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.

 

The apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii can de novo synthesise phospholipids such as phosphatidylcholine and phosphatidylethanolamine from choline and ethanolamine respectively [1, 2]. The analysis of the Piroplasma genomes showed that they can also de novo synthesise phosphatidylcholine from choline. They also possess the enzymes which catalyse the metabolism of the phospholipids. In contrast to T. gondii phosphatidylcholine metabolism pathway, Cryptosporidium and Piroplasma species do not possess the abilities to synthesise choline phosphate from O-phosphoethanolamine and betaine from choline. Unlike other apicomplexans incuding Babesia species, Theileria genomes have high copy numbers of choline kinase (8 copies in Theileria parva and 9 copies in Theileria annulata). Over expression of choline kinase in transformed cancer cell lines and the reversible blockage of cell proliferation with choline kinase inhibition [3] may suggest a role for choline kinase in pathogenesis of Theileria infection.

 

The bisthiozolium drug T16 was shown to selectively inhibit the de novo phosphatidylcholine biosynthesis pathway. It showed antibabesial activity with Babesia divergens and Babesia canis and antimalarial activity with P. falciparum [4]. This suggests that choline biosynthesis is a potential drug target not only for malaria, but also for Piroplasma infections.

 

Enzyme EC Number Gene id
Choline kinase 2.7.1.32 TP01_0546
Choline kinase 2.7.1.32 TP01_0942
Choline kinase 2.7.1.32 TP02_0655
Choline kinase 2.7.1.32 TP02_0656
Choline kinase 2.7.1.32 TP02_0657
Choline kinase 2.7.1.32 TP02_0658
Choline kinase 2.7.1.32 TP02_0659
Choline kinase 2.7.1.32 TP02_0660
Choline-phosphate cytidylyltransferase 2.7.7.15 TP02_0826
Diacylglycerol choline phosphotransferase 2.7.8.2 TP01_1171
Phospholipase A2 3.1.1.4 TP01_1049
Phospholipase A2 3.1.1.4 TP03_0786
Phospholipase A2 3.1.1.4 TP04_0897
Lysohospholipase 3.1.1.5 TP01_0667
Lysohospholipase 3.1.1.5 TP01_1185
Lysohospholipase 3.1.1.5 TP03_0200
Lysohospholipase 3.1.1.5 TP03_0738
Lysohospholipase 3.1.1.5 TP03_0739
Lysohospholipase 3.1.1.5 TP04_0044
Lysohospholipase 3.1.1.5 TP04_0172
Lysohospholipase 3.1.1.5 TP04_0172
Phospholipase C 3.1.4.3 TP01_0775
Glycerophosphodiester phosphodiesterase 3.1.4.46 TP01_0659
SEC14 none TP02_0781
SEC14 none TP03_0129
SEC14 none TP04_0548
SEC14 none TP04_0899

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Choline Host    
1,2-Diacylglycerol Phosphatidylethanolamine metabolism sn-glycerol-3P Phosphatidylethanolamine metabolism