Plasmodium falciparum phospholipid biosynthesis via choline metabolism

Plasmodium falciparum phospholipid biosynthesis via choline metabolism, primarily known as the Kennedy pathway, is an essential metabolic route for the malaria parasite during its intraerythrocytic developmental cycle [PMID: 14505520]. As the parasite multiplies within host red blood cells, it requires a massive expansion of its plasma membrane and the membranes of its organelles, with phosphatidylcholine (PC) being the most abundant phospholipid component [PMID: 15235017]. This pathway involves the uptake of choline from the host plasma through a specialized transporter, followed by a three-step enzymatic process: phosphorylation by choline kinase (PfCK), activation by CTP:phosphocholine cytidylyltransferase (PfCCT), and final assembly by cholinephosphotransferase (PfCPT) [PMID: 12834825]. Because the parasite survival is strictly dependent on this de novo synthesis and the enzymes involved differ structurally and regulatorily from their human counterparts, this pathway is a major focus for antimalarial drug discovery [PMID: 15590624]. Therapeutic agents like albitiazolium (SAR97276) target this pathway by inhibiting choline transport and enzymatic activity, effectively starving the parasite of the building blocks needed for membrane formation and leading to cell cycle arrest and death [PMID: 21149587].

Other names

Kennedy pathwayPhosphatidylcholine biosynthesis pathwayCholine metabolism pathwayPfCK-mediated phospholipid synthesis