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Glycosphingolipids
Glycosphingolipids
Functions
Glycosphingolipids (sometimes called glycolipids) have been found in
lower and higher eukaryotic sources. They are composed of a glycan
structure attached to a lipid tail that contains the sphingolipid ceramide.
The basic structure for a glycosphingolipid is a monosaccharide, usually
glucose or galactose, attached directly to a ceramide molecule and
resulting in, respectively, glucosylceramide (glucocerebroside; GlcCer) or
galactosylceramide (galactocerebroside; GalCer). The core glycan
structure may be extended by additional monosaccharides. This
combination structure results in an amphiphilic molecule with a
hydrophilic carbohydrate region and a hydrophobic lipid region. In
addition to variations in the structure of the glycan, the ceramide
structure may also show variation. The fatty acid attached to the
sphingosine may contain carbon chain lengths from C14 to C24 and vary
in degree of unsaturation and/or hydroxylation.
Glycosphingolipids are minor components of cell membranes and
membrane compartments, and are connected to cell growth, differentiation, and viral and oncogenic transformations. Like GPI anchored
proteins, glycosphingolipids aggregate to form membrane rafts on the
micromembrane and the outer leaflet of the apical membrane. The
hydrophobic lipid tail is embedded in the outer leaflet of cell
membranes, positioning the glycan structure into the extracellular
matrix. Gangliosides are the major constituents of neuronal cell
membranes and the endoplasmic reticulum.
Abbreviations for the oligosaccharide chains of glycosphingolipids have
been recommended by IUPAC to make the nomenclature less complex.1
The recommended root names are shown in Table 1.
Root Structure
Root Name
Symbol
Ganglio-
Gg
IV
Galb3GalNAcb4Galb4Glc-
III
II
I
Lacto-
Lc
Galb3GlcNAcb3Galb4Glc-
Neolacto (Lactoneo)
nLc (Lcn)
Galb4GlcNAcb3Galb4Glc-
Globo-
Gb
GalNAcb3Gala4Galb4Glc-
Isoglobo-
iGb
GalNAcb3Gala3Galb4Glc-
Mollu-
Mu
GlcNAcb2Mana3Manb4Glc-
Arthro-
At
GalNAcb4GlcNAcb3Manb4Glc-
Glycan Component Classes
Structure
Glycosphingolipids are thought to provide protection from harsh
conditions in the extracellular environment, such as low pH and
degrading enzymes. They help cells to interact with extracellular
matrices and other cells, and serve as surface receptors for bacterial
toxins and possibly endogenous extracellular molecules. In addition to
their function as membrane components, glycosphingolipids are
precursors for lipids involved in signal transduction and contribute to the
water permeability barrier of the skin. The skin and the brain are the key
organs in which functional aspects of mammalian glycosphingolipids are
important.
Galactosylceramide derivatives are necessary key components of myelin
and have demonstrated growth factor-like properties. Acidic gangliosides influence the electrical field across the cellular membrane, as well
as the concentration of ions on the external surface of the cells. In
addition, gangliosides may have a role in electrical insulation in myelin
cells in the nervous system.
Table 1. Root Names, Symbols, and Root Structures for Glycosphinoglipid Chains.
The outer extensions of glycosphingolipids contain sugars including
fucose, glucuronic acid, and sialic acid, and blood group structures that
are similar to those of O- and N-glycans. Like O- and N-glycans,
modifications such as 9‑O-acetylation, N-deacetylation of sialic acids, or
O-sulfation and O-acylation of galactose residues may also be present.
Glucosyl ceramide and galactosyl ceramide are neutral, while glycosphingolipids containing sulfate, phosphate, or sialic acid residues are
acidic and have a negative net charge. Gangliosides are glycosphingolipids that specifically contain one or more sialic acid (N-acetylneuraminic
acid; NANA) residues.
Biosynthesis and Degradation
Most animal glycosphingolipid families are derived from lactosylceramide (LacCer; β-D-galactosyl(1→4)-β-D-glucosyl-ceramide). The first
step in lactosylceramide synthesis is the acylation and desaturation of Derythro-sphinganine. The ceramide is then glucosylated on the cytosolic
face of the endoplasmatic reticulum (ER) and Golgi membranes followed
by β-galactosylation of glucosylceramide on the opposite face of the ER
and Golgi membranes to form lactosylceramide. The glycan chain can be
elongated by specific glycosyltransferases and sulfotransferases.
