Sphingolipids, biosynthesis

Wang, E. et ah, Inhibition of sphingolipids biosynthesis by fumonisin, implication for diseases associated with Fusariurn moniliforme, J. Biol. Chem., 266, 14486, 1991. 

Fumonisin inhibition of de novo sphingolipid biosynthesis (Merrill et ah, 2001 Riley et ah, 1996), resulting in depletion of complex glyco-sphingolipids, disruption of lipid rafts, and compromised folate transport via Folrl, which may have significant implications with respect to developmental anomalies such as NTDs (Hansen et ah, 2003 Piedrahita... 

Merrill, A.H. 2002. De novo sphingolipid biosynthesis A necessary, but dangerous, pathway. J. Biol. Chem. 277, 25843-25846. 

Yard BA, Carter LG, Johnson KA, Overton IM, Dorward M, Liu H, McMahon SA, Oke M, Puech D, Barton GJ, Nai-smith JH, Campopiano DJ. The structure of serine palmitoyltransferase gateway to sphingolipid biosynthesis. J. Mol. Biol. 2007 370 870-886. 

Hanada K, Nishijima M, Fujita T, Kobayashi S. Specificity of inhibitors of serine palmitoyltransferase (SPT), a key enzyme in sphingolipid biosynthesis, in intact cells. A novel evaluation system using an SPT-defective mammalian cell mutant. Biochem. Pharmacol. 2000 59 1211-1216. 

Kobayashi S, Furuta T, Hayashi T, Nishijima M, Hanada K. Catalytic asymmetric syntheses of antifungal sphingofungins and their biological activity as potent inhibitors of serine palmitoyltransferase (SPT). J. Am. Chem. Soc. 1998 120 908-919. Merrill AH Jr, Gilchrist DG, Riley RT. Fumonisins and other inhibitors of de novo sphingolipid biosynthesis. Adv. Lipid Res. 1993 26 215-234. 

Hallstrdm, T.C., Lambert, L., Schorling, S., Balzi, E., Goffeau, A., and Moye-Rowley W.S. (2001) Coordinate control of sphingolipid biosynthesis and multidrug resistance in Saccharomyces cerevisiae. The Journal of Biolt al Chemistry, 276, 23674-23680. 

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,... 

The latter half of the 20th century also saw the characterization of the intermediates and enzymes of sphingolipid biosynthesis — starting with key work on the initial steps by... 

R. Brady, W. Stoffel, and E. Snell — which enabled the first discoveries of diseases caused by disruption of sphingolipid biosynthesis by food-borne mycotoxins (E. Wang, 1991) and genetic defects (hereditary sensory neuropathy type I) (J.L. Dawkins, 2001 K. Bejaoui,... 

De novo sphingolipid biosynthesis begins with the condensation of palmitoyl-CoA and L-serine (Fig. 6) to form 3-ketosphinganine catalyzed by serine palmitoyltransferase (SPT). 

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