N-Glycinated lactosylsphingosine Reference: M2090-1 N-Glycinated lactosylsphingosine is an analogue of the important biomolecule lactosylsphingosine. It is ideal for use as an internal standard in the extraction and mass spectrometry analysis of lactosylsphingosine from natural samples.(1) The free amine group gives this product very similar physical characteristics to the natural glycosphingolipid while the glycine adds an additional 57 units to the molecule making it easy to detect by MS. Lactosylceramide is the precursor of many other glycosphingolipids and also functions as a second messenger and protein receptor, making it a very important biochemical. 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 act 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. It's role as a second messenger has been found to be vital and dysfunctions in its processes can lead to cancer and inflammation due to it being critical for neutrophil activity and in activating anti-inflammatory responses.(2) 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. Niemann-Pick Type C, a neurovisceral lysosomal cholesterol trafficking and lipid storage disorder, leads to an accumulation of multiple lipids, including excess unesterified cholesterol, GM2 and GM3 gangliosides, lactosylceramide, and glucosylceramide.(3) Lactosylceramide is also important in the activation of platelet/endothelial cell adhesion molecule-1 which causes adhesion and diapedesis of monocytes/lymphocytes.(4) In animals neutral lyso-glycosphingolipids occur naturally in small amounts. lyso-Lactosylceramide can release calcium stores from microsomes in the brain cortex and cerabellum.(5) Other lyso-glycosphingolipids also release calcium but in a mechanism different from lyso-lactosylceramide.
N-Glycinated galactosylsphingosine Reference: M2091-1 N-Glycinated galactosylsphingosine is an analogue of the important biomolecule galactosylsphingosine (psychosine). It is ideal for use as an internal standard in the extraction and mass spectrometry analysis of galactosylsphingosine 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 mass spectroscopy. Galactosylceramides are found primarily in neuronal tissues and are the major glycosphingolipids in the central nervous system. They constitute the largest single component of the myelin sheath of nerves and act, along with other components, to form part of the structural support of the myelin sheath.2 They are involved in a very wide range of biological activities such as cell agglutination, intracellular communication, cellular development, and antitumor/cytotoxic effects.3 Galactosylceramides can be metabolized into sulfatide which is also abundant in the nervous system and myelin sheaths. Krabbe disease is a demyelinating disease caused by a lack of the enzyme galactosylceramidase.4 This deficiency results in the accumulation of galactosylceramide and galactosylsphingosine in cells, making both of these lipids potentially useful biomarkers in Krabbe disease diagnosis.4 Galactosylsphingosine is highly cytotoxic and cannot be degenerated further in Krabbe cells due to the lack of galactosylceramidase. Although GM1 gangliosidase can degrade galactosylceramide it cannot degrade galactosylsphingosine. Galactosylsphingosine 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. Galactosylsphingosine has been found to induce cell apoptosis, cytokine activation, phospholipase activation, peroxisomal dysfunction, and altered calcium homeostasis.5
N-Glycinated lyso-sulfatide Reference: M2092-1 N-Glycinated lyso-sulfatide is an analogue of the important biomolecule lyso-sulfatide. It is ideal for use as an internal standard in the extraction and mass spectrometry analysis of lyso-sulfatide 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 mass spectroscopy. 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.2 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.3 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.4 An immunomodulatory role for sulfatides has been suggested in the pathogenesis of tuberculosis.
