The use of enzymopathic human red cells in the study of malarial parasite
glucose metabolism
E Roth , V Joulin, S Miwa, A Yoshida, J Akatsuka, M Cohen-Solal and R Rosa
Division of Hematology, Montefiore Medical Center/Albert Einstein College
of Medicine, Bronx, NY 10467.
The in vitro growth of Plasmodium falciparum malaria parasites was assayed
in mutant red cells deficient in either diphosphoglycerate mutase (DPGM) or
phosphoglycerate kinase (PGK). In addition, cDNA probes developed for human
DNA sequences coding for these enzymes were used to examine the parasite
genome by means of restriction endonuclease digestion and Southern blot
analysis of parasite DNA. In both types of enzymopathic red cells, parasite
growth was normal. In infected DPGM deficient red cells, no DPGM activity
could be detected, and in normal red cells, DPGM activity declined slightly
in a manner suggestive of parasite catabolism of host protein. However, in
infected PGK deficient red cells, there was a 100-fold increase in PGK
activity, and in normal red cells, a threefold increase in PGK activity was
observed. Parasite PGK could be recovered from isolated parasites, and a
marked increase in heat instability of parasite PGK as compared with the
host cell enzyme was noted. Neither cDNA probe was found to cross- react
with DNA sequences in the parasite genome. It is concluded that the
parasite has no requirement for DPGM, and probably has no gene for this
enzyme. On the other hand, the parasite does require PGK, (an adenosine
triphosphate [ATP] generating enzyme) and synthesizes its own enzyme, which
must have been encoded in the parasite genome. The parasite PGK gene most
likely lacks sufficient homology to be detected by a human cDNA probe.
Enzymopathic red cells are useful tools for elucidating the glycolytic
enzymology of parasites and their co- evolution with their human hosts.
Volume 71,
Issue 5,
pp. 1408-1413,
05/01/1988
Copyright © 1988 by The American Society of Hematology
