Leishmania membrane phospholipid metabolism

Leishmania membrane phospholipids and their metabolic pathways are essential for the structural integrity, survival, and virulence of Leishmania species, the causative agents of leishmaniasis (Dorlo et al., 2012; Zhang & Beverley, 2010). The parasite membrane is characterized by a unique composition of glycerophospholipids, including high levels of ether-linked phospholipids (plasmalogens) and specific sphingolipids that differ significantly from those of the mammalian host (Zhang & Beverley, 2010; Azzouz et al., 2005). Phospholipid metabolism in these protozoa involves a complex interplay between de novo synthesis via the Kennedy pathway and the scavenging of lipid precursors from the host environment (Azzouz et al., 2005). This metabolic network is the primary target of miltefosine, the only oral drug approved for leishmaniasis, which acts as an alkylphosphocholine analogue (Dorlo et al., 2012; Rakotomanga et al., 2007). Miltefosine interferes with phosphatidylcholine biosynthesis and lipid remodeling, leading to the disruption of membrane-bound signaling, altered membrane permeability, and the induction of an apoptosis-like programmed cell death (Dorlo et al., 2012; Rakotomanga et al., 2007). Consequently, targeting the enzymes and structural components of leishmanial phospholipid metabolism provides a viable strategy for developing selective anti-parasitic therapies due to the biochemical divergence between the parasite and the human host (Zhang & Beverley, 2010).

Other names

Leishmanial lipid metabolismPhospholipid biosynthetic pathway in LeishmaniaLeishmania ether lipid metabolismLeishmania glycerophospholipid metabolism

Inhibition of the Kennedy pathway for phosphatidylcholine biosynthesis, disruption of lipid remodeling, and induction of apoptosis-like cell death through membrane destabilization.