Ceramide sphingolipid

H The compounds in which Y = H are ceramides. Sphingolipids are often named as ceramide derivatives. 

The synthesis of all sphingolipids begins with the production of ceramide. Sphingolipids are degraded within lysosomes by specific hydrolytic enzymes. 

Ceramide Sphingolipid with an amide-linked fatty acid and an unsubstituted 1-hydroxyl. 

Ceramide types III and IV were isolated from stratum comeum lipid extracts and separated from cholesterol, free fatty acids, and triglycerides on a silica column (ELSD) in <15min using a 19/1 hexane/ethanol mobile phase [717]. Related compound classes (hydroxy fatty acid ceramide, C2 ceramide, sphingolipid, phyto-sphingosine) were separated on a silica column using a 90/10/1/1 chloroform/ ethanol/triethylamine/formic acid mobile phase. In this case elution was complete in 10 min. 

The emerging roles of ceramide in growth suppression, apoptosis and stress response have focused attention on the role of ceramide, sphingolipid-metabolizing enzymes, and ceramide targets in the pathology and treatment of disease (Table 3). 

FIGURE 25.25 Biosynthesis of sphingolipids in animals begins with the 3-ketosphinga-nine synthase reaction, a PLP-dependent condensation of palmitoyl-CoA and serine. Subsequent rednction of the keto group, acylation, and desatnration (via rednction of an electron acceptor, X) form ceramide, the precnrsor of other sphingolipids. 

Sphingolipids (ceramids, sphingomyelin, cerebrosides, sulfatides, gangliosides) and lipids with secondary amines produce blue spots on a white backgound (CAUTION benzidine is a carcinogen)... 

Because membranes components participate in nearly every cell activity their structures are also dynamic and far from the equilibrium states that are most readily understood in biophysical terms. Newly synthesized bilayer lipids are initially associated with endoplasmic reticulum (Ch.3) whereas phospholipids initially insert into the cytoplasmic leaflet while cholesterol and sphingolipids insert into the luminal endoplasmic reticulum (ER) leaflet. Glycosylation of ceramides occurs as they transit the Golgi compartments, forming cerebrosides and gangliosides in the luminal leaflet. Thus, unlike model systems, the leaflets of ER membranes are asymmetric by virtue of their mode of biosynthesis. 

Acetyl coenzyme A is the precursor of both cholesterol and fatty acids 39 Phosphatidic acid is the precursor of all glycerolipids 42 Sphingolipids are biosynthesized by adding head groups to the ceramide moiety 44... 

Sphinganine is acylated, then dehydrogenated to form ceramide. Free sphingosine, also termed sphingenine, salvaged from sphingolipid breakdown can be enzymatically acylated with acyl-CoA to form ceramide. 

Buccliero, R. and Futerman, H. The roles of ceramide and complex sphingolipids in neuronal cell function. Pharm. Res. 47 409-419, 2003. 

Figure 12.12 Sphingomyelins. Sphingomyelins are esters of a ceramide and phospho-ryl choline. However, similar compounds are ceramide-1-phosphoryl ethanolamines and phosphono forms of sphingolipids. Ceramides W-acyl-sphingosines) are amides of a long chain di- or trihydroxy base containing 12 to 22 carbon atoms, of which sphingosine (4-sphingenine) is the commonest, and a long chain fatty acid whose acyl chain is shown by R1. This may contain up to 26 carbon atoms.

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],... 

Figure 1. Scheme of sphingolipid metabolism and the central role of ceramide and ceramidases. 

Gatt, S., 1963, Enzymatic hydrolysis of sphingolipids. 1. Hydrolysis and synthesis of ceramides by an enzyme from rat brain. J. Biol. Chem. 238 3131-3133. 

Linke, T., Wilkening, G., Sadeghlar,. F, MozcaU, H., Bernardo, K., Schuchman, E., and Sandhoff, K., 2001, Interfacial Regulation of Acid Ceramidase Activity. Stimulation of ceramide degradation by lysosomal lipids and Sphingolipid Activator Proteins. J. Biol. Chem. 276 5760-5768. 

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