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PBPN_Topic1_April2019 1
Specific Learning Objectives
• Describe the structure, function & characteristics of the
biological membrane.
• Compare various modes of transport across the biological
membrane:
• Passive movement – simple & facilitated diffusion, osmosis,
filtration
• Active movement – primary & secondary active transport,
endocytosis, exocytosis
• Compare the transport mechanism mediated by channel &
carrier proteins.
• Describe the trans-epithelial transport of nutrients across the
enterocyte.
PBPN_Topic1_April2019 2
PBPN_Topic1_April2019 3
The cell membrane
PBPN_Topic1_April2019 4
What are phospholipids?
Phospholipids are compound lipids with one
or more phosphate residues.
Phospholipids have:
Polar head - phosphate portion (_________
hydrophilic
interacts with water)
hydrophobic
Non-polar tail - lipid portion (__________
avoids water)
H2O
Fatty Acids:
The membrane may contain both saturated (SFA) and
unsaturated fatty acids (UFA).
The ratio of SFAs and UFAs affect the fluidity of the
membrane.
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PBPN_Topic1_April2019
The SFAs and UFAs
SFAs – linear arrangement lead
to close packing of hydrocarbon
chains.
UFAs - The kinks in the structure
due to double bonds lead to
SFAs
loose packing of hydrocarbon
UFAs chains.
Membranes of internal organs contain higher % of saturated fat than
do the membranes of skin tissues.
Higher % of saturated fat keeps the membranes more solid at
internal body temperatures.
PBPN_Topic1_April2019 9
Membrane proteins
Although the lipid bilayer forms its basic structure,
proteins determine most of the membrane's specific
functions.
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PBPN_Topic1_April2019
Components of the cell membrane
EXTRACELLULAR FLUID CHO PORTION OF
GLYCOPROTEIN
INTEGRAL PHOSPHOLIPIDS
PROTEINS
GLYCOLIPIDS CHOLESTEROL
NON POLAR
REGION
POLAR REGION
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PBPN_Topic1_April2019
Surface carbohydrates
Antenna-like, protruding from the cell membrane are:
Glycoproteins - proteins with surface carbohydrates
Glycolipids - lipids with attached carbohydrates
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Cholesterol
Cholesterol enhances the mechanical stability of the
membrane and regulates its fluidity.
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PBPN_Topic1_April2019
Selective permeability Of cell
membranes
Hydrophobic molecules like hydrocarbons and oxygen,
can dissolve in the membrane and cross it with ease.
If two substrates are equally soluble, the smaller of the
two will cross the membrane faster.
The hydrophobic core of the membrane impedes the
transport of ions and polar molecules (which are
hydrophilic). LIPID BILAYERS ARE IMPERMEABLE TO
IONS.
PBPN_Topic1_April2019 15
Modes of transport across the cell
membrane
PASSIVE MOVEMENT ACTIVE MOVEMENT
• Simple diffusion • Active transport
• Facilitated • Vesicular transport
diffusion • Endocytosis
(Phagocytosis,
• Osmosis Pinocytosis,
• Filtration Receptor-mediated
endocytosis)
• Exocytosis
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Passive movement High Concentration
Definition: when substrates move
down a concentration gradient
(i.e. from an area of higher
substrate concentration to an
area of lower substrate
Passive
concentration) without the use of movement
cellular energy (ATP). Low
Concentration ATP
No energy utilized
Concentration gradient : difference
in concentration
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PBPN_Topic1_April2019
Passive movement example
PBPN_Topic1_April2019 19
PM - Simple diffusion
A process in which substrates simply Erythrocyte
pass through the phospholipid bilayer
of the cell membrane, CO2
PBPN_Topic1_April2019 20
PM - Simple diffusion
Occurs mainly for small non-polar molecules such as
oxygen, carbon dioxide and ethanol(alcohol).
PBPN_Topic1_April2019 21
What are the conditions for simple diffusion
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PM - Osmosis
Osmosis is diffusion of WATER through a semi-permeable
membrane from areas of higher WATER concentration to
areas of lower WATER concentration.
PBPN_Topic1_April2019 23
Semi-permeable
PM - Osmosis membrane
Solute Solute
concentration concentration
Water Water
concentration concentration
WATER
Dilute Concentrated 24
PBPN_Topic1_April2019
PM - Osmosis
Water flows in response to differences in WATER
concentration (molarity) across a membrane.
The size of the solute particles does not influence
osmosis.
Equilibrium is reached once sufficient water has moved
to equalize the solute concentration on both sides of the
membrane.
PBPN_Topic1_April2019 25
Terminology
Osmolarity = number or concentration of osmotically active
particles in solution. Measured in osmoles/litre solution.
