CSB327 Lecture 8 Summary

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Cell and Systems Biology
Maurice Ringuette

Lecture 8 Proteoglycan = core protein + link tetrasaccharide + GAG - The point of attachment is a Ser residue - The link tetrasaccharide is O-linked to Ser - The GAG is covalently (O-linked or N-linked) attached to the core protein via link tetrasaccharide, except HA o HA non-covalently attached to core protein - Proteoglycans act as organizers of the ECM and promoters of cell adhesion - There are four major classes of GAGs o HA = D-glucuronic acid + N-acetyl-D-glucosamine (non-covalently linked)  Has no sulfate group  Can be decorated with proteoglycans  Universal sequence in all organisms o CS = D-glucuronic acid + N-acetyl-D-galactosamine (O-linked)  Can be sulfated to increase the negative charge o DS = L-iduronic acid + N-acetyl-D-galactosamine (O-linked)  Epimerization of the COOH group on C5 to change the stereochemistry  Can be sulfated to increase the negative charge o HS = D-glucuronic acid or L-iduronic acid + N-acetyl-D-glucosamine or N-sulfo-glucosamine (O-linked)  Can be sulfated to increase the negative charge  Most negatively charged GAG  Binds the most counter ions o KS = D-galactose + N-acetyl-glucosamine (O-linked or N-linked)  Can be sulfated to increase the negative charge Hyaluronan - Properties o Resistant to compression o Space filler during embryogenesis o Lubricant o Viscoelasticity o Hydrogen bonds o Extremely hydrated o Flexible o Random extended coil - Synthesis o HA is synthesized on the cell surface by HA synthases  HAS-1 synthesizes small HA molecules  HAS-3 synthesizes small HA molecules  Found in most embryonic tissues, including chondrocytes  HAS-2 synthesizes large HA molecules  Found in most embryonic tissues, including chondrocytes o GAGs are synthesized in the Golgi - Location o Skin o Cartilage o Most body fluids  Synovial cavity of the joints  Vitreous humour of the eye  Umbilical cord - Osteoarthritis o Describes inflammation in joints o Associated with the breakdown of cartilage in joints in the hips, knees and spine  Does not produce enough new cartilage to replace the breakdown of cartilage o HA injection works by restoring the balance between the breakdown and production of HA in the joint  To coat the pain receptors and inflammatory cells in the joint  To decrease pain and stiffness in the join  To restore physiological elasticity to the joint  To make the joint more mobile  Requires frequent injections because it is not very long-lived - CD44 is a transmembrane receptor (e.g., on chondrocytes)
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