Lecture 17 Endomembrane System.pptx

The endomembrane system
Chapter 12: The World of the Cell
Lecture 17
7/12/2021
Lecture 18, Endomembrane system 7-4-2020

Endoplasmic Reticulum
• Endoplasmic- within the cytoplasm
• Reticulum – network
• Consists of a continuous network of flattened
sacs, tubules, and vesicles that stretches
throughout the cytoplasm of the eukaryotic cell.
Lecture 15, Endomembrane system

Endoplasmic Reticulum
Functions:
Biosynthesis of proteins destined for incorporation
into ER, Golgi, endosomes, lysosomes and plasma
membrane.
Synthesis of proteins destined for export from cell.
Biosynthesis and Incorporation of lipids
a) cholesterol
b) Triacylglycerol
into organelles of endomembrane system

The Two Basic Kinds of Endoplasmic Reticulum
Differ in Structure and Function
 Rough endoplasmic reticulum (RER) - has
ribosomes attached
 Smooth endoplasmic reticulum (SER) - no
ribosomes
Are different morphologically:
 RER forms flattened sheets
 SER forms tubular structures

Smooth & Rough ER
Both are present in eukaryotic cells, but relative
amounts vary
 Those that secrete a lot of proteins have more
RER
 Those that produce steroid hormones have more
SER

Rough ER - Functions
 Involved in biosynthesis and processing of
proteins.
 Specifically, RER is involved in synthesis of
transmembrane and soluble proteins.
 These proteins can be incorporated into
organelles of endomembrane system,
incorporated into cell membrane, or exported
from cell

 Most proteins that enter ER are inserted into ER
lumen cotranslationally, as ribosome
synthesizes protein.
 Soluble proteins are released into ER lumen.

Rough Endoplasmic Reticulum
• Responsible for addition of carbohydrates to
proteins.
• Folding of proteins.
• Recognition and removal of misfolded proteins.
• Assembly of multimeric proteins

 Contains enzymes for posttranslational and
cotranslational modification such as disulfide
bonds.
 Quality control – ER associated degradation
proteins ERAD (cytoplasmic proteases).

• Phospholipid translocators move phospholipids
from ER to their destination by fusing of
membrane.
• In cases of no fusion, phospholipid exchange
proteins recognize specific phospholipids and
move them to destination (mitochondria,
chloroplast, peroxisome).

Smooth Endoplasmic Reticulum
• No Ribosomes.
• Found often in ovary and testes.
• Continuous with rough endoplasmic reticulum.
• tubular

Smooth ER - Functions
Involved in many activities:
 Drug detoxification
 Carbohydrate metabolism
 Calcium storage
 Steroid biosynthesis
 Membrane biosynthesis

Drug Detoxification involves hydroxylation.
Addition of OH groups to organic molecules
making them are more soluble and easier to
excrete.
If not soluble, hydrophobic toxins may stay in
membrane of cells.
Depends upon cytochrome P-450, found in
smooth ER of liver cells

Drug detoxification
By hydroxylation (addition of hydroxyl groups
to hydrophobic drugs increasing their solubility
and excretion out of the body.
RH + NADPH + H+ + O2
Cytochrome -450
ROH + NADP+ + H2O
Mixed function oxidases
- monooxygenases

Smooth ER-
• Elimination of barbiturate drugs
• Phenobarbital is a cytochrome P450 hepatic
enzyme inducer.
• Extensive formation of smooth ER.
• Also hydroxylates useful drugs such as
antibiotics

Drug detoxification
Habitual users require an increasing amounts of
the drug (tolerance).
The enzyme induced by phenobarbital can
hydroxylate and therefore solubilize a variety of
other drugs, including such useful agents as
antibiotics, anticoagulants, and steroids. As a
result, the chronic use of barbiturates decreases
the effectiveness of many other clinically useful
drugs.

• Example:
• Member of Cytochrome P-450 protein family
• Aryl hydrocarbon hydroxylase involved in metabolizing polycyclic
hydrocarbons
• Changes carcinogens to chemically active form which results in
tumors
• Cigarette smoke is an inducer of aryl hydrocarbon hydroxylase

• Carbohydrate Metabolism
• Membrane of smooth ER of hepatocytes contain glucose-6-
phosphatase (breaks down glucose-6-phosphate into glucose)
• Glycogen is stored in liver
• Allows glucose to leave cell and travel into blood system

Figure 12-3

Smooth endoplasmic reticulum-
Carbohydrate metabolism
Free glucose leaves the
hepatocyte via glucose
transporter (GLUT 2)
Glucose-6-phosphatase is
not present in brain and
muscle cells. They retain
their glucose-6-P to use it
for energy production.

Calcium storage
 Ca2+ is pumped into the sER (Sarcoplasmic
reticulum) lumen by specific ATPase pumps (ATP
dependent calcium ATPases) and released in
response to cellular signals.
 Binding of nuerotransmitter molecules to receptors
on muscles triggers release of calcium from sER
and contraction of muscles.

