Glycolipid

Last updated

Glycolipid Glycolipid.svg
Glycolipid

Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. [1] Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connections that allow cells to connect to one another to form tissues. [2] Glycolipids are found on the surface of all eukaryotic cell membranes, where they extend from the phospholipid bilayer into the extracellular environment. [2]

Contents

Structure

The essential feature of a glycolipid is the presence of a monosaccharide or oligosaccharide bound to a lipid moiety. The most common lipids in cellular membranes are glycerolipids and sphingolipids, which have glycerol or a sphingosine backbones, respectively. Fatty acids are connected to this backbone, so that the lipid as a whole has a polar head and a non-polar tail. The lipid bilayer of the cell membrane consists of two layers of lipids, with the inner and outer surfaces of the membrane made up of the polar head groups, and the inner part of the membrane made up of the non-polar fatty acid tails.

The saccharides that are attached to the polar head groups on the outside of the cell are the ligand components of glycolipids, and are likewise polar, allowing them to be soluble in the aqueous environment surrounding the cell. [3] The lipid and the saccharide form a glycoconjugate through a glycosidic bond, which is a covalent bond. The anomeric carbon of the sugar binds to a free hydroxyl group on the lipid backbone. The structure of these saccharides varies depending on the structure of the molecules to which they bind.

Metabolism

Glycosyltransferases

Enzymes called glycosyltransferases link the saccharide to the lipid molecule, and also play a role in assembling the correct oligosaccharide so that the right receptor can be activated on the cell which responds to the presence of the glycolipid on the surface of the cell. The glycolipid is assembled in the Golgi apparatus and embedded in the surface of a vesicle which is then transported to the cell membrane. The vesicle merges with the cell membrane so that the glycolipid can be presented on the cell's outside surface. [4]

Glycoside hydrolases

Glycoside hydrolases catalyze the breakage of glycosidic bonds. They are used to modify the oligosaccharide structure of the glycan after it has been added onto the lipid. They can also remove glycans from glycolipids to turn them back into unmodified lipids. [5]

Defects in metabolism

Sphingolipidoses are a group of diseases that are associated with the accumulation of sphingolipids which have not been degraded correctly, normally due to a defect in a glycoside hydrolase enzyme. Sphingolipidoses are typically inherited, and their effects depend on which enzyme is affected, and the degree of impairment. One notable example is Niemann–Pick disease which can cause pain and damage to neural networks. [6]

Function

Cell–cell interactions

The main function of glycolipids in the body is to serve as recognition sites for cell–cell interactions. The saccharide of the glycolipid will bind to a specific complementary carbohydrate or to a lectin (carbohydrate-binding protein), of a neighboring cell. The interaction of these cell surface markers is the basis of cell recognitions, and initiates cellular responses that contribute to activities such as regulation, growth, and apoptosis. [7]

Immune responses

An example of how glycolipids function within the body is the interaction between leukocytes and endothelial cells during inflammation. Selectins, a class of lectins found on the surface of leukocytes and endothelial cells bind to the carbohydrates attached to glycolipids to initiate the immune response. This binding causes leukocytes to leave circulation and congregate near the site of inflammation. This is the initial binding mechanism, which is followed by the expression of integrins which form stronger bonds and allow leukocytes to migrate toward the site of inflammation. [8] Glycolipids are also responsible for other responses, notably the recognition of host cells by viruses. [9]

Blood types

Blood types are an example of how glycolipids on cell membranes mediate cell interactions with the surrounding environment. The four main human blood types (A, B, AB, O) are determined by the oligosaccharide attached to a specific glycolipid on the surface of red blood cells, which acts as an antigen. The unmodified antigen, called the H antigen, is the characteristic of type O, and is present on red blood cells of all blood types. Blood type A has an N-acetylgalactosamine added as the main determining structure, type B has a galactose, and type AB has all three of these antigens. Antigens which are not present in an individual's blood will cause antibodies to be produced, which will bind to the foreign glycolipids. For this reason, people with blood type AB can receive transfusions from all blood types (the universal acceptor), and people with blood type O can act as donors to all blood types (the universal donor). [10]

Chemical structure of glycolipids Glycolipids.svg
Chemical structure of glycolipids

Types of glycolipids

See also

Related Research Articles

<span class="mw-page-title-main">Glycoprotein</span> Protein with oligosaccharide modifications

Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.

