BCHS-4361-09-GLYCOPR_38891

BCHS-4361-09-GLYCOPR_38891 - GLYCOPROTEIN SYNTHESIS &...

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TRAFFICKING AND I-CELL DISEASE More than 50% of all proteins possess covalently bound carbohydrate. These include proteins intended for: – Secretion – Incorporation into membranes – Localization within membranous organelles Glycosylation of polypeptides and processing of the oligosaccharide (OS) moiety play key roles in sorting and targeting of these proteins to their intracellular and extracellular destinations. In I-cell disease , so named because of inclusions seen in cells of the patients, there is an enzymatic defect in a glycoprotein trafficking pathway.
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POST-TRANSLATIONAL PROTEIN MODIFICATION: GLYCOSYLATION Why glycosylation? Aids in proper protein folding . Provides protection against proteases (e.g. lysosomal membrane proteins) Employed for signaling. Most soluble and membrane-bound proteins made in the ER are glycoproteins, in contrast to cytsolic proteins. Oligosaccharides can be covalently attached to proteins via N- or O-links. N-linked protein glycosylation is a 3-part process: Assembly of the precursor oligosaccharide. En-bloc transfer to the protein. Modification of the oligosaccharide by removal and addition of sugars.
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Sugar Nucleotides and Their Corresponding Monosaccharides In Glycosyl Transferase Reactions UDP GDP CMP Gal Nac Fucose Sialic Acid Glc Nac Mannose Galactose Glucose Nucleotide Sugars Are Of Vital Importance In Oligosaccharide Synthesis
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TYPES OF OLIGOSACCHARIDE (OS) ATTACHMENT TO PROTEINS Two principal types: N-linked: OS is attached to an Asn side chain through amide N to form a β -N-glycosidic bond O-linked: attached to a ser side chain through the -OH to form an a-O-glycosidic bond. We are only going to consider N-linked OS structure and synthesis. The OS chains consist of monosaccharide units linked by glycosidic bonds. Ca. 80 different types of naturally occurring glycosidic linkages are known. (Note: CHO components attached to proteins or lipids are sometimes called glycans)
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N-Linked O-Linked Asparagin e (N) NB X not Proline GlcNac GalNac R = H or CH 3 Linked to OH by either Serine/Threonine (S) (T)
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STEPS IN SYNTHESIS OF N-LINKED GLYCANS 1) Synthesis of lipid-linked core oligosaccharide precursor. 2) Transfer of core oligosaccharide to NH 2 group of Asn on nascent polypeptide 3) Trimming of core oligosaccharide. 4) Addition of further residues to trimmed core oligosaccharide .
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Saturated α -isoprene unit Dolichol The carbohydrate precursors of N-linked glycans are synthesised as dolichol phosphate glycosides. n
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BCHS-4361-09-GLYCOPR_38891 - GLYCOPROTEIN SYNTHESIS &...

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