title: Glycerophospholipid acquisition in Plasmodium - a puzzling assembly of biosynthetic pathways.
abstract: Throughout the Plasmodium life cycle, malaria parasites repeatedly undergo rapid cellular growth and prolific divisions, necessitating intense membrane neogenesis and, in particular, the acquisition of high amounts of phospholipids. At the intraerythrocytic stage, glycerophospholipids are the main parasite membrane constituents, which mostly originate from the Plasmodium-encoded enzymatic machinery. Several proteins and entire pathways have been characterized and their features reported, thereby generating a global view of glycerophospholipid synthesis across Plasmodium spp. The malaria parasite displays a panoply of pathways that are seldom found together in a single organism. The major glycerophospholipids are synthesized via ancestral prokaryotic CDP-diacylglycerol-dependent pathways and eukaryotic-type de novo pathways. The parasite exhibits additional reactions that bridge some of these routes and are otherwise restricted to some organisms, such as plants, while base-exchange mechanisms are largely unexplored in Plasmodium. Marked differences between Plasmodium spp. have also been reported in phosphatidylcholine and phosphatidylethanolamine synthesis. Little is currently known about glycerophospholipid acquisition at non-erythrocytic stages, but recent data reveal that intrahepatocytic parasites, oocysts and sporozoites import various host lipids, and that de novo fatty acid synthesis is only crucial at the late liver stage. More studies on the different Plasmodium developmental stages are needed, to further assemble the different pieces of this glycerophospholipid synthesis puzzle, which contains highly promising therapeutic targets.
authors.affiliation: Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235, Centre National de la Recherche Scientifique (CNRS) - Universite Montpellier 2, cc 107, Place Eugene Bataillon, 34095 Montpellier Cedex 05, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Déchamps
authors.forename: Shilpa
authors.initials: S
authors.lastname: Shastri
authors.forename: Kai
authors.initials: K
authors.lastname: Wengelnik
authors.forename: Henri J
authors.initials: HJ
authors.lastname: Vial
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D020404:Glycerophospholipids / Q000096:biosynthesis*; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000469:parasitology*; D010961:Plasmodium / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism
chemical_list: D020404:Glycerophospholipids; D015800:Protozoan Proteins