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.

 

Toxoplasma gondii 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 genome. The enzymes which catalyse breakdown of phosphatidylcholine and enzymes which synthesise betaine from choline are also present in T. gondii genome. Of these enzymes, the enzymes which catalyse betaine synthesis are absent in Plasmodium falciparum. Other than these, all the enzymes in T. gondii are also present in P. falciparum.

 

Protein EC Number Gene id Protein localisation Localisation data source
Choline dehydrogenase 1.1.99.1 TGME49_313950    
Betaine aldehyde dehydrogenase 1.2.1.8 TGME49_222160 Cytosol Previous publication
Phosphoethanolamine N-methyltransferase 2.1.1.103 TGME49_293830 Nucleus Previous publication
Choline kinase 2.7.1.32 TGME49_320630    
Choline-phosphate cytidylyltransferase 2.7.7.15 TGME49_216930 Nucleus Previous publication
Diacylglycerol choline phosphotransferase 2.7.8.2 TGME49_257510    
Diacylglycerol choline phosphotransferase 2.7.8.2 TGME49_261760    
Diacylglycerol choline phosphotransferase 2.7.8.2 TGME49_276190    
Phospholipase A2 3.1.1.4 TGME49_212130 Plasma membrane Previous publication
Phospholipase A2 3.1.1.4 TGME49_231370    
Phospholipase A2 3.1.1.4 TGME49_254420    
Phospholipase A2 3.1.1.4 TGME49_305140 Nucleus Previous publication
Lysophospholipase 3.1.1.5 TGME49_226390    
Lysophospholipase 3.1.1.5 TGME49_306330 Cytosol Previous publication
Phospholipase C 3.1.4.3 TGME49_248830 Plasma membrane; Nucleus? Apiloc; Previous publication
Glycerophosphodiester phosphodiesterase 3.1.4.46 TGME49_256090 Mitochondrion Previous publication
Glycerophosphodiester phosphodiesterase 3.1.4.46 TGME49_263270 Plasma membrane Previous publication
SEC14 none TGME49_202410    
SEC14 none TGME49_237000 Cytosol Previous publication
SEC14 none TGME49_254390 Cytosol Previous publication

 

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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