Glycolipid

Glycolipid

Glycolipids are lipids with a carbohydrate attached by a glycosidic bond.[1] Their role is to serve as markers for cellular recognition and also to provide energy. The carbohydrates are found on the outer surface of all eukaryotic cell membranes. They extend from the phospholipid bilayer into the aqueous environment outside the cell where it acts as a recognition site for specific chemicals as well as helping to maintain the stability of the membrane and attaching cells to one another to form tissues[2]

Structure

The basic structure of a glycolipid is the presence of a carbohydrate monosaccharide or oligosaccharide bound to a lipid moiety. The lipid complex is most often composed of either a glycerol or sphingosine backbone, which gives rise to the two main categories of glycolipids, glyceroglycolipids and sphingolipids. Lipids are non-polar molecules, providing them the capability of interacting with the lipid-bilayer of the cell membrane and anchoring the glycolipid to the surface of the cell. Carbohydrates are used as the ligand component of glycolipids and their structure varies depending on the structure of the molecule it binds to. The carbohydrate contains polar groups that enable the molecule to be soluble in the aqueous environment surrounding the cell.[3] The two molecular groups form a glycoconjugate through a covalent bond referred to as a glycosidic bond. The anomeric carbon of the sugar binds to the hydroxyl group present on the lipid.

Metabolism

Glycosyltransferases

Glycolipids formation is dependent on the activity of glycosyltransferases. Glycoslytransferases are the enzymes responsible for catalyzing the reaction of the covalent bond formation linking the carbohydrate complex to the lipid molecule. It also functions to form the correct oligosaccharide that will be present in the complete structure to act as the receptor for cell signaling. The glycolipid is assembled in the golgi-apparatus and transported to the membrane via vesicles where the lipid remains embedded in the membrane and the carbohydrate is on the outer surface of the cell.[4]

Glycoside hydrolases

Glycoside hydrolases catalyze the breakage of glycosidic bonds. They are used to modify the glycan after it has been added onto the lipid to represent the final oligosaccharide structure. It is also involved in the natural degradation of glycolipids into their non-conjugated forms. The lipids and carbohydrates will then assume their common uses as energy in the body.[5]

Defects in Metabolism

Sphingolipidoses can be associated with defects in metabolism. Sphingolipidoses are a category of diseases that can be associated with the accumulation of sphingolipids from failure to degrade compounds correctly. Sphingolipidoses are typically inherited and have varying effects among the various types of diseases. One notable example is Niemann–Pick disease which can cause pain to, damage to neural networks, and, in severe cases, death.[6]

Function

Cell-Cell Interactions

The main function of glycolipids in the body is to serve as recognition sites for cell-cell interactions. The sugar moiety of the glycolipid will bind to a specific complementary carbohydrate or lectin, type of cell-surface protein, of a neighboring cell. The interaction of these cell surface markers initiates cellular responses that contribute to activities such as cell recognition, regulation, growth, and apoptosis.[7] Sphingolipidoses can be associated with defects in metabolism.

Immune Responses

An example of how glycolipids function within the body is the interaction between leukocytes and endothelial cells during inflammation. Selectins on the surface of leukocytes and endothelial cells will bind to the carbohydrates attached to glycolipids to initiate the immune response. This binding allows for leukocytes to leave circulation and congregate near the site of inflammation. This is the initial binding mechanism, after which it is followed by expression of integrins which form stronger bonds and allow leukocytes to migrate toward the specific site of inflammation.[8] Glycolipipds are also responsible for other immune responses, notably the recognition of viruses within the body.

Blood types

Blood type are an example of how glycolipids on cell membranes mediate cell interactions with the surrounding environment. There are four different blood types present in humans (A, B, AB, O) that are determined by the sugar moiety attached to a specific glycolipid on blood cells. Blood type A individuals have an N-acetylgalactosamine sugar attachment as the main determining structure, blood type B has a galactose, and Blood type O has no extra addition to the oligosaccharide. Erythroctes have the specific glycolipid for that individuals blood type covering their surface (with AB individuals have both types of antigens). Antibodies are produced in the body and bind to a specific blood type’s glycolipids. Blood type A individuals produce antibodies that bind to the B antigen and so forth, so that any cells possessing the corresponding antigen will be targeted by the antibodies.[9]

Chemical structure of glycolipids

Types of glycolipids

The following is an incomplete listing of glycolipid types.

