Decrease in subunit aggregation of phosphoribosylpyrophosphate synthetase:
a mechanism for decreased nucleotide concentrations in pyruvate
kinase-deficient human erythrocytes
CR Zerez, NA Lachant and KR Tanaka
Pyruvate kinase (PK)-deficient RBCs have several unexplained metabolic
abnormalities, such as decreased concentrations of total adenine
nucleotides (AMP, ADP, and ATP) and total (oxidized and reduced)
nicotinamide adenine dinucleotide (NAD). Because 5-phosphoribosyl-1-
pyrophosphate (PRPP) is an intermediate in the synthesis of adenine
nucleotides and NAD, we investigated PRPP synthetase (PRPPS), the enzyme
responsible for PRPP synthesis. This enzyme is regulated, in part, by
changes in its state of subunit aggregation. The proportion of aggregated
PRPPS can be altered in vitro by ATP and 2,3- diphosphoglycerate (DPG).
Because PK-deficient RBCs have decreased ATP and increased DPG
concentrations, we examined the state of subunit aggregation of PRPPS in
RBCs from normal and PK-deficient subjects, using gel permeation
chromatography. Young normal RBCs have more aggregated PRPPS than do older
RBCs. In contrast, due to their decreased ATP and increased DPG
concentrations, PK-deficient RBCs contain less aggregated PRPPS than do
RBCs of comparable age without PK deficiency. These data suggest that PRPPS
should be less active in vivo in PK-deficient RBCs. This may play a key
role in mediating the decreases in total adenine nucleotide and total NAD
concentrations in these RBCs.
Volume 68,
Issue 5,
pp. 1024-1029,
11/01/1986
Copyright © 1986 by The American Society of Hematology