Osmolality = number or concentration of osmotically active particles/kg water.
Measured in osmoles/kg.
Isosmotic, hyposmotic, hyperosmotic: these terms refer to the osmolar
concentration of the ECF
PBPN_Topic1_April2019 26
The effect of osmosis on RBCs
100 mOs 200 mOs ~300 mOs 400 mOs 500 mOs
blood serum
____TONIC ___TONIC _____TONIC
RBCs are swollen, No change in the Water has flown out
many have ruptured biconcave structure of of the RBCs , causing
(burst) leaving what the RBCs. them to collapse
are called RBC ghosts. (shrink) and assume a
spiky appearance.
PBPN_Topic1_April2019 27
How is water transported across the cell
membrane?
Water molecules are small enough and have great
kinetic energy to move rapidly across membranes in a
continuous stream.
PBPN_Topic1_April2019 28
PM - Filtration
A process by which water and solutes are forced through
a membrane by gravity, fluid or hydrostatic pressure.
High Low
Pressure Pressure
PBPN_Topic1_April2019 29
Filtration examples
tubule
glomerulus
PBPN_Topic1_April2019 30
How do ions and polar molecules cross the
cell membrane?
Lipid bilayers are impermeable to ions.
Movement of ions and polar molecules require the help
of membrane proteins (protein transporters).
Protein transporters act like special passages, providing
a way for substrates that are not soluble in lipids to
pass through.
Two categories of transporters : carrier proteins and
channel proteins
PBPN_Topic1_April2019 31
Movement of ions and polar molecules
Protein Transporters
Channel proteins Carrier proteins
• High stereo-specificity
• Less stereo-specificity
• Saturable
• Usually not saturable
• Transport rate well below limits of
• Transport rate can approach limits free/unhindered diffusion
of free/unhindered diffusion • If move substrates down
• Move substrates down concentration gradient = facilitated
concentration gradient = facilitated diffusion
diffusion • If move substrates against
concentration gradient = active
transport
PBPN_Topic1_April2019 32
Stereo-specificity
High stereo-specificity means the receptor contains a
region that is the ________ size and shape to match the
structure of a specific substrate.
Molecule
(glucose)
Carrier protein
(for glucose) Ion
(sodium)
Channel protein (for sodium)
PBPN_Topic1_April2019 33
Channel Proteins - mechanism of
movement
Channel proteins are integral proteins with pores that
allow passage of water and hydrophilic solutes through
the cell membrane.
Some are open while others are ‘gated’ - opened or
closed in response to different stimuli (chemical,
electrical potential, physical – stretch, pressure) via
conformational changes.
PBPN_Topic1_April2019 34
Movement of ions via ion channels
Ions cannot be readily transported across the membranes
due to their charges.
Ion channels are hydrophilic pores which selected ions can
diffuse through: K+ channels, Na+ channels, Ca2+ channels, Cl-
channels
PBPN_Topic1_April2019 35
Movement of ions via ion channels
Ions
PBPN_Topic1_April2019 37
Carrier Proteins - mechanism of movement
Proteins that act as carriers are integral proteins.
Spanning the membrane, they move substrates across
relying on conformational changes.
PBPN_Topic1_April2019 38
Carrier Proteins - mechanism of movement
Symport – 2 substrates are transported in the same direction
through the membrane
Substrate 1
Substrate 2
Substrate 1
Substrate 2
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PBPN_Topic1_April2019
Different mechanisms of carrier protein-mediated
transport
Substrate
Carrier
protein
Cell
membrane
COTRANSPORT
PBPN_Topic1_April2019 40
Facilitated Diffusion
A process of diffusion that is facilitated (helped) by
membrane proteins (carrier proteins or channel
proteins).
Carrier proteins ___________ bind with substrates,
allowing them to pass through the cell membranes
•substrates move down a concentration gradient
•cellular energy not required (no ATP)
= ________ movement
PBPN_Topic1_April2019 41
Facilitated diffusion example:
1.The Glucose Transporter (GluT) - A Uniport
Carrier
GluTs have glucose binding sites.
The movement of glucose into erythrocyte is facilitated by GluT1.
GluT1 allows glucose to enter the erythrocyte about 50,000 times
faster.
The low intracellular concentration of glucose makes facilitated
diffusion possible.
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PBPN_Topic1_April2019
Facilitated diffusion example:
2.The Erythrocyte Chloride-Bicarbonate Exchanger -
An Antiport Carrier
This carrier protein facilitates the reciprocal transport of chloride
and bicarbonate ions across the erythrocyte membrane.
