Sphingolipids properties

The use of sphingolipids in liposome formation is possible due to the natural amphipathic properties of the molecules. Some sphingolipids can lend structural advantages to the integrity... 

The distinguishing structural and functional protein for caveolae is caveolin. Caveolin proteins display properties that are likely involved in the distinguishing morphology of caveolae. Caveolins have a high affinity for both cholesterol and sphingolipids coupled with 3 carboxy-terminal palmitoylated cysteine residues. Three isoforms of caveolin exist and show distinct tissue distribution. Likely because it was discovered first and is perhaps most abundant, caveolin-1 has garnered the lion s share of research attention. 

Ferrying of molecules into cells via entry through caveolae may represent a way to traffic specifically cytotoxic molecules to specific action sites. For example, elevating the intracellular level of the sphingolipid ceramide is known to exert antimitogenic and proapoptotic effects. While ceramide is cell-permeable and displays antiapoptotic properties in vitro, systemic in vivo use of ceramide is hampered by its hydrophobicity. Using a C6-ceramide formulation in pegylated liposomes was shown to elicit a sixfold reduction in solid phase tumors, when compared to unloaded liposomes in a mouse model of breast adenocarcinoma [68],... 

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. 

Fig. 1.4.8. Concept for cell surface engineering exogenously added ceramide analogs can lead to modification of the hydrophobic and the hydrophilic part of membrane sphingolipids and alter the properties of membrane proteins.

Studies in vitro and in rats showed that short and medium chain fatty acids and monoacylglycerols hydrolyzed from milk triacylglycerols and digestion products of sphingolipids possess strong anti-bacterial and anti-viral properties. 

Interestingly, all of the enzymes that comprise the sphingolipid-catabolic pathway are glycoproteins and may be found in different places within the organelle. For example, glucocerebrosidase is firmly associated with the lysosomal membrane, whereas others, like hexoseaminidase A, exist largely in soluble form in the lysosomal matrix. A common property of the lysosomal hydrolases, however, is their expression of maximum activity at a relatively acidic pH (i.e., pH 4.0-5.5), hence the term acid hydrolase. This is not unexpected because ATP-driven proton pumps sustain an acidic milieu (pH 5.2) within the lysosome. 

Yavin, E., and Gatt, S., 1969, Enzymatic hydrolysis of sphingolipids. 8. Further purification and properties of rat brain ceramidase. Biochemistry 8 1692-1698. 

Lipids are made up of many classes of very different molecules that all show solubility properties in organic solvents. Mass spectrometry plays a key role in the biochemistry of lipids. Indeed, mass spectrometry allows not only the detection and determination of the structure of these molecules but also their quantification. For practical reasons, only the fatty acids, acylglycerols and bile acids are discussed here, although other types of lipids such as phospholipids, [253-256] steroids, [257-259] prostaglandins, [260] ceramides, [261,262] sphingolipids [263,264] and leukotrienes [265,266] have been analysed successfully by mass spectrometry. Moreover, the described methods will be limited to those that are based only on mass spectrometry, even if the majority of these methods generally are coupled directly or indirectly with separation techniques such as GC or HPLC. A book on the mass spectrometry of lipids was published in 1993. [267]... 

Jatzkewitz, H., Existence, localization and some properties of the activators of sphingolipid hydrolases. Adv. Exp. Med. Biol. 101, 561-571 (1978). 

A cell cannot divide or enlarge unless it makes sufficient amounts of additional membranes to accommodate the expanded area of its outer surface and internal organelles. Thus the generation of new cell membranes is as fundamentally important to the life of a cell as is protein synthesis or DNA replication. Although the protein components of biomembranes are critical to their biological functions, the basic structural and physical properties of membranes are determined by their lipid components—principally phospholipids, sphingolipids, and sterols such as cholesterol (Table 18-1). Cells must be able to synthesize or import these molecules to form membranes. 

Goni, F. M., and Alonso, A. (2006). Biophysics of sphingolipids I. Membrane properties of sphingosine, ceramides and other simple sphingolipids. Biochim Biophys Acta 1758, 1902-1921. 

All eukaryotic cells contain a lipid outer membrane composed of glycerolipids, sphingolipids and sterols. All three lipids have been found to exhibit a wide range of combinatorial diversity and their biochemical and biophysical properties determine functionality. 

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