Phosphatidylethanolamine and phosphatidylserine 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 groups and polar groups such as choline form the hydrophilic heads and the fatty acid chains in diacylglycerol form the hydrophobic tails in the membrane bilayer. Phosphatidic acids with ethanolamine and serine attached are referred to as phosphatidylethanolamine (cephalin) and phosphatidylserine respectively. Phosphatidylethanolamine is found in all living cells and it is the principal phospholipid in bacteria.

 

The apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii can de novo synthesise phospholipids such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine from choline, ethanolamine and serine respectively [1, 2]. The measurement of activities of enzymes catalysing phosphatidylserine and phosphatidylethanolamine synthesis suggested that phosphatidylserine synthase in T. gondii catalyses the reaction via base (simple molecule group) exchange and the activity is dependent on ca2+ and phospholipids rather than on CDP-diacylglycerol. In addition, the inclusion of phosphatidylethanolamine in reaction has led to 6-8 fold increase in phosphatidylserine synthesis. This suggests that phosphatidylethanolamine provides phosphatidyl moiety and the enzyme replaces ethanolamine residue with serine leading to base-exchange based phosphatidylserine biosynthesis [2].

 

The analysis of Cryptosporidium genomes showed that they can also de novo synthesise phosphatidylethanolamine and phosphatidylserine. The enzymes which belong to the catabolism branch of phosphatidylethanolamine metabolism and cardiolipin biosynthesis present in T. gondii are also present in Cryptosporidia. The only exception which is present in T. gondii and absent in Cryptosporidia is phosphatidylethanolamine N-methyltransferase (2.1.1.17, produces monomethyl-phosphatidylethanolamine).

 

Enzyme EC Number Gene id
Glycerol-3-phosphate O-acyltransferase 2.3.1.15 Chro.60161
Diacylglycerol O-acyltransferase 2.3.1.20 Chro.20121
Diacylglycerol O-acyltransferase 2.3.1.20 Chro.60038
1-Acylglycerol-3-phosphate O-acyltransferase 2.3.1.51 Chro.80165
Diacylglycerol kinase 2.7.1.107 Chro.30302
Diacylglycerol kinase 2.7.1.107 Chro.40493
Ethanolamine kinase 2.7.1.82 Chro.50319
Ethanolamine-phosphate cytidylyltransferase 2.7.7.14 Chro.70332
Phosphatidate cytidylyltransferase 2.7.7.41 Chro.70059
Cardiolipin synthetase 2.7.8.- Chro.30333
Ethanolaminephosphotransferase 2.7.8.1 Chro.40314
L-serine-phosphatidylethanolamine phosphatidyltransferase 2.7.8.29 Chro.10133
CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase 2.7.8.5 Chro.20123
Phospholipase A2 3.1.1.4 Chro.70299
Phospholipase A2 3.1.1.4; 3.1.1.3 Chro.20432
Phosphatidylglycerophosphatase 3.1.3.27 Missing in annotation
Phospholipase C 3.1.4.3 Chro.40288
Glycerophosphodiester phosphodiesterase 3.1.4.46 Chro.50344
Phosphatidylserine decarboxylase 4.1.1.65 Chro.30247
Acyl-CoA synthetase 6.2.1.3 Chro.30084
Acyl-CoA synthetase 6.2.1.3 Chro.40386
Acyl-CoA synthetase 6.2.1.3 Chro.50052
Acyl-CoA binding protein none Chro.10136
MSF-1 none Chro.50244

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Ethanolamine Host    
Fatty acid Fatty acid elongation in the cytosol, Fatty acid elongation in the ER, Host Cardiolipin Inner mitochondrial membrane
Glycerol-3P Glycolysis, Phosphatidylcholine metabolism Triacylglycerol Recycling of phospholipids, Storage in lipid bodies
Serine Host    
S-adenosylmethionine Methionine metabolism S-adenosylhomocysteine Methionine metabolism