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J. Biol. Chem., Vol. 276, Issue 21, 18115-18121, May 25, 2001
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From the School of Biochemistry and Molecular Biology, Australian
National University, Canberra, Australian Capital Territory
0200, Australia
Pantothenate, the precursor of coenzyme A, is an
essential nutrient for the intraerythrocytic stage of the malaria
parasite Plasmodium falciparum. Pantothenate enters the
malaria-infected erythrocyte via new permeation pathways induced by the
parasite in the host cell membrane (Saliba, K. J., Horner, H. A., and Kirk, K. (1998) J. Biol. Chem. 273, 10190-10195). We show here that pantothenate is taken up by the
intracellular parasite via a novel H+-coupled transporter,
quite different from the Na+-coupled transporters that
mediate pantothenate uptake into mammalian cells. The plasmodial
H+:pantothenate transporter has a low affinity for
pantothenate (Km ~23 mM) and a
stoichiometry of 1 H+:1 pantothenate. It is inhibited by
low concentrations of the bioflavonoid phloretin and the
thiol-modifying agent p-chloromercuribenzene sulfonate. On
entering the parasite, pantothenate is phosphorylated (and thereby
trapped) by an unusually high affinity pantothenate kinase
(Km ~300 nM). The combination of
H+-coupled transporter and kinase provides the parasite
with an efficient, high affinity pantothenate uptake system, which is distinct from that of the host and is therefore an attractive target
for antimalarial chemotherapy.
H+-coupled Pantothenate Transport in the
Intracellular Malaria Parasite*
*
This work was supported by grants from the Australian
National Health and Medical Research Council (971008 and 122814), the Australian Research Council (F97082), and the Ramaciotti Foundations.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Tel.: 61-2-6125-2284;
Fax: 61-2-6125-0313; E-mail: kiaran.kirk@anu.edu.au.
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