N-Tetracosanoyl-D-erythro-dihydrosphingosine Reference: M2093-5 Dihydroceramide is a critical intermediate in the de novo synthesis of ceramide, leading to many complex sphingolipids. It is synthesized by the acylation of dihydrosphingosine 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 dihydro-sphingolipids 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 Skin cells contain significant amounts of long chain ceramides, such as dihydroceramides, that are vital for maintaining skin barrier functions.6
N-(R)-alpha-Hydroxytetracosanoyl-phytosphingosine Reference: M2094-1 Phytosphingosine is a long-chain sphingoid base having important cellular functions such as signaling, skin barrier function, cytoskeletal structure, celluar cycle, and heat stress response. It is found largely in mammals, plants, and yeast. Phytosphingosine has seen much use in cosmetics due to its effects on the skin such as reducing inflammation by inhibiting the expression of the allergic cytokines IL-4 and TNF-α and the activation of the transcription factors NF-jB and c-jun in histamine-stimulated skin tissues.1 Phytosphingosine can lead to apoptosis via two distinct pathways and has been investigated as a possible cancer therapeutic treatment.2 Phytoceramides are distributed at the microvillous membrane of the epithelial cells of the small intestine. Crypt cells and the adjacent epithelial cells produce phytosphingoglycolipids in much greater quantities than more differentiated epithelial cells.3 The kidney and skin also contain phytosphingoglycolipids although in much lower concentrations than in the small intestine. Skin cells contain significant amounts of long chain ceramides, such as alpha-hydroxyphytoceramides, that are vital for maintaining skin barrier functions.4
N-(S)-alpha-Hydroxytetracosanoyl-phytosphingosine Reference: M2095-1 Phytosphingosine is a long-chain sphingoid base having important cellular functions such as signaling, skin barrier function, cytoskeletal structure, celluar cycle, and heat stress response. It is found largely in mammals, plants, and yeast. Phytosphingosine has seen much use in cosmetics due to its effects on the skin such as reducing inflammation by inhibiting the expression of the allergic cytokines IL-4 and TNF-α and the activation of the transcription factors NF-jB and c-jun in histamine-stimulated skin tissues.1 Phytosphingosine can lead to apoptosis via two distinct pathways and has been investigated as a possible cancer therapeutic treatment.2 Phytoceramides are distributed at the microvillous membrane of the epithelial cells of the small intestine. Crypt cells and the adjacent epithelial cells produce phytosphingoglycolipids in much greater quantities than more differentiated epithelial cells.3 The kidney and skin also contain phytosphingoglycolipids although in much lower concentrations than in the small intestine. Skin cells contain significant amounts of long chain ceramides, such as alpha-hydroxyphytoceramides, that are vital for maintaining skin barrier functions.4
N-(R)-alpha-Hydroxytetracosanoyl-D-erythro-sphingosine Reference: M2096-1 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. 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.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. 2-hydroxy fatty acid ceramides are especially abundant in nervous and epidermal cells. Skin cells contain significant amounts of long chain ceramides, such as alpha-hydroxyceramides, that are vital for maintaining skin barrier functions.4
N-(S)-alpha-Hydroxytetracosanoyl-D-erythro-sphingosine Reference: M2097-1 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. 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.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. 2-hydroxy fatty acid ceramides are especially abundant in nervous and epidermal cells. Skin cells contain significant amounts of long chain ceramides, such as alpha-hydroxyceramides, that are vital for maintaining skin barrier functions.4
N-(R)-alpha-Hydroxytetracosanoyl-D-erythro-dihydrosphingosine Reference: M2098-1 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. 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.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. 2-hydroxy fatty acid ceramides are especially abundant in nervous and epidermal cells. Skin cells contain significant amounts of long chain ceramides, such as alpha-hydroxy-dihydroceramides, that are vital for maintaining skin barrier functions.4
N-(S)-alpha-Hydroxytetracosanoyl-D-erythro-dihydrosphingosine Reference: M2099-1 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. 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.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. 2-hydroxy fatty acid ceramides are especially abundant in nervous and epidermal cells. Skin cells contain significant amounts of long chain ceramides, such as alpha-hydroxy-dihydroceramides, that are vital for maintaining skin barrier functions.4
N-(30-Linoleoyloxy-triacontanoyl)-phytosphingosine Reference: M2135-1 This product is a high purity omega-esterified phytoceramide that is ideal as a standard and for studies involving skin-barrier lipids. Omega-esterified phytoceramides are found almost exclusively in the epidermal layer, especially 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.1,2 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.3