An inherited molecular lesion of erythrocyte pyruvate kinase: Identification of a kinetically aberrant isozyme associated with premature hemolysis

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Abstract

Atypical cases of heritable hemolytic anemia have been noted that conform clinically and biochemically to anemias of the pyruvatekinase (PK)-deficient type, except for the presence of apparently adequate quantities of erythrocyte-PK activity by the usual assay procedure. Investigations of four such anomalous cases, occurring in two unrelated families, are presented. Erythrocytes contained a kinetically aberrant isozyme of pyruvate kinase (PK2). Michaelis constants for the pathologic isozyme relative to phosphoenolpyruvate were over 10-fold greater than control values, but no kinetic abnormality was evident for the second substrate, adenosine diphosphate. PK2 exhibited a pH optimum almost 1 U lower than the wild enzyme form (PK1). Significant differences were also evident in the functional stabilities of the isozymes. Leukocytes were unaffected.

Authors

Donald E. Paglia, William N. Valentine, Marjorie A. Baughan, Denis R. Miller, Claude F. Reed, O. Ross McIntyre