Sphingolipid Synthesis

1. 1

   Serine + palmitoyl-CoA -> 3-ketosphinganine + CO2 + CoA-SH

   Serine palmitoyltransferase (SPT) 2.3.1.50 ST-0324 Irreversible rate-limiting PLP (B6)
   In Serine Palmitoyl-CoA

   Out 3-Ketosphinganine CO2 CoA-SH
   › Notes

   Rate-limiting and committed step; located on the ER.

2. 2

   3-Ketosphinganine + NADPH -> sphinganine + NADP+

   3-Ketosphinganine reductase 1.1.1.102 ST-0325 Irreversible/directional NADPH
   In 3-Ketosphinganine NADPH

   Out Sphinganine NADP+
3. 3

   Sphinganine + fatty acyl-CoA -> dihydroceramide + CoA-SH

   Ceramide synthase (CerS1-6) 2.3.1.24 ST-0326 Irreversible/directional
   In Sphinganine Fatty acyl-CoA

   Out Dihydroceramide CoA-SH
   › Notes

   Six isoforms determine the acyl chain length of the ceramide pool.

4. 4

   Dihydroceramide -> ceramide

   Dihydroceramide desaturase (DEGS1) 1.14.19.17 ST-0327 Irreversible/directional O2 NAD(P)H
   In Dihydroceramide

   Out Ceramide
   › Notes

   Ceramide is the hub metabolite of all complex sphingolipids and a pro-apoptotic signal.

5. 5

   Ceramide + phosphatidylcholine -> sphingomyelin + diacylglycerol

   Sphingomyelin synthase (SGMS1/2) 2.7.8.27 ST-0328 Irreversible/directional
   In Ceramide Phosphatidylcholine

   Out Sphingomyelin Diacylglycerol
   › Notes

   Occurs in the Golgi; sphingomyelin is a major myelin and plasma-membrane lipid.

6. 6

   Ceramide + UDP-glucose -> glucosylceramide + UDP

   Glucosylceramide synthase (UGCG) 2.4.1.80 ST-0329 Irreversible/directional UDP-glucose
   In Ceramide UDP-glucose

   Out Glucosylceramide UDP
   › Notes

   Entry to the glycosphingolipid/ganglioside series; sequential glycosyltransferases then build lactosylceramide, globosides and gangliosides.

Showing all 6 steps.