Pyruvate kinase Greensboro. A four-generation study of a high K0.5s
(phosphoenolpyruvate) variant [published erratum appears in Blood 1988
Dec;72(6):2082]
WN Valentine, WB Herring, DE Paglia, MC Steuterman, RA Brockway and M Nakatani
Department of Medicine, University of California Center for Health
Sciences, Los Angeles 90024.
The proband with lifelong hemolytic anemia has a high K0.5s
phosphoenolypyruvate (PEP) erythrocyte pyruvate kinase (PK) variant
substantially but incompletely normalized by the allosteric modifier
fructose-1,6-diphosphate (F-1,6-P2) with conversion of sigmoidal to
hyperbolic kinetics. Heterozygotes in four generations express
qualitatively identical but less severely abnormal kinetics and lack overt
hemolysis. Kinetic abnormalities are closely mimicked by sulfhydryl
modification of normal PK. Three distinct clinical and metabolic phenotypes
characterize the proband and two sisters: variant PK and hemolytic anemia,
variant PK without clinical manifestations or hemolysis, and complete
normality. Their mother, whose red cell PK is entirely normal except for a
questionably slightly low Vmax, is postulated to express the gene products
of nonidentical alleles, one encoding a product with mildly less favorable
catalytic characteristics. At low PEP concentrations, the proband and
heterozygotes for the PK mutant express only a very small fraction of
normal PK activity despite apparent inheritance of one normal allele in the
latter. Evidence suggests that disproportionately lowered PK activity may
be a property of a heterotetrameric PK. Illusory abnormalities in
nucleotide specificity are artifacts of diminished substrate affinity
characterizing the mutant PK.
Volume 72,
Issue 3,
pp. 1054-1059,
09/01/1988
Copyright © 1988 by The American Society of Hematology
