N-Dotriacontanoyl-D-erythro-sphingosine Reference: M2048-5 This product is a high purity ceramide containing a very long chain fatty acid (C32:0) acylated to sphingosine, making it ideal as an internal standard and for biological studies. Ceramide is a fatty acid amide of sphingosine that functions as a precursor in the synthesis of sphingomyelin, glycosphingolipids, and of free sphingosine and fatty acids. Two of ceramide’s metabolites, sphingosine-1-phosphate and glucosylceramide, produce cell proliferation and are involved in a host of other cellular functions.1 Ceramide exerts numerous biological effects, including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.2 Because of these effects ceramide has been investigated for its use in cancer treatment and many potential approaches to cancer therapy have been presented.3 Other effects include producing reactive oxygen in mitochondria (followed by apoptosis) and stimulating phosphorylation of certain proteins (especially mitogen activated protein). It also stimulates some protein phosphatases (especially protein phosphatase 2A) making it an important controller of protein activity. Sphingolipids acylated with very long chain fatty acids (VLCFA) may be responsible for the maturation of epidermis cells of the spermatozoa/testes.4 omega-Hydroxylated 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 VLCFA-ceramides which causes a muscular dystrophy disease, defective skin-water permeability barrier function, and neurological disorders showing the importance of these VLCFA ceramides.5
N-Triacontanoyl-D-erythro-sphingosine Reference: M2049-1 This product is a high purity ceramide containing a very long chain fatty acid (C30:0) acylated to sphingosine, making it ideal as an internal standard and for biological studies. Ceramide is a fatty acid amide of sphingosine that functions as a precursor in the synthesis of sphingomyelin, glycosphingolipids, and of free sphingosine and fatty acids. Two of ceramide’s metabolites, sphingosine-1-phosphate and glucosylceramide, produce cell proliferation and are involved in a host of other cellular functions.1 Ceramide exerts numerous biological effects, including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.2 Because of these effects ceramide has been investigated for its use in cancer treatment and many potential approaches to cancer therapy have been presented.3 Other effects include producing reactive oxygen in mitochondria (followed by apoptosis) and stimulating phosphorylation of certain proteins (especially mitogen activated protein). It also stimulates some protein phosphatases (especially protein phosphatase 2A) making it an important controller of protein activity. Sphingolipids acylated with very long chain fatty acids (VLCFA) may be responsible for the maturation of epidermis cells of the spermatozoa/testes.4 omega-Hydroxylated 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 VLCFA-ceramides which causes a muscular dystrophy disease, defective skin-water permeability barrier function, and neurological disorders showing the importance of these VLCFA ceramides.5
N-Acetyl-sulfatide Reference: M2076-1 This product is a well-defined sulfatide containing an acetyl group acylated to the amine of the sphingosine and is ideal as an internal standard. Sulfatide is a type of sulfolipid that is found primarily in the central nervous system and is a myelinspecific 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 and other demyelinating diseases.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 and decrease the in vitro production of proinflammatory cytokines. Sulfatide also regulates the differentiation of oligodendroblasts. Central nervous system (CNS) myelin is strongly inhibitory to growing axons and sulfatides present in the myelin of the CNS have been identified as major myelin-associated axon growth inhibitors.4 A low level of serum sulfatides has been linked with an increased risk of cardiovascular disease in some situations. Sulfatides in the myelin, especially cistetracosenoyl- sulfatides, stimulate a distinct population of CD1d-restricted natural killer T cells giving these sulfatides important implications for the design of therapeutics that target T cells reactive for myelin glycolipids in autoimmune diseases of the central nervous system.5
N-Hexadecanoyl-D-erythro-sphingosine (C16 sphingolipid base) Reference: M2077-1 N-Hexadecanoyl-D-erythro-C16-sphingosine is a well-defined ceramide and is ideal for use as a standard and in biological systems1. This product has the C16 sphingoid base, which is less prevalent than the C18 base in most plants and animals, making it very useful in determining sphingosine metabolism and derivatives and as an internal standard.2 Hexadecanoyl ceramide comprises a significant amount of natural ceramides, often being the second most abundant species after C18:0- ceramide. Ceramides function as a precursor in the synthesis of sphingomyelin, glycosphingolipids, and of free sphingosine and fatty acids. The sphingosine can be phosphorylated to form sphingosine-1-phosphate. Two of ceramide’s metabolites, sphingosine-1-phosphate and glucosylceramide, produce cell proliferation and other cellular functions.3 Ceramide exerts numerous biological effects, including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.4 Because of these effects ceramide has been investigated for its use in cancer treatment and many potential approaches to cancer therapy have been presented.5 Other effects include producing reactive oxygen in mitochondria (followed by apoptosis) and stimulating phosphorylation of certain proteins (especially mitogen activated protein). It also stimulates some protein phosphatases (especially protein phosphatase 2A) making it an important controller of protein activity.
