Hexose permeation pathways in Plasmodium falciparum-infected erythrocytes.
Plasmodium falciparum requires glucose as its energy source to multiply within erythrocytes but is separated from plasma by multiple membrane systems. The mechanism of delivery of substrates such as glucose to intraerythrocytic parasites is unclear. We have developed a system for robust functional expression in Xenopus oocytes of the P. falciparum asexual stage hexose permease, PfHT1, and have analyzed substrate specificities of PfHT1. We show that PfHT1 (a high-affinity glucose transporter, K(m) approximately 1.0 mM) also transports fructose (K(m) approximately 11.5 mM). Fructose can replace glucose as an energy source for intraerythrocytic parasites. PfHT1 binds fructose in a furanose conformation and glucose in a pyranose form. Fructose transport by PfHT1 is ablated by mutation of a single glutamine residue, Q169, which is predicted to lie within helix 5 of the hexose permeation pathway. Glucose transport in the Q169N mutant is preserved. Comparison in oocytes of transport properties of PfHT1 and human facilitative glucose transporter (GLUT)1, an archetypal mammalian hexose transporter, combined with studies on cultured P. falciparum, has clarified hexose permeation pathways in infected erythrocytes. Glucose and fructose enter erythrocytes through separate permeation pathways. Our studies suggest that both substrates enter parasites via PfHT1.
Woodrow
C J
CJ
Department of Infectious Diseases, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom.
Burchmore
R J
RJ
Krishna
S
S
D000818:Animals; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D005260:Female; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006601:Hexoses / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014982:Xenopus laevis
D051272:Glucose Transporter Type 1; D006601:Hexoses; D009004:Monosaccharide Transport Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C495677:SLC2A1 protein, human; C118145:hexose transporter 1 protein, Plasmodium falciparum; D005632:Fructose; D005947:Glucose