Schematic of the <i>de novo</i> ceramide pathway.

<p>Rate-limiting enzyme, serine palmitoyltransferase (SPT), condenses serine and palmitoyl-CoA to 3-ketosphinganine, which is subsequently reduced to sphinganine. Dihydroceramide synthases 1-6 (CerS 1-6), each utilizing a preferred subset of fatty acid-derived acyl-CoAs, add a fatty acyl chain (green) to sphinganine to produce dihydroceramides. Dihydroceramide desaturase (DES1) converts dihydroceramides to ceramides by introduction of a 4,5-trans double bond into the sphinganine backbone of dihydroceramide. 4-HPR stimulates both SPT and CerS in certain cancer cell lines. Both 4-HPR and GT-11, a synthetic ceramide derivative, inhibit DES1. Asterisks (*) indicate variable carbon length and saturation.