Occurrence and Importance of Ether Lipids in Brain

Ether glycerophospholipids are major constituents of neural cell membranes. The overall physicochemical characteristics of ether glycerophospholipids are similar to those of ester-bonded glycerophospholipids except for differences in the phase-transition temperature from gel to liquid crystalline and from lamellar to hexagonal phases. These differences may be responsible for determining physical properties of neural membranes, such as bilayer thickness, area per molecule, side-chain packing, free volume, and lateral domains (Paltauf, 1994; Lohner, 1996). The replacement of one or both acyl ester bonds with an alkenyl or alkyl ether bond produces changes in membrane properties (Lohner, 1996), such as a decrease in membrane dipole potential and alterations in thermotropic phase behavior, ion permeability, and sidechain mobility (Paltauf, 1994). Although the occurrence of ether glycerophospholipid species with inositol or serine as a head group has been reported, the most abundant glycerophospholipid species in brain are those with ethanolamine and choline as head groups. Artificial model membranes composed of ether lipids show markedly different molecular dynamics than membranes consisting of diacyl phospholipids (Lohner, 1996). Studies on model membranes indicate that high ether lipid content provides membranes with an unique microenvironment that is necessary for their optimal function. This includes maintenance of activities of membrane-bound enzymes, regulation of permeability, and optimal function of receptors and ion channels. Perturbation of an ether lipid-rich microenvironment in membranes produces significantly more derangements in membrane dynamics than the perturbation of model membranes composed of diacyl glycerophospholipids. Some neutral lipids also contain ether bonds (Foglia et al., 1988; Bordier et al., 1996). They include 1-O-alkyl-2,3-O-diacylsn- glycerols, 1-O-alk-1' -enyl-2,3-O-diacyl-sn-glycerols, and 1-O-alkyl-2-O-acyl-snglycerols that are analogs of triacylglycerol and diacylglycerols, respectively (Snyder, 1996). These lipids protect against radiation damage and possess antitumor properties. 1-O-alk-1ȧ -enyl-2-O-acyl-sn-glycerols and 1-O-alkyl-2-acyl-sn-glycerols are natural constituents of myocardium. These ether lipids stimulate protein kinase C activity suggesting that ether lipids may play an important role in regulating protein kinase C-mediated cellular differentiation (Ford et al., 1989).

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