N-Hexadecanoyl-D-erythro-dihyrosphingosine Reference: M2078-10 This product is a high purity, well-defined dihydroceramide that is ideal as a standard and in biological systems. Dihydroceramide is a critical intermediate in the de novo synthesis of ceramide, leading to many complex sphingolipids. It is synthesized by the acylation of sphinganine and is subsequently converted to ceramide via the enzyme dihydroceramide desaturase or into phytosphingosine via the enzyme C4-hydroxylase.1 Inhibition of ceramide synthase by some fungal toxins (such as fumonisin B1) causes an accumulation of dihydrosphingosine and sphinganine-1-phosphate and a decrease in dihydroceramide and other dihydrosphingolipids, leading to a number of diseases including oesophageal cancer.2 The dihydroceramide desaturase inhibitor N-(4-Hydroxyphenyl) retinamide (4-HPR) has been tested as an anti-cancer agent; It inhibits the dihydroceramide desaturase enzyme in cells resulting in a high concentration of dihydroceramide and dihydrosphingolipids and this is thought to be the cause of its anti-cancer effects.3 Oxidative stress in cells causes an increase in the amount of dihydroceramide by potently inhibiting the desaturase enzyme.4 Dihydroceramide inhibits the formation of channels by ceramides and may thus reduce ceramide induced apoptosis in cells.5 While ceramide is well known for promoting apoptosis, dihydroceramide has long been considered to be inactive. However, there has recently been evidence that an accumulation of dihydroceramide can induce cell cycle arrest.6
N-omega-Hydroxytriacontanoyl-D-erythro-sphingosine Reference: M2080-5 This product is a high purity ceramide containing an omega-hydroxy very long-chain fatty acid (C30:0) acylated to sphingosine, making it ideal as an internal standard and for biological studies. Ceramide is a fatty acid amide of sphingosine that functions as a precursor in the synthesis of sphingomyelin, glycosphingolipids, and of free sphingosine and fatty acids. Two of ceramide’s metabolites, sphingosine-1-phosphate and glucosylceramide, produce cell proliferation and are involved in a host of other cellular functions.1 Ceramide exerts numerous biological effects, including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.2 Because of these effects ceramide has been investigated for its use in cancer treatment and many potential approaches to cancer therapy have been presented.3 Other effects include producing reactive oxygen in mitochondria (followed by apoptosis) and stimulating phosphorylation of certain proteins (especially mitogen activated protein). It also stimulates some protein phosphatases (especially protein phosphatase 2A) making it an important controller of protein activity. Sphingolipids acylated with very long chain fatty acids (VLCFA) may be responsible for the maturation of epidermis cells of the spermatozoa/testes.4 omega-Hydroxylated 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-hydroxy VLCFA-ceramides which causes a muscular dystrophy disease, defective skin-water permeability barrier function, and neurological disorders showing the importance of these VLCFA ceramides.5
N-Heptadecanoyl-D-erythro-dihydrosphingosine Reference: M2083-5 This product is a high purity, well-defined dihydroceramide that is ideal as an internal standard and in biological systems. Dihydroceramide is a critical intermediate in the de novo synthesis of ceramide, leading to many complex sphingolipids. It is synthesized by the acylation of sphinganine and is subsequently converted to ceramide via the enzyme dihydroceramide desaturase or into phytosphingosine via the enzyme C4-hydroxylase.1 Inhibition of ceramide synthase by some fungal toxins (such as fumonisin B1) causes an accumulation of dihydrosphingosine and sphinganine-1-phosphate and a decrease in dihydroceramide and other dihydrosphingolipids, leading to a number of diseases including oesophageal cancer.2 The dihydroceramide desaturase inhibitor N-(4-Hydroxyphenyl) retinamide (4-HPR) has been tested as an anti-cancer agent. It inhibits the dihydroceramide desaturase enzyme in cells resulting in a high concentration of dihydroceramide and dihydrosphingolipids and this is thought to be the cause of its anti-cancer effects.3 Oxidative stress in cells causes an increase in the amount of dihydroceramide by potently inhibiting the desaturase enzyme.4 Dihydroceramide inhibits the formation of channels by ceramides and may thus reduce ceramide induced apoptosis in cells.5 While ceramide is well known for promoting apoptosis, dihydroceramide has long been considered to be inactive. However, there has recently been evidence that an accumulation of dihydroceramide can induce cell cycle arrest.6
