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 cgd6_1270
Diacylglycerol O-acyltransferase 2.3.1.20 cgd2_1090
Diacylglycerol O-acyltransferase 2.3.1.20 cgd6_260
1-Acylglycerol-3-phosphate O-acyltransferase 2.3.1.51 cgd8_1400
Diacylglycerol kinase 2.7.1.107 cgd3_2630
Diacylglycerol kinase 2.7.1.107 cgd4_4340
Ethanolamine kinase 2.7.1.82 cgd5_720
Ethanolamine-phosphate cytidylyltransferase 2.7.7.14 cgd7_2950
Phosphatidate cytidylyltransferase 2.7.7.41 cgd7_450
Cardiolipin synthetase 2.7.8.- cgd3_2940
Ethanolaminephosphotransferase 2.7.8.1 cgd4_2790
L-serine-phosphatidylethanolamine phosphatidyltransferase 2.7.8.29 cgd1_1110
CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase 2.7.8.5 cgd2_1110
Phospholipase A2 3.1.1.4 cgd7_2630
Phospholipase A2 3.1.1.4; 3.1.1.3 cgd2_4050
Phosphatidylglycerophosphatase 3.1.3.27 Missing in annotation
Phospholipase C 3.1.4.3 cgd4_2560
Glycerophosphodiester phosphodiesterase 3.1.4.46 cgd5_490
Phosphatidylserine decarboxylase 4.1.1.65 cgd3_2100
Acyl-CoA synthetase 6.2.1.3 cgd3_640
Acyl-CoA synthetase 6.2.1.3 cgd4_3400
Acyl-CoA synthetase 6.2.1.3 cgd5_3200
Acyl-CoA binding protein none cgd1_1140
MSF-1 none cgd5_1390

 

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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