Generation of signaling molecules by de novo sphingolipid synthesis

Sphingolipids are abundant components of cellular membranes in eukaryotic cells as well as potent signaling molecules. De novo sphingolipid biosynthesis begins with condensation of L-serine and palmitoyl-CoA, generating sphingoid bases, ceramide, and other species through a series of reactions. Ceramide can also be formed from free sphingoid bases, which has been termed the' salvage' pathway. Sphingolipids from both the de novo and salvage pathways increase with exposure of yeast or mammals to various stimuli such as Fas ligands, chemotherapeutic drugs, tumor necrosis factor-γ and heat stress, and then act as lipid second messengers mediating inflammatory responses, senescence, cell cycle arrest, apoptosis or stress responses. Therefore, generation of signaling molecules by de novo synthesis and/or salvage accounts not only for homeostasis, but also for several disorders resulting from aberrant sphingolipid accumulation or depletion.