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50 Cards in this Set
- Front
- Back
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What makes a protein N-linked?
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When there's a sugar attached to an asparagine.
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What imparts a negative charge on carbohydrates? (p428)
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The carboxylate group.
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Before becoming an oligosaccharide attached to proteins, the nucleosides are charged with:
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UDP or GDP
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The enzyme class that transfers nucleoside to proteins (to become an oligosaccharide) are called:
How many are there? |
Glycosyltransferases, 300
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Glycosyltransferases are specific for three things:
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1. Sugar that is transfered
2. Acceptor substrate 3. Type of linkage generated |
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Where does nucleotide sugar synthesis take place?
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Cytoplasm
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Where do glycosyltransferases reside? (p430)
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In the secretory pathway that utilizes the ER and the golgi apparatus. The sugar residues are confined to the the lumen of each organelle.
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N-glycosidic linkage requires this triplet sequence:
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Asn-X-Ser/Thr.
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(Step 1) What serves as the precursor to Dolichol Phosphate?
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Mevalonic Acid
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Regulation of dolichol Phosphate is directly related to:
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Cholesterol metabolism
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What does dol-P do?
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It serves as a shuttle that transfers oligosaccharide to proteins
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What does Oligosaccharyltransferase do?
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It transfers an oligosaccharide chain (specifically GlcNAc2Man9Glc3) from dol-P to the Asn residue in a protein.
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All glycoproteins with an N-oligosaccharide on them start with:
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Glc3Man9GlcNAc2
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Where does the transfer of dol-P to Asn via oligosaccharyltransferase occur?
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Exclusively in the ER
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How many glycosyltransferases are required to synthesize Oligosaccharide-Dol-P?
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14
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The 1st 7 steps of oligosaccharide-Dol-P synthesis occurs where? The last 7 steps?
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1st seven: Cytosolic Face of RER
2nd seven: lumen of RER |
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Transfer of oligosaccharide chain from dol-P to the Asn residue happens...
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co-translationally
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After the oligosaccharide chain is transferred from dol-P to Asn by Oligosaccharyltransferase (OT), the chain can be modified to create 1000's of different molecules. What to enzymes modify the chain and what do they do specifically?
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1. Glycosyltransferases - add sugars one at a time.
2. Glycosidases - enzyme that removes a single carbohydrate (named by the sugar they remove, eg. manosylase, glycosylase) |
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Where does modification of the 14 carbohydrate sugar chain occur?
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Happens in the ER in different stacks of the Golgi
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Why is the particular GlcNAc2Man9Glc3 structure used?
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Bc it helps with folding proteins. The cells use it bc it is recognized by different chaperones.
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Define Glycosaminoglycans (GAG):
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The are negatively charged polysaccharides composed of repeating disaccharide units.
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Define proteoglycans:
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They are glycoproteins that contain a specific type of oligosaccharide called glycosaminoglycan (GAG); proteoglycans often contain large numbers of GAG chains.
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Proteoglycans have this type of linkage:
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O-glycosidic between Xyl & Ser
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What molecule serves as a scaffold for proteoglycans?
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Hyaluronic acid.
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Described the characteristics of Glycosaminoglycans:
1. Charge? 2. What is the repeating unit? 3. Sulfation? Yes or No? |
1. Negative
2. Amino sugar GlcN or GalN AND uronic acid GlcUA or IdUA 3. Can undergo sulfation - Hyaluronic acid is the exception. |
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Where are proteoglycans typically found and where are they highly enriched?
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1. Found in virtually all cell surfaces.
2. Highly enriched in cartilages |
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What is a unique property of Proteoglycans? Why is this important?
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Absorbs water. It allows to offset forces between joints.
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What does Erythropoietin (EPO) do? How can it it be used clinically?
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A growth factor secreted by the kidney that stimulates the production of RBCs. Clinically, it can be used to treat anemia caused by bone marrow supression
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How is EPO it relevant to this lecture?
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Bc it is a 165-residue protein that contains N-linked oligosaccharides; it is heavily glycosylated with carbohydrate constituting ~40% of its mass.
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Without the oligosaccharides attached to EPO, what happens to its activity?
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Its activity is only at about 10%
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How does heparin affect the blood? How does it work?
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It is an anticoagulant that works by forming a high affinity complex with antithrombin. When this happens, antithrombin undergoes a conformation change that increases its activity 1000 to 10,000 fold.
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How does Anithrombin work? (p437)
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It inhibits two principle procoagulant proteases, factor Xa and thrombin, thereby decreasing the production of fibrin clots.
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What symptoms is a result of defective synthesis of heparin sulfate?
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Elevated tryglycerides - recall this from cholesterol pathways.
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What defect can cause abnormal cartilage formation?
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A defect in sulfation of glycosaminoglycans
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What three important functions do the carbohydrates linked to proteins serve?
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1. Cellular recognition (eg leukocyte adhesion)
2. Intracellular targeting (lysosomal enzymes) 3. Binding sites for bacterial toxins/parasites (cholera toxin) |
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What does the Influenza virus have on its surface that recognizes host molecules? What are these host molecules?
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Influenza includes Hemagglutinin and Sialidase.
Hemagglutinin recognizes host Glycoproteins and Glycolipids that contain sialic acid. |
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Tamiflu and Relenza are drugs that target:
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Sialidase - the enzyme that helps virus move through the mucosa of the respiratory tract.
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Virus encodes a surface enzyme called:
What does it do? |
Sialidase - it cleaves terminal sialic acid residues from glycoproteins. This allows it to move through mucus and helps virus to be released from infected cells.
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Where are glyoproteins and glycolipids degraded? By what are they degraded by>?
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In the lysosome - they are degraded by glycosidases.
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Glycosidases are called:
...because they degrade the carbohydrate units in this way: |
They are Exoglycosidases bc they degrade by the sequential action of hydrolytic enzymes solely from the nonreducing end of the oligosaccharide
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Describe how lysosomal storage disorders are caused.
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They result from a deficiency of the catabolic enzyme in the lysozome that results in an accumulation of material
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ADP-Ribosylation:
1. pre- or post-translational mod? 2. is it reversible? 3. Pos or neg charged phosph groups are added? 4. How is it important in disease? |
1. Post-trans
2. Reversible 3. Neg charged phosph 4. Bacterial toxins such as diptheria, cholera, and pertussis induce mono-ADP-ribosylation rxns that induce these bacterial toxins cause disease. |
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Hydrophobic modifications of proteins allow what?
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Association with lipid bilayer
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Palmitoylation is a pre- or post-translational modification? What is the donor?
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Post. Palmitoyl CoA
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Palmitic acid is linked to a protein through what?
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A thioester bond to cysteine
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What sequence do Farnesylation rxns recognize?
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CAAX - C = cystein; A= aliphatic amino acid X = any amino acid
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What is an example of a protein that undergoes Farnesylation?
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Ras
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What is Farnesylation?
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It is the addition of hydrophobic groups to a protein
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What causes Hutchinson-Gilford Progeria Syndrome?
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Accumulation of a mutant form of prelamin A. It cannot be farnesylated and therefore Lamin A, a structural protein of the nuclear lamin, cannot be made.
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Cholesterol is also used to modify proteins...which one?
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Hedgehog - it's essential for development.
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