Sphinganine, synthesis

Figure 11.24 A summary of the reactions involved in synthesis of sphingomyelin. Reaction between serine and palmitoyl-CoA produces 3-oxosphinganine, which is converted to sphingamine. Attachment of a Long-chain fatty acid to the amino group of sphinganine produces dihydroxyceramide. Ceramide reacts with phosphatidylcholine the phosphocholine component forms an ester bond with the hydroxyl group at position one of ceramide.

Enders D, Muller-Huwen A (2004) Asymmetric synthesis of 2-amino-1,3-diols and D-erythro-sphinganine. Eur J Org Chem 2004 1732 Enders D, Niemeier O (2004) Thiazol-2-ylidene catalysis in intramolecular crossed aldehyde-ketone benzoin reactions. Synlett 2004 2111-2114... 

The synthesis of the ceramide lipid moiety of GSLs is initiated in the endoplasmic reticulum (ER) (6) via the condensation of serine and palmitoylCoA. This enzyme has been cloned (7). The product is 3-keto-sphinganine that then is reduced to sphinga-nine and acylated by ceramide synthase with a long-chain fatty acid to form dihydroceramide, which is converted to ceramide by ceramide desaturase, which inserts the 4,5-trans double bond. 

Sphingolipid biosynthesis is catalyzed by membrane-bound enzymes of the endoplasmic reticulum. Sphingo-sine, an acylaminoalcohol, is synthesized from palmitoyl-CoA and serine in a reaction that requires pyridoxal phosphate, NADPH, and Mn + (Figure 19-7). The exact pathway of ceramide synthesis is not known. The acyl group may be added to the 2-amino group of sphinganine,... 

Schick, A., Schwarzmann, G., Kolter, T., and Sandhoff, K., Synthesis of tritium labeled phosphonate analogs of sphinganine-1-phosphate, J. Labelled Compd. Radiopharm., 39, 441, 1997. 

The synthesis of sphinganine occurs on the ER. Sphingomyelin and glycosphingolipid are synthesized on the lumenal side of Golgi complex membrane. 

Ichihashi, M. and Mori, K. (2003) Determination of the absolute configuration of (+)-xestoaminol C, (2S,3R)-2-amino-3-tetradecanol, a metabolite of Eiji sponge, Xe stospongia sp., by the synthesis of its N, Odiacetyl derivative. Biosci. Biotechnol. Biochem., 67, 329-333. Abraham, E., Davies, S.G., Millican, N.L., Nicholson, R.L., Roberts, P. M., and Smith, A.D. (2008) Asymmetric synthesis of vicinal amino alcohols xestoaminol C, sphinganine and sphingosine. Org. Biomol. Chem., 6,1655—1664. 

Sphingosine and sphingosine 1-phosphate can induce DNA synthesis in growth-arrested Swiss 3T3 cells. FBj incubated with the cells elevated sphingosine and induced an increase in [ H] thymidine incorporation into DNA (59). Further studies showed that sphinganine was required for stimulation of DNA synthesis. Studies with LLC-PK renal cells showed a close correlation between fumonisin-induced cytotoxicity and inhibition of de novo sphingolipid biosyntheses (82). However, studies with primary rat hepatocytes have not shown any relationship between cytotoxicity and elevation of free sphingoid bases (38). 

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