Decreased pyrimidine nucleoside monophosphate kinase activity in sickle
erythrocytes
CR Zerez, NA Lachant, KM Lent and KR Tanaka
Department of Medicine, Harbor-UCLA Medical Center, Torrance 90502-2064.
We have previously shown that physiologic concentrations of hemin cause
marked inhibition of several red blood cell (RBC) enzymes. Because
endogenous heme content is elevated in sickle RBCs, we have examined the
activity of hemin-sensitive enzymes in these RBCs. One of the hemin-
sensitive enzymes, pyrimidine nucleoside monophosphate kinase (PNMK), was
shown to have decreased activity in sickle RBCs relative to RBCs of
equivalent cell age. The other hemin-sensitive enzymes, including adenylate
kinase (AK), pyrimidine 5'-nucleotidase (P5N), 6- phosphogluconate
dehydrogenase (6PGD), and aldolase, had activities that were appropriate
for cell age. We have also examined the affinity of the hemin-sensitive
enzymes to hemin. Using two different methods, PNMK was shown to have the
highest binding affinity to hemin. The exquisite sensitivity of PNMK to
inhibition by hemin, coupled with the enzyme's high affinity to hemin, may
account for the decrease in PNMK activity and the lack of significant
decrease in the other hemin- sensitive enzymes in sickle RBCs. These
results suggest that the increased endogenous heme content in sickle RBCs
may be responsible for the decrease in PNMK activity. Whether the increased
endogenous heme content of sickle RBCs can cause hemolysis indirectly by
inhibiting RBC enzymes remains to be determined.
Volume 80,
Issue 2,
pp. 512-516,
07/15/1992
Copyright © 1992 by The American Society of Hematology
