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Glycolysis in Plasmodium falciparum results in modulation of host enzyme activities
oleh: Monika Mehta, Haripalsingh M. Sonawat & Shobhona Sharma
| Format: | Article |
|---|---|
| Diterbitkan: | Wolters Kluwer Medknow Publications 2006-09-01 |
Deskripsi
Background & objectives: Plasmodium falciparum, the causative agent of the most serious formof malaria, infects about 5–10% of the world human population per year. It is well established thatthe erythrocytic stages of the malaria parasite rely mainly on glycolysis for their energy supply. Inthe present study, the glucose utilisation of erythrocyte population with parasitaemia levels similarto that of malaria patients was measured. The results allowed us to assess the effect of the parasiteson the glucose utilisation of the vast majority of uninfected erythrocytes.Methods: Using [2-13C]glucose and nuclear magnetic resonance (NMR) technique, the glucoseutilisation in normal red blood cell (RBC) and P. falciparum infected red blood cell (IRBC)populations was measured. The IRBC population consisted of > 96% RBC and < 4% of parasiteinfected red blood cells (PRBC). The glycolytic enzymes were assayed to assess the effect ofinfected red cells on the enzymatic activities of uninfected ones.Results: The rate of glucose utilisation by IRBC was considerably higher than that of RBC. Uponaddition of 25% v/v conditioned culture medium (CM) of IRBC, RBCs exhibited a significantdecrease in glucose utilisation. The CM could directly inhibit the activities of RBC glycolyticenzymes—phosphofructokinase (PFK) and pyruvate kinase (PK), without interfering with theactivity of the pentose phosphate pathway enzyme—glucose-6-phosphate dehydrogenase(G-6-PD).Interpretation & conclusion: The present study showed that the clinical level of P. falciparuminfected RBCs (< 4% parasitaemia) significantly enhance the glycolytic flux as well as downregulatethe glucose utilisation rate in the majority of uninfected RBC population. The mechanismof inhibition seems to be direct inhibition of the regulatory glycolytic enzymes—PFK and PK.