The human malaria parasite Plasmodium falciparum is not dependent on host coenzyme A biosynthesis.
Pantothenate, a precursor of the fundamental enzyme cofactor coenzyme A (CoA), is essential for growth of the intraerythrocytic stage of human and avian malaria parasites. Avian malaria parasites have been reported to be incapable of de novo CoA synthesis and instead salvage CoA from the host erythrocyte; hence, pantothenate is required for CoA biosynthesis within the host cell and not the parasite itself. Whether the same is true of the intraerythrocytic stage of the human malaria parasite, Plasmodium falciparum, remained to be established. In this study we investigated the metabolic fate of [(14)C]pantothenate within uninfected and P. falciparum-infected human erythrocytes. We provide evidence consistent with normal human erythrocytes, unlike rat erythrocytes (which have been reported to possess an incomplete CoA biosynthesis pathway), being capable of CoA biosynthesis from pantothenate. We also show that CoA biosynthesis is substantially higher in P. falciparum-infected erythrocytes and that P. falciparum, unlike its avian counterpart, generates most of the CoA synthesized in the infected erythrocyte, presumably necessitated by insufficient CoA biosynthesis in the host erythrocyte. Our data raise the possibility that malaria parasites rationalize their biosynthetic activity depending on the capacity of their host cell to synthesize the metabolites they require.
Spry
Christina
C
Research School of Biology, College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT 0200, Australia.
Saliba
Kevin J
KJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003065:Coenzyme A / Q000737:chemistry*; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology; D008954:Models, Biological; D008956:Models, Chemical; D010205:Pantothenic Acid / Q000493:pharmacokinetics; D010766:Phosphorylation; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000378:metabolism; D013997:Time Factors
D015800:Protozoan Proteins; D010205:Pantothenic Acid; D003065:Coenzyme A