Alterations in raft lipid metabolism in aging and neurodegenerative disorders

Sphingolipids are a prominent type of membrane phospholipid in eukaryotic cells and are particularly abundant in the nervous systems of mammals. They consist of a glycerol backbone with a phosphocholine zwitterionic hydrophilic headgroup and two long hydrocarbon chains that form a hydrophobic domain (Fig. 1). The hydrocarbon chains of sphingomyelin are relatively long (>20 carbons) and contain more saturated bonds than are present in phosphatidylcholine. Sphingomyelin contributes prominently to the biophysical properties of membranes, and in particular, the large disparity in the lengths of the two chains of sphingomyelin may allow for interdigitation between the hydrocarbons in the two opposing monolayers of the phospholipid bilayer, thereby providing a means for coupling-phase separation with the marked curvature of cell membranes. Sphingolipids also have a Tm near body temperature (37°C). The collective biophysical properties of sphingolipids suggest that they play important roles in the formation of specialized domains in membranes such as lipid rafts. Sphingolipid synthesis is initiated by serine palmitoyltransferase (SPT), which catalyzes the condensation of palmitoyl-CoA (acyl) with serine to form 3-dihydrosphinganine, and additional biosynthetic steps result in formation of sphingosine, which is then acylated to form ceramide. Choline can then be added to ceramide by choline-phosphotransferase, which results in the synthesis of sphingomyelin.