Fig. 1.

Ceramides can be synthesized through three different pathways: de novo biosynthesis, sphingomyelinase pathway, and the salvage pathway. The de novo pathway of ceramide generation is regulated by its rate-limiting enzyme, serine palmitoyl-CoA transferase (SPT). Furthermore, SPT has high specificity for its substrate, palmitoyl-CoA, a saturated fatty acid that is required for the formation of the sphingoid backbone of ceramides. Distinct from the de novo pathway, ceramides can also be generated by neutral sphingomyelinase (N-SMase)-catalyzed hydrolysis of sphingomyelin in cell membranes. Finally, ceramides can also be synthesized through the “salvage pathway” by breakdown of complex sphingolipids mediated by ceramide synthase.