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a. Glycosylation in the RER
i. nearly all proteins produced on membrane-bound ribosomes—whether integral components of a membrane, soluble lysosomal or vacuolar enzymes, or parts of the ECM—become __
1. __ have key roles in the function of many __, particularly as bidning sites in their interactions with other __, as occurs during many cellular processes
- glycoproteins
- carbohydrate groups
- glycoproteins
- macromolecules
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i. they also aid in the __ and __of the protein to which they are attached
1. the sequences of sugars that comprise the __ of __are highly specific; if the __are isolated from a purified protein of a given type of cell, their sequence is consistent and predictable
- proper folding and stabilization
- oligosaccharides
- glycoproteins
- oligosaccharides
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i. the addition of sugars to an __chain is catalyzed by enzymes called __, each of which transfers a specific monosaccharide from a __sugar to the growing end of the carb chain
1. the sequence in which they are transferred during assembly of an oligosaccharide depends on the __ that participate in the process
- oligosaccharide
- glycosyltransferases
- nucleotide
- sequence of action of glycosyltransferases
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a. this in turn depends on the location of specific __within the various memrbaens of the __
i. thus, the arrangement of sugars int eh oligosaccharide chains of a glycoprotein depends on the __ of particular __in the __
- enzymes
- secretory pathway
- spatial localization
- enzymes
- assembly line
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i. the initial steps in the assembly of __ of both soluble proteins and integral membrane proteins
1. __, or __, segment of each carb chain is not assembled on the protein itself but put together independently on a __ and then transferred, as a __, to specific __ of the polypeptide
- N-linked oligosaccharides
- basal
- core
- lipid carrier
- block
- asparagines residues
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a. this lipid carrier, which is named __, is embedded in the ER membrane
i. sugars are added to the __ molecule one at a time by membrane-bound __
- dolichol phosphate
- dolichol phosphate
- glycosyltransferases
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1. this part of __ process is invariant; in mammals, it begins with the transfer of __, then __ and three __units in the precise pattern, which is then transferred by the ER enzyme __from __ to certain __ in the nascent polypeptide as the polypeptide is being translocated into the eR lumen
- glycosylation
- N-acetylglucosamine
- nine mannose
- glucose
- oligosaccharyltransferase
- dolichol phosphate
- asparagines
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i. mutations that lead to the total absence of __ cause the death of embryos prior to __
1. mutatiosn that lead to partial disruption of the __pathway in the ER are responsible for serious inherited disorders affecting nearly every organ system
a. these diseases are called __ and they are usually identified through blood tests that detect abnormal __ of serum proteins
- N-glycosylation
- implantation
- glycosylation
- Congenital Diseases of Glycosylation
- glycosylation
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i. shortly after it is transferred to the nascent polypeptide, the __ undergoes a process of __
1. this modification begins int eh ER with the enzymatic removal of two of the three __
a. this sets the stage for an important event in the life of a newly synthesized __in which it is screened by a system of quality control that determines whether or not it is fit to move on to the next compartment of the __
- oligosaccharide chain
- gradual modification
- terminal glucose residues
- glycoprotein
- biosynthetic pathway
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i. to begin this __process, each __, which at this stage contains a single remaining glucose, binds to an __
1. removal of the remaining glucose by __ leads to release of the glycoprotein from the __
- screening
- glycoprotein
- ER chaperone
- glucosidase II
- chaperone
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a. if a __ at this stage has not completed its folding or has misfolded, it is recognized by a __that adds a __ back to one of the __residues at the exposed end of the recently trimmed oligosaccharide
i. __recognizes incompletely folded or misfolded proteins because they display exposed __ that are absent from properly folded proteins
- glycoprotein
- conformation-sensing enzyme (UGGT)
- single glucose residue
- mannose
- UGGT
- hydrophobic residues
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1. once glucose residues added, the “__” glycoprotein is recognized by the same __, which give the protein another chance to fold properly
a. after some time with the __, the added glucose residue is removed and the __ checks it again to see if it has achieved its proper 3D structure
- tagged
- ER chaperones
- chaperone
- conformation-sensing enzyme
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i. if it is still partially unfolded or misfolded, another __ is added and the process is repeated until, eventually, the __has either folded correctly and continues on its way, or remains misfolded and is destroyed
ii. studies say the decision to destroy the defective protein begins with the __ that trims a __ from an exposed end of the __of a protein that has been in the ER for an extended period
iii. once one or more of these __ have been remove, the protein can no longer be recycled and, instead, is sentenced to degradation
- glucose residue
- glycoprotein
- activity of a slow-acting enzyme in the ER
- mannose residue
- oligosaccharide
- mannose resiudes
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i. Mechanisms that Ensure the Destruction of Misfolded Proteins
1. misfolded proteins are not destroyed in the ER, but instead are __
2. once in the cytosol, the __ are removed, and the __are destroyed in __, which are protein-degrading machines; this process is called __
a. it ensures that aberrant proteins are not transported to other parts of the cell, but it can have __
- transported into the cytosol by a process of dislocation
- oligosaccharide chains
- misfolded proteins
- proteasomes
- ER-associated degradation (ERAD)
- negative consequences
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1. under certain circumstances, misfolded proteins can be generated in the __ at a rate faster than they can be __to the cytoplasm
a. accumulation of misfolded proteins, which is potentially lethal to cells, triggers a comprehensive “__” within the cell called __
i. the ER contains __ that monitor the concentration of unfolded or misfolded proteins in the ER lumen
1. the sensors are normally kept in an __ state by molecular __, particularly __
- ER
- exported
- plan of action
- unfolded protein response (UPR)
- protein sensors
- inactive
- chaperones
- BiP
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i. if circumstances should lead to an accumulation of __, the __ molecules in the __ are called into service as __ for the misfolded proteins, rendering them incapable of inhibiting the sensors
- misfolded proteins
- BiP
- ER lumen
- chaperones
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i. activation of the __leds to a multitude of signals that are transmitted into both the nucleus and cytosol and result in :
1. the __ whose encoded proteins have the potential to alleviate stressful conditions within the ER
- sensors
- expression of hundreds of different genes
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a. these include genes that encode:
i. __ that can help misfolded proteins reach the native state
ii. proteins involved in the __
iii. proteins involved in the __ of abnormal proteins
- ER-based molecular chaperones
- transport of the proteins out of the ER
- selective destruction
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1. __of a key proiten is required for protein synthesis
a. this modification inhibits __ and decreases the flow of newly synthesized proteins into the ER
i. this gives the cell an opportunity to remove those proteins that are already present in the __
- phosphorylation
- protein synthesis
- ER lumen
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i. The __ is more than a __ mechanism; it also includes the activation of a pathway that leads to the __
1. it is presumed that the __provides a mechanism to relieve itself of the stressful conditions
a. if these corrective measures are not successful, the __ is triggered and the cell is destroyed
- UPR
- cell-survival
- death fo the cell
- UPR
- cell-death pathway
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a. From Erà Golgi
i. the __ contain specialized exit sites that are devoid of ribosomes and serve as places where the__ in the __pathway are formed
ii. soon after they bud from the ER membrane, __ fuse with one another to form larger vesicles and interconnected tubules in the region between the __ and __
- RER cisternae
- first transport vesicles
- biosynthetic
- transport vesicles
- ER and Golgi complex
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1. this region is called __, and the vesicular-tubular carriers that form these are called __
a. once formed, the __move farther away from the ER toward the __
ii. movement of __occurs along tracks composed of microtubules
- ERGIC (ER Gogli intermediate compartment)
- VTCs
- VTCs
- Golgi complex
- VTCs
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