Skip to main content
. Author manuscript; available in PMC: 2022 Aug 24.
Published in final edited form as: Annu Rev Nutr. 2022 May 18;42:115–144. doi: 10.1146/annurev-nutr-062220-112920

Figure 1.

Figure 1

Intracellular and intestinal ceramide metabolism. (a) Sphingolipids are metabolized in various subcellular compartments. Ceramides are produced via a de novo biosynthetic pathway in the endoplasmic reticulum (ER) and are transported to the Golgi apparatus for synthesis of complex sphingolipids. Ceramide can be regenerated from SM hydrolysis in the mitochondria, lysosome, plasma membrane, and circulating lipoproteins. Deacylation of ceramides generates sphingosine, which can be phosphorylated to form S1P. (b) Dietary SM and ceramide are digested in the small intestine by alk-SMase and nCDase, respectively, to form sphingosine, which is absorbed by enterocytes. In the large intestine, dietary and de novo sphingolipids are metabolized by gut microbiota to generate unique odd-chain and deoxysphingolipid species. Abbreviations: 3-KDS, 3-ketosphinganine; aCDase, acid ceramidase; ADIPOR, adiponectin receptors; alkCDase, alkaline ceramidase; alk-SMase, alkaline sphingomyelinase; C1P, ceramide-1-phosphate; cer, ceramide; CERK, ceramide kinase; CERS, (dihydro)ceramide synthase; CERT, ceramide transport protein; dCer, dihydroceramide; DES, dihydroceramide desaturase; dSph, dihydrosphingosine; FA, fatty acid; hCer, hexosylceramide; KDSR, 3-ketodihydrosphingosine reductase; lSMase, lysosomal ceramidase; MA-SMase, mitochondria-associated sphingomyelinase; nCDase, neutral ceramidase; nSMase, neutral sphingomyelinase; S1P, sphingosine-1-phosphate; SL, sphingolipid; SM, sphingomyelin; SMS, sphingomyelin synthase; sph, sphingosine; SPHK1, sphingosine kinase 1; SPHK2, sphingosine kinase 2; SPP, sphingosine-1-phosphate phosphatase; SPT, serine palmitoyltransferase; sSMase, secretory sphingomyelinase; UGCG, glucosylceramide synthase.