Last edited: 2/17/2023

ENDOPLASMIC RETICULUM STRUCTURE & FUNCTION

Endoplasmic Reticulum Structure & Function Medical Editors: Aldrich Christiandy

OUTLINE
I) ENDOPLASMIC RETICULUM OVERVIEW III) SMOOTH ENDOPLASMIC RETICULUM IV) APPENDIX
II) ROUGH ENDOPLASMIC RETICULUM FUNCTIONS V) REVIEW QUESTIONS
FUNCTIONS (A) LIPID SYNTHESIS VI) REFERENCES
(A) ROUGH ENDOPLASMIC RETICULUM FUNCTION (B) BIOTRANSFORMATION
(B) TYPES OF CELLS THAT ARE RICH IN ROUGH (C) GLUCOSE RELEASE
ENDOPLASMIC RETICULUM (D) CALCIUM STORAGE AND RELEASE

I) ENDOPLASMIC RETICULUM OVERVIEW

Two types of endoplasmic reticulum Big differences between the two

Rough endoplasmic reticulum (ER) There are red dots outside of the rough ER
Smooth endoplasmic reticulum (ER) o That’s why we call it rough
[Link] o It has many ribosomes on its surface
Overview of endoplasmic reticulum
Smooth ER has no ribosomes on its surface
A tubular structure that’s continuous with the outer
membrane of the nuclear envelope Quick recap
They’re both having their membranes made up of The endoplasmic reticulum is a membranous tubular
phospholipid bilayers structure made up of the nuclear envelope
o Rough ER has ribosomes on the surfaces
o Smooth ER has no ribosomes on the surfaces

II) ROUGH ENDOPLASMIC RETICULUM FUNCTIONS

Endoplasmic Reticulum Structure & Function CELL BIOLOGY: Note #13. 1 of 7

[Link]
 (A) ROUGH ENDOPLASMIC RETICULUM FUNCTION
Let’s start with the ones with ribosomes!
What’s his job?
o The big thing is all the time when we’re in school;
we get stuck with having to memorize these lines
 [Robotic voice] “Oh, it’s involved in approaching
synthesis and modification and sending.”
o No, no, don’t memorize! Understand!

(1) Transcription → produces mRNA o We’re going to bud it off the rough ER into a little
We have a nucleus, and inside of it, there’s DNA vesicle
o DNA can make mRNA via transcription o Inside the little vesicle, there’s a protein linked to
sugar residue (glycoprotein)
mRNA is carrying the code
o It goes ahead and leaves the nucleus via the The vesicle needs to know where it’s going
nuclear pores o There are proteins stuck on the edges of the
o It goes and binds onto the ribosomes on the rough vesicles
ER o It tags the vesicles and says, “Hey, you have to go to
the Golgi apparatus.”
(2) mRNA → protein synthesis by ribosomes  The protein is called COP II protein
And then the ribosomes, in combination with tRNA and COP II protein is basically a tag that says we need to
rRNA, will help to be able to translate mRNA and go from rough ER to Golgi apparatus
synthesize proteins Remember Golgi apparatus has two ends
Quick recap o A cis end, which Is coming from rough ER
o mRNA will be translated by ribosomes and make o A trans end which is leaving and goes to the cell
proteins membrane
(3) Proteins pushed into the lumen of rough ER → On the cis end, the vesicle will fuse with the Golgi
protein modification apparatus
o “Here you go, Golgi, here’s this protein that I
Once the protein pushed into the lumen of the ER
synthesized and modified a little bit by doing N-
o It has to go through ER, and along the way, it
undergoes modification
[Link] linked glycosylation. You do any more
modifications. Do what you need to do, but then
 So, the protein is not fit to be excreted yet
after that, I want you to package him, and I want you
 We got to modify and tag it
to send him to 3 locations that you feel appropriate.”
There’s a protein and enzyme
o The enzyme has two “hands.” (5) Protein transport to specific locations
 The enzyme will bind to a particular amino acid on After the Golgi apparatus modifies it, he then says, “The
the protein called asparagine rough ER tagged a specific type of vesicle to send to me.
 On the other hand, it has oligosaccharide, which Now from here, I can send this vesicle to 3 locations.”
is basically sugar molecules
o The enzyme will take oligosaccharide to be added (i) The cell membrane (Incorporate) → membrane protein
to the asparagine
Proteins that will be incorporated into the cell membrane
 This process is called N-linked glycosylation
o Channel protein
 This is the primary way that rough ER modifies
o Carrier protein
specific types of proteins
o Peripheral protein that acts as an enzyme or links
o We’re taking protein and adding sugar residue onto it;
different things together
we’re making glycoprotein
 When we make glycoprotein, there are only a (ii) The cell membrane (release) → secretory protein
couple of destinations that are primed for
glycoproteins Go to the cell membrane and fuse with the cell membrane
o But in this case, we’re going to release the
glycoprotein
These are secretory proteins that might be released
o Hormone
o Neurotransmitter

