N-Hexanoyl-L-erythro-sphingosine Reference: M1848-1 This product is the L-erythro stereoisomer of natural D-erythro-hexanoyl ceramide. L-erythro ceramides are inactive in some ceramide functions, have different activities in other functions, and exhibit the same activity in yet other functions. Lerythro- N-acetyl ceramide has been shown to induce accumulation of greater levels of sphingosine than in control cells.1 Generation of endogenous long-chain ceramide can be induced by exogenous short chain D-erythro-hexanoyl-ceramide but not by non-natural L-erythro-hexanoyl-ceramide.2 Other examples of functions demonstrated by D-erythro, but not Lerythro, ceramides are several key downstream biological activities such as growth inhibition, cell cycle arrest, and modulation of telomerase activity.2 Some viruses require the presence of ceramide in a membrane to be able to fuse to that membrane and it has been demonstrated that only D-erythro ceramide, and not L-erythro or D- or L-threo ceramides, supports the viral fusion.3
N-Octadecanoyl-L-erythro-sphingosine Reference: M1850-1 This product is a high purity, non-natural L- erythro ceramide that is ideal as a standard and for biological studies. D-erythro ceramide is the natural ceramide isomer and is involved in many biological processes including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.1 Natural sphingosine induces dephosphorylation of retinoblastoma gene product and inhibits cell growth while L-erythro-sphingosine is 5-8-fold less active. However, the Lerythro- sphingosine is taken up by cells to the same extent as the natural sphingosine indicating that cellular uptake was not the factor influencing activity.2 Both the natural D-erythro and the non-natural L-erythro and the D- and L-threo ceramides display similar effectiveness in inducing apoptotic damage in cells.3 The protein phosphatases PP1 and PP2A, which are involved in regulating apoptosis and cell growth, are activated by D-erythro ceramide but inhibited by L-threo, D-threo, and L-erythro ceramide.4 Both D-erythro and D-threo C2 ceramides have been found to be potent inducers of IL-6 production, while neither the L-threo or L-erythro stereoisomers of ceramide were effective.5 D- and L-erythro ceramide and D- and Lthreo ceramide are also comparably effective inhibitors of protein kinase C.6
D-threo-Dihydrosphingosine Reference: M1851-1 This product is a high purity, well-defined, D-threo-dihydrosphingosine which demonstrates unique properties as compared with the natural D-erythro isomer and is therefore ideal for use in comparison studies of dihydrosphingosine. Sphinganine (dihydrosphingosine) is the precursor of dihydroceramide which is then desaturated to form ceramide. It is a critical intermediate in the synthesis of many complex sphingoid bases and ceramide analogs. It has been found that sphinganine can induce cell death in a number of types of malignant cells and is being tested for its pharmacological properties.1 While both D-threo and L-threo-C2-dihydroceramide induced apoptosis in cells neither D-erythro nor L-erythro-C2-dihydroceramide showed activity.2 A report has concluded that only the erythro isomers of dihydrosphingosine act as substrates for the enzyme sphingosine kinase with both of the threo isomers inhibiting its activity.3
D-erythro-Dihydrosphingosine-1-phosphate Reference: M1852-5 Dihydrosphingosine-1-phosphate (DhS1P) is the saturated analog of the more common sphingosine-1-phosphate (S1P) and has recently been found to have many important and unique functions. It has been found to activate ERK1/2 and to stimulate MMP1 production. DhS1P induces MMP1 (a key enzyme in matrix degradation) while S1P does not1 and S1P enhances TGF-beta through cross-activation of Smad signaling while DhS1P inhibits it.2 DhS1P or its derivatives have been suggested as effective therapeutic antifibrotic agents. Because of their unique actions in vivo DhS1P can be used as a negative control for S1P for intracellular effects. However, DhS1P is a ligand for many S1P receptors. It has been found that SK1 overexpression, but not SK2, in different primary cells and cultured cell lines results in predominant upregulation of the synthesis of DhS1P compared to S1P. A new functional role for SK1 has been presented, which can control the survival/death (DhS1P-S1P/ceramides) balance by targeting sphingolipid de novo biosynthesis and selectively generating DhS1P at a metabolic step preceding ceramide formation.3
N-Octanoyl-D-erythro-dihydrosphingosine Reference: M1854-5 This high purity and well-defined product is ideal as a standard and for biological studies.1 Dihydroceramide is a critical intermediate in the synthesis of many complex sphingoid bases. Inhibition of dihydroceramide synthesis by some fungal toxins (such as fumonisin B1) that have a similar structure causes an increase in sphinganine and sphinganine-1-phosphate and a decrease in other sphingolipids leading to a number of diseases including oesophageal cancer. Dihydroceramide, synthesized by the acylation of sphinganine, is subsequently converted into ceramide via a desaturase enzyme or into phytosphingosine via the C4-hydrozylase enzyme2. N-(4-Hydroxyphenyl) retinamide (4-HPR) has been tested as an anticancer agent. It inhibits the dihydroceramide desaturase enzyme in cells resulting in a high concentration of dihydroceramide and dihydro-sphingolipids and this is thought to be the cause of the anti-cancer effects.3 Dihydrosphingosine induces cell death in a number of types of malignant cells.
