Sphingomyelin sphingolipid synthesis

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

Figure 26.3. Synthesis of Sphingolipids. Sphingosine is converted into ceramide, which is an intermediate in the formation of sphingomyelin and gangliosides.

Sphingomyelin is a phospholipid as well as sphingolipid. CDP-choline is the source of the phosphocholine moiety (cf. phosphatidylcholine synthesis. Section 11.2.1). As with cerebroside formation there seem to be two ways of converting a sphingosine base to sphingomyelin. These two pathways differ in the order in which acylation (Fig. 11.23) or phosphocholine transfer take place. The relative importance of these pathways and various features of the reactions are discussed by Thompson (1973) and by Barenholz and Gatt (1982). 

Sphingosine, the essential component of sphingolipids (10.44c) requires phosphate energy carriers and pyridoxal phosphate for its enzymatic synthesis. This is then converted into sphingomyelin according to scheme (11.104). 

This asymmetric Mannich-type reaction was successfully applied to the synthesis of (1 J ,31 )-N-(3-hydroxy-l-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12), which is the first compound that specifically inhibits sphingomyelin synthesis in mammalian cells, and is also expected to act as a drug that inhibits intracellular trafficking of sphingolipids (Scheme 3.27). ... 

Studies on sphingolipids. VII. Synthesis and configuration of natural sphingomyelins. 

Synthetic studies on sphingolipids. IV. The synthesis of sphingomyelin. J. Amer. 

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