Figure 1

Formation of bioactive sphingolipids in mammalian cells. Ceramide can be produced by degradation of sphingomyelin (SM) by sphingomyelinases (SMase), or by de novo synthesis through the concerted action of serine palmitoyltransferase and dihydroceramide synthase. It can also be generated through metabolism of more complex sphingolipids. Ceramide can be metabolized to ceramide-1-phosphate by ceramide kinase, or to glucosylceramide by glucosylceramide synthase (GCS). The reverse reaction is catalyzed by ceramide-1-phosphate phosphatase, or by lipid phosphate phosphatases. Alternatively, ceramide can be degraded by ceramidases to form sphingosine, which can, in turn, be phosphorylated to sphingosine-1-phosphate by sphingosine kinase. The reverse reaction is catalyzed by sphingosine-1-phosphate phosphatases, or by lipid phosphate phosphatases. Sphingomyelin N-deacylase generates sphingosylphosphorylcholine.