Download Ch 4. Movement of Molecules across Cell Membrane

2011/10/12
I.
Ch 4. Movement of Molecules across
Cell Membrane
•
•
•
•
•
Diffusion
us o
Mediated-Transport Systems
Osmosis
Endocytosis and Exocytosis
Epithelial Transport
II.
Diffusion
A. Magnitude and direction of diffusion
B. Diffusion through cell membranes
1. Diffusion through the lipid bilayer
g protein
p
channels
2. Diffusion of ions through
Mediated transport
A. Difference between mediated transport and diffusion
B. Passive mediated transport (facilitated diffusion)
C. Active transport
a y active
act ve transport
t a spo t
1.. Primary
2. Secondary (gradient-driven) active transport
Question: Is it diffusion, facilitated diffusion, or active
transport?
III.
IV.
V.
Osmosis
Endocytosis and exocytosis
A. Kinds of endocytosis
B. Fate of endocytotic vesicles
C. Functions of exocytosis
Epithelial transport
Diffusion
Definition: solute moves down its concentration gradient
• simple diffusion:
small (e.g., oxygen, carbon dioxide)
lipid soluble (e.g., steroids)
• facilitated diffusion:
requires transporter (e.g., glucose)
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Active transport
Active transport: solute moves against its concentration
gradient
• primary
i
active
ti transport:
t
t
ATP directly consumed (e.g., Na+ K+ATPase)
Figure 4-1
START: Initially higher
concentration of molecules randomly
move toward lower concentration.
Over time,
solute molecules
placed in a solvent
will evenly distribute
themselves.
• secondary active transport:
energy of ion gradient (usually Na+) used to move
second solute (e
(e.g.,
g nutrient absorption in gut)
Terms
Diffusional
equilibrium
ilib i
is the result
Figure 4-2
At time B, some glucose has
crossed into side 2 as some
cross into side 1.
• Flux: amount of molecule movement/ unit time
• net flux
fl
• diffusion equilibrium
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The magnitude of the net flux depends on
Note: the partition between the two
compartments is a membrane that
allows this solute to move through it.
Figure 4-3
• magnitude of the net flux: J=PA (Co-Ci),
P=membrane ppermeabilityy coefficient
(Co-Ci)=concentration difference across membrane
A= surface area of membrane
• temperature
• mass of the molecule
• medium
di
through
h
h which
hi h the
h molecules
l l are moving
i
eg. Faster in air than in water
Net flux accounts for solute
movements in both directions.
Figure 4.04
Diffusion rate vs distance
• Diffusion time α (distance)2
• human: diffusion too slow, use circulation system
with a pressure source (heart)
• 20 μm diameter cell: reach equilibrium with
extracelluar oxygen in 15 ms
basketball size cell: 265 days
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Ion channels
Diffusion through the lipid bilayer
• polar molecules diffuse into cells very slowly ,
because of the hydrophobic interior of the lipid
bilayer
• Oxygen, carbon dioxide, fatty acids, and steroids are
non-polar molecules, diffuse rapidly through the
membranes
• diffusion of ions through protein channels
Na+, K+, Cl-, Ca 2+
Ion movement
• Ions are charged
• A seperation of electrical charge across plasma membranes
is known as membrane potential
• The direction of ion movement depend on both
concentration difference and the electrical difference
 Electrochemical gradient
• Ion diffusion needs channels, otherwise very slow
• Small size of channels prevents larger, polar, organic
g
molecules from enteringg or leaving
• selectivity
A thin shell of positive (outside) and negative (inside)
charge provides the electrical gradient that drives
ion movement across the membranes of excitable cells.
Figure 4-6
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Regulation of diffusion through ion channels
Figure 4-7
• Channel gating: channel open and close
pass through
g a channel depends
p
on how
• Number of ions p
often the channel open and how long it stays open
The opening and closing of ion channels results
from conformational changes in integral proteins.
Discovering the factors that cause these
changes is key to understanding excitable cells.
An example of ion channel
3 types of ion channels according to
factors that induce conformational
changes of ion channels
• Ligand-gated channels
• Voltage gated channels
• Mechanically gated channels
The regulated opening
and closing of these
channels is the basis of
how neurons function.
Figure 4-5
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Figure 7.38
Ach gated ion channel
Hair cell
Neurotoxins act on postsynaptic receptors
作用在突觸後受氣之神經毒素
Cone Snail
Bungarus Multicinctus
雨傘節
Betel Nuts
檳榔
Hundreds of peptide
--conotoxins, block
Neuromuscular junction Addictive nervous
ion channels
--Ach receptor
system stimulant–
nicotinic Ach receptor
Puffer
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Black Widow Spider
Mediated transport systems
• Diffusion through channels, not enough
• Some molecules are too large for ion channel & too
polar to diffuse through membrane (eg. a.a., glucose)
 need transporters (or carriers)
Neuromuscular junction: increase and then
eliminates ACh(neurotransmitter) release
Process of transporting molecules through
transporters
Carrier-mediated transport: Facilitated Diffusion
e.g. glucose
• Solute bind to a specific site on a transporter
• Change shape
• Expose this binding site to the opposite side of the
membrane
• Dissociation of the solute from the transporter
The solute acts as a
ligand
Figure 4-8
protein shape change
releases the
solute on the other side
of the membrane.
