Comparison of effects of green tea catechins on apicomplexan hexose transporters and mammalian orthologues.
Here we have investigated the inhibitory properties of green tea catechins on the Plasmodium falciparum hexose transporter (PfHT), the Babesia bovis hexose transporter 1 (BboHT1) and the mammalian facilitative glucose transporters, GLUT1 and GLUT5, expressed in Xenopus laevis oocytes. (-)-Epicatechin-gallate (ECG) and (-)-epigallocatechin-gallate (EGCG) inhibited D-glucose transport by GLUT1 and PfHT, and D-fructose transport by GLUT5, with apparent K(i) values between 45 and 117 microM. BboHT1 was more potently inhibited by the ungallated catechins (-)-epicatechin (EC) and (-)-epigallocatechin (EGC), with apparent K(i) values of 108 and 168 microM, respectively. Site-directed mutagenesis experiments provided little further support for previously reported models of catechin binding to hexose transporters. Furthermore, P. falciparum growth inhibition by catechins was not affected by the external D-glucose concentration. Our results provide new data on the inhibitory action of catechins against sugar transporters but were unable to elucidate the antimalarial mechanism of action of these agents.
Slavic
Ksenija
K
Centre for Infection, Division of Cellular and Molecular Medicine, St. George's, University of London, Cranmer Terrace, London, UK.
Derbyshire
Elvira T
ET
Naftalin
Richard J
RJ
Krishna
Sanjeev
S
Staines
Henry M
HM
D000818:Animals; D016793:Babesia bovis / Q000201:enzymology*; D002392:Catechin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors*; D051296:Glucose Transporter Type 5 / Q000037:antagonists & inhibitors*; D008322:Mammals; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors*; D009865:Oocytes; D010963:Plasmodium falciparum / Q000201:enzymology*; D013662:Tea / Q000737:chemistry*; D014982:Xenopus laevis
D004791:Enzyme Inhibitors; D051272:Glucose Transporter Type 1; D051296:Glucose Transporter Type 5; D009004:Monosaccharide Transport Proteins; D013662:Tea; D002392:Catechin