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 TA06525
Choline kinase 2.7.1.32 TA14375
Choline kinase 2.7.1.32 TA14380
Choline kinase 2.7.1.32 TA14385
Choline kinase 2.7.1.32 TA14390
Choline kinase 2.7.1.32 TA14405
Choline kinase 2.7.1.32 TA14410
Choline kinase 2.7.1.32 TA14415
Choline kinase 2.7.1.32 TA20330
Choline-phosphate cytidylyltransferase 2.7.7.15 TA15365
Diacylglycerol choline phosphotransferase 2.7.8.2 TA09530
Phospholipase A2 3.1.1.4 TA11025
Phospholipase A2 3.1.1.4 TA17010
Phospholipase A2 3.1.1.4 TA18220
Lysohospholipase 3.1.1.5 TA02875
Lysohospholipase 3.1.1.5 TA03315
Lysohospholipase 3.1.1.5 TA09615
Lysohospholipase 3.1.1.5 TA17285
Lysohospholipase 3.1.1.5 TA18005
Phospholipase C 3.1.4.3 TA06965
Glycerophosphodiester phosphodiesterase 3.1.4.46 TA02915
SEC14 none TA05300
SEC14 none TA08980
SEC14 none TA10965
SEC14 none TA15075

 

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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