N-Octadecanoyl-D-threo-sphingosine Reference: M1855-1 This product is a high purity, non-natural D-threo ceramide that is ideal as a standard and for biological studies. D-erythro ceramide is the natural ceramide isomer and is involved in many biological processes including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.1 Both the natural D-erythro and the non-natural L-erythro and the D- and L-threo ceramides display similar effectiveness in inducing apoptotic damage in cells.2 The protein phosphatases PP1 and PP2A, which are involved in regulating apoptosis and cell growth, are activated by D-erythro ceramide but inhibited by D-threo ceramide and the other two non-natural ceramide stereoisomers.3 Both D-erythro and Dthreo C2 ceramides have been found to be potent inducers of IL-6 production, while neither of the L- isomers of ceramide were effective.4 D- and L-erythro ceramide and D- and L-threo ceramide are also comparably effective inhibitors of protein kinase C.5
N-Hexanoyl-NBD-L-threo-sphingosine Reference: M1857-1 This product is a high purity, non-natural L-threo ceramide containing a fluorescent NBD label and is ideal as a standard and for biological studies. NBD (7-nitrobenzofurazan) has been shown to have only a small influence on lipid adsorption into cells and cellular membranes especially when the fatty acid is a short chain. The fluorescent analog of natural ceramide is comparable to C6:0-ceramide in many biological functions such as inhibition of VSV-G protein transport1, and transport of sphingomyelin and glucocerebroside from the golgi apparatus to the cell surface.2 Both the natural D-erythro and the nonnatural L-erythro and the D- and L-threo ceramides display similar effectiveness in inducing apoptotic damage in cells.3 The protein phosphatases PP1 and PP2A, which are involved in regulating apoptosis and cell growth, are activated by D-erythro ceramide but inhibited by L-threo, D-threo, and L-erythro ceramide.4 Both D-erythro and D-threo C2 ceramides have been found to be potent inducers of IL-6 production, while neither the L-threo or L-erythro stereoisomers of ceramide were effective.5 D- and L-erythro ceramide and D- and L-threo ceramide are also comparably effective inhibitors of protein kinase C.6
N-Hexanoyl-NBD-L-threo-sphingosine Reference: M1857-100 This product is a high purity, non-natural L-threo ceramide containing a fluorescent NBD label and is ideal as a standard and for biological studies. NBD (7-nitrobenzofurazan) has been shown to have only a small influence on lipid adsorption into cells and cellular membranes especially when the fatty acid is a short chain. The fluorescent analog of natural ceramide is comparable to C6:0-ceramide in many biological functions such as inhibition of VSV-G protein transport1, and transport of sphingomyelin and glucocerebroside from the golgi apparatus to the cell surface.2 Both the natural D-erythro and the nonnatural L-erythro and the D- and L-threo ceramides display similar effectiveness in inducing apoptotic damage in cells.3 The protein phosphatases PP1 and PP2A, which are involved in regulating apoptosis and cell growth, are activated by D-erythro ceramide but inhibited by L-threo, D-threo, and L-erythro ceramide.4 Both D-erythro and D-threo C2 ceramides have been found to be potent inducers of IL-6 production, while neither the L-threo or L-erythro stereoisomers of ceramide were effective.5 D- and L-erythro ceramide and D- and L-threo ceramide are also comparably effective inhibitors of protein kinase C.6
N-Hexadecanoyl-sulfatide Reference: M1875-1 Sulfatide is a type of sulfolipid that is found primarily in the central nervous system and is a myelin-specific sphingolipid. A deficiency of sulfatide in white and gray matter has been associated with Alzheimer’s disease and other types of dementia. Apoliprotein E plays an important regulating role in the metabolism of sulfatides.1 A production of anti-sulfatide antibodies in the cerebrospinal fluid, leading to a deficiency in sulfatides, may be a cause of degeneration of the myelin sheath, leading to multiple sclerosis.2 Metachromatic leukodystrophy is an inherited disorder characterized by a deficiency of the lysosomal enzyme arylsulfatase A and the subsequent accumulation of sulfatide in neural and visceral tissues.3 An immunomodulatory role for sulfatides has been suggested in the pathogenesis of tuberculosis.