(iii) Lysosome
The third vesicle becomes specialized
o They can be incorporated into lysosomes
The proteins inside the vesicles are lysosomal enzymes
o Very useful in breaking down other different things
inside the cells

(4) Vesicle formation & protein transport to Golgi

We have glycoprotein that we help to synthesize and
modify

2 of 7 CELL BIOLOGY: Note #13. Endoplasmic Reticulum Structure & Function

[Link]
 [Link]

QUICK RECAP
Rough ER is heavily involved in the synthesis of the proteins
o Push into the lumen → modified via N-linked glycosylation
o Makes vesicles and tags them to send them to the Golgi
Golgi does more modifications and says, “Okay, rough ER told me to do three things with these.”
o Incorporate into the cell membrane
o Secrete it
o Turn it into lysosomal proteins
(B) TYPES OF CELLS THAT ARE RICH IN ROUGH ENDOPLASMIC RETICULUM

[Link]

(1) Exocrine portion of the pancreas

Pumping out pancreatic digestive enzymes to break
down foods that we eat QUICK RECAP

(2) Plasma cells We know rough ER is involved heavily in the synthesis of

proteins
Pumps out antibodies
o Modification of proteins
o Remember, antibodies are glycoproteins o Packaging them to send them to Golgi
(3) Goblet cell  And then they’re destined for three particular
endpoints
It can be found a lot in the tracheal lining, stomach lining
Produces massive amounts of mucin to coat the lining Which cells are rich in them?
of the cells o The ones that make lots of proteins

(4) Neurons
There are specific ER that are found in the soma (cell
body) of the neuron → Nissl body
o Can be seen with the Nissl stain
o Rough ER is charged, and the particular dye will bind
with the proteins of the rough ER and gives a
particularly stained color
They need to have lots of rough ER because they need to
make tons of neurotransmitters

Endoplasmic Reticulum Structure & Function CELL BIOLOGY: Note #13. 3 of 7

 [Link]

III) SMOOTH ENDOPLASMIC RETICULUM FUNCTIONS

We’ve talked about rough ER → a site of protein synthesis, modification of proteins, packaging, and sending them to
Golgi
o From the Golgi, the proteins can become membrane, secretory, or lysosomal proteins

(A) LIPID SYNTHESIS

Smooth ER is the site of lipid synthesis
What can we do with those fatty acids?
o Remember, we can make different types of lipids
Make things like triglyceride
Enzymatic reaction Utilize them for ATP production
We take glucose and amino acids and convert them into o We could break down fatty acids via 𝛽𝛽-oxidation to
acetyl-CoA make ATP
o We know that acetyl-CoA can actually go into the Combine them with glycerol and make triglyceride
Krebs cycle and help to generate ATP Make phospholipids
o Remember, they’re part of the cell membrane
Acetyl-CoA can get taken up into the smooth ER
Synthesize ring structure called cholesterol
o Within the smooth ER, acetyl-CoA can go through
o Incorporated into the cell membrane
various different types of reactions which are carried
o Make bile acids
out by multiple enzymes
 Emulsify fat
 We can take acetyl-CoA and start linking these
o Make lipoproteins
two carbon chains together → forming fatty acid
o Make sex hormones
 The enzyme involved here is fatty acid synthase
o Make steroid hormones
We can take the fatty acid that we make from acetyl-CoA
All of these are carried out by these little enzymes that are
and combine them to make phospholipids
located within the smooth ER
o We can add a phosphate group to that
o They help take acetyl-CoA and convert it into all
o We can make residue like choline and make
intermediates and forms
phospholipid
(1) Fatty acids
Utilized for ATP via 𝜷𝜷-oxidation
Make triglyceride via combination with glycerol
(2) Phospholipids
We add phosphate group and other types of residues
(3) Cholesterol
Make cell membrane components (for fluidity)
Bile acid
Lipoprotein
Sex hormones
Steroid hormones

