Efflux of 6-deoxy-D-glucose from Plasmodium falciparum-infected erythrocytes via two saturable carriers.
Glucose transport in human erythrocytes infected with the malaria parasite, Plasmodium falciparum, has been studied using 6-deoxy-D-glucose (6DOG) as a non-metabolised glucose analogue. Inhibition studies using cytochalasin B, a powerful inhibitor of the erythrocyte glucose transporter, GLUT1, indicate that in the infected red blood cell (IRBC), glucose is transported via a saturable carrier. However, inhibition is not as complete as in the uninfected erythrocyte. The synergistic inhibition effect of 6DOG entry by niflumic acid, an inhibitor of the non-specific malaria-induced pore, in the presence of cytochalasin B suggests that some glucose may also enter the infected erythrocytes through the pore, if entry via the carrier is blocked. The time course of 6DOG efflux from infected erythrocytes in the presence of cytochalasin B did not follow simple first-order kinetics. To elucidate the kinetic mechanism of 6DOG efflux from the infected erythrocytes, the concentration dependence of efflux was determined. Eight two-compartment kinetic models were simulated, involving first-order pore diffusion and carrier-mediated saturable diffusion in two systems, one ductless and one assuming the existence of a parasitophorous duct. The only two models showing reasonable fits to the efflux data each involve two saturable carriers. It is likely that one of the saturable carriers is associated with the parasite itself. Evidence that the parasite carrier has different inhibitor sensitivities from that of GLUT1 is presented.
Goodyer
I D
ID
School of Biology and Biochemistry, University of Bath, UK.
Hayes
D J
DJ
Eisenthal
R
R
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology*; D051272:Glucose Transporter Type 1; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000097:blood; D009544:Niflumic Acid / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000472:pathogenicity*
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D003571:Cytochalasin B; D009544:Niflumic Acid; D003847:Deoxyglucose; C037904:6-deoxyglucose; D010693:Phloretin