Ceramide synthase (CerS)

Ceramide synthases (CerS) are a family of membrane-associated enzymes critical for the de novo, salvage, and recycling pathways of ceramide biosynthesis. They catalyze the acylation of a sphingoid long-chain base (sphinganine or sphingosine) with a fatty acyl-CoA, forming ceramide. Six mammalian isoforms (CerS1–CerS6) differ in their specificity for fatty acyl chain length, tissue distribution, and biological roles. The acyl chain composition of ceramide variants dictates their bioactivity: for instance, CerS6-driven C16:0 ceramide synthesis is implicated in obesity, insulin resistance, and liver disease. Ceramide synthases are attractive therapeutic targets for metabolic disorders, but selective targeting is required to avoid broad disruption of sphingolipid homeostasis. Several drugs and toxins (such as fumonisin B1) act as CerS inhibitors. Ceramide levels and isoform expression may function as disease biomarkers and guide targeted therapeutic approaches.

Other names

CerSLasssphinganine N-acyltransferase

Inhibition of ceramide synthase reduces synthesis of specific ceramides (notably C16:0), thereby modulating cellular lipid signaling and metabolism. Specific inhibitors block the N-acylation step, blocking downstream sphingolipid production. Fumonisin B1 forms a stable intermediate and irreversibly inhibits the enzyme.