Complex sphingolipids

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

Gangliosides, the most complex sphingolipids, have oligosaccharides as their polar head groups and one or more residues of Ai-acetylneuraminic acid (Neu5Ac), a sialic acid (often simply called sialic acid ), at the... 

Group of complex sphingolipids containing sphingo-sine linked to a fatty acid and a branched chain polysaccharide molecule. 

Wang, E., Ross, P. F., Wilson, T. M., Riley, R. T., and Merrill, A. H., Jr. (1992). Increases in serum sphingosine and sphinganine and decreases in complex sphingolipids in ponies given feed containing fumonisins, mycotoxins produced by Fusarium moniliforme. /. Nutr. 122(8), 1706-17016. 

Schmelz et al. (2000) then isolated the complex sphingolipids, gluco-sylceramide, lactosylceramide and the ganglioside GD3, from milk. These sphingolipids were added individually to the diet of mice at a level of 0.025 or 0.1%. All three sphingolipids reduced the number of DMH-induced ACF by about 40%, a reduction that was comparable to that obtained by sphingomyelin in earlier experiments. 

NH3)3Ru-0-Ru(NH3) -0-Ru(NH3) )]C1( ) (metal coordination complex) Sphingolipid-gated Ca2+ channel (Sphingolipid receptor) (SPH-R) [Psychosine (= D-Galactosyl- Widespread lipid mediator in 4.4F Inactive as SPFI-R ligand... 

Although ceramides are found usually at trace levels in tissues, they play important biologic roles (1). Moreover, they are synthesized as the key intermediates in the biosynthesis of complex sphingolipids, in which glucosylceramide is a key precursor of complex oligoglycolipids (Table 1). 

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

In gangliosides, the most complex sphingolipids, an oligosaccharide chain attached to the ceramide contains at least one acidic sugar. The acidic sugar is H-acetylneuraminate or -glycolylneuraminate. These acidic sugars are called sialic acids. Their nine-carbon backbones are synthesized from phosphoenolpyruvate (a three-carbon unit) and N-acetylmannosamine 6-phosphate (a six-carbon unit). 

Ceramide is composed of sphingosine, which is an amide-linked to a fatty acyl chain, varying in length from C14 to C26 (Fig. 16.1). Ceramide then serves as the metabolic and structural precursor for complex sphingolipids, which are composed of hydrophilic head groups, such as sphingomyelin (SM), ceramide... 

Dolgachev, V., Farooqui, M.S., Kulaeva, O.I., Tainsky, M.A., Nagy, B., Hanada, K., and Separovic, D. De novo ceramide accumulation due to inhibition of its conversion to complex sphingolipids in apoptotic photosensitized cells. J Biol Chem, 279, 2004, 23238-23249. 

SM is the major phosphosphingolipid in mammalian tissues and lipoproteins, and has been studied extensively with respect to its role in the formation of sterol-enriched ordered membrane domains and cell signaling (J. Slotte, 2006). Like Cers (and most other complex sphingolipids), SMs typically have high phase-transition temperatures (>37°C), which is a factor in their tendency to associate with rafts. 

Complex sphingolipids are lost from cells by multiple processes (1) membrane internalization, recycling, and degradation (2) turnover of membrane sphingolipids to release bioactive products that participate in cell signaling and (3) secretion and shedding of sphingolipids from cells. 

Fig. lO. Catabolism of complex sphingolipids and diseases associated with deficiencies in the enzymes (modified from T. Kolter and K. Sandhoff, 2006). Abbreviations are as in the text. 

Recent studies have revealed that marine viruses encode unexpected and novel proteins which would not be expected to occur within a virus genome. For example, the giant algal viruses have been shown to encode novel glycosylases, potassium pumps, and a pathway for the synthesis of complex sphingolipids. This biochemical diversity indicates that marine viruses could be a rich source for exploitation in the future for new types of carbohydrate and lipid as well as new proteins and enzymes. 

What about (a) the receptor for botulinum toxin, (b) the means by which the toxin enters neurons, and (c) the toxin s enzymatic activity First, the receptor. For many years, the observation that complex sphingolipids prevented toxicity was taken to indicate that gangliosides were receptors for the toxins. However, there is as much evidence suggesting that gangliosides are not the receptor (or receptors) as there is that they are.24 An important study25 published in 1986 presented good evidence that the different serotypes of botulinum toxin do not share the same receptor. It is not yet clear if there are distinct receptors for each serotype. 

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