Sphingolipid functions

Schneiter, R. (1999) Brave little yeast, please guide us to Thebes sphingolipid function in S. cerevisiae. BioEssays 21, 1004 1010. 

The dermatitis associated with total EFA deficiency is most likely due to the role of linoleic acid in skin. Linoleic acid is the major fatty acid component of skin ceramides. This sphingolipid functions to prevent water loss through the skin (Simopoulos, 1989). Other fatty acids are not incorporated into skin ceramides to any great extent (Hansen and Jensen, 1985). Linoleic acid is also an efficient source of energy when compared to stearic and oleic acids. This is due to the more rapid oxidation of linoleic acid versus these 18 carbon saturated and mono-unsaturated fatty acids (Dupont, 1988). 

Dickson, RC and Lester, RL (2002) Sphingolipid functions in Saccharomyces cerevisiae. Biochint Biophys Acta, 1583, 13-25. 

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. 

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

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. 

Hannun, Y.A. and Bell, R.M., 1989, Functions ofsphingolipids and sphingolipid breakdown products in cellular regulation, Science 243 500-507. 

Igarashi, Y. Functional roles of sphingosine, sphingosine 1-phosphate, and methylsphingosines in regard to membrane sphingolipid signaling pathways (1997) I Biochem. (Tokyo) 122, 1080-7... 

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. 

FIGURE 21-31 Biosynthesis of sphingolipids. Condensation of palmitoyl-CoA and serine followed by reduction with NADPH yields sphinganine, which is then acylated to N-acylsphinganine (a ceramide). In animals, a double bond (shaded pink) is created by a mixed-function oxidase, before the final addition of a head group phosphatidylcholine, to form sphingomyelin glucose, to form a cerebroside. 

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. 

Targeting of proteins to specialized domains of a membrane are less well understood. These include caveolae and lipid rafts, domains that are high in cholesterol and sphingolipids and which function in endocytosis and in cell signaling. A recent proposal is that proteins with hydrophobic surfaces needed in these domains become coated with a lipid "shell" before entering the membrane.6173... 

Glycosphingolipids Function as Structural Components and as Specific Cell Receptors Defects in Sphingolipid Catabolism Are Associated with Metabolic Diseases... 

This is an advanced chapter (11) on the chemistry, metabolism, and function of the sphingolipids. 

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