Figure 1.

Synthesis of ceramide and other measured sphingolipids. Shown are simplified pathways leading to ceramide, sphingomyelin, glucosyl ceramide, and lactosyl ceramide, the four sphingolipids measured in the study. In the de novo synthesis pathway and the salvage pathway, ceramide is formed by acylation of a fatty acid (FA) to a “sphingoid” backbone, dihydrosphinganine and sphingosine, respectively. There are six ceramide synthases in humans with different fatty acid specificities, resulting in multiple ceramide species carrying different fatty acids. Synthesis of ceramide by the two pathways occurs in the endoplasmic reticulum. Ceramide can also be formed by sphingomyelinases on the plasma membrane. Sphingomyelin is synthesized by sphingomyelin synthase by addition of a choline head group to ceramide transported to the Golgi. Glucosyl ceramide is synthesized by addition of a glucose head group to ceramide, and lactosyl ceramide by further addition of galactose to glucosyl ceramide, also in the Golgi.