4 of 7 CELL BIOLOGY: Note #13. Endoplasmic Reticulum Structure & Function

[Link]
 Cells rich in smooth ER (3) Hepatocytes

If we think about cholesterol, when we know it helps to be They have lots of smooth ER in them
able to make sex hormones They can take cholesterol and modify them into
Bile acids
(1) Testes and ovaries o Really important for being able to emulsify big fat
Just like rough ER is rich in globules
o Pancreatic exocrine cells Lipoproteins
o Plasma cells o vLDL
o Goblet cells o LDL
o Neurons o HDL
Testes make testosterone QUICK RECAP
Ovaries make estrogen and progesterone
It’s really important when we think about what actual
(2) Adrenal cortex smooth ER does for lipid synthesis, and it helps to make
The outer part of the adrenal glands o Fatty acids
o They’re also super rich in smooth ER o Phospholipids
o Cholesterol
They take acetyl-CoA and make a bunch of cholesterol
o Modify cholesterol and make steroid hormones In certain cells, we can take that cholesterol, and cells that
 Zona fasciculata → cortisol are rich in smooth ER can make hormones
 Zona glomerulosa → aldosterone o Sex hormones in testes and ovaries
 Zona reticularis → gonadocorticoids like o Mineralocorticoid in the adrenal cortex
dehydroepiandrosterone (DHEA) and o Bile acids and lipoproteins in hepatocytes
epiandrosterone
(B) BIOTRANSFORMATION

[Link]

Remember, we’ve covered lipid synthesis In short

o Fatty acids It takes a drug, toxin, or alcohol to be metabolized into a
o Phospholipids particular substance that is very water soluble
o Cholesterol o This is important because water-soluble substances
 Steroid hormone are easy to be able to excreted into feces and urine
 Sex hormone
 Bile acids So, smooth ER will metabolize the drugs, alcohol, and
 Lipoproteins toxin, making them water soluble
o It will enhance the ease of excretion of these
We have a liver that’s involved in the biotransformation
o Basically, drug and toxin metabolism QUICK RECAP
o We have hepatocytes that we already know are rich
in smooth ER for lipoproteins and bile acids Hepatocytes are rich in smooth ER for
o Lipid synthesis for cholesterol because they make
Smooth ER is involved in the biotransformation
bile acids and lipoproteins
o In smooth ER, there’s a special enzyme called
 Fatty acid synthesis
CYP450 (cytochrome p450 system)
 Phospholipid synthesis
Let’s say we come in contact with a drug, toxin, or alcohol o They also play a role in biotransformation
o When these things are taken up into hepatocytes  Taking drugs, toxins, and alcohol; neutralizing and
o They all can be brought into a smooth ER metabolizing them
 They interact with the CYP450 system • Making them water soluble to be easy to be
 CYP450 system will metabolize these by adding excreted
on different types of groups to make them super
water-soluble (e.g., hydroxyl group)

(C) GLUCOSE RELEASE

Endoplasmic Reticulum Structure & Function CELL BIOLOGY: Note #13. 5 of 7

[Link]
 [Link]

