Sphingomyelin and ceramide metabolism
Sphingolipids are a class of lipids which possesses sphingoid bases such as sphingosine as backbone. Like other membrane phospholipids, sphingolipids are ampipathic possessing hydrophilic heads and hydrophobic tails. Sphingolipids are important in various cell signalling processes as first and second messengers including cell proliferation, differentiation and apoptosis in higher eukaryotes. They are also important constituents of lipid rafts of cell membranes. The simplest sphingolipids is ceramide which has very limited hydrophilicity as it only has 2 hydroxyl groups and no other polar groups are present. In addition to its role in signalling processes, it is also the precursor for the biosynthesis of other complex sphingolipids [1]. Animals possess two different types of these complex sphingolipids, which are sphiongophospholipids and glycosphingolipids respectively. The main sphingophospholipid in mammals is sphingomyelin. Sphingomyelin possesses a phosphocholine group attached to the ceramide backbone. The glycosphingolipids are molecules which have sugar residues attached to the ceramide backbone. The three different types of glycosphingolipids are cerebrosides (1 sugar moiety attached to hydroxyl-group in ceramide), globosides (more than 1 sugar groups attached to ceramide) and gangliosides (at least 1 N-acetylneuraminic acid residue is attached to the sugar chain). In contrast to animals, inositol phosphorylceramide is generated from ceramide in plants, fungi and kinetoplastids such as Trypanosoma and Leishmania [2].
There are biochemical evidence available in both Plasmodium falciparum and Toxoplasma gondii to suggest the presence of sphingomyelin and ceramide metabolism pathway. For further details refer to the T. gondii page on sphingomyelin and ceramide metabolism. All the enzymes of this pathway present in T. gondii are also found in Neospora caninum genome.
Enzyme | EC Number | Gene id |
---|---|---|
3-dehydrosphinganine reductase | 1.1.1.102 | NCLIV_019810 |
Sphingolipid delta-4 desaturase | 1.14.-.- | NCLIV_051070 |
Sphingosine N-acyltransferase | 2.3.1.24 | NCLIV_015310 |
Sphingosine N-acyltransferase | 2.3.1.24 | NCLIV_058920 |
Serine C-palmitoyltransferase | 2.3.1.50 | NCLIV_042840 |
Serine C-palmitoyltransferase | 2.3.1.50 | NCLIV_042850 |
Ceramide glucosyltransferase | 2.4.1.80 | NCLIV_068040 |
UTP-glucose-1-phosphate uridylyltransferase | 2.7.7.9 | NCLIV_040400 |
Sphingomyelin synthase | 2.7.8.27 | NCLIV_063280 |
Ceramide cholinephosphotransferase | 2.7.8.3 | NCLIV_063870 |
Sphingomyelin phosphodiesterase | 3.1.4.12 | NCLIV_035700 |
Sphingomyelin phosphodiesterase | 3.1.4.12 | NCLIV_065140 |
Long-chain-fatty-acid-CoA ligase | 6.2.1.3 | NCLIV_006300 |
Long-chain-fatty-acid-CoA ligase | 6.2.1.3 | NCLIV_018500 |
Long-chain-fatty-acid-CoA ligase | 6.2.1.3 | NCLIV_054200 |
Long-chain-fatty-acid-CoA ligase | 6.2.1.3 | NCLIV_054250 |
Long-chain-fatty-acid-CoA ligase | 6.2.1.3 | NCLIV_063970 |
Glycolipid transfer protein | none | NCLIV_006120 |
Neutral-sphingomyelinase activator | none | NCLIV_024920 |
Sources and fates of metabolites
Substrate | Source pathways | Product | Fate pathways |
---|---|---|---|
Palmitoyl-CoA | Fatty acid elongation in the ER | ||
Fatty acid | Fatty acid biosynthesis in the apicoplast, Fatty acid elongation in the cytosol, Fatty acid elongation in the ER, Host | ||
Serine | Glycine, serine and cysteine metabolism | ||
Glucose-1P | Glycolysis | ||
CDP-Choline | Phosphatidylcholine metabolism | Choline phosphate | Phosphatidylcholine metabolism |
Phosphatidylcholine | Phosphatidylcholine metabolism | 1,2-Diacylglycerol | Phosphatidylethanolamine and phosphatidylserine metabolism |
Sphingomyelin | Host | Sphingomyelin/Glucosylceramide | Membranes |
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