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. A phospholipid with choline as simple organic molecule is phosphatidylcholine and it is also known as lecithin.
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%) . This study also demonstrated that phosphatidylcholine is de novo synthesised from choline acquired from the medium. The phosphatidylcholine synthesis is doubled in intracellular type medium when compared to the extracellular type medium. The presence of de novo biosynthesis pathway is also confirmed by measuring the specific activity of the terminal enzyme, diacylglycerol-choline phosphotransferase. In addition, the treatment with choline analogue, dimethyl-ethanolamine has resulted in reduced phosphatidylcholine production and has slowed down growth and division of T. gondii parasites. This reduced level of progeny is due to its inability to produce cell membranes. It also showed the de novo synthesis of phosphatidylethanolamine from ethanolamine in medium. There was no significant methylation of phosphatidylethanolamine to phosphatidylcholine observed even with addition of co-substrate S-adenosylmethionine in the medium . Although one of the two enzymes required for this methylation (126.96.36.199) is absent (phosphatidylethanolamine and phosphatidylserine metabolism), the enzyme phosphoethanolamine N-methyl transferase (converts phosphoethanolamine to choline phosphate) is present in T. gondii and N. caninum genomes. The enzymes which catalyse breakdown of phosphatidylcholine and enzymes which synthesise betaine from choline are also present in these Coccidian genomes. Of these enzymes, the enzymes which catalyse betaine synthesis are absent in Plasmodium falciparum. Other than these, all the enzymes in T. gondii and N. caninum are also present in P. falciparum.
|Enzyme||EC Number||Gene id|
|Betaine aldehyde dehydrogenase||188.8.131.52||NCLIV_005550|
|Diacylglycerol choline phosphotransferase||184.108.40.206||NCLIV_006960|
|Diacylglycerol choline phosphotransferase||220.127.116.11||NCLIV_025720|
|Diacylglycerol choline phosphotransferase||18.104.22.168||NCLIV_029590|
Sources and fates of metabolites
|Substrate||Source pathways||Product||Fate pathways|
|O-Phosphoethanolamine||Phosphatidylethanolamine and phosphatidylserine metabolism||Phosphatidylcholine||Phosphatidylethanolamine and phosphatidylserine metabolism|
|S-adenosylmethionine||Methionine metabolism||S-adenosylhomocysteine||Methionine metabolism|
|1,2-Diacylglycerol||Phosphatidylethanolamine and phosphatidylserine metabolism, Inositol phosphate metabolism|