Impaired erythrocyte phosphoribosylpyrophosphate formation in hemolytic
anemia due to pyruvate kinase deficiency
CR Zerez, MD Wong, NA Lachant and KR Tanaka
Department of Medicine, Harbor-UCLA Medical Center, University of
California, School of Medicine, Torrance 90509.
RBCs from patients with hemolytic anemia due to pyruvate kinase (PK)
deficiency are characterized by a decreased total adenine and pyridine
nucleotide content. Because phosphoribosylpyrophosphate (PRPP) is a
precursor of both adenine and pyridine nucleotides, we investigated the
ability of intact PK-deficient RBCs to accumulate PRPP. The rate of PRPP
formation in normal RBCs (n = 11) was 2.89 +/- 0.80 nmol/min.mL RBCs. In
contrast, the rate of PRPP formation in PK-deficient RBCs (n = 4) was
markedly impaired at 1.03 +/- 0.39 nmol/min.mL RBCs. Impaired PRPP
formation in these cells was not due to the higher proportion of
reticulocytes. To study the mechanism of impaired PRPP formation, PK
deficiency was simulated by incubating normal RBCs with fluoride. In normal
RBCs, fluoride inhibited PRPP formation, caused adenosine triphosphate
(ATP) depletion, prevented 2,3-diphosphoglycerate (DPG) depletion, and
inhibited pentose phosphate shunt (PPS) activity. These results together
with other data suggest that impaired PRPP formation is mediated by changes
in ATP and DPG concentration, which lead to decreased PPS and perhaps
decreased hexokinase and PRPP synthetase activities. Impaired PRPP
formation may be a mechanism for the decreased adenine and pyridine
nucleotide content in PK-deficient RBCs.
Volume 72,
Issue 2,
pp. 500-506,
08/01/1988
Copyright © 1988 by The American Society of Hematology
