Sphingolipids formation

Oh C. S., Toke D. A., Mandala S. and Martin C. E. (1997) EL02 and EL03, homologues of the Saccharomyces cerevisiae ELOl gene, function in fatty acid elongation and are required for sphingolipid formation. J. Biol. Chem. 272, 17376-17384. 

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. 

Haidar, K. Sphingolipid synthesis and membrane formation by Plasmodium. Tr. Cell Biol. 1996, 6, 398 05. 

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 polar character of the liposomal core makes the encapsulation of polar drug molecules possible. Amphiphilic and lipophilic molecules are solubilized within the phospholipid bilayer according to their affinity toward the phospholipids. Participation of nonionic surfactants instead of phospholipids in the bilayer formation results in Niosomes . The term sphingosomes is suggested for vesicles from sphingolipids. However, the nomenclature is not consistent, and the term liposomes is used as a general term, although vesicles would be the better choice. 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

Synthesis of plasmalogens involves formation of their characteristic double bond by a mixed-function oxidase. The head groups of sphingolipids are attached by unique mechanisms. 

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. 

Sphingolipid Regulation of Signaling via Control of Raft Formation and Stability... 

Conversely, addition of C8-L-fftreo-LacCer (Fig. 14) inhibited the formation of microdomains in the plasma membrane, which resulted in the inhibition of both endocytosis and pi-integrin signaling (170). Thus, non-natural sphingolipids that can block the formation of microdomains in the plasma membrane may offer a novel means for interfering with the cell entry mechanism that is employed by various pathogens and viruses. 

Figure 26.3. Synthesis of Sphingolipids. Sphingosine is converted into ceramide, which is an intermediate in the formation of sphingomyelin and gangliosides.

It is necessary for the synthesis of sphingolipids necessary for myelin formation. This explains the irritability, nervousness and depression found with mild deficiency and peripheral neuropathy and convulsions observed with severe deficiency. 

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