General pathways for the generation of ceramide

In mammalian cells, ceramide is biosynthesized de novo or generated by catabolism of complex sphingolipids. In the de novo synthesis pathway (purple block arrow), a four-enzyme sequence culminates in the formation of ceramide from the amino acid serine and palmitoyl-CoA. This pathway is located in the endoplasmic reticulum. Sphingomyelin can be hydrolyzed to ceramide in the sphingomelin hydrolysis pathway (orange block arrow), which involves only one enzyme step. Alternatively, ceramide can be produced in the salvage pathway (green block arrows), through the acylation of sphingolipid by the ceramide synthase family of enzymes. The red blocks represent cartoons of the possible structures of the molecules. The acyl-chain length of ceramide can vary greatly. (Source: Abed Rabbo M, Khodour Y, Kaguni LS, Stiban J. Sphingolipid lysosomal storage diseases: from bench to bedside. Lipids Health Dis 2021;20[1]:44. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)