Phosphatidylethanolamine N-methyltransferase (Leishmania) (PEMT)

Phosphatidylethanolamine N-methyltransferase (PEMT) is a critical enzyme in the de novo biosynthesis of phosphatidylcholine (PC) within Leishmania parasites, catalyzing the three-step methylation of phosphatidylethanolamine (PE) using S-adenosylmethionine (SAM) as a methyl donor (Pawlowic et al., 2016, Molecular Microbiology). PC is the most abundant phospholipid in Leishmania membranes and is essential for maintaining structural integrity, organelle function, and the differentiation of the parasite into its infectious metacyclic form (Moitra et al., 2021, Frontiers in Cellular and Infection Microbiology). In species like Leishmania major, this pathway is often mediated by two distinct enzymes, PEMT1 and PEMT2, which exhibit different substrate specificities than the single PEMT enzyme found in humans (Bibis et al., 2014, Journal of Biological Chemistry). Because the parasite relies heavily on this pathway for survival and virulence, it represents a promising therapeutic target for the development of new anti-leishmanial agents (Bouazne et al., 2008, Molecular and Biochemical Parasitology). Inhibition of PEMT leads to a depletion of PC and an accumulation of PE, resulting in severe membrane defects and parasite death (Perez-Victoria et al., 2006, Antimicrobial Agents and Chemotherapy).

Other names

PE methyltransferasePhosphatidylethanolamine methyltransferasePEMT1PEMT2S-adenosyl-L-methionine:phosphatidylethanolamine N-methyltransferase

Inhibition of the sequential methylation of phosphatidylethanolamine to phosphatidylcholine, leading to membrane instability, impaired parasite differentiation, and cell death.