Ceramides conversion

It should be noted here that the synthesis of sphingomyelin, the lipid whose synthesis and breakdown are most intricately involved in the process of apoptosis, is dependent on the presence of PC, since the final step in SM synthesis involves the exchange of the phosphocholine head group from PC to ceramide (see Eigure 1). Theoretically, therefore, inhibition of PC synthesis may lead to an inhibition of SM generation and an accumulation of pro-apoptotic ceramides. On the other hand, an increased breakdown of SM by SMases as frequently observed in apoptotic cells, was shown to increase the conversion of PC to anti-apoptotic DAG (Sillence and Allan, 1998, for anti-apoptotic action of DAG see below). 

H]-ethanolamine into PE was inhibited by C6-ceramide in a dose and time-dependent manner (b) delayed disappearance of label from CDP-choline and CDP-ethanolamine in pulse-chase experiments indicated impaired conversion of these CDP-metaboUtes to PC and PE by CPT and EPT, respectively (c) the activities of CPT and EPT are decreased upon C6-ceramide treatment (see Eigure 2 adapted from Bladergroen et al. 1999b). In contrast to BHK cells the activity of CT was not affected significantly in rat-2 fibroblasts by short-chain ceramides. 

Michel, C, and van Echten-Deckert, G., 1997, Conversion of dfliydroceramide to ceramide occurs at the cytosolic face of the endoplasmic reticulum. FEES Lett 416 153-155. 

The GC separation of dihydric alcohols of natural origin may be carried out after their conversion into alkyl boronates. Methaneboronates of ceramides [44] were prepared by treatment with methaneboronic acid in pyridine solution. They offer excellent GC properties on stationary phases of the OV-1 and SE-30 types and are particularly suitable for GC-MS. 

Prior to protein attachment, the fatty acids of the GPI anchor may be replaced in a conversion process termed fatty acid remodeling [91]. Although myristate is the sole fatty acid component in mature trypanosome GPI anchors, earlier GPI intermediates contain more hydrophobic stearate fatty acids. These longer fatty acid chains are replaced by an alternating sequence of removal and replacement of a fatty acid from each position on the glycerol [91]. Lipid remodeling may not be unique to trypanosome GPI anchor biosynthesis since mature yeast GPI anchors contain ceramide, whereas an early yeast GPI intermediate has a diacylglycerol species [33]. 

Starting from ceramide D-glucoside, enzymic synthesis has been studied for producing gangliosides222,223 and for the conversion of Tay-Sachs ganglioside into monosialoganglioside by the uridine 5 -pyrophosphate of brain.224... 

Previous studies suggest that understanding the intrinsic mechanisms of action for ceramide and SIP can open doors to new therapies to battle cancer. It has been well established that increases in intracellular ceramide will promote apoptosis. Thus, finding ways to intrinsically elevate ceramide in cancer cells is desirous. Conversely, SIP has been shown to promote cancer pathogenesis, thus, suppression of its generation/accumulation could suppress tumor growth. Some of these therapeutic approaches are summarized in Table 16.1. 

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. 

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