Glucose-6-phosphate metabolism in Plasmodium falciparum.
Malaria is still one of the most threatening diseases worldwide. The high drug resistance rates of malarial parasites make its eradication difficult and furthermore necessitate the development of new antimalarial drugs. Plasmodium falciparum is responsible for severe malaria and therefore of special interest with regard to drug development. Plasmodium parasites are highly dependent on glucose and very sensitive to oxidative stress; two observations that drew interest to the pentose phosphate pathway (PPP) with its key enzyme glucose-6-phosphate dehydrogenase (G6PD). A central position of the PPP for malaria parasites is supported by the fact that human G6PD deficiency protects to a certain degree from malaria infections. Plasmodium parasites and the human host possess a complete PPP, both of which seem to be important for the parasites. Interestingly, there are major differences between parasite and human G6PD, making the enzyme of Plasmodium a promising target for antimalarial drug design. This review gives an overview of the current state of research on glucose-6-phosphate metabolism in P. falciparum and its impact on malaria infections. Moreover, the unique characteristics of the enzyme G6PD in P. falciparum are discussed, upon which its current status as promising target for drug development is based.
Chair of Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, Giessen, Germany.
Janina
J
Preuss
Esther
E
Jortzik
Katja
K
Becker
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D001692:Biological Transport; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D015195:Drug Design; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000378:metabolism*
D000962:Antimalarials; D009249:NADP; D019298:Glucose-6-Phosphate; D005954:Glucosephosphate Dehydrogenase; D006593:Hexokinase; D002265:Carboxylic Ester Hydrolases; C022363:6-phosphogluconolactonase