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59 Cards in this Set
- Front
- Back
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What is the definition of a glycoprotein?
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Protein with a single sugar or complex of polysaccs are covalently bound.
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What is the general structure, i.e. is it:
Hydrophobic/philic Hydrated/non-aqueous Small/Bulky? |
Hydrophilic/Hydrated/Bulky
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The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as ___.
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glycosylation
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In proteins that have segments extending extracellularly, the extracellular segments are often ___.
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glycosylated
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Glycoproteins are often important in Integral/Peripheral membrane proteins, where they play a role in cell-cell interactions.
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Integral
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There are two types of glycosylation: ___ and ___
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N-glycosylation and O-glycosylation
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In N-glycosylation , the addition of sugar chains can happen at the amide nitrogen on the side chain of the ___.
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Asparagine
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In O-glycosylation, the addition of sugar chains can happen on the ___ oxygen on the side chain of hydroxylysine, hydroxyproline, ___, or ___.
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In O-glycosylation, the addition of sugar chains can happen on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, serine, or threonine.
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AND... because we were all confused... what is fucose?
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Fucose is a hexose deoxy sugar with the chemical formula C6 H12 O5. It is found on N-linked glycans on the mammalian, insect and plant cell surface, and is the fundamental sub-unit of the fucoidan polysaccharide. Alpha1→3 linked core fucose is a suspected carbohydrate antigen for IgE-mediated allergy.
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What type of linkage doe the carbs on the glycoproteins exhibit?
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1,3,4,6 linkage that is alpha or beta. Remember this is unlike the proteoglycans that cannot have branched 1,6 linkage.
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What is the major role of glycoproteins?
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Primarily extracellular or cell surface proteins. They can be Ig, cell surface receptors, Ag, ECM, and act as mucin and secreted proteins.
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Why are they such great carriers of biological information?
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Because of structure diversity. They have numerous different configurations due to the linkages (1,3,4,6; alpha and beta).
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Glycoproteins can undergo two additional modifications. What are theses?
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Phosphorylation and Sulfation.
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Again, the two peptide-carb linkages are N and O linkage. N can link to what?
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amide N of asparagine
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Generally the protein primary sequence is Ser, X, and then Asn attached to the carb. What is unique about X? Page 127 if your lost.
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X is generally a SMALL amino acid, due to steric constraints of the bulky addition.
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The general leader sequence of the oligosacc is what? Hint: There are five sugars linked and they look like a fork.
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Ser-X-Asn (peptide) linked to:
GlcNAc (B1,4) GlcNAc (B1,4) Man and two forked Man, with one B1,3 and the other B1,6 (this is the branced portion). |
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Again:
In O-glycosylation, the addition of sugar chains can happen on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, ___ or ___. |
In O-glycosylation, the addition of sugar chains can happen on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, serine, or threonine.
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Does the O-linked have a leader sequence?
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No.
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What is one major clinically relevant usage of O-linked glycoproteins?
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BLOOD TYPE. These glycoproteins make the cell Ag: O, B, and A. Also note Bombay disease, to be discussed subsequently.
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A, B, O all have what unique carb added?
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Fucose.
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The general leader sequence of the oligosacc is what? Hint: There are five sugars linked and they look like a fork.
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Ser-X-Asn (peptide) linked to:
GlcNAc (B1,4) GlcNAc (B1,4) Man and two forked Man, with one B1,3 and the other B1,6 (this is the branced portion). |
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Again:
In O-glycosylation, the addition of sugar chains can happen on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, ___ or ___. |
In O-glycosylation, the addition of sugar chains can happen on the hydroxyl oxygen on the side chain of hydroxylysine, hydroxyproline, serine, or threonine.
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Does the O-linked have a leader sequence?
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No.
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What is one major clinically relevant usage of O-linked glycoproteins?
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BLOOD TYPE. These glycoproteins make the cell Ag: O, B, and A. Also note Bombay disease, to be discussed subsequently.
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A, B, O all have what unique carb added?
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Fucose. This will be important during discussion of O-linked synthesis and Bombay disease.
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Biosynthesis of N-linked:
Where does this occur? |
RER
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Biosynthesis of N-linked:
Addition of N-linked common oligosaccharide occurs on which side of the ER? |
lumen
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Biosynthesis of N-linked:
Where does the inital trimming of the oligo occur? |
RER
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Biosynthesis of N-linked:
Where does the final processing of the N-linked oligo to mature form occur? |
Golgi
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Biosynthesis of N-linked:
What is the duty of dolichol phosphate? |
Tethers and transports the sugars.
