Functional analysis, overexpression, and kinetic characterization of pyruvate kinase from Plasmodium falciparum

Adenosine Triphosphate Depletion of Erythrocytes Simulates the Phenotype Associated with Pyruvate Kinase Deficiency and Confers Protection againstPlasmodium falciparumIn Vitro

“…Therefore, it is intriguing that, although parasite invasion is inhibited in PKD and NaFtreated erythrocytes, the parasite is able to mature and replicate once it enters the erythrocyte. Of note, it has been reported that P. falciparum parasites can express PfPyrK during infection, allowing parasites to utilize erythrocyte glucose to produce ATP [28]. RT-qPCR analysis of PfPyrK expression in parasitized erythrocytes revealed increased levels of PfPyrK mRNA in parasitized NaF-treated erythrocytes, compared with parasitized normal, thalassemic, and G6PDd parasitized erythrocytes.…”

“…Quantification of P. falciparum pyruvate kinase mRNA. To quantify PfPyrK mRNA, a real-time quantitative polymerase chain reaction (PCR) assay was performed with forward and reverse primers 5 -GACCAAGAACCCAAGACCAA-3 and 5 -ACCACCTGCAGTTTCTCCTG-3 , as described elsewhere [28,29].…”

“…P. falciparum parasites have been shown to possess pyruvate kinase (PfPyrK), making it possible for the parasite to utilize erythrocyte glucose to produce ATP [28]. To test the hypothesis that increased ATP levels in parasitized PKD and NaF-treated erythrocytes were the result of parasite-specific ATP generation via up-regulation of PfPyrK, we determined expression of PfPyrK mRNA in parasitized AA, G6PDd, thalassemic, and NaF-treated erythrocytes by use of reverse-transcription quantitative PCR (RT-qPCR) ( Figure 3D).…”

Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments

“…Furthermore, pepck - ookinetes were motile, although they failed to develop into mature oocysts and subsequent sporozoites, thus blocking transmission. PEPCK-derived PEP can be converted to pyruvate in the cytosol by the glycolytic enzyme, pyruvate kinase 1 [58] and be further catabolized in the mitochondrion TCA cycle [13] generating the ATP required for multiple rounds of DNA replication in sporogony. Alternatively it can enter the apicoplast where it can be converted to pyruvate and acetyl-CoA by pyruvate kinase 2 [59] and apicoplast-resident pyruvate dehydrogenase [60], respectively (Fig 2A).…”

Mechanisms of genetically-based resistance to malaria

“…It has been found that PK activity becomes greatly increased in infected erythrocytes (Min-Oo et al, 2003). PK has also been recognized as a promising target for new drugs against P. falciparum, since the parasite's intraerythrocytic life-cycle is highly dependent on glucose for obtaining energy (Chan and Sim, 2005;Zanella et al, 2007).…”