the glycolytic rate was observed. No acceleration of glycolysis occurred in PK‐supplemented normal or reticulocyte‐rich haemolysates. These studies re‐emphasize the heterogeneity of PK deficiency and demonstrate that this deficiency alone can result in an impairment in red cell glycolysis.