Inhibition of hexose transport and abrogation of pH homeostasis in the intraerythrocytic malaria parasite by an O-3-hexose derivative.
An O-3-hexose derivative, shown previously to inhibit a malaria parasite hexose transporter expressed in Xenopus oocytes as well as to suppress the multiplication of parasites, both in vitro and in vivo, was shown here to block the uptake of hexose sugars into isolated blood-stage parasites. This led to a decline in ATP levels and the loss of intracellular pH control. The results are consistent with those obtained with the cloned transporter. They support the notion that the transporter mediates uptake of glucose into the intraerythrocytic parasite and provide further support for the view that it is a suitable antimalarial drug target.
Saliba
Kevin J
KJ
School of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra ACT 0200, Australia. kevin.saliba@anu.edu.au
Krishna
Sanjeev
S
Kirk
Kiaran
K
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006601:Hexoses / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D009865:Oocytes / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D013997:Time Factors; D014981:Xenopus
D006601:Hexoses; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D005947:Glucose