It increases the permeability of the erythrocyte membrane to
bicarbonate (HCO3-) more than a million fold.
The ratio of exchange is 1:1
Also called the erythrocyte anion exchange protein
PBPN_Topic1_April2019 43
The Erythrocyte Chloride-Bicarbonate
Exchanger
Erythrocyte chloride-
bicarbonate exchanger
4. HCO3-
3. Carbonic
anhydrase
transported out
HCO3-
CO2
+ H 2O
+ H+ Cl- 5. Cl- transported
in
2. Diffuses in, simple
diffusion
Facilitated diffusion
CO2
Erythrocyte
Electro-neutrality maintained
1. Respiring tissues
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PBPN_Topic1_April2019
The Erythrocyte Chloride-Bicarbonate
Exchanger
Erythrocyte Erythrocyte
3 Carbonic
anhydrase 8 Carbonic
anhydrase
CO2 + H O HCO3- CO2
2 HCO 3
-
+ H+
+ H+ 4 + H2O
9
Cl-
2 CO2
6 7
5 Cl-
CO2
HCO3-
1 Respiring tissues Lungs
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PBPN_Topic1_April2019
Transport of polar and non-polar ions and
molecules
EXTRACELLULAR FLUID
Channel Carrier
Small lipid
insoluble protein protein
molecules
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PBPN_Topic1_April2019 CYTOSOL
PBPN_Topic1_April2019 47
Active movement
High Concentration
Definition: when substrates
move against a concentration
gradient (i.e. from an area of
lower substrate concentration
to an area of higher substrate
concentration) with the help Active
of a ___________ and use of movement
Low
cellular energy (ATP). Concentration ATP ATP
Energy utilized
An Uphill task
PBPN_Topic1_April2019 48
Active movement - types
1. ACTIVE TRANSPORT - Primary
- Secondary
Vesicular transport:
2. ENDOCYTOSIS
a. pinocytosis
b. phagocytosis
c. receptor-mediated endocytosis (RME)
3. EXOCYTOSIS
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PBPN_Topic1_April2019
Mechanism of active transport
A molecule of substrate outside the cell binds with a carrier
protein, forming a molecule-carrier protein complex.
The complex moves through the cell membrane and then
the molecule is released inside the cell.
The carrier protein returns to its original conformation and
repeats the process with another molecule of substrate.
_____ supplies the energy to move substrates across the
membrane against a concentration gradient.
PBPN_Topic1_April2019 50
Primary active transport example:
1.The Na+/K+ ATPase - An Antiport Carrier
PBPN_Topic1_April2019 51
Functioning of Na+/K+ ATPase
out
PHOSPHORYLATION of the
carrier protein EXTRA-CELLULAR
Na +
ADP Na +
ATP Na + Na + Na +
Na+ P
Na+ Na +
Na+
K+ in
K+
INTRA- P
CELLULAR
P
K+ K+
Affinity of the carrier
P protein is altered through
K+
K+
phosphorylation.
DEPHOSPHORYLATION of
the carrier protein
PBPN_Topic1_April2019 52
Functioning of Na+/K+ ATPase
3 Na+ from the ICF bind to the Na+ binding site of the carrier
protein.
Then 2 K+ from the ECF bind to the K+ binding site of the carrier
protein
Dephosphorylation of the carrier protein takes place.
The carrier protein returns to its original conformation and K+ is
released into the cell.
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PBPN_Topic1_April2019
Na+/K+ ATPase
ECF In virtually every animal cell,
Na+ the concentration of Na+ is
Na+ lower in the ICF and the
Na+ concentration of K+ lower in
the ECF.
This antiport system pumps
Na+ and K+ ________ their
ATP ADP + Pi
concentration gradients.
ATP provides energy for the
transport of these ions.
K+ K+
CYTOSOL
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PBPN_Topic1_April2019
Primary active transport example:
2.The H+/K+ ATPase - An Antiport Carrier
The parietal cells of the stomach use this pump to secrete gastric
juice. Huge amounts of energy are utilized for this process.
PBPN_Topic1_April2019 55
Functioning of H+/K+ ATPase
1
CO2 CO2 + H20
Carbonic
2
anhydrase
HCO3- + H+
6 3
Cl- ATP 4
Cl -
H+
5 K+
7
Cl-
PBPN_Topic1_April2019 57
INTESTINAL
Secondary Active Transport
Na+ Na + Na+ Na+
LUMEN
Na+
CELL
ATP ADP + Pi
3 GluT 1 Na+/K+ ATPase
Na+
BLOOD
Low glucose
concentration High Na+ Na + K+
PBPN_Topic1_April2019
concentration Na+ K+ 58
Functioning of the Na+/glucose transporter
PBPN_Topic1_April2019 59
Functioning of the Na+/glucose transporter
(cont)
3. Glucose concentration in the epithelial cell is high. It moves
down the concentration gradient into the blood via GluT
(_________ _________).
