When present as a trophozoite in human erythrocytes,
the malarial parasite Plasmodium falciparum exhibits
an intense glutathione metabolism. Glutathione plays
a role not only in antioxidative defense and in maintaining
the reducing environment of the cytosol. Many
of the known glutathione-dependent processes are
directly related to the specific lifestyle of the parasite.
Reduced glutathione (GSH) supports rapid cell
growth by providing electrons for deoxyribonucleotide
synthesis and it takes part in detoxifying
heme, a product of hemoglobin digestion. Free radicals
generated in the parasite can be scavenged in reaction
sequences involving the thiyl radical GS as
well as the thiolate GS. As a substrate of glutathione
S-transferase, glutathione is conjugated to nondegradable
compounds including antimalarial drugs.
Furthermore, it is the coenzyme of the glyoxalase system
which detoxifies methylglyoxal, a byproduct of
the intense glycolysis taking place in the trophozoite.
Proteins involved in GSH-dependent processes include
glutathione reductase, glutaredoxins, glyoxalase
I and II, glutathione S-transferases, and thioredoxins.
These proteins, as well as the ATP-dependent
enzymes of glutathione synthesis, are studied as factors
in the pathophysiology of malaria but also as potential
drug targets. Methylene blue, an inhibitor of
the structurally known P. falciparum glutathione reductase,
appears to be a promising antimalarial medication
when given in combination with chloroquine.
Biological Chemistry keeps you up-to-date with the latest advances in the molecular life sciences. The journal publishes Research Articles, Short Communications, Reviews and Minireviews. Areas include: general biochemistry/pathobiochemistry, structural biology, molecular and cellular biology, genetics and epigenetics, virology, molecular medicine, plant molecular biology/biochemistry and novel experimental methodologies.