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 CMU_008720
Diacylglycerol O-acyltransferase 2.3.1.20 CMU_009280
Diacylglycerol O-acyltransferase 2.3.1.20 CMU_027950
1-Acylglycerol-3-phosphate O-acyltransferase 2.3.1.51 CMU_025330
Diacylglycerol kinase 2.7.1.107 CMU_000790
Diacylglycerol kinase 2.7.1.107 CMU_002110
Ethanolamine kinase 2.7.1.82 CMU_041200
Ethanolamine-phosphate cytidylyltransferase 2.7.7.14 CMU_022910
Phosphatidate cytidylyltransferase 2.7.7.41 CMU_006430
Cardiolipin synthetase 2.7.8.- CMU_000460
Ethanolaminephosphotransferase 2.7.8.1 CMU_017860
L-serine-phosphatidylethanolamine phosphatidyltransferase 2.7.8.29 CMU_035840
CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase 2.7.8.5 CMU_009260
Phospholipase A2 3.1.1.4 CMU_034720
Phospholipase A2 3.1.1.4; 3.1.1.3 CMU_002900
Lysohospholipase 3.1.1.5 CMU_020670
Phosphatidylglycerophosphatase 3.1.3.27 Missing in annotation
Phospholipase C 3.1.4.3 CMU_017610
Glycerophosphodiester phosphodiesterase 3.1.4.46 CMU_041430
Phosphatidylserine decarboxylase 4.1.1.65 CMU_001440
Acyl-CoA synthetase 6.2.1.3 CMU_015960
Acyl-CoA synthetase 6.2.1.3 CMU_018550
Acyl-CoA synthetase 6.2.1.3 CMU_038070
Acyl-CoA binding protein none CMU_035870
MSF-1 none CMU_040480

 

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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