Hexose permeation pathways in Plasmodium falciparum-infected erythrocytes

Plasmodium falciparum requires glucose as its energy source to multiply wit hin erythrocytes but is separated from plasma by multiple membrane systems. The mechanism of delivery of substrates such as glucose to intraerythrocyt ic parasites is unclear, We have developed a system for robust functional e xpression in Xenopus oocytes of the P. falciparum asexual stage hexose perm ease, PfHT1, and have analyzed substrate specificities of PfHT1. We show th at PfHT1 (a high-affinity glucose transporter, K-m approximate to 1.0 mM) a lso transports fructose (K-m approximate to 11.5 mM), Fructose can replace glucose as an energy source for intraerythrocytic parasites. PfHT1 binds fr uctose in a furanose conformation and glucose in a pyranose form. Fructose transport by PfHT1 is ablated by mutation of a single glutamine residue, Q1 69, which is predicted to lie within helix 5 of the hexose permeation pathw ay. Glucose transport in the Q169N mutant is preserved. Comparison in oocyt es of transport properties of PfHT1 and human facilitative glucose transpor ter (GLUT)1, an archetypal mammalian hexose transporter, combined with stud ies on cultured P, falciparum, has clarified hexose permeation pathways in infected erythrocytes, Glucose and fructose enter erythrocytes through sepa rate permeation pathways. Our studies suggest that both substrates enter pa rasites via PfHT1.