GAGs and Glycoproteins Flashcards
General Structure of Proteoglycans
heteropolysacchrides
Core proteinn with one or more covalently attached GAG to a Ser residue.
GAGs are repeat disaccharides of amino and acid sugars.
Functions of GAGs
Cell shape maintenance, Adhesion, Migration, Cell-Cell communication, source of growth factors.
Amino sugars in GAGs
D-glucosamine or D-galactosamine
Acidic Sugars in GAGs
D-glucuronic acid or C-5 epimer: Liduronic
acid
Hyaluron
Found in synovial fluid; vitreous humour; ECM of loose connective tissue;
Large polymers; shockabsorbing
Only GAG not containing sulfate; only GAG not
found covalently attached to proteins in proteoglycans
Chondroitin Sulfate
Found in Bone, Heart Vales.
Most abundant GAG
Keratan Sulfate
Found in Cornea, Bone, Cartilage
Aggregated with chondroitin sulfate.
Dermatan Sulfate
Found in skin, blood vessles, and heart valves.
Heparin Sulfate
Component of intracellular granules of mast
cells lining the arteries of lungs; liver and skin
More sulfated than heparan sulfates.
Has a natural anticoagulation property
Heparan Sulfate
Basement membranes; components of cell surfaces
Contains higher acetylated glucosamine than
heparin
Cartilage proteoglycan structure
Chondroitin Sulfate and Keratan Sulfate attached to a protein core via Ser residues
GAGs linked to hyaluronic acid via a linking protein
GalNAc
N-acetylgalactosamine
trihexoside in GAG link to Ser
Gal-Gal-Xyl
PAPS
phosphoadenosine- phosphosulfate
Sulfate donor in GAG synthesis
Sulfotransferase
Transfers sulfate group from PAPS to GAG
Steps in proteoglycan synthesis
- synthesis of amino sugars
- synthesis of acidic sugars
- synthesis of core protein
- synthesis of carbohydrate chain (sugars must be in UDP form for assembly similar to glycogen synthesis)
- addition of sulfate groups
Heparin and Warfarin
Heparin induces the release of endothelial cell TFPI (tissue factor pathway inhibitor) that is part of the bodies anti-clotting mechanism.
Warfarin is a synthetic analog of vitamin K and has a slower anticoagulation effect compared to heparin
General Overview and functions/types of glycoproteins
Proteins attached to oligosaccharides (90% proteins, 10% sugars)
Oligosaccharides are attached via N or O glycosidic linkages of Asn or Ser/Thr
Cell surface receptors
Blood group determinants
Found in collagen and fibronectin
Protective Barrier in cells.
Blood Types
Type A Blood contains a terminal GalNAc
Type B Blood contains a terminal Gal
Type AB blood contains both
Type O is missing the terminal glycoprotein
Mucins
Large glycoproteins with negatively charged sialic acid, N-acetylneuraminic acid (NANA)
Functions to trap water and as protective barriers.
Core N-linked oligosaccharides in mammalian glycoprotein serum
GlcNAc - GlcNAc - Man - (Man, Man) [Y branched Man residues attache to a Man residue]
Synthesis of O-linked glycosides
Protein synthesized in rER then extruded in the ER lumen
Glycosylation in the golgi through sequential addition of sugars via glycosyltransferase
Glycosylation begins with N-acetylgalactosamine in UDP form onto Ser or Thr OH group.
glycoproteins then move through golgi for packaging
Synthesis of N-linked glycosides
- Protein Synthesized in rER and enters lumen
- Branched oligosaccharide synthesized on dolichol
- oligosaccharide is transferred from the dolichol to Asn residue on the protein
- trimming of the carb chain as is moves through the rER
- further trimming &/or addition of monosaccharides in the golgi
protein-oligosaccharide transferase
Moves the oligosaccharide from the dolichol to the Asn residue of the protein
