Abstract
To characterise plasmodial glycolysis, we generated two transgenic Plasmodium falciparum lines, one expressing P. falciparum hexokinase (PfHK) tagged with GFP (3D7-PfHKGFP) and another overexpressing native PfHK (3D7-PfHK+). Contrary to previous reports, we propose that PfHK is cytosolic. The glucose analogue, 2-deoxy-d-glucose (2-DG) was nearly 2-fold less toxic to 3D7-PfHK+ compared with control parasites, supporting PfHK as a potential drug target. Although PfHK activity was higher in 3D7-PfHK+, they accumulated phospho-[14C]2-DG at the same rate as control parasites. Transgenic parasites overexpressing the parasite’s glucose transporter (PfHT) accumulated phospho-[14C]2-DG at a higher rate, consistent with glucose transport limiting glucose entry into glycolysis.
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