Glucose‐6‐phosphate metabolism in <i>Plasmodium falciparum</i>

Preuss, Janina; Jortzik, Esther; Becker, Katja

doi:10.1002/iub.1047

Cited by 46 publications

(36 citation statements)

References 69 publications

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“…Glucose is the main energy source of Plasmodium during the asexual blood stage, and the enzymes related to its metabolism are increased around 70-fold during the trophozoite stage [51]. After this point, parasite metabolism decreases during maturation.…”

Section: Discussionmentioning

confidence: 99%

Lys48 ubiquitination during the intraerythrocytic cycle of the rodent malaria parasite, Plasmodium chabaudi

et al. 2017

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Ubiquitination tags proteins for different functions within the cell. One of the most abundant and studied ubiquitin modification is the Lys48 polyubiquitin chain that modifies proteins for their destruction by proteasome. In Plasmodium is proposed that post-translational regulation is fundamental for parasite development during its complex life-cycle; thus, the objective of this work was to analyze the ubiquitination during Plasmodium chabaudi intraerythrocytic stages. Ubiquitinated proteins were detected during intraerythrocytic stages of Plasmodium chabaudi by immunofluorescent microscopy, bidimensional electrophoresis (2-DE) combined with immunoblotting and mass spectrometry. All the studied stages presented protein ubiquitination and Lys48 polyubiquitination with more abundance during the schizont stage. Three ubiquitinated proteins were identified for rings, five for trophozoites and twenty for schizonts. Only proteins detected with a specific anti- Lys48 polyubiquitin antibody were selected for Mass Spectrometry analysis and two of these identified proteins were selected in order to detect the specific amino acid residues where ubiquitin is placed. Ubiquitinated proteins during the ring and trophozoite stages were related with the invasion process and in schizont proteins were related with nucleic acid metabolism, glycolysis and protein biosynthesis. Most of the ubiquitin detection was during the schizont stage and the Lys48 polyubiquitination during this stage was related to proteins that are expected to be abundant during the trophozoite stage. The evidence that these Lys48 polyubiquitinated proteins are tagged for destruction by the proteasome complex suggests that this type of post-translational modification is important in the regulation of protein abundance during the life-cycle and may also contribute to the parasite cell-cycle progression.

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Section: Discussionmentioning

confidence: 99%

Lys48 ubiquitination during the intraerythrocytic cycle of the rodent malaria parasite, Plasmodium chabaudi

et al. 2017

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“…In addition to interfering with host nutrition through altering consumption and absorption, helminths can also affect blood glucose and lipid levels directly. Many pathogens rely on blood glucose for energy [128, 129] and pathogen-induced immune activation is costly, requiring significant increases in resting metabolic rate and glucose utilization [38, 130, 131]. Increasing evidence suggests that host lipids are manipulated by, and allocated to pathogens.…”

Section: Cardio-metabolic Protective Effects Of Helminth Infectionmentioning

confidence: 99%

Cardiovascular disease and type 2 diabetes in evolutionary perspective: A critical role for helminths?

Gurven

Trumble

Stieglitz

et al. 2016

EMPH

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Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases. Chronic infections, especially helminths, may offer protection against heart disease and diabetes through direct and indirect pathways. As part of a strategy to insure their own survival and reproduction, helminths exert multiple cardio-protective effects on their host through their effects on immune function and blood lipid metabolism. Helminths consume blood lipids and glucose, alter lipid metabolism, and modulate immune function towards Th-2 polarization—which combined can lower blood cholesterol, reduce obesity, increase insulin sensitivity, decrease atheroma progression, and reduce likelihood of atherosclerotic plaque rupture. Traditional cardiometabolic risk factors, coupled with the mismatch between our evolved immune systems and modern, hygienic environments may interact in complex ways. In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminths in the etiology of cardio-metabolic disease.

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“…Two gene products required for the function of the non-OxPPP, transaldolase and NAD + kinase, could not be detected in a bioinformatic analysis of completed Plasmodium genomes [17]. However, the ability to label P. falciparum nucleic acids with cells fed [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C-glucose suggests that this non-oxidative arm is intact, because the 1-C position of glucose would not be incorporated into ribose 5-phosphate synthesised via the oxidative arm [19].…”

Section: Pfglupho Is a Target Of The Antimalarial Compound Ellagic Acidmentioning

confidence: 99%

Plasmodium falciparum glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase is a potential drug target

et al. 2015

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The malarial parasite Plasmodium falciparum is exposed to substantial redox challenges during its complex life cycle. In intraerythrocytic parasites, haemoglobin breakdown is a major source of reactive oxygen species. Deficiencies in human glucose‐6‐phosphate dehydrogenase, the initial enzyme in the pentose phosphate pathway (PPP), lead to a disturbed redox equilibrium in infected erythrocytes and partial protection against severe malaria. In P. falciparum, the first two reactions of the PPP are catalysed by the bifunctional enzyme glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase (PfGluPho). This enzyme differs structurally from its human counterparts and represents a potential target for drugs. In the present study we used epitope tagging of endogenous PfGluPho to verify that the enzyme localises to the parasite cytosol. Furthermore, attempted double crossover disruption of the PfGluPho gene indicates that the enzyme is essential for the growth of blood stage parasites. As a further step towards targeting PfGluPho pharmacologically, ellagic acid was characterised as a potent PfGluPho inhibitor with an IC50 of 76 nm. Interestingly, pro‐oxidative drugs or treatment of the parasites with H2O2 only slightly altered PfGluPho expression or activity under the conditions tested. Furthermore, metabolic profiling suggested that pro‐oxidative drugs do not significantly perturb the abundance of PPP intermediates. These data indicate that PfGluPho is essential in asexual parasites, but that the oxidative arm of the PPP is not strongly regulated in response to oxidative challenge.

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Glucose‐6‐phosphate metabolism in Plasmodium falciparum

Cited by 46 publications

References 69 publications

Lys48 ubiquitination during the intraerythrocytic cycle of the rodent malaria parasite, Plasmodium chabaudi

Lys48 ubiquitination during the intraerythrocytic cycle of the rodent malaria parasite, Plasmodium chabaudi

Cardiovascular disease and type 2 diabetes in evolutionary perspective: A critical role for helminths?

Plasmodium falciparum glucose‐6‐phosphate dehydrogenase 6‐phosphogluconolactonase is a potential drug target

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