Figure 1.

Sphingolipid metabolism pathway. Ceramide acts as the central molecule of the sphingolipid metabolism pathway. Ceramide may be synthesized through either the de novo (blue text and arrows) or the salvage pathway (orange text and arrows). Synthesis of ceramide through the de novo pathway occurs through serine palmitoyltransferase (SPT), 3-ketosphinganine reductase, (dihydro)CerS1-6 (which determine fatty acyl chain length), and finally dihydroceramide desaturase (DES). Ceramide synthesis through the salvage pathway occurs through conversion of sphingosine-1-phosphate by S1P-phosphatase (S1PP) and (dihydro)CerS1-6. Ceramide may be metabolized to produce sphingosine 1-phosphate by ceramidases (CDases) and sphingosine kinase 1/2 (SphK1/2). Sphingosine-1-phosphate can be hydrolyzed by sphingosine 1-phosphate lyase (S1P lyase) to ethanolamine 1-phosphate and C₁₆ fatty aldehyde. Ceramide may also be used as a substrate for the generation of complex sphingolipids via conversion to glucosylceramide (GlcCer) by glucosylceramide synthase (GCS) (green arrows and text). Glucosylceramidase (GlcCDase) and galactosylceramidase (GCDase) (cerebrosides) catalyze conversion of complex sphingolipids back to ceramide. Ceramide may also be used as a substrate for sphingomyelin through sphingomyelin synthase (SMS) or ceramide 1-phosphate through ceramide kinase (CERK). Sphingomyelin can similarly be broken down by sphingomyelinase (SMase) to produce ceramide once again. Created with BioRender.com (accessed on 11 May 2021).