Studies with the Plasmodium falciparum hexokinase reveal the PfHT limits the rate of glucose entry into glycolysis

Erick T. Tjhin, Henry M. Staines, Donelly A. Van Schalkwyk, Sanjeev Krishna, Kevin J. Saliba

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3182-3187
Number of pages6
JournalFEBS Letters
Volume587
Issue number19
DOIs
Publication statusPublished - 2013

Keywords

  • Plasmodium
  • glucokinase
  • glucose
  • malaria

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