Malaria parasite-infected erythrocytes inhibit glucose utilization in uninfected red cells.
The erythrocytic stages of the malaria parasite depend on anaerobic glycolysis for energy. Using [2-13C]glucose and nuclear magnetic resonance, the glucose utilization rate and 2,3-diphosphoglycerate (2,3-DPG) level produced in normal RBCs and Plasmodium falciparum infected red blood cell populations (IRBCs, with <4% parasite infected red cells), were measured. The glucose flux in IRBCs was several-folds greater, was proportional to parasitemia, and maximal at trophozoite stage. The 2,3-DPG levels were disproportionately lower in IRBCs, indicating a downregulation of 2,3-DPG flux in non-parasitized RBCs. This may be due to lowered pH leading to selective differential inhibition of the regulatory glycolytic enzyme phosphofructokinase. This downregulation of the glucose utilization rate in the majority (>96%) of uninfected RBCs in an IRBC population may have physiological implications in malaria patients.
Mehta
Monika
M
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400 005, India.
Sonawat
Haripalsingh M
HM
Sharma
Shobhona
S
D019794:2,3-Diphosphoglycerate / Q000378:metabolism; D000328:Adult; D000818:Animals; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010963:Plasmodium falciparum / Q000502:physiology*
D019794:2,3-Diphosphoglycerate; D005947:Glucose