Plasmodium falciparum carbohydrate metabolism: a connection between host cell and parasite.
Selected aspects of the metabolism of Plasmodium falciparum are reviewed, but conclusions based on the study of other species of plasmodia are intentionally not included since these may not be applicable. The parasites increase glucose consumption 50-100 fold as compared to uninfected red cells; most of the glucose is metabolized to lactic acid. The parasite contains a complete set of glycolytic enzymes. Some enzymes such a hexokinase, enolase and pyruvate kinase are vastly increased over corresponding levels in uninfected red cells. However, the pathway for synthesizing 2,3-diphosphoglycerate (2,3-DPG) is absent. Parasitized red cells show a decline in the concentration of 2,3-DPG which may function as an inhibitor for certain essential enzyme pathways. Pentose shunt activity is increased in absolute terms, but as a percent of total glucose consumption, there is a decrease during parasite infection of the red cell. The parasite contains a gene for G6PD and can produce a small quantity of parasite-encoded enzyme. It is not clear if the production of this enzyme can be up-regulated in G6PG deficient host red cells. The NADPH normally produced by the pentose shunt can be obtained from other parasite pathways (such as glutamate dehydrogenase). NADPH may subserve additional needs in the infected red cell such as driving diribonucleotide reductase activity--a rate limiting enzyme in DNA synthesis. The role of NADPH in protecting the parasite-red cell system against oxidative stress (via glutathione reduction) remains controversial. Parasitized red cells contain about 10 times more NAD(H) than uninfected red cells, but the NADP(H) content is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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Division of Hematology, Albert Einstein College of Medicine, Bronx, NY 10467.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D050260:Carbohydrate Metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis; D006790:Host-Parasite Interactions; D006801:Humans; D010427:Pentose Phosphate Pathway; D010963:Plasmodium falciparum / Q000378:metabolism*
D000255:Adenosine Triphosphate; D005978:Glutathione