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

 

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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