The Endoplasmic Reticulum and the Endomembrane System

Question 1

Rough ER

• characterized by?
• what does the rough ER form?

Answer 1

• characterized by ribosomes on the cytosolic side of the membrane
• form large flattened sacs

Question 2

What is the subdomain of the rough ER?

• what is the role of this subdomain?
• resemble?

Answer 2

• Transitional elements (TEs)
• important role in formation of transition vesicles that shuttle lipids and proteins from the ER to the Golgi complex
• resemble smooth ER

Question 3

Smooth ER

• lacks?
• what do they form?

Answer 3

• lacks ribosomes and has other roles in the cells

- form tubular structures

Question 4

Variation in amounts of rough and smooth ER:

-both types present?

Answer 4

-both types of ER are present in most cells but there is a variation in the relative amounts

Question 5

-where would you find prominent rough ER networks?

Answer 5

cells involved in synthesis of secretory proteins

Question 6

-where would you find prominent smooth ER networks?

Answer 6

-cells producing steroid hormones

Question 7

how are microsomes formed?

Answer 7

when tissue is homogenized for subcellular fractionation, the ER membranes often break into smaller fragments that spontaneously close to form sealed vesicles known as microsomes

Question 8

What are microsomes useful for?

Are they formed naturally in cells?

Answer 8

• useful for studying both types of ER

- not found naturally in cells

Question 9

Rough ER Is Involved in the Biosynthesis and Processing of Proteins:
where are proteins synthesized?

Answer 9

-ribosomes on the cytosolic side of the rough ER membrane synthesize both membrane bound and soluble proteins for the endomembrane system

Question 10

How do proteins enter the endomembrane system from the point of synthesis?

Answer 10

-newly synthesized proteins are inserted into the endomembrane system through a pore complex as they are synthesized (contranslationally)

Question 11

Rough ER is the site for (4) ?

Answer 11

1. initial steps of addition of carbohydrates to glycoproteins
2. folding of polypeptides
3. recognition and removal of misfolded proteins
4. assembly of multimeric protein complexes

Question 12

What is ER associated degradation (ERAD)?

where does is occur?

Answer 12

• proteins that are incorrectly folded, modified, or assembles are exported for degradation
• degradation occurs in cytosolic proteasomes

Question 13

Smooth ER is involved in? (4)

Answer 13

1. drug detoxification
2. carbohydrate metabolism
3. calcium storage
4. steroid biosynthesis

Question 14

Smooth ER and drug detoxification:
-what does drug detoxification often involve?
-what is it?
-what is hydroxylation catalyzed by?
-

Answer 14

• hydroxylation
• adding hydroxyl groups to hydrophobic drugs increases their solubility, making it easier to excrete from the body
• catalyzed by monooxygenases (member of the cytochrome P-450 family of proteins)

Question 15

Smooth ER and drug detoxification:

how is the hydroxylation for drug detoxification work?

Answer 15

an electron transport system in the smooth ER transfers electrons from either of the reduced coenzymes NADPH or NADH to a heme group in the cytochrome P-450, later donated to O2, activating the organic acceptor molecule for hydroxylation

• one oxygen atom forms H2O
• another is added to the substrate group as a hydroxyl group

Question 16

Smooth ER and drug detoxification:
Another cytochrome P-450 is part of a complex called?
-what is this involved in?
-disadvantage of this? 
-cigarette smoke...

In general…

Answer 16

Arly hydrocarbon hydroxylases

• inolved in metabolizing polycyclic hydrocarbons
• products can be more toxic than the original compounds
• cigarette smoke is an important inducer of aryl hydrocarbon hydroxylase

In general, increase in drugs/poisons = increase of smooth ER = greater detoxification (may lead to tolerance)

Question 17

Smooth ER and carbohydrate metabolism:

• smooth ER is involved in breakdown of?
• what does the smooth ER contain that allows it to do this?
• how does it work?

Answer 17

• smooth ER in hepatocytes (liver cells) are involved i the breakdown of stored glycogen
• contains glucose-6-phosphatase (enzyme unique to smooth ER) which hydrolyzes the phosphate from glucose-6-phosphate to form free glucose

Question 18

Smooth ER and carbohydrate metabolism:

• the liver stores glucose as?
• what happens when glucose is needed by the body?
• what must happen then?

Answer 18

• stores glucose as glycogen in granules associated with smooth ER
• when glucose is needed by the body, glycogen is broken down by phosphorylysis, producing glucose-6-phosphate
• the must be converted to free glucose in order to leave the cell and enter the bloodstream

Question 19

The smooth ER and calcium storage:

• example of smooth ER that stores calcium?
• in these cells, the ER lumen contains..?
• how are calcium ions released?

Answer 19

• sarcoplasmic reticulum found in muscle cells specializes in the storage of calcium
• ER lumen contains high concentrations of calcium-binding proteins
• calcium ions are pumped into the ER by ATP-dependent calcium ATPases and are released when needed for muscle contraction

Question 20

The smooth ER and steroid biosynthesis:

• smooth ER is the site of?
• smooth ER associated with what in some plants?

Answer 20

• site of cholesterol and steroid hormone synthesis

- associated with plastids in some plants; may be involved in phytohormone synthesis

Question 21

Smooth ER and cholesterol:

• cholesterol, cortisol, and steroid hormones share what and differ in what?
• what is the committed step in cholesterol biosynthesis?

Answer 21

• share a four ring structure, but differ in the number and arrangement of carbon side chains and hydroxyl groups
• hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) is the committed step in cholesterol biosynthesis, which is found in the smooth ER of liver cells and is targeted by cholesterol-lowering drugs called statins

Question 22

The ER Plays a Central Role in the Biosynthesis of Membranes:
In euk cells, the ER is the primary source of? with what exceptions?

Answer 22

• primary source of membrane lipids
• exceptions include: mitochondria (synthesize phosphatidylethanolamine) , peroxisomes ( synthesize cholesterol) , chloroplasts (contain enzymes for chloroplast-specific lipids)

Question 23

The ER Plays a Central Role in the Biosynthesis of Membranes: Membrane Biosynthesis

• where are the fatty acids for membrane phosphlipids synthesized?
• where are they transferred to after synthesis and how?
• what does the type of phosphlipid molecule being transferred across the membrane depend on?
• what happens to the distinct compostion of cytosolic and lumenal monolayers?
• what is problematic?
• so what happens instead?

Answer 23

1. fatty acids for membrane phospholipids are synthesized in the cytoplasm and incorporated into the ER membrane on the cytosolic side
2. they are transferred to the lumenal side of the bilayer by enzymes called phosphlipid translocators (flippases)
3. the type of phospholipid molecule transferred across the membrane depends on the particular translocator present, leading to membrane asymmetry
4. the distinct composition of cytosolic and lumenal monolayers established in the ER is transferred to other cellular membranes
5. movement of phospholipids from ER to mitochondria, chloroplasts, peroxisomes, is problematic
6. phospholipid exchage proteins convey specific phosphlipids to these organelles