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Studies with the Plasmodium falciparum hexokinase reveal that PfHT limits the rate of glucose entry into glycolysis
Author(s) -
Tjhin Erick T.,
Staines Henry M.,
van Schalkwyk Donelly A.,
Krishna Sanjeev,
Saliba Kevin J.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.07.052
Subject(s) - glycolysis , hexokinase , glucose transporter , plasmodium falciparum , cytosol , biochemistry , transporter , biology , chemistry , enzyme , gene , endocrinology , immunology , malaria , insulin
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.