N-(30-Linoleoyloxy-triacontanoyl)-sphingosine Reference: M2084-1 This product is a high purity omega-esterified ceramide that is ideal as a standard and for studies involving skin-barrier lipids. It is found almost exclusively in the epidermal layer, especially in the stratum corneum. The stratum corneum is the outermost cellular layer of the epidermis and functions as the permeability barrier in mammals. It contains 12 extractable ceramide fractions containing sphingosine, 6-hydroxysphingosine, dihydrosphingosine and phytosphingosine bases. The omega-esterified ceramides are formed from glucosylceramide and sphingomyelin in special lamellar bodies in epidermal cells from which they are excreted into the extracellular domain of the outermost cell layer of the epidermis. Mammalian skin contains significant amounts of sphingolipids (as much as 50% of the total lipids), particularly very long chain linoleoyl esterified ceramide and glucosylceramide (also called O-acylceramide and O-acylglucosylceramide). These lipids, which are mostly found in the extracellular domains, are vital to the water permeability barrier to prevent lethal loss of water and pathogen invasion. The omega-esterified ceramides can be covalently bound to proteins of the cornified envelope where they form a hydrophobic layer. A deficiency of linoleoyl omega-esterified ceramides is strongly correlated with skin diseases such as psoriasis and atopic dermatitis.
Glucosylsphingosine, synthetic Reference: M2086-5 Glucosylsphingosine is the lyso-derivative of the common glycolipid glucocerebroside. This product is a fully synthetic standard containing only one isomer as opposed to glucosylsphingosine derived from natural sources. Glucosylceramide and glucosylsphingosine are important biological species that are the precursors for many complex glycosphingolipids. These lipids are involved in critical cellular functions such as cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis. One of the most important roles of glucosylsphingosine is as a biomarker for the lysosomal storage disorder Gaucher disease. Gaucher disease is characterized by an accumulation of glucocerebroside due to a deficiency in the enzyme glucocerebrosidase and it has now been found that glucosylsphingosine also accumulates in this disease.1 This accumulation of glucopsychosine contributes to neuronal dysfunction and destruction in patients with neuronopathic Gaucher disease2 and it has been found to be a potent inhibitor of glucocerebrosidase. At least some instances of Gaucher disease also have a deficiency in the activity of glucosylsphingosine beta-glucosidase, the enzyme responsible for cleaving off the glucose of glucopsychosine and glucocerebroside. Like glucocerebroside and galactocerebroside, glucosylsphingosine can increase Ca2 + mobilization from intracellular stores although it uses a different mechanism.3 Conduritol B epoxide (CBE), an inhibitor of beta-glucosidase, and l-phenyl-2-decanoylamino-3-morpholino-l-propanol (PDMP), an inhibitor of glucosylceramide synthase, can be used to create a model of Gaucher disease and consequently an accumulation of glucosylsphingosine.4
Psychosine, synthetic Reference: M2087-5 This psychosine product is a fully synthetic standard containing only the most common naturally occurring isomer. Psychosine is a beta-galactose linked to a sphingosine and is an intermediate in the biosynthesis of cerebrosides, the largest single component of the myelin sheath of nerves. It is formed biologically by the reaction of sphingosine with UDPgalactose followed by acylation with a fatty acid. Krabbe disease is a demyelinating disease caused by a lack of the enzyme galactosylceramidase.1 This deficiency results in the accumulation of cerebroside and psychosine in cells. Psychosine is highly cytotoxic and cannot be degenerated further due to the lack of galactosylceramidase in Krabbe cells. Although GM1 gangliosidase can degrade cerebrosides it cannot degrade psychosine. Psychosine can cause oligodendrocyte death, astrocyte activation and the formation of multinuclear globoid-like cells. It is present naturally in small amounts and has a role in the sphingosine-1-phosphate receptor superfamily. Psychosine has been found to induce cell apoptosis, cytokine activation, phospholipase activation, peroxisomal dysfunction, and altered calcium homeostasis.2 Much attention has been given to psychosine due to its many important characteristics and standards are needed for ongoing research. 3
