Sphingomyelin

Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids.Ball-and-stick model of sphingomyelinSkeletal formula of sphingomyelinceramideSphingosine Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids. Sphingomyelin was first isolated by German chemist Johann L.W. Thudicum in the 1880s. The structure of sphingomyelin was first reported in 1927 as N-acyl-sphingosine-1-phosphorylcholine. Sphingomyelin content in mammals ranges from 2 to 15% in most tissues, with higher concentrations found in nerve tissues, red blood cells, and the ocular lenses. Sphingomyelin has significant structural and functional roles in the cell. It is a plasma membrane component and participates in many signaling pathways. The metabolism of sphingomyelin creates many products that play significant roles in the cell. Sphingomyelin consists of a phosphocholine head group, a sphingosine, and a fatty acid. It is one of the few membrane phospholipids not synthesized from glycerol. The sphingosine and fatty acid can collectively be categorized as a ceramide. This composition allows sphingomyelin to play significant roles in signaling pathways: the degradation and synthesis of sphingomyelin produce important second messengers for signal transduction. Sphingomyelin obtained from natural sources, such as eggs or bovine brain, contains fatty acids of various chain length. Sphingomyelin with set chain length, such as palmitoylsphingomyelin with a saturated 16 acyl chain, is available commercially. Ideally, sphingomyelin molecules are shaped like a cylinder, however many molecules of sphingomyelin have a significant chain mismatch (the lengths of the two hydrophobic chains are significantly different). The hydrophobic chains of sphingomyelin tend to be much more saturated than other phospholipids. The main transition phase temperature of sphingomyelins is also higher compared to the phase transition temperature of similar phospholipids, near 37 C. This can introduce lateral heterogeneity in the membrane, generating domains in the membrane bilayer. Sphingomyelin undergoes significant interactions with cholesterol. Cholesterol has the ability to eliminate the liquid to solid phase transition in phospholipids. Due to sphingomyelin transition temperature being within physiological temperature ranges, cholesterol can play a significant role in the phase of sphingomyelin. Sphingomyelin are also more prone to intermolecular hydrogen bonding than other phospholipids. Sphingomyelin is synthesized at the endoplasmic reticulum (ER), where it can be found in low amounts, and at 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. 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. 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.