Glycoconjugates

Glycoconjugates

1. Glycoconjugates are glucids covalently bonded with other chemical species such as proteins, peptides, lipids

2. They are formed from complex carbohidrates

   • Sugar + protein/peptide/aminoacids
     • Glycosaminoglycan (GAG)
       • linear copolymers of acidic disaccharide repeating units, each typically containing a hexosamine (GlcN or GalN) and a hexose (Gal) or hexuronic acid (GlcA or IdoA)
       • According with the type of disaccharide units are defined as
         • Chondroitin or dermatan sulfate (GalNAcβ1-4GlcA/IdoA)
           • Chondroitin sulfate is the most abundant GAG in humans
           • is part of
             • cartilages
             • joints
             • tendons
             • ligaments
             • large blood vessesl
             • Skin
             • cardiacal valves
         • heparin or heparan sulfate (GlcNAcα1-4GlcA/IdoA)
           • Used as anticoagulan/ present in arteries/liver/lungs
         • keratan sulfate (Galβ1-4GlcNAc)
           • is actually a 6-O-sulfated form of poly-N-acetyllactosamine attached to an N- or O-glycan core
           • Formed with Gal+aminosugar
             • A polylactosamine [Galβ1-4GlcNAcβ1-3]n with sulfate esters at C-6 of N-acetylglucosamine and galactose residues, found as a side chain of a keratan sulfate proteoglycan
         • hyaluronan (a polymer of GlcNAcβ1-4GlcA)
           • appears to exist primarily as a free glycan unattached to any aglycone
             • acts as lubricant/ is present in the sinovial capsules/humor vitreus/ and is used in aesthetic medicine
       • Are heteropolysacarides with a strength negative charge
       • attracts large amounts of water
         • Builds a extracellular gel (extracellular matrix)
           • Lubricant /Adhesion /absorption
       • in tissues
         • serve as a flexible support/ structural
         • regulates movement
       • biosynthesis in the Golgi apparatus of eukaryotes
       • catalyzed by glycosyltransferases and sulfotransferases (except in hyaluronan)
       • Degrated in lysosome by the acid hydrolase enzime
         • alteration in degradation could lead to
           • Mucopolysaccharidosis
             • MPS-IH ( Hurler's disease ) is the most dangerous
             • (MPS II), also known as Hunter syndrome. This is the only MPS linked to X chromosome
             • Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome
             • (MPS IV) is a mucopolysaccharide storage disease that exists in two forms (MPS IVA and MPS IVB). These are autosomal recessive genetic conditions that comprise a continuum consisting of a severe form with rapid progression and another slowly progressing form
     • Proteoglycan
       • Is a glycoconjugate that has one or more glycosaminoglycan (GAG) chains
       • Synthetized in the RER (prtein) and golgi aparatus (GAG)
       • Are components of extra cellular matrix
     • Glycoprotein
       • Is a glycoconjugate in which a protein carries one or more glycans covalently attached to a polypeptide backbone, usually via N- or O-linkages. An N-glycan (N-linked oligosaccharide, N-[Asn]-linked oligosaccharide) is a sugar chain covalently linked to an asparagine residue of a polypeptide chain, commonly involving a GlcNAc residue in eukaryoates
       • acts as
         • Hormons
           • FSH/LH
         • Cellular surface receptors
         • antigens
         • AB0 systems
         • some globular proteins are glycoproteins for instance hemoglobine attached with glucose is a glycosilated hemoblobine
         • Extra cellular matrix components
         • Lubricants
         • immune funtion
       • synthesis: Ribosomes (free or RER) and packaged in the golgi aparatus
       • glycan–protein linkages in nature
   • sugar+ lipids
     • Glycolips
       • can be classified based on their lipid moieties
         • glycoglycerolipids
         • glycophosphatidylinositols
           • A lipid in the plasma membrane of cells that anchors proteins on the cell's surface.
           • Several disorders of GPI-anchor synthesis with neurologic features have been described.
             • Mabry syndrome
             • comprising intellectual disability
             • hyperphosphatasia
             • unusual facial features
             • hypotonia
             • seizures
         • glycosphingolipids
           • Glycosphingolipids (GSLs), a subclass of glycolipids found in the cell membranes of organisms from bacteria to humans, are the major glycolipids of animals.
           • The ceramide lipid component of GSLs consists of a sphingoid base with a fatty acid amide at the C-2 amine
           • have essential roles in the structure and function of myelin, the insulator that allows for rapid nerve conduction
           • GSL series are expressed in tissue-specific patterns. In mammals, for example, ganglio-series GSLs, although broadly distributed, predominate in the brain, whereas neolacto-series glycolipids are common on certain hematopoietic cells including leukocytes
           • Their functions fall into two major categories
             • mediating cell–cell interactions via binding to complementary molecules on apposing plasma membranes (trans recognition)
             • modulating activities of proteins in the same plasma membrane (cis regulation).
           • Mutations in a gene required for biosynthesis of ganglioside GM3, ST3GAL5, result in severe infantile seizures accompanied by profound motor and intellectual deficits
           • Gaucher disease
             • mutations in the enzyme β-glucocerebrosidase
       • are glycoconjugates where sugars are covalently bonded to lipids. Due to their amphiphilic character, they have a natural ability to self-insert in cell membranes and have similar biological behavior as the other glycoconjugates.

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