Glycosphingolipid biosynthesis, degradation, and intracellular transport
are highly regulated, and cells demonstrate type-specific expression and
stable glycosphingolipid patterns.
Key to Monosaccharide Symbols
β-D-Glucose (Glc)
β-D-Xylose (Xyl)
β-D-Mannose (Man)
α-N-Acetylneuraminic acid;
Sialic acid (NeuNAc)
β-D-Galactose (Gal)
β-D-Glucuronic acid (GlcA)
β-D-N-Acetylglucosamine (GlcNAc)
α-L-Iduronic acid (IdoA)
β-D-N-Acetylgalactosamine (GalNAc)
α-L-Fucose (Fuc)
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GLY FINAL 1207 PGD cleanxrefs2
Glycan Component Classes
Glycosphingolipids
Some gangliosides, such as those that contain the sialyl Lewis X (sLeX)
structure (see Figure 11), are useful as cancer cell markers, since they
are elevated in the membranes of certain types of tumor cells such as
melanomas and metastatic brain tumors. Purified gangliosides are
frequently used as markers for characterization of various cell types.
They may also serve as substrates and inhibitors of glycosidases and
glycosyltransferases.
α1,3
α2,3
β1,4
β1,4
Gangliosides are named in accordance with the IUPAC Guidelines
“Nomenclature of Glycolipids, IUPAC Recommendations 1997)”, Pure
Appl. Chem., 69, 2475‑2487 (1997). The letter “G” is used to indicate
ganglioside and the number of sialic acid residues are abbreviated as M
(mono), D (di) or T (tri).
Reference:
1. International Union of Pure and Applied Chemistry (IUPAC) and International Union of
Biochemistry and Molecular Biology (IUBMB) Joint Commission on Biochemical
Nomenclature (JCBN) Nomenclature of Glycolipids, Recommendations (1997). http://
www.chem.qmul.ac.uk/iupac/misc/glylp.html
β1,1
Cer
Figure 11. Structure of the tetrasaccharide sialyl Lewis X (sLex) attached to
galactosylceramide (GalCer). Cer represents the ceramide moiety.
Neutral Glycosphingolipids
Name
Assay
Cat. No.
Galactocerebrosides from bovine brain
~99%, TLC
C4905-10MG
C4905-25MG
Globotriaosylsphingosine from porcine blood
-
G9534-1MG
Glucocerebrosides from human (Gaucher's) spleen
≥98.0%, TLC
49108-1MG
Lactocerebrosides from bovine brain
~95%
C3166-1MG
C3166-5MG
Psychosine from bovine brain
≥98%, TLC
P9256-1MG
P9256-10MG
Gangliosides
Gangliosides are major constituents of neuronal cell membranes and endoplasmic reticulum. They contain a sialylated polysaccharide chain linked to
ceramide through a β-glycosidic linkage. For classification of gangliosides see Svennerholm, L., et al. (eds.), Structure and Function of Gangliosides,
New York, Plenum, 1980.
Name
Assay
Sterilization
Cat. No.
Asialoganglioside GM1 from bovine brain
~98%
-
G3018-.5MG
G3018-1MG
Asialoganglioside-GM2 from bovine brain
~95%
-
G9398-50UG
G9398-.1MG
Monosialoganglioside GM1 from bovine brain
≥95%
-
G7641-1MG
G7641-5MG
G7641-10MG
Monosialoganglioside GM1 from bovine brain
≥95%, TLC
γ-irradiated
G9652-1MG
Monosialoganglioside GM2 from bovine brain
≥95%, TLC
-
G8397-1MG
Monosialoganglioside GM3 from canine blood
≥98%
-
G5642-.5MG
G5642-1MG
Monosialoganglioside GM3 from canine blood
~95%
γ-irradiated
G0153-1MG
Disialoganglioside GD1a from bovine brain
≥95%, TLC
-
G2392-1MG
G2392-5MG
Disialoganglioside GD1b from bovine brain
~95%
-
G8146-.5MG
G8146-1MG
Disialoganglioside-GD2
~95%
-
G0776-.1MG
Trisialoganglioside-GT1b from bovine brain
≥96%, TLC
-
G3767-1MG
G3767-5MG
Lysoganglioside-GM1 from bovine brain
≥95%
-
G5660-1MG
semisynthetic
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