Fig. 1. Sphingolipid metabolic pathways. De novo synthesis of ceramide consists of decarboxylation of a serine residue and condensation with a fatty acyl-CoA. Hydrolysis of SM by various SMases can also produce ceramide. The subsequent reactions catalyzed by CK, GCS, and GalCS lead to the production of other sphingolipids from ceramide. Many of these biochemical reactions are bidirectional. C1PP, ceramide-1-phosphate phosphatase; CDase, ceramidases; CK, ceramide kinase; CerS, ceramide synthase; DAG, diacylglycerol; DES, dihydroceramide desaturases; GalCS, galactosylceramide synthase; GCase, glucocylceramidase; GCS, glucosylceramide synthase; PC, phosphatidylcholine; S1P, sphingosine-1-phosphate; S1PP, S1P phosphatase; SK, sphingosine kinase; SMase, sphingomyelinase; SMS, sphingomyelinase synthase; SPL, S1P lyase; SPT, serine palmitoyl transferase.