TRANSPORT AND METABOLISM OF THE ESSENTIAL VITAMIN PANTOTHENIC-ACID INHUMAN ERYTHROCYTES INFECTED WITH THE MALARIA PARASITE PLASMODIUM-FALCIPARUM

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.