An oligosaccharide is a saccharide polymer containing a small number of monosaccharides. Oligosaccharides can have many functions including cell recognition and cell adhesion.

<span class="mw-page-title-main">Lipid raft</span>

The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. It has been proposed that they are specialized membrane microdomains which compartmentalize cellular processes by serving as organising centers for the assembly of signaling molecules, allowing a closer interaction of protein receptors and their effectors to promote kinetically favorable interactions necessary for the signal transduction. Lipid rafts influence membrane fluidity and membrane protein trafficking, thereby regulating neurotransmission and receptor trafficking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but float freely within the membrane bilayer. Although more common in the cell membrane, lipid rafts have also been reported in other parts of the cell, such as the Golgi apparatus and lysosomes.

<span class="mw-page-title-main">Sphingolipid</span> Family of chemical compounds

Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with a terminal hydroxyl group is a ceramide. Other common groups bonded to the terminal oxygen atom include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.

Glycosphingolipids are a subtype of glycolipids containing the amino alcohol sphingosine. They may be considered as sphingolipids with an attached carbohydrate. Glycosphingolipids are a group of lipids and are a part of the cell membrane. They consist of a hydrophobic ceramide part and a glycosidically bound carbohydrate part. This oligosaccharide content remains on the outside of the cell membrane where it is important for biological processes such as cell adhesion or cell–cell interactions. Glycosphingolipids play also important role in oncogenesis and ontogenesis.

<span class="mw-page-title-main">Ganglioside</span> Class of chemical compounds

A ganglioside is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. NeuNAc, an acetylated derivative of the carbohydrate sialic acid, makes the head groups of gangliosides anionic at pH 7, which distinguishes them from globosides.

<span class="mw-page-title-main">Glycerophospholipid</span> Class of lipids

Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes in eukaryotic cells. They are a type of lipid, of which its composition affects membrane structure and properties. Two major classes are known: those for bacteria and eukaryotes and a separate family for archaea.

CD1 is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. CD1 glycoproteins are structurally related to the class I MHC molecules, however, in contrast to MHC class 1 proteins, they present lipids, glycolipids and small molecules antigens, from both endogenous and pathogenic proteins, to T cells and activate an immune response. Both αβ and γδ T cells recognise CD1 molecules.

<span class="mw-page-title-main">Hemagglutinin esterase</span> Glycoprotein present in some enveloped viruses

Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. Viruses that possess HEs include influenza C virus, toroviruses, and coronaviruses of the subgenus Embecovirus. HEs is a dimer transmembrane protein consisting of two monomers, each monomer is made of three domains. The three domains are: membrane fusion, esterase, and receptor binding domains.

<span class="mw-page-title-main">Cerebroside</span> Lipid classification

Cerebrosides (monoglycosylceramides) are a group of glycosphingolipids which are important components of animal muscle and nerve cell membranes.

Sulfatide, also known as 3-O-sulfogalactosylceramide, SM4, or sulfated galactocerebroside, is a class of sulfolipids, specifically a class of sulfoglycolipids, which are glycolipids that contain a sulfate group. Sulfatide is synthesized primarily starting in the endoplasmic reticulum and ending in the Golgi apparatus where ceramide is converted to galactocerebroside and later sulfated to make sulfatide. Of all of the galactolipids that are found in the myelin sheath, one fifth of them are sulfatide. Sulfatide is primarily found on the extracellular leaflet of the myelin plasma membrane produced by the oligodendrocytes in the central nervous system and in the Schwann cells in the peripheral nervous system. However, sulfatide is also present on the extracellular leaflet of the plasma membrane of many cells in eukaryotic organisms.

