Pathways of Sphingolipid Metabolism. De novo synthesis begins with condensation of serine and palmitoyl CoA by serine palmitoyl-CoA transferase (SPT), the rate-limiting step in the production of 3-ketosphinganine, which is immediately reduced to sphinganine by ketodihydrosphingosine reductase (KDHR). Sphinganine can be phosphorylated by sphingosine kinases (SPHK) to sphinganine-1-phosphate or acylated by ceramide synthases (CERS) to form dihydroceramides. Dihydroceramides are converted to ceramides by dihydroceramide desaturase (DEGS), which are subsequently recycled as sphingosine, also by CERS, or converted to sphingomyelins by sphingomyelin synthase (SMS). Additional abbreviations SPP-1 (S1P phosphatase), and SMase (sphingomyelinase).