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 .
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 (126.96.36.199, produces monomethyl-phosphatidylethanolamine).
|Enzyme||EC Number||Gene id|
|Phospholipase A2||188.8.131.52; 184.108.40.206||cgd2_4050|
|Phosphatidylglycerophosphatase||220.127.116.11||Missing in annotation|
|Acyl-CoA binding protein||none||cgd1_1140|
Sources and fates of metabolites
|Substrate||Source pathways||Product||Fate pathways|
|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|
|S-adenosylmethionine||Methionine metabolism||S-adenosylhomocysteine||Methionine metabolism|