Category:Glycosphyngolipids

From Ganfyd

A type of glycolipid containing the amino alcohol sphingosine. They are the major glycans of the vertebrate brain. The human brain is unique in terms of having O-acetylated N-acetylneuraminic acid derivatives.

Glycosylphosphatidylinositols are a subtype important in membrane protein anchoring. Glycosphyngolipids include:

• Galactosylceramide (GalCer, sphingosine) and its analog sulfatide, with sulfate at the C-3 hydroxyl of galactose, are the major glycans in the myelin of the brain
• Sphingomyelin
• Gangliosides as found in Tay-Sachs disease
  • All the sialylated glycosphingolipids
  • eg Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-4GlcβCer (II3NeuAc-Gg4Cer, GM1)
  • The sialic acids of human gangliosides are exclusively in the form of N-acetylneuraminic acid (NeuAc) and its O-acetylated derivatives, but those of all other mammals, contain both N-acetylneuraminic acid and N-glycolylneuraminic acid (NeuGc). This is due to a specific mutation in humans of the enzyme that hydroxylates CMP-NeuAc to form CMP-NeuGc.
• Glucosylceramide (GlcCer) as found in Gaucher’s disease
• Seminolipid essential for spermatogenesis
• Sialylated GalCer (NeuAcα2-3GalβCer, GM4) also found in myelin

Functions

Glycosphingolipids mediate and modulate intercellular coordination in multicellular organisms. They are not uniformly distributed in the cell membrane, but cluster in lipid rafts. The outer parts of these lipid rafts are enriched in sphingolipids which self-associate due to their long unsaturated carbon chains. They:

• Are involved in lipid-raft-associated signaling:
  • Cell–cell interactions via binding to complementary molecules on apposing cell membranes (trans recognition)
    • eg interaction of leukocytes with the blood vessel wall during the process of inflammation
  • Modulating activities of proteins in the same plasma membrane (cis regulation).
    • eg Modulate associated membrane receptors such as the epidermal growth factor (EGF) receptor, insulin receptor, and the nerve growth factor receptor
• Facilate nerve transmission - Galactosylceramide
• Water barrier in skin - Glucosylceramide and its derivatives, acylGlcCer as well as the ceramide produced by it hydrolysis
• Antigens
  • eg ABO, Lewis, and P blood group antigens

Pathology

• Lipid storage diseases
• Autoimmune disease such as Guillain-Barre syndrome
• Toxin binding as with Cholera toxin or Escherichia coli heat-labile entero-toxin
• Bacterial binding to human tissue via adhesins.
• Malignant transformation associations as with melanoma increase of GD3 or GM2
• Immunomodulation when produced in excess by certain malignancies