lyso-Lactosylceramide, synthetic Reference: M2088-1 lyso-lactosylceramide, synthetic is a fully synthetic standard containing only the most common naturally occurring d18:1 sphingosine isomer. It is ideal as a standard for mass spectroscopy analysis and for in vivo studies. Lactosylceramide is the precursor of many other glycosphingolipids and also functions as a second messenger and protein receptor making it a very important organic molecule. Many cellular processes are dependent on lactosylceramide since it is the substrate for neutral oligoglycosylceramides and gangliosides, all of which have their own vital functions. Lactosylceramide also helps to stabilize the lipid membrane, activate receptor molecules and acts as a receptor for certain bacteria and toxins. In animals, where it is found mostly in epithelial and neuronal cells, it is expressed on neutrophils and macrophages where it binds to toxins and bacteria, which are then engulfed and eliminated. Its role as a second messenger has been found to be vital and dysfunctions in its processes can lead to cancer and inflammation since it is critical to neutrophil activity and in activating anti-inflammatory responses.1 Therefore, it is being studied for its use in cancer therapies and as a therapy for other diseases. Other examples of lactosylceramide second messenger functions are tumor necrosis factor α and platelet-derived growth factor. A deficiency in the enzyme responsible for hydrolyzing the galactose of lactosylceramide leads to lactosylceramidosis, which is characterized by an accumulation of lactosylceramide that causes a primary neurological disorder.2 Lactosylceramide is also important in the activation of platelet/endothelial cell adhesion molecule-1 which causes adhesion and diapedesis of monocytes/lymphocytes.3 In animals neutral lyso-glycosphingolipids occur naturally in small amounts. lyso-Lactosylceramide can release calcium stores from microsomes in the brain cortex and cerabellum.4 Other lyso-glycosphingolipids also release calcium but in a mechanism different from lyso-lactosylceramide.
N-Glycinated glucosylsphingosine Reference: M2089-1 N-Glycinated glucosylsphingosine is an analogue of the important biomolecule glucosylsphingosine. It is ideal for use as an internal standard in the extraction and mass spectrometry analysis of glucosylsphingosine from natural samples.(1) The free amine group gives this product very similar physical characteristics to the natural glycolipid while the glycine adds an additional 57 units to the molecule making it easy to detect by MS. Glucosylceramide and glucosylsphingosine are important biological species that are the precursors for many complex glycosphingolipids. These lipids are involved in critical cellular functions such as cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis. One of the most important roles of glucosylsphingosine is as a biomarker for the lysosomal storage disorder Gaucher disease. Gaucher disease is characterized by an accumulation of glucocerebroside due to a deficiency in the enzyme glucocerebrosidase and it has now been found that glucosylsphingosine also accumulates in this disease.(2) This accumulation of glucopsychosine contributes to neuronal dysfunction and destruction in patients with neuronopathic Gaucher disease(3) and it has been found to be a potent inhibitor of glucocerebrosidase. At least some instances of Gaucher disease also have a deficiency in the activity of glucosylsphingosine beta-glucosidase, the enzyme responsible for cleaving off the glucose of glucopsychosine and glucocerebroside. Like glucocerebroside and galactocerebroside, glucosylsphingosine can increase Ca2 + mobilization from intracellular stores although it uses a different mechanism.(4)