An @entity74 of erythrocyte XXXX kinase. Identification of a kinetically aberrant isozyme associated with premature hemolysis.

@entity2388 @entity7954 @entity5714 @entity74 @entity857 @entity942
Atypical cases of heritable @entity5714 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 @entity2388 kinase (PK(2)). Michaelis constants for the pathologic isozyme relative to @entity7954 were over 10-fold greater than control values, but no kinetic abnormality was evident for the second substrate, @entity857 . PK(2) exhibited a pH optimum almost 1 U lower than the wild enzyme form (PK(1)). Significant differences were also evident in the functional stabilities of the isozymes. Leukocytes were unaffected. Family studies revealed paternal heterozygosity for quantitative @entity942 of the usual type. Clinically normal maternal relatives and some siblings demonstrated intermediate deviations in erythrocyte-PK kinetics and reaction characteristics compatible with coexistence of normal PK(1) and kinetically abnormal PK(2). @entity5714 in the propositi appeared to require simultaneous inheritance of the gene governing PK(2) production and its presumed allele resulting in quantitative @entity942 . Both @entity74 were traced through three generations, the defective gene in both instances apparently resident on autosomes.A revision of the PK assay technique is suggested, since catalytic inefficiency of PK(2) was manifested only at low substrate concentrations and was therefore undetectable at the relatively high @entity7954 levels employed in the conventional assay.
