Sphingolipid

Sphingolipids are a class of lipids derived from the aliphatic amino alcohol sphingosine. Sphingolipids are often found in neural tissue, and play an important role in both signal transmission and cell recognition.

tructure

The sphingosine backbone is O-linked to a (usually) charged head group such as ethanolamine, serine, or choline.

The backbone is also amide-linked to an acyl group, such as a fatty acid.

Types

* ceramides. Ceramide is the fundamental structural unit common to all sphingolipids. They consist simply of a fatty acid chain attached through an amide linkage to sphingosine. There are three main types of sphingolipids, differing in their head groups:
* sphingomyelins. Sphingomyelins have a phosphorylcholine or phosphoroethanolamine molecule esterified to the 1-hydroxy group of a ceramide.
* glycosphingolipids, which differ in the substituents on their head group (see image). Glycosphingolipids are ceramides with one or more sugar residues joined in a β-glycosidic linkage at the 1-hydroxyl position.
** Cerebrosides have a single glucose or galactose at the 1-hydroxy position.
* Gangliosides have at least three sugars, one of which must be sialic acid.

Function and transport

Sphingolipids are commonly believed to protect the cell surface against harmful environmental factors by forming a mechanically stable and chemically resistant outer leaflet of the plasma membrane lipid bilayer. Certain complex glycosphingolipids were found to be involved in specific functions, such as cell recognition and signaling. The first feature depends mainly on the physical properties of the sphingolipids, whereas signaling involves specific interactions of the glycan structures of glycosphingolipids with similar lipids present on neighboring cells or with proteins.

Recently, relatively simple sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate, have been shown to be important mediators in the signaling cascades involved in apoptosis, proliferation, and stress responses. [Hannun, Y. A., and Obeid, L. M. (2002) "J. Biol. Chem." 277, 25847-25850 ( [http://www.jbc.org/cgi/content/full/277/29/25847 full text online] )] [Spiegel, S., and Milstien, S. (2002) "J. Biol. Chem." 277, 25851-25854 ( [http://www.jbc.org/cgi/content/full/277/29/25851 full text online] )] Ceramide-based lipids self-aggregate in cell membranes and form separate phases less fluid than the bulk phospholipids. These sphingolipid-based microdomains, or "lipid rafts" were originally proposed to sort membrane proteins along the cellular pathways of membrane transport. At present, most research focuses on the organizing function during signal transduction. [Brown, D. A., and London, E. (2000) "J. Biol. Chem." 275, 17221-17224 ( [http://www.jbc.org/cgi/content/full/275/23/17221 full text online] )]

Sphingolipids are synthesized in the ER and Golgi apparatus, but are enriched in the plasma membrane and in endosomes, where they perform many of their functions, thus travelling and evolving between organelles. Transport occurs via vesicles and monomeric transport in the cytosol. Sphingolipids are virtually absent from mitochondria and the ER, but constitute a 20-35 molar fraction of plasma membrane lipids. [van Meer, G., and Lisman, Q. (2002) "J. Biol. Chem." 277, 25855-25858 ( [http://www.jbc.org/cgi/content/full/277/29/25855 full text online] )]

Disorders

There are several disorders of sphingolipid metabolism, known as sphingolipidoses. The most common is Gaucher's disease.

Also of note is Fabry's disease, an X-linked recessive condition wherein a buildup of glycosphingolipids in lysosomes of various tissues is due to alpha-galactosidase deficiency. These patients tend to present with peripheral neuropathies and develop chronic renal conditions.

=Additional

References

Sources

* Grisham & Garret (2005). "Biochemistry" (3rd ed.). Thomson Brooks/Cole.
***P. Gergely (2004). "Organic and Bioorganic Chemistry" (3rd ed.).

External links

*