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 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. 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.

Toxoplasma gondii can de novo synthesise phospholipids such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine. Gupta et al has quantified the composition of different phospholipids in free T. gondii parasites. According to this, the most abundant phospholipid is phosphatidylcholine (75%) and it is followed by phosphatidylethanolamine (10%). Other phospholipids quantified are phosphatidylinositol (7.5%), phosphatidylserine (6%) and phosphatidate (1%) [1]. The labelling experiments showed that phosphatidylserine and phosphatidylethanolamine can be produced from serine in extracellular parasites. In addition, phosphatidylethanolamine can be synthesised from ethanolamine acquired from extracellular type medium in the parasites. The rate of synthesis of these phospholipids did not change between extracellular type and intracellular type media. The measurement of activities of important enzymes of phosphatidylserine and phosphatidylethanolamine biosynthesis was measured. This 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. Phosphatidylserine decarboxylase showed 200-fold higher activity in comparison to other key enzymes studied and 10-fold higher activity than phosphatidylserine decarboxylase enzymes from other species. In addition, the activity of ethanolamine phosphotransferase confirmed the presence of phosphatidylethanolamine generation from ethanolamine (acquired from external medium) [1].

The enzymes which belong to the catabolism branch of phosphatidylethanolamine metabolism are also present in T. gondii. Although, the enzyme phosphatidylethanolamine N-methyltransferase (2.1.1.17, produces monomethyl-phosphatidylethanolamine) is present, the enzyme phosphatidyl-N-methylethanolamine N-methyltransferase (2.1.1.71) which leads to synthesis of phosphatidylcholine is absent. The enzymes 2.1.1.17  and 2.1.1.71 are absent in Plasmodium falciparum. According to MPMP annotation, the phosphatidylserine synthase present in P. falciparum is CDP-diacylglycerol serine-O-phosphatidyltransferase (2.7.8.8). This is one of the main differences between Plasmodium and Toxoplasma as Toxoplasma possesses base-exchange phosphatidylserine synthase (2.7.8.29). The enzymes involved in cardiolipin biosynthesis are present in both T. gondii and P. falciparum.

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Sources and fates of metabolites