the trans Golgi. It is enriched at the plasma membrane with a greater concentration on the outer than the inner leaflet. The Golgi complex represents an intermediate between the ER and plasma membrane, with slightly higher concentrations towards the trans side. Metabolism Synthesis The synthesis of sphingomyelin involves the enzymatic transfer of a phosphocholine from phosphatidylcholine to a ceramide. The first committed step of sphingomyelin synthesis involves the condensation of L-serine and palmitoyl-CoA. This reaction is catalyzed by serine palmitoyltransferase. The product of this reaction is reduced, yielding dihydrosphingosine. The dihydrosphingosine undergoes N-acylation followed by desaturation to yield a ceramide. Each one of these reactions occurs at the cytosolic surface of the endoplasmic reticulum. The ceramide is transported to the Golgi apparatus where it can be converted to sphingomyelin. Sphingomyelin synthase is responsible for the production of sphingomyelin from ceramide. Diacylglycerol is produced as a byproduct when the phosphocholine is transferred. Degradation Sphingomyelin breakdown is responsible for initiating many universal signaling pathways. It is hydrolyzed by sphingomyelinases (sphingomyelin specific type-C phospholipases). The phosphocholine head group is released into the aqueous environment while the ceramide diffuses through the membrane. Function Membranes The membranous myelin sheath that surrounds and electrically insulates many nerve cell axons is particularly rich in sphingomyelin, suggesting its role as an insulator of nerve fibers. The plasma membrane of other cells is also abundant in sphingomyelin, though it is largely to be found in the exoplasmic leaflet of the cell membrane. There is, however, some evidence that there may also be a sphingomyelin pool in the inner leaflet of the membrane. Moreover, neutral sphingomyelinase-2 – an enzyme that breaks down sphingomyelin into ceramide - has been found to localise exclusively to the inner leaflet, further suggesting that there may be sphingomyelin present there. Signal transduction The function of sphingomyelin remained unclear until it was found to have a role in signal transduction. It has been discovered that sphingomyelin plays a significant role in cell signaling pathways. The synthesis of sphingomyelin at the plasma membrane by sphingomyelin synthase 2 produces diacylglycerol, which is a lipid-soluble second messenger that can pass along a signal cascade. In addition, the degradation of sphingomyelin can produce ceramide which is involved in the apoptotic signaling pathway. Apoptosis Sphingomyelin has been found to have a role in cell apoptosis by hydrolyzing into ceramide. Studies in the late 1990s had found that ceramide was produced in