Figure 2. Sphingolipid metabolism.

Ceramide is the centerpiece of the sphingolipid metabolism and can be synthesized by multiple pathways. Ceramide can be generated by the de novo pathway (orange box) from the condensation of serine and palmitoyl-CoA to generate 3-ketodihydrosphingosine, which is then reduced to dihydrosphingosine (also known as sphinganine) and further acylated by ceramide synthases (CerS). Ceramide can be hydrolyzed to sphingosine and then reacylated back to ceramide in the salvage/ recycling pathway or phosphorylated to sphingosine-1-phosphate by sphingosine kinase (SK) and exit the sphingolipid metabolism by the action of the sphingosine-1-phosphate lyase (SPL) (blue box). Ceramide can also be formed by the hydrolysis of more complex sphingolipids such as sphingomyelin (purple box), glucosylceramide (turquoise box) and galactosylceramide (black box). Serine palmitoyltransferase (SPT); 3-ketodihydrosphingosine reductase (KDHR); (dihydro)ceramide synthase (CerS); dihydroceramide desaturase (DES); ceramidase (CDase); sphingosine-1-phosphate phosphatases (SPP); sphingomyelinases (SMase); sphingomyelin synthase (SMS); glucosylceramide synthase (GCS); glucosylceramidase (GCase); ceramide galactosyltransferase (CGT); galactosylceramidase (GALC); ceramide kinase (CERK); ceramide-1-phosphate phosphatase (C1PP).