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a. __ comprises a network of membranes that penetrates much of the cytoplasm and probably evolved from invaginations of the plasma membrane
i. enclosed within it is an extensive space, or __, that is separated from the surrounding cytosol by the ER membrane
1. the composition of the__ inside the ER membranes is different from that of the surrounding __
- the endoplasmic reticulum
- lumen
- luminal (or cisternal) space
- cytosolic space
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a. a highly dynamic structure undergoing __ and __
b. ER= __(no ribosomes bound) and __(ribosomes bound)
- continual turnover and reorganization
- SER
- RER
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Explain the RER
1. composed of a network of flattened sacs and continuous with the outer membrane of the nuclear envelope, which also bears ribosomes on its cytosolic surface
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SER
- 1. highly curved and tubular, forming an interconnecting system of pipelines traversing the cytoplasm
- 2. when cells are homogenized, the SER tubules fragment into smooth-surfaced vesicles, whereas the RER sheets fragment into rough-surfaced vesicles
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a. __ and __ can diffuse from one type of ER into the other, indicating that their membranes are continuous
i. the two types share many of the same __ and engage in certain __, such as the __of certain lipids and cholesterol
- Fluorescently labeled proteins and lipid
- proteins
- common activities,
- synthesis
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1. also, numerous proteins are found in only one
a. ex: high degree of curvature of the SER tubules is induced and maintained by the presence of __, which are largely absent from the __
- membrane-bending proteins, called reticulons
- flattened RER sheets
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i. in contrast, the RER contains proteins involved in the __
e. Different types of cells contain different __of the two types, depending on their activities
- movement of nascent proteins into the ER lumen
- ratios
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a. Smooth Endoplasmic Reticulum
i. developed in a lot of cell types
ii. functions: _(3)_
- 1. synthesis of steroid hormones of endocrine cells of gonad and adrenal cortex
- 2. detoxification in liver of organic comounds
- 3. sequestering calcium ions within the cytoplasm of cells
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Explain detoxification.
- a. chronic use can lead to proliferation of the SER
- b. detox carried out by a collection oxygen-transferring enzymes (oxygenases), including the cytochromes P450 family
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Detoxification and lack of substrate specificity
i. lack of substrate specificity, being able to oxidize thousands of different hydrophobic compounds and convert them into more hydrophilic, more readily excreted derivatives
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Explain calcium ion sequestering
a. regulated release leads to contraction
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a. Rough Endoplasmic Reticulum
i. contains __from one end to the other
1. __ and __ are located near the __ of the cell, which faces the blood supply
2. __located in central region of the cell
3. __ of the cell faces a __that carries the secreted proteins out of the organ
- polarity
- nucleus and extensive array of RER cisternae
- basal surface
- Golgi
- apical surface
- duct
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a. the cytoplasm at the __ of the cell is filled with __ whose contents are ready to be released into the duct upon arrival of the appropriate signal
ii. polarity of the __ reflects the movement of __proteins through the cell from ther site of synthesis to their site of __
- apical end
- secretory granules
- glandular epithelial cells
- secretory
- discharge
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i. Rough ER is the __; it is the site of __, __, and __ that journey through the membranous compartments of the cell
- starting point of the biosynthetic pathway
- synthesis of the proteins, carbohydrate chains, and phospholipids
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a. Synthesis of Proteins on Membrane-Bound versus Free Ribosomes
i. Polypeptides are synthesized at two distinct locales within the cell. What are the two?
- 1. 1/3 of the proteins encoded by a mammalian genome are synthesized on ribosomes attached to the cytosolic surface of the RER membranes
- 2. other polypeptides are synthesized on free ribosomes and are released into the cytosol
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Explain the proteins created on the ribosomes of the RER.
a. these include secreted proteins, integral membrane proteins, and soluble proteins that reside within compartments of the endomembrane system, including the ER, Golgi complex, lysosomes, endosomes, vesicles, and plant vacuoles
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Polypeptides from free ribosomes:
a. this class includes proteins destined to __, __proteins of the __surface of membranes, proteins that are transported to the __, and proteins to be incorporated into __, __, and __
i. proteins in the latter two groups are synthesized ot completion in the __and then imported __into the appropriate organelle across its boundary membranes
- remain in the cytosol
- peripheral
- cytosolic
- nucleus
- peroxisomes, chloroplasts, and mitochondria
- cytosol
- posttranslationally
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i. what determines the location where a protein is synthesized
1. the site of synthesis of a protein is determined by the __ in the__ of the polypeptide, which is the first part to emerge from the ribosome during protein synthesis.
