Sphingoid bases structures

De Jonge, S., Van Overmeire, 1., Poulton, S., Hendrix, J., Busson, R., Van Calenbergh, S., De Keukeleire, D., Spiegel, S. Herdewijn, P., 1999, Structure-activity relationship of short-chain sphingoid bases as inhibitors of sphingosine kinase, Bioorg. Med. Chem. Lett. 9 3175-3180. 

The chemical structure of fumonisin (Fig. 5.IB) is remarkably similar to that of the sphingoid bases sphinganine (Sa) and sphingosine (So), and fumonisin has been shown to inhibit the enzyme ceramide synthase in de novo sphingolipid metabolism (Wang et al., 1991). Ceramide synthase... 

Norred, W. P., Plattner, R. D., Meredith, F. I., and Riley, R. T. (1997). Mycotoxin-induced elevation of free sphingoid bases in precision-cut rat liver slices Specificity of the response and structure-activity relationships. Toxicol. Appl. Pharmacol. 147, 63-70. 

FIGURE 12.1 GSL structures, (a) Sphingoid bases, (b) Examples of GSLs and their classification based on the basic structural features in parentheses. Ac, acetyl. 

Figure 1 The structural feature common to all sphingolipids is a long-chain sphingoid base. Sphingoid bases are 2-amino-1,3-diols that bear an aliphatic chain. The chain length varies from about 14 to 24 carbon atoms, and the extent of unsaturation, hydroxylation, and methyl-branching in the chain also varies. 1, (2S,3/ ,4f)-sphingosine 2, (2S,3/ )-dihydrosphingosine 3, (2S,3S,4/ )-phytosphingosine 4, 4f,6f-sphingadiene.

Figure 2 The structures of ceramide 1, a schematic structure of ceramide that illustrates the sites at which structural modifications may be introduced by chemical synthesis, and the structure of a representative ceramide found in human skin (2). Structural changes in the ceramide molecule have been introduced at many sites. Alterations include the configuration at C-2 and C-3 the lengths of the fatty amide chain and of the aliphatic chain attached to C-5 the positions of the unsaturation and the secondary hydroxy group the replacement of the hydroxyl groups with other atoms (hydrogen or fluorine) or functionalities (methoxy, methylthio, and keto) the incorporation of aromatic, heteroaromatic, and other rings in place of the alkenyl side chain of the sphingoid base and the replacement of the carbonyl group of the carboxamide group. In addition, the 2-amino-1,3-diol functionalities have been incorporated into cyclic structures.

MerriU AH Jr, Nimkar S, Menaldino D, Hannun YA, Loomis C, BeU RM, Tyagi SR, Lambeth JD, Stevens VL, et al. Structural requirements for long-chain (sphingoid) base inhibition of protein kinase C in vitro and for the cellular effects of these compounds. Biochemistry 1989 28 3138-3145. 

The use of silica gel TLC plates (impregnated or not with arsenite) allows the separation of ceramide species into different groups of relative structural homology. This is based on the position and numbers of hydroxyl groups on the ceramide molecules. However, TLC allows a possible further fractionation of ceramide species according to the unsaturation of sphingoid bases or fatty acids. This is made possible by the impregnation of the silica gel plates with borate and silver nitrate. 

The 18-carbon sphingoid base shown in Fig. 1 has the chemical structure (2S,3R,4E)-... 

Fig. 3. Structures of major sphingoid bases of mammalian cells and examples of sphingoid bases found in other...

Fig. 6. A probable reaction mechanism for serine palmitoyltransferase (modified from K. Krisnangkura, 1976) and structure of the adduct that presumably accounts for the high-affinity inhibition by myriocin (inset). The asterisk on palmitoyl-CoA conveys that other chain-length sphingoid bases are produced utilizing the appropriate fatty acyl-CoA (e.g. dodecyl-CoA, C,2g, to produce the dl4 1 sphingoid base backbone of most insects).

Figure 1.2 Example of lipid subclasses, which are classified based on the different hnk-ages at a certain position or a unique structural feature of a lipid class, (a) The subclasses of phosphatidyl-, plasmanyl-, and plasmenyl- are present in GPL as a result of the different linkages (i.e., ester, ether, and vinyl ether) of a fatty acyl chain to the hydroxyl group at sn- position of glycerol, (b) The different core structures of sphingoid bases in the presence or absence of a double bond between C4 and C5 carbon atoms lead to the common subclasses of sphingolipids and dihydrosphingolipids. Other less common subclasses of sphingolipids are also present due to other structures of the sphingoid bases (see Figure 1.6).

Figure 1.3 Simplified pathways and network of the common sphingolipid classes and other related lipids. The network and the pathways are derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. The pathways indicate the origins of sphingoid base core structures and their derivatives. Other sphingoid bases can be biosynthesized from other fatty acyl CoA by the replacement of palmitoyl CoA or some other amino acids replacing serine. The structures of individual lipid classes and their abbreviations used in the book are indicated in Figure 1.6.

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