+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Exploring the folate pathway in Plasmodium falciparum

Exploring the folate pathway in Plasmodium falciparum

Acta Tropica 94(3): 191-206

As in centuries past, the main weapon against human malaria infections continues to be intervention with drugs, despite the widespread and increasing frequency of parasite populations that are resistant to one or more of the available compounds. This is a particular problem with the lethal species of parasite, Plasmodium falciparum, which claims some two million lives per year as well as causing enormous social and economic problems. Amongst the antimalarial drugs currently in clinical use, the antifolates have the best defined molecular targets, namely the enzymes dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), which function in the folate metabolic pathway. The products of this pathway, reduced folate cofactors, are essential for DNA synthesis and the metabolism of certain amino acids. Moreover, their formation and interconversions involve a number of other enzymes that have not as yet been exploited as drug targets. Antifolates are of major importance as they currently represent the only inexpensive regime for combating chloroquine-resistant malaria, and are now first-line drugs in a number of African countries. Aspects of our understanding of this pathway and antifolate drug resistance are reviewed here, with a particular emphasis on approaches to analysing the details of, and balance between, folate biosynthesis by the parasite and salvage of pre-formed folate from exogenous sources.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 004156779

Download citation: RISBibTeXText

PMID: 15845349

DOI: 10.1016/j.actatropica.2005.04.002

Related references

Folate metabolism pathway and Plasmodium falciparum malaria infection in pregnancy. Nutrition Reviews 69(1): 34-40, 2011

Characterization of three genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum. Parasitology 122 Pt 1: 1-13, 2001

Transfection studies of the pppk-dhps gene in the folate biosynthetic pathway of Plasmodium falciparum. Experimental Parasitology 105(1): 74, 2003

Exploring Drug Targets in Isoprenoid Biosynthetic Pathway for Plasmodium falciparum. Biochemistry Research International 2014: 657189, 2014

Transcriptional analysis of genes encoding enzymes of the folate pathway in the human malaria parasite Plasmodium falciparum. Molecular Microbiology 46(1): 179-190, 2002

Completing the folate biosynthesis pathway in Plasmodium falciparum: p-aminobenzoate is produced by a highly divergent promiscuous aminodeoxychorismate lyase. Biochemical Journal 455(2): 149-155, 2013

Dynamic subcellular localization of isoforms of the folate pathway enzyme serine hydroxymethyltransferase (SHMT) through the erythrocytic cycle of Plasmodium falciparum. Malaria Journal 9: 351, 2011

The molecular basis of folate salvage in Plasmodium falciparum: characterization of two folate transporters. Journal of Biological Chemistry 286(52): 44659-44668, 2012

Identification of a novel putative inhibitor of the Plasmodium falciparum purine nucleoside phosphorylase: exploring the purine salvage pathway to design new antimalarial drugs. Molecular Diversity 21(3): 677-695, 2017

Folate and cobalamin metabolism in Plasmodium falciparum. Parasitology Today 6(12): 388-391, 1990

PI-3 kinase pathway in Plasmodium falciparum Identification and characterization of Plasmodium falciparum homologues of PI-3 kinase and Protein Kinase B. Bioscience Reports 23(1): 34, 2003

Inhibitors of de novo folate enzymes in Plasmodium falciparum. Drug Discovery Today 11(19-20): 939-944, 2006

Characterisation of exogenous folate transport in Plasmodium falciparum. Molecular and Biochemical Parasitology 154(1): 40-51, 2007

Cross serological reactions between Plasmodium falciparum and Plasmodium cynomolgi Bastianellii. Application to the serodiagnosis, by immunofluorescence, of human Plasmodium falciparum malaria. Bulletin de la Societe de Pathologie Exotique et de Ses Filiales 59(3): 316-325, 1966

Comparison of the Clinical Profile and Complications of Mixed Malarial Infections of Plasmodium Falciparum and Plasmodium Vivax versus Plasmodium Falciparum Mono-infection. Sultan Qaboos University Medical Journal 11(3): 377-382, 2011