This list is incomplete; you can help by expanding it.

[15]

See also

References

  1. Voet, Donald; Voet, Judith; Pratt, Charlotte (2013). Fundamentals of Biochemistry Life at the Molecular Level (Fourth ed.). Hoboken, NJ: John Wiley & Sons, Inc. ISBN 9781118129180.
  2. "Glycolipids". nature. Nature Publishing Group. Retrieved November 2015.
  3. Aureli, Massimo; et al. (August 2015). "Lipid Membrane domains in the Brain". BBA Molecular and Cell Biology of Lipids 1851 (8): 1006–1016. doi:10.1016/j.bbalip.2015.02.001. PMID 25677824.
  4. Williams, GJ; Thorson, JS (2009). "Natural product glycosyltransferases: properties and applications.". Advances in Enzymology and Related Areas of Molecular Biology 76: 55–119. doi:10.1002/9780470392881.ch2. PMID 18990828.
  5. Sinnott, M. L. "Catalytic mechanisms of enzymatic glycosyl transfer". Chem. Rev. 1990, 90, 1171-1202.
  6. Sandhoff, Kondrad (December 2015). "Sphingolipidoses". Journal of Clinical Pathology 68 (12): 94–105. doi:10.1136/jcp.s3-8.1.94.
  7. Schnaar, Ronald (June 15, 2004). "Glycolipid-mediated cell–cell recognition in inflammation and nerve regeneration". Archives of Biochemistry and Biophysics 426 (2): 163–172. doi:10.1016/j.abb.2004.02.019.
  8. Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Cell-Cell Interactions. Available from: http://www.ncbi.nlm.nih.gov/books/NBK9851/
  9. Erb IH (1 May 1940). "Blood Group Classifications, a Plea for Uniformity". Canadian Medical Association Journal 42 (5): 418–21. PMC 537907. PMID 20321693.
  10. 1 2 Neufeld, Elizabeth (January 1964). "Formation of galactolipids". Biochemical and Biophysical Research 14 (6): 503–508. doi:10.1016/0006-291X(64)90259-1.
  11. Harwood, John L.; Nicholls, Rodney G. (1979). "The plant sulfolipid. A major component of the sulfur cycle". Biochemical Society Transactions 7 (2): 440–7. doi:10.1042/bst0070440. PMID 428677.
  12. Hakomori, S (December 1995). "Functional role of glycosphingolipids in cell recognition and signaling". The Journal of Biochemistry 118 (6): 1091–1103. PMID 8720120.
  13. Jurevics, H; Hostettler, J; Muse, ED; Sammond, DW; Matsushima, GK; Toews, AD; Morell, P (May 2001). "Cerebroside synthesis as a measure of the rate of remyelination following cuprizone-induced demyelination in brain.". Journal of Neurochemistry 77 (4): 1067–76. doi:10.1046/j.1471-4159.2001.00310.x. PMID 11359872.
  14. Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease - a review-JOURNAL OF LIPID RESEARCH Volume: 49 Issue: 6 Pages: 1157-1175 Published: JUN 2008
  15. Paulick, Margot G.; Bertozzi, Carolyn R. (2008-07-08). "The Glycosylphosphatidylinositol Anchor: A Complex Membrane-Anchoring Structure for Proteins". Biochemistry 47 (27): 6991–7000. doi:10.1021/bi8006324. ISSN 0006-2960. PMC 2663890. PMID 18557633.

Genetic Science Learning Center. "Genes and Blood Type." Learn.Genetics 24 November 2015 <http://learn.genetics.utah.edu/content/inheritance/blood/>

External links

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