Carrier the preassembled oligosaccharide Glc3-Man9-GlcNAc2 (where Glc is glucose, Man is mannose, and GlcNAc is N-acetylglucosamine) into the lumen which is transferred to certain asparagine residues of nascent polypeptide chains. |
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Is dolichol phosphate hydrophobic or hydrophilic?
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Hydrophobic.
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The phosphate attachment site of the dolichol phosphate is initially on what side of the ER (before it has oligos attached)?
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cytosolic side
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The sugars must first be activated in order to be added to the growing oligo on the cystolic side (pg 131). What are GlcNAc and Man activated with?
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UDP-GlcNAc and GDP-Man. Also, Dolichol-P-Man and Dolichol-P-Glc.
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How many sugars are on the common oligosaccharide?
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14 sugars.
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How many sugars are added on the cytosolic side before the growing structure is flipped into the lumen?
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5 main sequence + 2 additonal manose.
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Once the 7 sugar structure is flipped in by dp how are additional Man added?
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On the cytosolic side the GDP activated Man are added to dp and then flipped in and added to the growing dolichol pyrophosphate sugar chain in the lumen.
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The final addition of GlcNAc is done in what manner?
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Similar to the added Man. On the cytosolic side the GDP activated GlcNAc are added to dp and then flipped in and added to the growing dolichol pyrophosphate sugar chain in the lumen.
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After the common sugar is complete what occurs?
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The 14 common sugar is added to the Asn in an N-linked fashion (INSIDE the lumen).
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Initial trimming occurs where?
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RER lumen
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Final processing occurs where?
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Golgi
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What does Bacitracin block?
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The dolichol pyrophsophate (P-P) must lose a phosphate and be reconverted back to dolichol phosphate (P) to start the new process over. Bacitracin blocks this last step in the cycle. Step 10.
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Tunicamycin-hydrophobic analog of UDP-GlcNAc blocks which step?
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Step 1. The addition of the P-GlcNAc to the dichol phosphate.
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In the RER the initial trimming involves what two enzymes?
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alpha-glucosidase
alpha-mannosidase |
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In the golgi you are primarily adding things via ___.
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Transferases (see page 132 for list, but big important one is fucosyl transferase).
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Where is GDP-fucosyl transferase located and what is its function? What is this important in?
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Located in the golgi and transfers fucose to glycoproteins. Important in blood antigens.
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LAD Type II is a rare AR syndrome characterized by Bombay blood type. What enzyme is disfunctional?
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GDP-L-Fucose Transporter
(Notice I'm kicking the horse, i.e. as Bick would say, THREE TIMES) |
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If the carbs on a growing membrane proteins are located on the inside of the ER lumen where will they be located when the vesicly fuses with the cytoplasmic membrane?
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exposed OUTSIDE of cell
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The biosynthesis of O-linked glycoproteins occurs in the ___ of the ___.
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lumen of the golgi
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Elongation and branching continue to occur one at a time in the ___.
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golgi
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The sugars are activated by ___.
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nucleotides
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Forming ___ targets the glycoprotein for usage in the lysosome?
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mannose-6-P
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What is the enzyme that performs this function?
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UDP-GlcNAc phosphotransferase
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What does the UDP-GlcNAc phosphotransferase do?
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Adds the GlcNAc-P to the Man followed by removal of the GlcNAc by a phosphoglycosidase to create a mannose-6-P that is recognized by the lysosome.
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Is this newly formed glycoprotein degraded in the lysosome?
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NO! It is the degrader.
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What happens to the lysosomal enzymes that do not attain a phosphate group on the 6 position?
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They are exported out of the cell via the golgi system.
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Explain I cell disease.
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I cell disease is loss of UDP-GlcNAc phosphotransferase. The lysozomal enzymes are exported out of the cell and found in the plasma instead of being sent to the lysosome.
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Why is this so dangerous?
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Not because the enzymes are in the plasma causing damage. Instead, the main problem of this disease is that the lysosome is basically nonfunctional. It brings in things, but it cannot degrade them. Causes huge storage problems, inlclusion bodies, and that's why it's called I cell disease.
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Besides lysosome enzymes what other functions do O-linked glycoproteins have?
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RBC Ag
LDL receptors Protein Structure- stabilize confirmation, control uptake, control lifetime, and increase solubility. |
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What is removed first when the lysosome is degrading the glycoprotein?
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fucose removed first by alpha-fucosidase. See page 135 and 136 for further. Chart on page 137 is also good for this lecture.
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