Sphingolipids cell membranes

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

In aqueous systems, membrane lipids may exist in a gel-like solid state or as a two-dimensional liquid. In the case of pure phospholipids, these states interconvert at a well-defined transition temperature, Tc, that increases with alkyl chain length and decreases with introduction of alkyl chain unsaturation. In cell membranes, which have marked heterogeneity in both the polar and nonpolar domains of the bilayer, this state is described as liquid disordered . The presence of sufficient sphingolipids, with... 

GalNAcl—>3Gall—>4Gall—>4G1c Present in sphingolipid of red blood cell membranes... 

Recent evidence also suggests that the distribution of phospholipids and proteins within the cell membrane is not random, but that certain areas of the cell membrane are organized into special regions or domains. 35,52 63 In particular, certain domains appear to consist primarily of lipids such as cholesterol and sphingolipids.27,50 These lipid domains are often described as lipid rafts that move freely about the cell membrane and these lipid rafts appear to be important in controlling various cell functions including cell signaling, endocytosis, and ion channel function.27,50 Future research will help further define the role of the lipid rafts and other specific domains within the cell membrane. 

Lipids have several important functions in animal cells, which include serving as structural components of membranes and as a stored source of metabolic fuel (Griner et al., 1993). Eukaryotic cell membranes are composed of a complex array of proteins, phospholipids, sphingolipids, and cholesterol. The relative proportions and fatty acid composition of these components dictate the physical properties of membranes, such as fluidity, surface potential, microdomain structure, and permeability. This in turn regulates the localization and activity of membrane-associated proteins. Assembly of membranes necessitates the coordinate synthesis and catabolism of phospholipids, sterols, and sphingolipids to create the unique properties of a given cellular membrane. This must be an extremely complex process that requires coordination of multiple biosynthetic and degradative enzymes and lipid transport activities. 

Fatty acyl residues (R) commonly found in membrane lipids are summarized in Table 1.2 [2]. Generally, four lipid structures are mainly found in eucaryotic cells phospholipids, sphingolipids, glycolipids, and sterols [2]. The various organs differ in their phospholipid composition (Table 1.3). As an example, the composition of the liver cell membrane is given [2].There is also a considerable difference in the proportion of phospholipids in different cell types and in different species. Figure 1.2... 

Ahmed, S.N., Brown, D.A., and London, E. (1997) On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes physiological concentrations of cholesterol and sphingohpid induce formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes. Biochemistry 36 10944-10953. 

Tay-Sachs disease. A member of a family of disorders identified as the Gm2 gangliosidoses. As neural cell membranes are enriched in Gm2 gangliosides, the inability to degrade this class of sphingolipid resnlts in neural cell death. In addition to Tay-Sachs disease the family includes the Sandhoff diseases and the Gm2 activator deficiencies. Tay-Sachs disease resnlts from defects in the HEXA gene encoding the a-subunit of /3-hexosaminidase. 

Lipid rafts on cell membranes are cholesterol- and sphingolipid-rich domains that function as platforms for signal transduction and other cellular processes [6], Tethered lipid bilayers have been proposed as a promising model membrane to describe the structure and function of cell membratKs [7]. Based on these facts, we endeavor to array the lipid rafts as a form of tethered bilayer lipid membrare into the nanopattemed substrates to generate a raft membrane-based biosensing platform (Fig. Ic). 

Sphingolipids are the second major group of phospholipids. These compounds, which have sphingosine or a related dihydroxyamine as their backbone, are constituents of plant and animal cell membranes. They are... 

Phosphoglycerides such as lecithin and cephalin are closely related to fats. The glycerol backbone in these molecules is esterified to two fatty acids (one saturated and one unsaturated) and to one phosphate ester. Sphingolipids, another major class of phospholipids, have an amino alcohol such as sphingosinc for their backbone. These compounds are important constituents of cell membranes. 

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