Sphingosine

Sphingosine is an 18-carbon amino alcohol that forms the backbone of most sphingolipids. It has the chemical name 2-amino-4-octadecene-1,3-diol and features an amino group at carbon 2, hydroxyl groups at carbons 1 and 3, and a trans double bond between carbons 4 and 5 along the long hydrocarbon chain.

In cellular metabolism, sphingosine is produced from dihydrosphingosine by desaturation, a step that follows the de novo sphingolipid biosynthesis pathway in which serine and palmitoyl-CoA are condensed to form 3-ketosphinganine, then reduced to dihydrosphingosine. The basic sphingoid base can be N-acylated to form ceramides, glycosylated to create glycosphingolipids, or phosphorylated to yield sphingosine-1-phosphate. Sphingosine itself can be liberated by hydrolysis of complex sphingolipids and serves as a precursor to various lipid species.

Sphingosine participates in lipid signaling primarily through its phosphorylation to sphingosine-1-phosphate (S1P) by sphingosine kinases. S1P acts on a family of G-protein-coupled receptors to influence cell growth, survival, migration, and angiogenesis. In contrast, sphingosine and ceramide can promote pro-apoptotic pathways, contributing to the balance known as the sphingolipid rheostat that modulates cellular fate.

Clinically and in research, sphingosine and related sphingolipids are studied in lipidomics due to their roles in metabolism, development, and disease. Abnormal sphingolipid metabolism is associated with lysosomal storage disorders, metabolic diseases, and neurodegenerative conditions.