Ceramide sphingomyelin synthesis from

Sphingomyelin Is Formed Directly from Ceramide Glycosphingolipid Synthesis Also Starts from Ceramide... 

Yasuda S, Kitagawa H, Ueno M, Ishitani H, Fukasawa M, Nishijima M, Kobayashi S, Hanada K. A novel inhibitor of ceramide trafficking from the endoplasmic reticulum to the site of sphingomyelin synthesis. J. Biol. Chem. 2001 276 43994-44002. Lister MD, Ruan ZS, Bittman R. Interaction of sphingomyelinase with sphingomyelin analogs modified at the C-1 and C-3 positions of the sphingosine backbone. Biochim. Biophys. Acta 1995 1256 25-30. 

It should be noted here that the synthesis of sphingomyelin, the lipid whose synthesis and breakdown are most intricately involved in the process of apoptosis, is dependent on the presence of PC, since the final step in SM synthesis involves the exchange of the phosphocholine head group from PC to ceramide (see Eigure 1). Theoretically, therefore, inhibition of PC synthesis may lead to an inhibition of SM generation and an accumulation of pro-apoptotic ceramides. On the other hand, an increased breakdown of SM by SMases as frequently observed in apoptotic cells, was shown to increase the conversion of PC to anti-apoptotic DAG (Sillence and Allan, 1998, for anti-apoptotic action of DAG see below). 

Fig. 6.12. Formation and function of the messenger substance ceramide. The starting point for the synthesis of ceramide is sphingomyelin, which is converted to phosphocholine and ceramide by the action of a sphingomyelinase. Sphingomyelinase is activated via a pathway starting from tumor necrosis factor a (TNFa) and its receptor. Ceramide serves as an activator of protein kinases and protein phosphatases. RI fatty add side chain.

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... 

This enzyme, which has been purified some 200-fold, also catalyzes the synthesis of ceramide from sphingosine and free fatty acid. Acyl CoA derivatives are active only after hydrolysis by thiolase to release free fatty acid which is then available to condense with sphingosine. Attempts to dissociate these enzymic processes from one another have been unsuccessful. The preparation showed hydrolytic activity (ceramidase) toward A-palmitoyl, oleoyl, and stearoyl sphingosine, as well as with. V-palmitoyl dihydrosphingosine. Cerefarosides, sphingomyelin, and iV-acetyl sphingosine were not cleaved. 

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