Transport and metabolism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum.
The growth of the human malaria parasite, Plasmodium falciparum, within its host erythrocyte is reliant on the uptake of a number of essential nutrients from the extracellular medium. One of these is pantothenic 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 parasite in the host cell membrane. The transport of pantothenate therefore constitutes a critical physiological role for these pathways. Inside the parasitized cell pantothenate undergoes phosphorylation, the first step in its conversion to coenzyme A. Parasites within saponin-permeabilized erythrocytes were shown to take up and phosphorylate pantothenate, consistent with the intracellular parasite having both a pantothenate 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 activity 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 intracellular parasite. These results contrast with those of previous studies 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 preformed coenzyme A from the host cell cytosol.
Saliba
K J
KJ
Division of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra ACT 0200, Australia.
Horner
H A
HA
Kirk
K
K
D000818:Animals; D001692:Biological Transport; D002457:Cell Extracts; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D010205:Pantothenic Acid / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000378:metabolism*; D012503:Saponins
D002457:Cell Extracts; D012503:Saponins; D010205:Pantothenic Acid; D005665:Furosemide