Sialyl-Lewis <sup>X</sup> Chemical compound

Sialyl LewisX (sLeX), also known as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1), is a tetrasaccharide carbohydrate which is usually attached to O-glycans on the surface of cells. It is known to play a vital role in cell-to-cell recognition processes. It is also the means by which an egg attracts sperm; first, to stick to it, then bond with it and eventually form a zygote.

<span class="mw-page-title-main">Membrane lipid</span> Lipid molecules on cell membrane

Membrane lipids are a group of compounds which form the lipid bilayer of the cell membrane. The three major classes of membrane lipids are phospholipids, glycolipids, and cholesterol. Lipids are amphiphilic: they have one end that is soluble in water ('polar') and an ending that is soluble in fat ('nonpolar'). By forming a double layer with the polar ends pointing outwards and the nonpolar ends pointing inwards membrane lipids can form a 'lipid bilayer' which keeps the watery interior of the cell separate from the watery exterior. The arrangements of lipids and various proteins, acting as receptors and channel pores in the membrane, control the entry and exit of other molecules and ions as part of the cell's metabolism. In order to perform physiological functions, membrane proteins are facilitated to rotate and diffuse laterally in two dimensional expanse of lipid bilayer by the presence of a shell of lipids closely attached to protein surface, called annular lipid shell.

Carbohydrate–protein interactions are the intermolecular and intramolecular interactions between protein and carbohydrate moieties. These interactions form the basis of specific recognition of carbohydrates by lectins. Carbohydrates are important biopolymers and have a variety of functions. Often carbohydrates serve a function as a recognition element. That is, they are specifically recognized by other biomolecules. Proteins which bind carbohydrate structures are known as lectins. Compared to the study of protein–protein and protein–DNA interaction, it is relatively recent that scientists get to know the protein–carbohydrate binding.

A kodecyte (ko•de•cyte) is a living cell that has been modified (koded) by the incorporation of one or more function-spacer-lipid constructs to gain a new or novel biological, chemical or technological function. The cell is modified by the lipid tail of the FSL construct incorporating into the bilipid membrane of the cell.

<span class="mw-page-title-main">Cell–cell recognition</span>

Cell–cell recognition is a cell's ability to distinguish one type of neighboring cell from another. This phenomenon occurs when complementary molecules on opposing cell surfaces meet. A receptor on one cell surface binds to its specific ligand on a nearby cell, initiating a cascade of events which regulate cell behaviors ranging from simple adhesion to complex cellular differentiation. Like other cellular functions, cell-cell recognition is impacted by detrimental mutations in the genes and proteins involved and is subject to error. The biological events that unfold due to cell-cell recognition are important for animal development, microbiomes, and human medicine.

<span class="mw-page-title-main">Cell membrane</span> Biological membrane that separates the interior of a cell from its outside environment

The cell membrane is a biological membrane that separates and protects the interior of a cell from the outside environment. The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of a cell, being selectively permeable to ions and organic molecules. In addition, cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity, and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall and the carbohydrate layer called the glycocalyx, as well as the intracellular network of protein fibers called the cytoskeleton. In the field of synthetic biology, cell membranes can be artificially reassembled.

<span class="mw-page-title-main">Function-spacer-lipid Kode construct</span>

Function-Spacer-Lipid (FSL) Kode constructs are amphiphatic, water dispersible biosurface engineering constructs that can be used to engineer the surface of cells, viruses and organisms, or to modify solutions and non-biological surfaces with bioactives. FSL Kode constructs spontaneously and stably incorporate into cell membranes. FSL Kode constructs with all these aforementioned features are also known as Kode Constructs. The process of modifying surfaces with FSL Kode constructs is known as "koding" and the resultant "koded" cells, viruses and liposomes are respectively known as kodecytes, and kodevirions.

