Phosphatidylcholine 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. 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%) [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 [1]. Although one of the two enzymes required for this methylation (2.1.1.71) 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
Choline dehydrogenase 1.1.99.1 NCLIV_057150
Betaine aldehyde dehydrogenase 1.2.1.8 NCLIV_005550
Phosphoethanolamine N-methyltransferase 2.1.1.103 NCLIV_000800
Choline kinase 2.7.1.32 NCLIV_009640
Choline-phosphate cytidylyltransferase 2.7.7.15 NCLIV_059380
Diacylglycerol choline phosphotransferase 2.7.8.2 NCLIV_006960
Diacylglycerol choline phosphotransferase 2.7.8.2 NCLIV_025720
Diacylglycerol choline phosphotransferase 2.7.8.2 NCLIV_029590
Phospholipase A2 3.1.1.4 NCLIV_008710
Phospholipase A2 3.1.1.4 NCLIV_031630
Phospholipase A2 3.1.1.4 NCLIV_049240
Lysophospholipase 3.1.1.5 NCLIV_044560
Lysophospholipase 3.1.1.5 NCLIV_046570
Phospholipase C 3.1.4.3 NCLIV_064970
Glycerophosphodiester phosphodiesterase 3.1.4.46 NCLIV_024660
Glycerophosphodiester phosphodiesterase 3.1.4.46 NCLIV_029010
SEC14 none NCLIV_008680
SEC14 none NCLIV_022520
SEC14 none NCLIV_050900

 

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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
Choline Host Betaine Host
1,2-Diacylglycerol Phosphatidylethanolamine and phosphatidylserine metabolism, Inositol phosphate metabolism