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Transporters
• Protein
• Encoded by different genes & expressed in different
cells
• Vary in binding site affinity
• Vary in maximal rates of transport
• Modulation, e.g. hormone insulin
insulin
# of glucose transporters in muscle &
adipocyte
insulin
# of glucose transporters
can’t
efficiently transport glucose
glucose in
extracellular
Diabetes
3 factors determine the magnitude of solute flux
in transporter systems
• Degree of binding site saturation
• Number of transporters
• Rate of conformation change
Similarity and difference between ion channels
and transporters
• Similarity: 1. involve membrane protein
2. chemical specificity
• Difference: ion channels move thousands times more
ions/ unit time than do transporters (transporter need
to change shape for each molecule)
Figure 4-9
In simple diffusion,
flux rate is limited
only by the
concentration
gradient.
In carrier-mediated transport,
the number of available
carriers places an upper limit
on the flux rate.
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2 types of mediated transporter
• Facilitated diffusion: downhill, high concentration to
low,, no energy
gy needed
• Active transport: uphill, use energy, low to high
Figure 4-10
membrane
2011/10/12
Do nhill
Downhill
Concentration gradient
Uphill
Concentration gradient
Two types of active transporters
• uphill,
uphill referred to as pumps
• Requires substances to bind to transporters
• Saturation
• Specificity
• Need energy
• Primary active transporters
use ATP as energy
transporter is an ATPase
e.g. Na-K ATPase pump, Ca 2+ -ATPase,
H+-ATPase, H+/K+ATPase
• Secondary active transporters
use
se electrochemical gradient
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Primary active transporter, e.g. Na+-K+ ATPase
Need ATP
phosphorylation
High Na affinity
conformation change
Important role of Na-K ATPase transporters (pumps):
Move 3 Na out & 2 K in net 1 positive out
Maintain negative membrane potential, low [Na]i, high[K]i
Na affinity
dephosphorylation
High K affinity
low K affinity
Figure 4-11
Figure 4-12
Other major primary active-transporters
Two types of active transporters
• Ca 2+ -ATPase, keep low[Ca2+ ]i
Pumpp direction:
plasma membrane: Cytosol extracellular
organelle membrane: cytosol organelle
• Primary active transporters
use ATP as energy
transporter is an ATPase
e.g. Na-K ATPase pump, Ca 2+ -ATPase,
H+-ATPase, H+/K+ATPase
• H+-ATPase, move H+ out of cell to maintain cellular
pH
• Secondary active transporters
use
se electrochemical gradient
• H+/K+-ATPase, one H+ out of and one K+ into the
cell in the plasma membrane of acid secreting cells in
the stomach & kidney
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Secondary active transport
Secondary active transport
• Electrochemical gradient as energy source
• Ion
I move down
d
the
th electrochemical
l t h i l gradient
di t andd cotransport another molecule, e.g. glucose or amino acid
• 2 binding sites, ion( typically Na) and co-transported
molecule
Na binding solute
binding site affinity
Na: downhill
Solute: uphill
High affinity
Conformational change
Low affinity
Figure 4-13
The most important difference between
primary and secondary active transport
• Energy source
primary: ATP
secondary: use stored energy of an electrochemical
gradient to move both an ion and a second
solute
• Creation and maintenance of the electrochemical
gradient depends on primary active transporters
If no ATP primary active transport of Na
Na concentration gradient
 secondary
y active transport
p
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Figure 4-14
Cotransport and countertransport during
secondary active transport driven by sodium
Cotransport or Symport:
Na and solute move in
same direction
Na: downhill
Solute: uphill
Countertransport or
antiport: Na & solute
move in opposite
direction
Table 4-1
Diverse examples of carrier-mediated transport.
Reality: Co≠ Ci
Table 4-2
Figure 4-15
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Ch 4. Movement of Molecules across
Cell Membrane
•
•
•
•
•
Diffusion
us o
Mediated-Transport Systems
Osmosis
Endocytosis and Exocytosis
Epithelial Transport
How to change the water concentration?
Osmosis
• Osmosis: The net diffusion of water across
membranes
• Water is a polar molecule
molecule, diffuse very slowly across
the membrane
• Facilitaed Water diffussion through water channels:
aquaporins
• Types of water channel vary between cells
permeability difference
• Water channels permeability can be altered in
response to various signals
Addition of solute molecules to pure water
lowers water concentration in the solution
• Which one has higher water concentration?