<span class="mw-page-title-main">Milk fat globule membrane</span>

Milk fat globule membrane (MFGM) is a complex and unique structure composed primarily of lipids and proteins that surrounds milk fat globule secreted from the milk producing cells of humans and other mammals. It is a source of multiple bioactive compounds, including phospholipids, glycolipids, glycoproteins, and carbohydrates that have important functional roles within the brain and gut.

<span class="mw-page-title-main">CD1b</span> Mammalian protein found in Homo sapiens

T-cell surface glycoprotein CD1b is a protein that in humans is encoded by the CD1B gene.

References

  1. Voet D, Voet J, Pratt C (2013). Fundamentals of Biochemistry Life at the Molecular Level (Fourth ed.). Hoboken, NJ: John Wiley & Sons, Inc. ISBN   9781118129180.
  2. 1 2 "Glycolipids". nature. Nature Publishing Group. Retrieved 1 November 2015.
  3. Aureli M, Grassi S, Prioni S, Sonnino S, Prinetti A (August 2015). "Lipid membrane domains in the brain". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851 (8): 1006–16. 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. Advances in Enzymology - and Related Areas of Molecular Biology. Vol. 76. pp. 55–119. doi:10.1002/9780470392881.ch2. ISBN   9780470392881. PMID   18990828.
  5. Sinnott ML (November 1990). "Catalytic mechanism of enzymic glycosyl transfer". Chemical Reviews. 90 (7): 1171–1202. doi:10.1021/cr00105a006.
  6. Sandhoff K (1974). "Sphingolipidoses". Journal of Clinical Pathology. 8 (12): 94–105. doi:10.1136/jcp.s3-8.1.94. PMC   1347206 . PMID   4157247.
  7. Schnaar RL (June 2004). "Glycolipid-mediated cell-cell recognition in inflammation and nerve regeneration". Archives of Biochemistry and Biophysics. 426 (2): 163–72. doi:10.1016/j.abb.2004.02.019. PMID   15158667.
  8. Cooper GM (2000). "Cell-Cell Interactions". The Cell: A Molecular Approach (2nd ed.). Sunderland (MA): Sinauer Associates.
  9. Wang B, Boons G (9 September 2011). Carbohydrate Recognition: Biological Problems, Methods, and Applications. John Wiley & Sons. p. 66. ISBN   9781118017579.
  10. Erb IH (May 1940). "Blood Group Classification: A Plea for Uniformity". Canadian Medical Association Journal. 42 (5): 418–21. PMC   537907 . PMID   20321693.
  11. 1 2 Neufeld EF, Hall CW (January 1964). "Formation of galactolipids by chloroplasts". Biochemical and Biophysical Research Communications. 14 (6): 503–8. doi:10.1016/0006-291X(64)90259-1. PMID   5836548.
  12. Harwood JL, Nicholls RG (April 1979). "The plant sulpholipid-- a major component of the sulphur cycle". Biochemical Society Transactions. 7 (2): 440–7. doi:10.1042/bst0070440. PMID   428677.
  13. Hakomori S, Igarashi Y (December 1995). "Functional role of glycosphingolipids in cell recognition and signaling". Journal of Biochemistry. 118 (6): 1091–103. doi: 10.1093/oxfordjournals.jbchem.a124992 . PMID   8720120.
  14. 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.
  15. Ariga T, McDonald MP, Yu RK (June 2008). "Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease--a review". Journal of Lipid Research. 49 (6): 1157–75. doi: 10.1194/jlr.R800007-JLR200 . PMC   2386904 . PMID   18334715.
  16. Paulick MG, Bertozzi CR (July 2008). "The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins". Biochemistry. 47 (27): 6991–7000. doi:10.1021/bi8006324. PMC   2663890 . PMID   18557633.