Smooth ER also plays a role in glucose release In short

o Remember, hepatocytes are super rich in smooth ER Smooth ER has an enzyme called glucose 6-
The liver does gluconeogenesis phosphatase
o Basically, this is where the liver will synthesize It will cut the phosphate off the 6th carbon of glucose
glucose from non-carbohydrate sources o Liberate glucose so it can now be released out of the
 E.g., lactate, amino acids, odd-chain fatty acid cell
When glucose is brought into the cell
QUICK RECAP
o Usually, glucose gets converted into glucose 6-
phosphate via glucokinase or hexokinase process Lipid synthesis
Glucose 6-phosphate can’t leave the cell Biotransformation
o The only way glucose 6-phosphate can leave is when o A fancy thing for drug, alcohol, toxin metabolism, or
we pump it into the smooth ER neutralization to be excreted
o And then glucose 6-phosphate will react with Glucose release
glucose 6-phosphatase o Cutting off the phosphate of the 6th carbon of glucose
 It will rip off the phosphate and convert it into so it can be liberated
glucose
 So, we can pump glucose out of the cell
(D) CALCIUM STORAGE AND RELEASE

Ca2+ is a really interesting thing in specific types of cells If we stimulate this smooth ER
o Skeletal, cardiac, and smooth muscle cells o We’re going to open up channels that are kind of
They have modified smooth ER → sarcoplasmic storing Ca2+ inside of it to release it
reticulum
[Link]
Ca2+ helps to activate myofilaments
o Located very close to the cell membrane of the o It will bind onto very specific molecules that are
muscle cell (sarcolemma) present on the myofilaments and stimulate them to
We have sarcolemma and neuron initiate the contraction process
o The neuron stimulates (depolarizes) the cell
membrane
 Because neurons release acetylcholine
The depolarization will then travel to make the entire cell
membrane positive
o There’s invagination in the cell membrane called T-
tubule
o The positive charges move down the cell
membrane and activate the sarcoplasmic
reticulum
 Inside of the sarcoplasmic reticulum is rich in
Ca2+

QUICK RECAP

6 of 7 CELL BIOLOGY: Note #13. Endoplasmic Reticulum Structure & Function

 [Link]
So, we know now that smooth ER is involved in
Lipid synthesis
Biotransformation
Glucose release
Modified smooth ER in muscle cells that contains Ca2+
o When it’s stimulated or depolarized by nerve
 It will release Ca2+ into the cytoplasm to allow for these muscle cells (myofilaments) to contract
o When we’re done with contraction
 We don’t want Ca2+ sitting in the cytoplasm all the time
 Ca2+ has to go back into the sarcoplasmic reticulum to be stored for the next contraction to be pushed back out

IV) APPENDIX

b) Cardiac muscle cell

V) REVIEW QUESTIONS c) Smooth muscle cell
d) Pancreas
1) Rough endoplasmic reticulum has ribosomes on its
e) Hepatocyte
surface
f) Goblet cell
a) True
g) Plasma cells
b) False
h) Nerve cells

2) Rough endoplasmic reticulum involves which VI) REFERENCES

processes? (May choose more than 1) ● Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for the USMLE
a) Biotransformation Step 1 2018. New York, NY: McGraw-Hill Medical; 2017
b) Bile acid production ● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ: Pearson; 2020.
c) Calcium storage ● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
● Urry LA, Cain ML, Wasserman SA, Minorsky PV, Orr RB, Campbell NA.
d) Cholesterol synthesis Campbell Biology. New York, NY: Pearson; 2020
e) Depolarization of the cell ● Hahn S. (2014). Ellis Englesberg and the discovery of positive control in
f) DNA replication gene regulation. Genetics, 198(2), 455–460.
g) DNA transcription [Link]
h) Make cell membrane proteins ● Nelson, D. L., & Cox, M. M. (2017). Lehninger principles of biochemistry
(7th ed.). W.H. Freeman.
i) Neurotransmitter secretion ● Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2015).
j) Glucose release Molecular biology of the cell. New York: Garland Science.
k) Production of peripheral protein
l) Lysosomal enzyme production

3) Smooth endoplasmic reticulum can be found

primarily in which cells or organs? (May choose more
than 1)
a) Adrenal cortex

Endoplasmic Reticulum Structure & Function CELL BIOLOGY: Note #13. 7 of 7

[Link]