Kj. Saliba et al., TRANSPORT AND METABOLISM OF THE ESSENTIAL VITAMIN PANTOTHENIC-ACID INHUMAN ERYTHROCYTES INFECTED WITH THE MALARIA PARASITE PLASMODIUM-FALCIPARUM, The Journal of biological chemistry, 273(17), 1998, pp. 10190-10195
The growth of the human malaria parasite, Plasmodium falciparum, withi
n its host erythrocyte is reliant on the uptake of a number of essenti
al nutrients from the extracellular medium. One of these is pantotheni
c acid, a water-soluble vitamin that is a precursor of coenzyme A. In
this study we show that normal uninfected erythrocytes are impermeable
to pantothenate but that the vitamin is taken up rapidly into malaria
-infected cells via a transport pathway that has the characteristics (
furosemide sensitivity, nonsaturability) of previously characterized,
broad specificity permeation pathways induced by the intracellular par
asite in the host cell membrane. The transport of pantothenate therefo
re constitutes a critical physiological role for these pathways. Insid
e the parasitized cell pantothenate undergoes phosphorylation, the fir
st step in its conversion to coenzyme A. Parasites within saponin-perm
eabilized erythrocytes were shown to take up and phosphorylate pantoth
enate, consistent with the intracellular parasite having both a pantot
henate transporter and a pantothenate kinase, Comparisons of the rate
of phosphorylation of pantothenate by lysates prepared from uninfected
and infected erythrocytes revealed that the pantothenate kinase activ
ity of the P., falciparum trophozoite is some 10-fold higher than that
of its host cell and that most, if not all, of the phosphorylation of
pantothenate within the malaria-infected cell occurs within the intra
cellular parasite. These results contrast with those of previous studi
es in which it was proposed that the avian malaria parasite Plasmodium
lophurae lacks pantothenate kinase (as well as the other enzymes for
the synthesis of coenzyme A) and is reliant upon the uptake of preform
ed coenzyme A from the host cell cytosol.