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Non-canonical metabolic pathways in the malaria parasite detected by isotope-tracing metabolomics. | LitMetric

Non-canonical metabolic pathways in the malaria parasite detected by isotope-tracing metabolomics.

Mol Syst Biol

Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Vic., Australia.

Published: April 2021

AI Article Synopsis

  • - The malaria parasite *Plasmodium falciparum* grows quickly in human red blood cells by taking nutrients, but there's been a lack of comprehensive research on its metabolism.
  • - Researchers created a draft metabolome of the parasite and host, identifying 911 metabolites for *P. falciparum* and 577 for red blood cells, revealing that a significant portion of metabolic reactions were unaccounted for by genome predictions.
  • - The study uncovered four unknown enzymes that play crucial roles in processes like lipid metabolism and parasite growth, pointing to potential new targets for malaria treatment efforts.

Article Abstract

The malaria parasite, Plasmodium falciparum, proliferates rapidly in human erythrocytes by actively scavenging multiple carbon sources and essential nutrients from its host cell. However, a global overview of the metabolic capacity of intraerythrocytic stages is missing. Using multiplex C-labelling coupled with untargeted mass spectrometry and unsupervised isotopologue grouping, we have generated a draft metabolome of P. falciparum and its host erythrocyte consisting of 911 and 577 metabolites, respectively, corresponding to 41% of metabolites and over 70% of the metabolic reaction predicted from the parasite genome. An additional 89 metabolites and 92 reactions were identified that were not predicted from genomic reconstructions, with the largest group being associated with metabolite damage-repair systems. Validation of the draft metabolome revealed four previously uncharacterised enzymes which impact isoprenoid biosynthesis, lipid homeostasis and mitochondrial metabolism and are necessary for parasite development and proliferation. This study defines the metabolic fate of multiple carbon sources in P. falciparum, and highlights the activity of metabolite repair pathways in these rapidly growing parasite stages, opening new avenues for drug discovery.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022201PMC
http://dx.doi.org/10.15252/msb.202010023DOI Listing

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