3-keto-Dihydrosphingosine•HCl Reference: M1876-10 3-keto-Dihydrosphingosine is a vital intermediate in the biosynthesis of ceramides.1,2 3-keto-Dihydrosphingosine is formed by the condensation of L-serine and palmitoyl-CoA by the serine palmitoyl transferase enzyme.3 It is then reduced to dihydrosphingosine, converted to ceramide, and eventually synthesized into many types of sphingolipids. C18-ketodihydrosphingosine is the major sphingolipid precursor in the early and intermediate stages of cell life with C20-ketodihydrosphingosine as a minor component. Towards the end of the cell’s life the ratio of C18 to C20 ketodihydrosphingosine becomes more equal. It seems to be a critical regulating step in the availability of sphingolipids in cells. Vitamin K deficiency results in the inactivation of the serine palmitoyl transferase enzyme causing a resultant shortage of sphingolipids.
20-Hydroxyeicosanoic acid Reference: M1877-25 This product is a high purity omega-hydroxy very long chain fatty acid that is ideal as a standard and for biological studies. Omega-oxidation is a minor fatty acid pathway used for fatty acid metabolism and usually occurs in the smooth endoplasmic reticulum. Eicosanoic acid is enzymaticaly converted to the 20-hydroxyeicosanoic acid as well as to the eicosadicarboxylic acid as part of the omega-oxidation metabolic pathway. Stimulation of omega-hydroxylation has been proposed as a method for treating X-linked adrenoleukodystrophy, a disease that is characterized by elevated levels of very long chain fatty acids.1 Omega-hydroxy fatty acids have an important role acylated to various lipids. Omega-hydroxylated very long chain fatty acid (VLCFA) ceramides are vital to skin barrier functions and a deficiency of these lipids can cause death from water loss through the skin. A mutation in an elongase enzyme for VLCFA results in a deficiency in omega-hydroxylated VLCFAceramides which causes a muscular dystrophy disease, defective skin-water permeability barrier function, and neurological disorders showing the importance of these VLCFA ceramides.2 Sphingolipids (such as sphingomyelin, ceramides, and glucosylceramides) acylated with polyunsaturated and alpha- or omega-hydroxylated VLCFA have been found in the spermatozoa/testes and in the epidermis. Sphingolipids with VLCFA may be responsible for the maturation of these cell.3
Methyl 20-hydroxyeicosanoate Reference: M1878-25 This product is a high purity omega-hydroxy very long chain fatty acid methyl ester that is ideal as a standard and for biological studies. Omega-oxidation is a minor fatty acid pathway used for fatty acid metabolism and usually occurs in the smooth endoplasmic reticulum. Eicosanoic acid is enzymaticaly converted to the 20-hydroxyeicosanoic acid as well as to the eicosadicarboxylic acid as part of the omega-oxidation metabolic pathway. Stimulation of omega-hydroxylation has been proposed as a method for treating X-linked adrenoleukodystrophy, a disease that is characterized by elevated levels of very long chain fatty acids.1 Omega-hydroxy fatty acids have an important role acylated to various lipids. Omega-hydroxylated very long chain fatty acid (VLCFA) ceramides are vital to skin barrier functions and a deficiency of these lipids can cause death from water loss through the skin. A mutation in an elongase enzyme for VLCFA results in a deficiency in omegahydroxylated VLCFA-ceramides which causes a muscular dystrophy disease, defective skin-water permeability barrier function, and neurological disorders showing the importance of these VLCFA ceramides.2 Sphingolipids (such as sphingomyelin, ceramides, and glucosylceramides) acylated with polyunsaturated and alpha- or omega-hydroxylated VLCFA have been found in the spermatozoa/testes and in the epidermis. Sphingolipids with VLCFA may be responsible for the maturation of these cell.3