The Role of Sphingosine-1-Phosphate and Ceramide-1-Phosphate in Inflammation and Cancer

Figure 1

Biosynthesis of ceramide, sphingosine-1-phosphate, and ceramide-1-phosphate (a). Chemical structures of sphingolipids (b). Ceramide is the central sphingolipid molecule of sphingolipid metabolic pathways. Three major pathways are responsible to produce ceramide. Ceramide is produced by de novo pathway in the ER with a series of enzymatic reactions. Ceramide is produce from SM by SMase action. The salvage pathway generates ceramide from sphingosine that generates from the metabolism of complex sphingolipids. Ceramide is now can be converted to C1P by CERK enzyme. Ceramide can be converted to sphingosine by ceramidase. Sphingosine is now phosphorylated by sphingosine kinases to form S1P. S1P can be converted back to sphingosine by SPPase or can be irreversibly broken down by sphingosine phosphate lyase (SPL) to ethanolamine phosphate and 2-trans hexadecenal for phosphatidylethanolamine and glycerolipids, respectively.

(a)

(b)