Globoside

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N-Acetylgalactosamine Acetylgalactosamine.svg
N-Acetylgalactosamine
Sphingosine Sphingosine structure.svg
Sphingosine

Globosides are a sub-class of the lipid class glycosphingolipid [1] with three to nine sugar molecules as the side chain (or R group) of ceramide. The sugars are usually a combination of N-acetylgalactosamine, D-glucose or D-galactose. One characteristic of globosides is that the "core" sugars consists of Glucose-Galactose-Galactose (Ceramide-βGlc4-1βGal4-1αGal), like in the case of the most basic globoside, globotriaosylceramide (Gb3), [2] also known as pk-antigen. Another important characteristic of globosides is that they are neutral at pH 7, because they usually do not contain neuraminic acid, a sugar with an acidic carboxy-group. However, some globosides with the core structure Cer-Glc-Gal-Gal do contain neuraminic acid, e.g. the globo-series glycosphingolipid "SSEA-4-antigen".

The side chain can be cleaved by galactosidases and glucosidases. The deficiency of α-galactosidase A causes Fabry's disease, an inherited metabolic disease characterized by the accumulation of the globoside globotriaosylceramide. [3]

Globoside (GB4) has been known as the receptor for parvovirus B19, due to observations that B19V binds to the thin-layered chromatogram of the structure. However, the binding on its surface does not match well with the virus, which raised debates on whether or not GB4 is the cause for productive infection. [4] Additional research using the technique Knockout Cell Line has shown that although GB4 does not have the direct entry receptor for B19V, it plays a post-entry role in productive infection. [5]

Globoside (Gb4) are a type of SSEA, stage-specific embryonic antigen, that is present in cellular development and tumorous tissues without the mechanism of Gb4 being completely known. However a study has shown Gb4 directly activates the epidermal growth factor receptor through a ERK signaling. When the globo-series glycosphingolipid (GSL) was reduced in the experiment the ERK signaling from the receptor tyrosine kinase was also inhibited. The ERK was reactivated with the addition of the Gb4 and henceforth heightened proliferation of tumorous cells and opened up the possibility of testing Gb4 for further studies on potential drugs that can target cancerous cells. [6]

Related Research Articles

<span class="mw-page-title-main">Galactose</span> Monosaccharide sugar

Galactose, sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecule linked with a glucose molecule forms a lactose molecule.

<span class="mw-page-title-main">Fifth disease</span> Medical condition

Erythema infectiosum, fifth disease, or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19. Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect humans of all ages, only two out of ten individuals will present with physical symptoms.

<span class="mw-page-title-main">Parvovirus B19</span> Human virus that infects RBC precursors

Human parvovirus B19, generally referred to as B19 virus(B19V),parvovirus B19 or sometimes erythrovirus B19, is a known human virus in the family Parvoviridae, genus Erythroparvovirus; it measures only 23–26 nm in diameter. Human parvovirus b19 is a below-species classification of Erythroparvovirus primate1. The name is derived from Latin parvum, meaning small, reflecting the fact that B19 ranks among the smallest DNA viruses. B19 virus is most known for causing disease in the pediatric population; however, it can also affect adults. It is the classic cause of the childhood rash called fifth disease or erythema infectiosum, or "slapped cheek syndrome". The name comes from it being the fifth in a list of historical classifications of common skin rash illnesses in children.

<span class="mw-page-title-main">Lipid raft</span> Combination in the membranes of cells

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 controversial. Indeed, Kervin and Overduin imply that lipid rafts are misconstrued protein islands, which they propose form through a proteolipid code. Nonetheless, 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">Glycolipid</span> Class of chemical compounds

Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. 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. Glycolipids are found on the surface of all eukaryotic cell membranes, where they extend from the phospholipid bilayer into the extracellular environment.

<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">Cerebroside</span> Lipid classification

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

α-Galactosidase Enzyme

α-Galactosidase is a glycoside hydrolase enzyme that catalyses the following reaction:

<span class="mw-page-title-main">Lipid signaling</span> Biological signaling using lipid molecules

Lipid signaling, broadly defined, refers to any biological cell signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.

Galactosidases are enzymes that catalyze the hydrolysis of galactosides into monosaccharides.

<span class="mw-page-title-main">UDP-glucose 4-epimerase</span> Class of enzymes

The enzyme UDP-glucose 4-epimerase, also known as UDP-galactose 4-epimerase or GALE, is a homodimeric epimerase found in bacterial, fungal, plant, and mammalian cells. This enzyme performs the final step in the Leloir pathway of galactose metabolism, catalyzing the reversible conversion of UDP-galactose to UDP-glucose. GALE tightly binds nicotinamide adenine dinucleotide (NAD+), a co-factor required for catalytic activity.

In enzymology, a globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">UGT8</span> Protein-coding gene in the species Homo sapiens

2-hydroxyacylsphingosine 1-beta-galactosyltransferase is an enzyme that in humans is encoded by the UGT8 gene.

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

Globotriaosylceramide is a globoside. It is also known as CD77, Gb3, GL3, and ceramide trihexoside. It is one of the few clusters of differentiation that is not a protein.

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

The Lactosylceramides, also known as LacCer, are a class of glycosphingolipids composed of a variable hydrophobic ceramide lipid and a hydrophilic sugar moiety. Lactosylceramides are found in microdomains on the plasma layers of numerous cells. Moreover, they are a type of ceramide including lactose, which is an example of a globoside.

O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii.

Isoglobotriosylceramide, Gal(α1→3)Gal(β1→4)Glcβ(1→1)Cer, abbreviated as iGb3, is an iso-globo-series of glycosphingolipid, which mysteriously disappeared in most mammals studied, except trace amount reported in the thymus.

Globo H (globohexaosylceramide) is a globo-series glycosphingolipid antigen that is present on the outer membrane of some cancer cells. Globo H is not expressed in normal tissue cells, but is expressed in a number of types of cancers, including cancers of the breast, prostate, and pancreas. Globo H's exclusivity for cancer cells makes it a target of interest for cancer therapies.

References

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  2. "Globotriaosylceramide". Lipid Maps.
  3. Germain DP (2002). "[Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects]". Journal de la Société de Biologie. 196 (2): 161–173. doi:10.1051/jbio/2002196020161. PMID   12360745. S2CID   87466647.
  4. Nasir W, Nilsson J, Olofsson S, Bally M, Rydell GE (May 2014). "Parvovirus B19 VLP recognizes globoside in supported lipid bilayers". Virology. 456–457: 364–369. doi: 10.1016/j.virol.2014.04.004 . PMID   24889255.
  5. Bieri J, Ros C (October 2019). "Globoside Is Dispensable for Parvovirus B19 Entry but Essential at a Postentry Step for Productive Infection". Journal of Virology. 93 (20). doi: 10.1128/JVI.00972-19 . PMC   6798098 . PMID   31341051.
  6. Park SY, Kwak CY, Shayman JA, Kim JH (July 2012). "Globoside promotes activation of ERK by interaction with the epidermal growth factor receptor". Biochimica et Biophysica Acta (BBA) - General Subjects. 1820 (7): 1141–1148. doi:10.1016/j.bbagen.2012.04.008. PMC   3645941 . PMID   22542783.