Phosphatidylethanolamine and phosphatidylserine metabolism

Phospholipids are crucial components of the cell membrane bilayers. Most of these phospholipids are composed of a diglyceride (diacylglycerol) moiety, a phosphate group and a simple organic molecule such as choline, serine or ethanolamine. The anionic phosphate group and polar groups such as choline forms the hydrophilic head and the fatty acid chains in diacylglycerol forms the hydrophobic tails in the membrane bilayer. Phosphatidic acids with ethanolamine and serine attached are referred to as phosphatidylethanolamine (cephalin) and phosphatidylserine respectively. Phosphatidylethanolamine is found in all living cells and it is the principal phospholipid in bacteria.


Coccidians such as Toxoplasma gondii and Neospora caninum can de novo synthesise phospholipids such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine. Gupta et al has quantified the composition of different phospholipids in free T. gondii parasites. According to this, the most abundant phospholipid is phosphatidylcholine (75%) and it is followed by phosphatidylethanolamine (10%). Other phospholipids quantified are phosphatidylinositol (7.5%), phosphatidylserine (6%) and phosphatidate (1%) [1]. The labelling experiments showed that phosphatidylserine and phosphatidylethanolamine can be produced from serine in extracellular parasites. In addition, phosphatidylethanolamine can be synthesised from ethanolamine acquired from extracellular type medium in the parasites. The rate of synthesis of these phospholipids did not change between extracellular type and intracellular type media. The measurement of activities of important enzymes of phosphatidylserine and phosphatidylethanolamine biosynthesis was measured. This suggested that phosphatidylserine synthase in T. gondii catalyses the reaction via base (simple molecule group) exchange and the activity is dependent on ca2+ and phospholipids rather than on CDP-diacylglycerol. In addition, the inclusion of phosphatidylethanolamine in reaction has led to 6-8 fold increase in phosphatidylserine synthesis. This suggests that phosphatidylethanolamine provides phosphatidyl moiety and the enzyme replaces ethanolamine residue with serine leading to base-exchange based phosphatidylserine biosynthesis. Phosphatidylserine decarboxylase showed 200-fold higher activity in comparison to other key enzymes studied and 10-fold higher activity than phosphatidylserine decarboxylase enzymes from other species. In addition, the activity of ethanolamine phosphotransferase confirmed the presence of phosphatidylethanolamine generation from ethanolamine (acquired from external medium) [1].


The enzymes which belong to the catabolism branch of phosphatidylethanolamine metabolism are also present in T. gondii and N. caninum. Although, the enzyme phosphatidylethanolamine N-methyltransferase (, produces monomethyl-phosphatidylethanolamine) is present, the enzyme phosphatidyl-N-methylethanolamine N-methyltransferase ( which leads to synthesis of phosphatidylcholine is absent. The enzymes  and are absent in Plasmodium falciparum. According to MPMP annotation, the phosphatidylserine synthase present in P. falciparum is CDP-diacylglycerol serine-O-phosphatidyltransferase ( This is one of the main differences between Plasmodium and Coccidia as Coccidia possesses base-exchange phosphatidylserine synthase ( The enzymes involved in cardiolipin biosynthesis are present in both Coccidia and P. falciparum.


Enzyme EC Number Gene id
Phosphatidylethanolamine N-methyltransferase NCLIV_065190
Glycerol-3-phosphate O-acyltransferase NCLIV_029980
Glycerol-3-phosphate O-acyltransferase NCLIV_035870
Diacylglycerol O-acyltransferase NCLIV_007300
Diacylglycerol O-acyltransferase NCLIV_032680
Diacylglycerol O-acyltransferase NCLIV_046590
1-Acylglycerol-3-phosphate O-acyltransferase NCLIV_006550
1-Acylglycerol-3-phosphate O-acyltransferase NCLIV_017010
Diacylglycerol kinase NCLIV_015910
Diacylglycerol kinase NCLIV_022470
Diacylglycerol kinase NCLIV_027060
Ethanolamine kinase NCLIV_040230
Ethanolamine kinase NCLIV_044730
Ethanolamine-phosphate cytidylyltransferase NCLIV_054370
Phosphatidate cytidylyltransferase NCLIV_023660
Phosphatidate cytidylyltransferase NCLIV_024160
Cardiolipin synthetase 2.7.8.- NCLIV_054060
Cardiolipin synthetase 2.7.8.- NCLIV_068780
Ethanolaminephosphotransferase NCLIV_025720
Ethanolaminephosphotransferase NCLIV_029590
L-serine-phosphatidylethanolamine phosphatidyltransferase NCLIV_026010
L-serine-phosphatidylethanolamine phosphatidyltransferase NCLIV_034110
CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase NCLIV_063320
Triacylglycerol lipase NCLIV_008610
Triacylglycerol lipase NCLIV_025430
Triacylglycerol lipase NCLIV_037100
Phospholipase A2 NCLIV_008710
Phospholipase A2 NCLIV_031630
Phospholipase A2; NCLIV_049240
Lysohospholipase NCLIV_044560
Lysohospholipase NCLIV_046570
Phospholipase C NCLIV_064970
Glycerophosphodiester phosphodiesterase NCLIV_024660
Glycerophosphodiester phosphodiesterase NCLIV_029010
Phosphatidylserine decarboxylase NCLIV_036670
Phosphatidylserine decarboxylase NCLIV_047160
Acyl-CoA synthetase NCLIV_006300
Acyl-CoA synthetase NCLIV_018500
Acyl-CoA synthetase NCLIV_054200
Acyl-CoA synthetase NCLIV_054250
Acyl-CoA synthetase NCLIV_063970
Phosphatidylethanolamine binding protein none NCLIV_002850
MSF-1 none NCLIV_008510
Acyl-CoA binding protein none Missing in annotation (Absent?)


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Sources and fates of metabolites


Substrate Source pathways Product Fate pathways
Ethanolamine Host O-Phosphoethanolamine Phosphatidylcholine metabolism
Fatty acid Fatty acid biosynthesis in the apicoplast, Fatty acid elongation in the cytosol, Fatty acid elongation in the ER, Host Cardiolipin Inner mitochondrial membrane
Glycerol-3P Glycolysis Triacylglycerol Recycling of phospholipids, Storage in lipid bodies
Serine Glycine, serine and cysteine metabolism Monomethyl-phosphatidylethanolamine ?
S-adenosylmethionine Methionine metabolism S-adenosylhomocysteine Methionine metabolism