- sequence of amino acids
- N-terminal portion
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1. Suggestions:
a. secretory proteins contain a __ at their __ that directs the emerging polypeptide and ribosome to the __
b. the polypeptide moves into the __ of the ER through a protein-lined, aqueous channel in the ER membrane
- signal sequence
- N-terminus
- ER membrane
- cisternal space
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i. the polypeptide moves through the membrane as it is being synthesized, that is, __
1. this proposal, called __, has been substantiated by a large body of experimental evidence
- cotranslationally
- signal hypothesis
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i. synthesis of the polypeptide begins after an __binds to a __, that is, one that is not attached to a __ membrane
1. all ribosomes are thought to be __: those employed in the synthesis of __, __, or __are taken from the same pool as those used for production of proteins that remain in the __
- mRNA
- free ribosome
- cytoplasmic
- identical
- secretory, lysosomal, or plant vacuolar proteins
- cytosol
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i. polypeptides synthesized on membrane-bound ribosomes contain a __—which typically includes a stretch of 6-15 hydrophobic amino acid residues—that targets the __ to the ER membrane and leads to the __fo the polypeptide within the __
1. although the __ is usually located at or near the__, it occupies an internal position in some polypeptides
- signal sequence
- nascent polypeptide
- compartmentalization
- ER lumen
- signal sequence
- N-terminus
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i. as it emerges from the ribosome, the __ is recognized by a __, which consists in mammalian cells of six distinct polypeptides and a small RNA molecule, called the __
- hydrophobic signal sequence
- signal recognition particle
- 7SL RNA
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1. the __binds to both the __ of the nascent polypeptide and the ribosome, temporarily addressing further synthesis of the polypeptide
a. the bound __serves as a __that enables the entire complex to bind specifically to the __surface of the ER membrane
- SRP
- signal sequence
- SRP
- tag
- cytosolic
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i. binding to the ER occurs through two sequential interactions: one between the __ and the other between the __, which is a __ channel embedded in the ER membrane through which the nascent polypeptide is able to move in its passage from the ribosome to the __
- SRP and the SRP receptor
- ribsome and the translocon
- protein-lined
- ER lumen
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i. Determination of the 3D structure of a prokaryotic version of the __by __
1. this revealed the presence within the __of a pore in the shape of an hourglass with a ring of six hydrophobic amino acids situated at its narrowest diameter
- translocon
- X-ray crystallography
- translocon
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a. in the inactive state, the opening in the pore ring is __
i. debate: the __seals the channel, preventing the unwanted passage of calcium and other ions between the cytosol and the ER lumen
- plugged by a short alpha helix
- plug
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i. once the __ binds to the ER membrane, the __is released from its ER receptor, the ribosome becomes attached to the __end of the __, and the signal sequence on the __is inserted into the narrow aqueous channel of the __
- SRP-ribosome-nascent chain complex
- SRP
- cytosolic
- translocon
- nascent polypeptide
- translocon
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1. it is proposed that contact of the signal sequene with the interior of the __leads to __of the plug and opening of the passageway
a. the growing poypeptide is translocated through the __and into the __
- translocon
- displacement
- hydrophobic pore ring
- ER lumen
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i. because the __ observed in the crystal structure has a diameter that is considerably smaller than that of a helical polypeptide chain, it is presumed that the __expands as the nascent chain traverses the channel
1. expansion is possible because the residues that make up the ring are situated on different helices of the __protein
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i. upon __ and passage of the completed polypeptide through the __, the __ is released from the ER membrane and the __is reinserted into the __channel
- termination of translation
- translocon
- membrane-bound ribosome
- helical plug
- translocon
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i. Several of the steps involved are regulated by __ and __, which play key regulatory roles in any different cellular processes
GTP and GTP proteins
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how can G proteins be?
1. G proteins can be either GTP bound molecules or GDP bound, both of which have different conformations and have different abilities to bind other proteins
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a. GTP-bound protein typically __, and __ turns it off
i. both__ and the __ are__ that interact with one another in their __-bound states
ii. __ bound to these two proteins occurs between steps 2 and 3 and triggers the __and its __
- turns the process on
- hydrolysis of the bound GTP
- SRP and the SRP receptor
- G proteins
- GTP
- hydrolysis of GTP
- release of the signal sequence by the SRP
- insertion into the translocon
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