PBPN_Topic1_April2019 60
INTESTINAL
Secondary Active Transport
Na+ Na + Na+ Na+
LUMEN
Na+
CELL
ATP ADP + Pi
Na+/K+ ATPase
PBPN_Topic1_April2019 63
Pinocytosis – mechanism of action
Tiny droplets of fluids adhere to the
Outside the cell plasma membrane
The vesicle pinches off
from the membrane,
moves inside the cell
All cells can perform pinocytosis - e.g. kidney cells
use pinocytosis to regulate their fluid environment.
PBPN_Topic1_April2019 64
Phagocytosis – mechanism of action
A macrophage engulfing a RBC Lysosome fuses
with phagosome
RBCs The membrane folds to
engulf the RBC which is
then contained in a RBC digested
phagosome
Outside the cell
Z K Z Z
Z K
The receptors are
recycled back to the
Upon binding the plasma
membrane folds to form a membrane
Y
Lysosome fuses
Receptors coated pit with the
Y endosome and
Y Y YY digests the
Y molecules
Y
The coated pit pinches off to Y
become a coated vesicle
The vesicle loses its coat and fuses to
a bigger vesicle called an endosome
PBPN_Topic1_April2019 66
Receptor-mediated endocytosis
Receptor-mediated endocytosis is a _________ process. Substances
taken up by this process:
• hormone insulin
• LDL (Low Density Lipoproteins)
• transferrin (iron)
PBPN_Topic1_April2019 67
Receptor-mediated endocytosis
LDL particles (containing cholesterol) bind ECF
with LDL receptors on the cell membrane Plasma membrane
Z K Z Z
Z K The LDL receptors are
recycled back to the
Upon binding the plasma membrane
membrane folds to form a
Y
Y Y YY endosome and
Y digests the LDL
particles,
releasing
cholesterol
The coated pit pinches off to
Y Y
become a coated vesicle
The vesicle loses its coat and fuses to
a bigger vesicle called an endosome
PBPN_Topic1_April2019 68
Exocytosis – the reverse of endocytosis
PBPN_Topic1_April2019 69
Exocytosis – mechanism of action
Examples: 1. Human plasma cells manufacture antibody
molecules and then secrete them into the blood using
exocytosis. Cytoplasm
2. Pancreatic enzymes are released from the cells by
exocytosis.
The vesicle moves to, and fuses
with, the plasma membrane
ECF
Substances to be released are
The content of the first enclosed in a vesicle
vesicle is released
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PBPN_Topic1_April2019
PBPN_Topic1_April2019 71
Nutrient absorption
The stomach lining is a poor absorptive
surface as it lacks villi.
Only a few highly lipid-soluble substances, (alcohol and
some drugs like aspirin) can be absorbed in small
quantities.
PBPN_Topic1_April2019 72
Absorption and transport of macronutrients
(overview - 1):
Carbohydrates
Proteins
Na+ dependent indirect
Amino acids
active transport
33% (overlapping Na+ dependent
specificity) Na+ independent active indirect active
transport transport
Na+ dependent indirect active Na+ independent
Di-/tripeptides 67%
transport, some carriers transport
associated with H+
PBPN_Topic1_April2019
EPITHELIAL CELL BLOOD 73
INTESTINAL LUMEN
Absorption and transport of macronutrients
(overview - 2):
Lipids
Transported bound to
MCFA albumin, to the portal
Simple diffusion vein
2-monoglycerides
glycerol
Micelles
LCFA
Facilitated diffusion
cholesterol
Absorption of nutrients
occurs by active and passive Exocytosis to lacteals
movement. Only after (part of the lymphatic
absorption into the intestinal system)
mucosa it is considered to be Packaged as the
in the body. lipoprotein, chylomicron
74
INTESTINAL LUMEN EPITHELIAL CELL BLOOD
Absorption of micronutrients (overview):
Fat-soluble Vitamins
Water-soluble Vitamins
Minerals
Ca2+, Mg2+, Cu2+, Fe2+
Active transport
EPITHELIAL CELL 75
INTESTINAL LUMEN
Additional learning resources - Videos:
1. Active, Passive & Bulk Cell Transport
https://www.youtube.com/watch?v=BGeSDI03aaw
In this short video the term ‘bulk transport’ is used for vesicular transport
This video gives a lot of details on GluTs and SGLTs, which we will cover in the
upcoming topics
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PBPN_Topic1_April2019