ArticleThe Journal of biological chemistry2011
The molecular basis of folate salvage in Plasmodium falciparum: characterization of two folate transporters.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 53 citations in OpenAlex.
- Folate transporters at the plasma membrane of fungi and plants: specificity, mechanism of transport, and importance.Biochemical Society transactions · 2026Review
- Inhibition of PfCLK3 interferes with malaria parasite RNA splicing and explains the mechanism of action of a new class of antimalarial candidates.Antimicrobial agents and chemotherapy · 2026Article
- Direct long-read visualization reveals hidden variation in GCH1 gene copy number and precise expansion steps.BMC genomics · 2025Article
- Direct long read visualization reveals metabolic interplay between two antimalarial drug targets.bioRxiv : the preprint server for biology · 2023Article
- Roles of the apicoplast across the life cycles of rodent and human malaria parasites.The Journal of eukaryotic microbiology · 2022Review
- An apicoplast-resident folate transporter is essential for sporogony of malaria parasites.Cellular microbiology · 2021Article
- Review
- Vitamin and cofactor acquisition in apicomplexans: SynthesisThe Journal of biological chemistry · 2020Review
- Metabolic dependency of chorismate in Plasmodium falciparum suggests an alternative source for the ubiquinone biosynthesis precursor.Scientific reports · 2019Article
- Review on Abyssomicins: Inhibitors of the Chorismate Pathway and Folate Biosynthesis.Molecules (Basel, Switzerland) · 2018Review
- Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.BMC genomics · 2017Article
- The role of folate in malaria - implications for home fortification programmes among children aged 6-59 months.Maternal & child nutrition · 2015Review
- The malaria parasite cation ATPase PfATP4 and its role in the mechanism of action of a new arsenal of antimalarial drugs.International journal for parasitology. Drugs and drug resistance · 2015Review
- Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps.Cell reports · 2015Article
- The molecular basis of antifolate resistance in Plasmodium falciparum: looking beyond point mutations.Annals of the New York Academy of Sciences · 2015Review
- The role of antioxidants treatment on the pathogenesis of malarial infections: a review.Parasitology research · 2014Review
- Transport proteins of parasitic protists and their role in nutrient salvage.Frontiers in plant science · 2014Review
- Decreased activity of folate transporters in lipid rafts resulted in reduced hepatic folate uptake in chronic alcoholism in rats.Genes & nutrition · 2013Article
- Inhibition of p-aminobenzoate and folate syntheses in plants and apicomplexan parasites by natural product rubreserine.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Tetrahydrofolates are essential cofactors for DNA synthesis and methionine metabolism. Malaria parasites are capable both of synthesizing tetrahydrofolates and precursors de novo and of salvaging them from the environment. The biosynthetic route has been studied in some detail over decades, whereas the molecular mechanisms that underpin the salvage pathway lag behind. Here we identify two functional folate transporters (named PfFT1 and PfFT2) and delineate unexpected substrate preferences of the folate salvage pathway in Plasmodium falciparum. Both proteins are localized in the plasma membrane and internal membranes of the parasite intra-erythrocytic stages. Transport substrates include folic acid, folinic acid, the folate precursor p-amino benzoic acid (pABA), and the human folate catabolite pABAG(n). Intriguingly, the major circulating plasma folate, 5-methyltetrahydrofolate, was a poor substrate for transport via PfFT2 and was not transported by PfFT1. Transport of all folates studied was inhibited by probenecid and methotrexate. Growth rescue in Escherichia coli and antifolate antagonism experiments in P. falciparum indicate that functional salvage of 5-methyltetrahydrofolate is detectable but trivial. In fact pABA was the only effective salvage substrate at normal physiological levels. Because pABA is neither synthesized nor required by the human host, pABA metabolism may offer opportunities for chemotherapeutic intervention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.