Sphinganine-1-phosphate

Constable, P. D., Riley, R. T., Waggoner, A. L., Hsiao, S. H., Foreman, J. H., Tumbleson, M. E., and Haschek, W. M. (2005). "Serum sphingosine-l-phosphate and sphinganine-l-phos-phate are elevated in horses exposed to fumonisin Bi" AOAC International Midwest Section Final Program, pp. 63-64. 

Sphingosine-1-phosphate receptors EDG-1 and EDG-3 bind SIP generated from phosphorylation of sphingosine by sphingosine kinase. The binding of SIP and sphinganine 1-phosphate (dihydrosphingosine 1-phosphate) to EDG-1 promotes chemotaxis via a Gai-mediated mechanism. 

Kim DH, et al. Elevation of sphinganine 1-phosphate as a predictive biomarker for fumonisin exposure and toxicity in mice. / Toxicol Environ Health A. 2006 69 2071-2082. 

Van Veldhoven PP, Mannaerts GP (1994) Sphinganine 1-phosphate metabohsm in cultured skin fibroblasts evidence for the existence of a sphingosine phosphatase. Biochem J 299 597-601... 

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. 

Fumonisins have been used widely in studies of the roles of de novo synthesized Cer in cell regulation. Such studies must be interpreted with care because the elevation of sphinganine and sphinganine 1-phosphate may affect additional signaling pathways. In addition, A -acetylsphinganine (C2-dihydroceramide) is also found in fumonisin-treated cells and in vivo (A.H. Merrill, 2001), and recent studies have shown that Cj-Cers can be phosphorylated (H. Van Overloop, 2007). Therefore, the number of potentially bioactive metabolites in fumonisin-treated cells is quite large. 

N-acetylneuraminic acid N-glycolylneuraminic acid palmitoyl-CoA sphingosine 1-phosphate sphinganine 1-phosphate sphingolipid-activator protein serine... 

The product-ion spectrum of protonated sphinganine-1-phosphate in the positive-ion mode that differs from the protonated sphingosine-1-phosphate is the presence of two abundant ions at m/z 284 and 266, instead of one at m/z 264 in the case of sphingosine-l-phosphate. The ion at m/z 284 probably arises from the neutral loss of H3PO4 while the m/z 266 ion results from the further loss of a water molecule from the ion at m/z 284. 

This compound also could be synthesized by Mendershausen and Sweeley (1969) and Gaver and Sweeley (1966). In vivo it is formed from 1-serine- and palmityl-CoA. The reaction requires pyridoxal phosphate. The next step is catalyzed by a S-3-dehydrosphinganine /3-NADPH oxidoreductase (Stoffel et al., 1968), and the major product is sphinganine (Braun et al., 1970 Morrell and Radin, 1970b). Starting with stearoyl-CoA, eicosasphinganine is the main product. The final introduction of a carbon double bond yields sphing-4-enine ... 

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). 

Sphingosine, ceramide, and sphingomyelin suppressed both the IL-2-dependent proliferation of cell lines HT-2 and CTLL, and the cell proliferation in MLC [10,15,27]. Sphingosine-1-phosphate inhibited integrin-dependent cell motility, but not integrin-de-pendent adhesion. Sphinganine-1-phosphate was less effective in this experiment [50]. 

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