Sphingolipid Metabolism
Biosynthesis and degradation of sphingolipids including ceramide signaling.
Overview
Sphingolipid synthesis begins with condensation of serine and palmitoyl-CoA by serine palmitoyltransferase (SPT) to form 3-ketosphinganine, which is reduced to sphinganine and acylated to dihydroceramide, then desaturated to ceramide. Ceramide is the central hub: it can be converted to sphingomyelin (by SMS), glucosylceramide (by GCS), or phosphorylated to ceramide-1-phosphate. Sphingomyelinase generates ceramide from sphingomyelin in response to stress signals. Ceramide is a pro-apoptotic lipid mediator.
Cellular Location
ER, Golgi, plasma membrane, lysosomes
Clinical Significance
S1P receptor modulator fingolimod treats MS; ceramide mediates apoptosis in cancer therapy; sphingolipid storage diseases (Gaucher, Niemann-Pick, Fabry) from enzyme deficiencies; S1P regulates immune cell trafficking.