TY - JOUR
T1 - Resistance of glucose-6-phosphate dehydrogenase deficiency to malaria
T2 - Effects of fava bean hydroxypyrimidine glucosides on Plasmodium falciparum growth in culture and on the phagocytosis of infected cells
AU - Ginsburg, H.
AU - Atamna, H.
AU - Shalmiev, G.
AU - Kanaani, J.
AU - Krugliak, M.
PY - 1996
Y1 - 1996
N2 - The balanced polymorphism of glucose-6-phosphate dehydrogenase deficiency (G6PD-) is believed to have evolved through the selective pressure of malaria combined with consumption of fava beans. The implicated fava bean constituents are the hydroxypyrimidine glucosides vicine and convicine, which upon hydrolysis of their β-O-glucosidic bond, become potent pro-oxidants. In this work we show that the glucosides inhibit the growth of Plasmodium falciparum, increase the hexose-monophosphate shunt activity and the phagocytosis of malaria-infected erythrocytes. These activities are exacerbated in the presence of β-glucosidase, implicating their pro-oxidant aglycones in the toxic effect, and are more pronounced in infected G6PD- erythrocytes. These results suggest that G6PD- infected erythrocytes are more susceptible to phagocytic cells, and that fava bean pro-oxidants are more efficiently suppressing parasite propagation in G6PD- erythrocytes, either by directly affecting parasite growth, or by means of enhanced phagocytic elimination of infected cells. The present findings could account for the relative resistance of G6PD- bearers to falciparum malaria, and establish a link between dietary habits and malaria in the selection of the G69D- genotype.
AB - The balanced polymorphism of glucose-6-phosphate dehydrogenase deficiency (G6PD-) is believed to have evolved through the selective pressure of malaria combined with consumption of fava beans. The implicated fava bean constituents are the hydroxypyrimidine glucosides vicine and convicine, which upon hydrolysis of their β-O-glucosidic bond, become potent pro-oxidants. In this work we show that the glucosides inhibit the growth of Plasmodium falciparum, increase the hexose-monophosphate shunt activity and the phagocytosis of malaria-infected erythrocytes. These activities are exacerbated in the presence of β-glucosidase, implicating their pro-oxidant aglycones in the toxic effect, and are more pronounced in infected G6PD- erythrocytes. These results suggest that G6PD- infected erythrocytes are more susceptible to phagocytic cells, and that fava bean pro-oxidants are more efficiently suppressing parasite propagation in G6PD- erythrocytes, either by directly affecting parasite growth, or by means of enhanced phagocytic elimination of infected cells. The present findings could account for the relative resistance of G6PD- bearers to falciparum malaria, and establish a link between dietary habits and malaria in the selection of the G69D- genotype.
KW - Convicine
KW - Glucose-6-phosphate dehydrogenase deficiency
KW - Hexose monophosphate
KW - Phagocytosis
KW - Plasmodium falciparum
KW - Shunt activity
KW - Vicine
UR - http://www.scopus.com/inward/record.url?scp=0029899980&partnerID=8YFLogxK
U2 - 10.1017/s0031182000066221
DO - 10.1017/s0031182000066221
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C2 - 8710417
AN - SCOPUS:0029899980
SN - 0031-1820
VL - 113
SP - 7
EP - 18
JO - Parasitology
JF - Parasitology
IS - 1
ER -