Steriod biosynthesis
Cholesterol, cortisol, testosterone, estrogen
All share a 4-ring structure but differ by
hydroxyl groups & carbons side chains
•Found in Adrenal cells
•Leydig cells of testes
•Live cells producing Cholesterol
•Follicular cells of ovary
•Plastids of some plants (phytohormone
synthesis).

Smooth endoplasmic reticulum- Steroid
biosynthesis
Hydroxymethylglutaryl- CoA reductase (HMG-CoA
reductase) - cholesterol biosynthesis present in large
amounts in the sER
Statin (cholesterol lowering drug) inhibit HMG-CoA
reductase

The ER plays a central role in the
biosynthesis of membranes
The ER is the primary source of membrane lipids,
including phospholipids and cholesterol.
Exception
Mitochondria
Chloroplast
Peroxisomes

Movement of phospholipids from ER to mitochondria,,
choloplast and peroxisomes
 Through Phospholipids exchange proteins
(phospholipids transfer proteins)
 Each recognizes a specific Phospholipid to transfer.

Role of ER in the biosynthesis of membranes
Lecture 15, Endomembrane system,24/11/2020
 Biosynthesis and incorporation of membrane
phospholipids is restricted to the monolayer of the ER
membrane facing the cytosol.
Cytosol
ER Lumen

Lecture 15, Endomembrane system,24/11/2020
The translocation of phospholipids through the
ER membrane is dependent on the action of
Phospholipid translocators (Flippases).
Flip-flop (flippase)

Phospholipid translocators – Flippases- are quite
specific.
Translocator for phosphatidylcholine, is found in
both monolayers of the ER membrane.
No translocator for phosphatidylethanolamine,
phosphatidylinositol, or phosphatidylserine, which
are therefore confined to the cytosolic monolayer.

phospholipid translocator proteins ("flippases")
are required to transfer selected lipid
molecules from the cytosolic half to
the luminal half so that the
membrane grows as a bilayer.
flippase in the ER membrane
preferentially recognizes and
transfers choline-containing head
groups, an asymmetric bilayer is
generated, with the luminal
monolayer (which produces the
outer half of the plasma
membrane bilayer) highly
enriched for phosphatidylcholine.
Alberts et al., 1994

The composition of cellular membranes vary
significantly from the ER membrane.
Plasma membrane of hepatocytes are rich in
cholesterol, sphingomyelin and glycolipids and
lower amounts of phosphoglyceraldehyde.

 In general, Membrane content of cholesterol
increases from the ER to the compartments of
endomembrane system.
It correlates with
 Increasing gradient of membrane thickness, ER
is 5 nm Plasma membranes is 8 nm thick

The ER is the primary source of membrane
lipids including phospholipids and cholesterol.
Contains all the enzymes required for the
biosynthesis of phospholipids,
except:

 Mitochondria synthesizing phosphotidyl
ethanolamine
 Peroxisomes synthesizing cholesterol
 Chloroplast synthesizing some specific lipids

• Protein Glycosylation
• N-linked glycosylation –oligosaccharide unit to attach to nitrogen on
asparagine
• O-linked glycosylation – oligosaccharide unit to attach to oxygen on
hydroxyl group of serine or threonine

N-linked glycosylation of proteins in the ER
1. Insertion of dolichol phosphate in the ER membrane.

Carbohydrate groups are added to the phosphate
group of dolichol phosphate:
 Two N-acetyleglucosamine (GlcNAc)
 5 Mannose units

Note that early steps of core oligosaccharide synthesis occur on
the cytosolic side of the ER membrane and later steps occur in the
ER lumen.
3. Flippase is responsible for the translocation of the core
oligosaccharide from the cytosol to the ER lumen

4. Inside the ER
lumen, further
glucose and
mannose residues
are added.

5. Transfer of core
oligosaccharide as a
single unit from dolichol
to an aspargine residue
of the recipient protein
By the action of
oligosaccharyl
transferase

6. The attached protein is
trimmed and modified
3 glucose units and one
mannose units are
removed by glucosidase
and mannosidase

• Oligosaccharide is usually added cotranslationally
• Promotes proper folding

Golgi (apparatus, body, complex)
Lecture 19, 12-4-2020 Endomembrane system and
peroxisomes

Golgi (apparatus, body, complex)
peroxisomes
The Golgi is a series of discrete membranous
compartments that "communicate" with the
endoplasmic reticulum as well as other
membranous structures including the plasma
membrane.

Golgi Apparatus
• The Golgi Complex
• (1898) Camillo Golgi
• Flattened sacs or cisternae
• Cis (CGN) or Trans face of Golgi (TGN)
• Between cis & trans is medial cisternae of Golgi
where processing occurs
peroxisomes

FIGURE 6-21
peroxisomes

Lecture 17 Endomembrane System.pptx

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