Sphingolipids Synthesis, Transport and Cellular Signaling

Summary

Sphingolipids are comprised of a sphingoid base backbone (sphingosine, sphinganine or other species) that is synthesized de novo from serine and a fatty acyl-coenzyme A then converted into more complex compounds (ceramides, phosphosphingolipids, glycosphingolipids and protein adducts) that are key to the structures of cell membranes, lipoproteins, and the lamellar water barrier of the skin. Many complex sphingolipids as well as simpler sphingoid bases and derivatives are highly bio-active as extra- and intra-cellular regulators of growth, differentiation, migration, survival and numerous cellular responses to stress. The large numbers of functionally significant species requires careful control of sphingolipid biosynthesis, intracellular trafficking and turnover, and the regulatory mechanisms are still being discovered using genetic, biochemical and “sphingolipidomic” approaches. In the approximately 120 years since the compound “sphingosin” was first described, many biological mysteries have been explained by the biophysical and regulatory properties of sphingolipids, and it is certain that clarification of the remaining enigmas of sphingolipidology will contribute profoundly to our understanding of normal and abnormal cell behavior, and new ways to prevent, detect and treat disease.