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Fig. 1. Sphingolipid synthesis pathways and structures. (A) Ceramide is generated by a de novo synthetic pathway and further metabolized via a salvage pathway. Once synthesized, ceramide is converted to either glucosylceramide or sphingomyelin by adding glucose or phosphocholine, respectively. Ceramide is degraded via a catabolic pathway to sphingosine is phosphorylated by sphingosine kinase (SphK), which can be degraded by S1P lyase. (B) Ceramide is synthesized by adding fatty acyl CoA to the long chain bases (sphingosine or sphinganine) and further metabolized to ceramide 1-phosphate (by phosphorylation), sphingomyelin (by adding phosphocholine), glucosylceramide (by adding glucose), and complexed glycoceramide (by adding various sugars). Ceramide is also degraded to sphingosine, which can be phosphorylated to S1P. GCS, glucosylceramide synthase; GBA, glucocerebrosidase; SMase, sphingomyelinase; SMS, sphingomyelin synthase; SPT, serine palmitoyltransferase; KDHR, 3-keto-dehydrosphingosine reductase; CerS, ceramide synthase; DES, dihydroceramide desaturase; S1P lyase, sphingosine-1-phosphate lyase; SphK, sphingosine kinase; SPP, S1P-specific phosphatases; LPP, lipid phosphate phosphatase.
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