L-threo-Sphingosine

L-threo-Sphingosine is an inactive or less active isomer of the naturally occurring D-erythro-sphingosine. Natural sphingosine induces dephosphorylation of retinoblastoma gene products and inhibits cell growth while L-threo-sphingosine is less active. However, the L-threo-sphingosine is taken up by cells to the same extent as the natural sphingosine indicating that cellular uptake was not the factor influencing activity.¹ L-threo-sphingosine, along with other sphingosine isomers, has been found to be an activator of 3-Phosphoinositide-dependent kinase-1.² Natural D-erythro-sphingosine is a positive regulator of cell growth in fibroblasts whereas L-threo-sphingosine has no regulatory effect.³ However, non-natural stereoisomers of sphingosine are not always inactive; L-threo-sphingosine has been shown to inhibit protein kinase C a little more potently than D-erythro-sphingosine.⁴ Sphingosine is a characteristic structural unit of many sphingolipids such as ceramides, gangliosides, globosides, sulfatides, sphingomyelin, and others. It is most abundant in nervous tissue and cell membranes. Sphingosine with an 18-carbon chain and a double bond at carbon 4 is the most abundant sphingosine in animal tissues. Lysosphingolipids inhibit protein kinase C activity resulting in the pathogenesis of sphingolipidoses such as Krabbe's disease and Gaucher's disease. Sphingosine can be phosphorylated via two kinases to form sphingosine-1-phosphate, which has important signaling functions. While sphingosines and ceramides can induce apoptosis, sphingosine-1-phosphate can promote cell survival or proliferation. Sphingosine has been shown to cause an increase in the cytoplasmic calcium level of cells.