title: Studies with the Plasmodium falciparum hexokinase reveal that PfHT limits the rate of glucose entry into glycolysis.
abstract: To characterise plasmodial glycolysis, we generated two transgenic Plasmodium falciparum lines, one expressing P. falciparum hexokinase (PfHK) tagged with GFP (3D7-PfHK(GFP)) 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-[(14)C]2-DG at the same rate as control parasites. Transgenic parasites overexpressing the parasite's glucose transporter (PfHT) accumulated phospho-[(14)C]2-DG at a higher rate, consistent with glucose transport limiting glucose entry into glycolysis.
authors: Research School of Biology, College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT 0200, Australia.
authors: Erick T
authors: ET
authors: Tjhin
authors: Henry M
authors: HM
authors: Staines
authors: Donelly A
authors: DA
authors: van Schalkwyk
authors: Sanjeev
authors: S
authors: Krishna
authors: Kevin J
authors: KJ
authors: Saliba
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D049452:Green Fluorescent Proteins / Q000235:genetics; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000502:physiology*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000201:enzymology*
chemical_list: D009004:Monosaccharide Transport Proteins; D049452:Green Fluorescent Proteins; D006593:Hexokinase; D005947:Glucose
keywords: Glucose; Hexokinase; Hexose transport; Malaria; Plasmodium