Sphingoid bases

YPClp and YDClp have different substrate specificity such that YPClp prefers phytoceramide (phytoCer) over dihydroceramide (dhCer) whereas YDClp prefers dhCer over phytoCer, however, neither enzyme uses the most common mammalian type ceramide having a 4-5 trans double bond on the sphingoid base as substrate. Both enzymes have a narrow pH optimum of 9.4-10, hence, are classified as alkaline ceramidases. Calcium ions activate but are not absolutely required for the activities of both enzymes. and inhibit the activities of both enzymes. None of the sphingoid bases inhibit the activities of YPC Ip and YDClp. 

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. 

Jarvis, W.D., Fornari Jr, F.A., Traylor, R.S., Martin, H.A., Kramer, L.B., ErukuUa. R.K., Bittman, R. and Grant, S., 1996, Induction of apoptosis and potentiation of ceramide-mediated cytotoxicity by sphingoid bases in human myeloid leukaemia cells, J. Biol. 

Lavie, Y. and Liscovitch, M., 1990, Activation of phospholipase D by sphingoid bases in NG108-15 neural-derived cells,/. Biol. Chem. 265 3868-3872. 

Stevens VL, Nimkar S, Jamison WC, Liotta DC, Merrill AJJr (1990) Characteristics of the growth inhibition and cytotoxidty of long-chain (sphingoid) bases for Chinese hamster ovary cells evidence for an involvement of protein kinase C. Bio-chim Biophys Acta 1051 37-45... 

In contrast to the striking divergences in the carbohydrate parts, respective ceramide moieties resemble those of other cestode glycosphingolipids in so far as sphinganine (d18 0) and 4-hydroxy-sphingoid bases (tl 8 0, t20 0) as well as, in part hydroxylated, fatty acids with 16 to 28 carbon atoms, in particular C26 0 and C28 0, represent predominant ceramide constituents, which might be an indication of similar biosynthetic routes. 

Hertweck, C. Boland, W. Asymmetric a-chloroallylboration of amino aldehydes a novel and highly versatile route to D- and L-erythro-sphingoid bases. /. Org. Chem. 1999, 64, 4426-4430. 

Long chain sphingoid base Polar head group... 

Wakita, H., Nishimura, K., and Takigawa, M., Composition of free long-chain (sphingoid) bases in stratum corneum of normal and pathologic human skin conditions, J. Invest. Dermatol., 99, 617,... 

D. Fumonisin and accumulation of bioactive sphingoid base-l-phosphates 164 E. Fumonisin depletion of glycosphingolipids and disruption of folate transport 166 VI. Conclusions 170 References 171... 

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... 

D. Fumonisin and accumulation of bioactive sphingoid base-l-phosphates... 

The activation of SIP receptors reduces renal and mesenteric blood flow in rats (Bischoff et ah, 2001), and it can be speculated that decreased blood flow and hypoxia contribute to the extreme sensitivity of rat kidneys to fumonisins. Fumonisin exposure has also been shown to decrease cardiac output, heart rate, and mean arterial pressure as well as increase pulmonary arterial pressure and pulmonary resistance in pigs (Constable et ah, 2000,2003), findings which suggest that left-sided cardiac insufficiency underlies porcine pulmonary edema. Plasma sphingoid base... 

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. 

Riley, R. T. and Voss, K. A. (2006). Differential sensitivity of rat kidney and liver to fumonisin toxicity Organ-specific differences in toxin accumulation and sphingoid base metabolism. Toxicol Sci. 92(1), 335-345. 

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. 

The l,5-dioxaspiro[3,2]hexane (42) has been shown to be a useful precursor for both aminodiol and aminotriol sphingoid bases. The synthesis of oxetane (42) started with serine via a Mitsunobu lactone formation followed by sequential titanium-mediated methylenation and oxidation with dimethyldioxirane <02OL1719>. 

Schmelz, E.M., Bushnev, A.S., Dillehay, D.L., Liotta, D.C., Merrill, A.H. Jr. 1997. Suppression of aberrant colonic crypt foci by synthetic sphingomyelins with saturated or unsaturated sphingoid base backbones. Nutr. Cancer. 28, 81-85. 

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