Sphingolipid metabolism

While sphingolipids are abundant in a wide variety of foodstuffs, these dietary molecules are mostly degraded by the intestinal flora and intestinal enzymes. The body primarily depends on de novo synthesis for its sphingolipid supply. De novo synthesis proceeds in four steps: the condensation of palmitoyl-CoA and serine to form 3-ketosphinganine, the reduction of 3-ketosphinganine to sphinganine, the acylation of sphinganine with a long-chain fatty acyl CoA to form dihydroceramide, and the desaturation of dihydroceramide to form ceramide.

Other sphingolipids involved in signaling are derived from ceramide and its biosynthetic intermediates. These include sphinganine (dihydrosphingosine) 1-phosphate, phytoceramide, sphingosine, and sphingosine 1-phosphate.

Sphingomyelin is synthesized in a single step in the membrane of the Golgi apparatus from ceramides generated in the endoplasmic reticulum (ER) membrane and transferred to the Golgi by CERT (ceramide transfer protein), an isoform of COL4A3BP that is associated with the ER membrane as a complex with PPM1L (protein phosphatase 1-like) and VAPA or VAPB (VAMP-associated proteins A or B). Sphingomyelin synthesis appears to be regulated primarily at the level of this transport process through the reversible phosphorylation of CERT.