5 liter of gglucose solution or
5 liter of pure water
Solvent + Solute = Solution
• Adding solute to a solution will dilute water
concentration
Figure 4-16
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water concentration is decreased by the
addition of solute
• It depends on the number of solute particles in solution
• example: 1mol of glucose, 1mol of amino acid, 1mol of urea
or any other molecule that exists as a single particle in
solution
2mol solute
• example: 1 mol of NaCl Na+ + Cl+
•
1 mol of MgCl2 Mg2 + 2Cl3 mol solute
Figure 4-17
Begin:
The partition between
the compartments
is permeable to water
and to the solute.
After equilibrium has occurred:
solute and water concentrations
on both sides of the partition are
equilized.
Osmolarity
• Definition: The total solute concentration of a solution is
known as its osmolarity
• 1 osmol is equal to 1 mol of solute particle
• 1 Osm = 1 osmol per liter
• example: 1M glucose  1 Osm
1M NaCl 2 Osm
• refer to the concentration of the solute particles, also
determine the water concentration, higher the osmolarity,
lower the water concentration
Figure 4-18
Begin:
The partition between
the compartments
is permeable to water only.
After equilibrium has occurred:
Water and solute concentrations
are equalized.
equalized Volume in
compartment 1 is reduced by 1/3
Conatant solute amount
2 Osm x 1L = 3 Osm x ?L
? = 0.67
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Osmotic pressure
• when a solution containing solute is separated from
pure water by a semipermeable membrane (only
permeable to water)
water), the pressure that must be applied to
solution to prevent the net flow of water into it is termed
the osmotic pressure
• the lower the water concentration, the higher the
osmotic pressure
Figure
4-19
Extracellular osmolarity and cell volume
A. Solutes are not permeable
• hypertonic solution
extracellular solution osmolarity > 300 mOsm
• isotonic solution
extracellular = 300mOsm
• hypotonic solution
extracellular < 300 mOsm
Table 4.03
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Ch 4. Movement of Molecules across
Cell Membrane
•
•
•
•
•
Diffusion
us o
Mediated-Transport Systems
Osmosis
Endocytosis and Exocytosis
Epithelial Transport
Figure 4-20
Endocytosis and Exocytosis
• endocytosis: plasma membrane fold into the cell,
forming small pockets that pinch off to produce
intracellular, membrane-bound vesicles that enclosed a
small volume of extracellular fluid
• exocytosis: membrane bound vesicles in the cytoplasm
fuse with the plasma membrane and release their
contents
co
e s too thee outside
ou s de of
o thee cell
ce
Three types of endocytosis
• fluid endocytosis (pinocytosis, cell drinking)
non-specific, water, ion, nutrients, small molecules
g y
(cell
(
eating),
g), eg.
g Immune system,
y
,
• pphagocytosis
bacteria, large molecules, cell debris
internalized phagosomes migrate to and fuse with lysosomes
 destroyed
• receptor mediated endocytosis
specific, molecules bind to membrane bound receptors,
leads to a concentrated specific ligand in the endocytotic
vesicles
e.g. cholesterol bind lipoprotein then bind lipoprotein
_receptorendocytosis cholesterol delivered into the cell_
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Figure 4-21
3 types of endocytosis
Alternative functions
of endocytosis:
1 Transcellular
1.
transport
2. Endosomal
processing
3. Recycling the
membrane
4. Destroying
engulfed materials
Exocytosis
• 2 functions: 1. replace portions of plasma membrane
2. a pathway for membrane impermeable
molecule to be secreted into extracellular fluid
• exocytosis is triggered by stimuli increase cytosolic Ca
concentration  exocytosis
Ch 4. Movement of Molecules across
Cell Membrane
•
•
•
•
•
Diffusion
us o
Mediated-Transport Systems
Osmosis
Endocytosis and Exocytosis
Epithelial Transport
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Epithelial cells
• luminal membrane: one surface of an epithelial cell
faces a hollow or fluid filled chamber and the plasma
membrane on this side is referred to
• basaolateral membrane: the opposite side of luminal
membrane
Transcellular transport
Luminal membrane
2 Pathways for Epithelial Transport
• diffusion(paracellular pathway)
--between
between adjacent cells
--require tight junction
--small area available for diffusion
• transcellular pathway
--move into the cell, through cytosol, exit across the
whole cell
--luminal and basolateral membranes contain different
transporters & ion channels
Transepithelial transport of most organic solute
basolateral membrane
(transporter)
diffusion
Figure 4-22
Primary active
transport
Na downhill
Figure 4-23
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Figure 4-24
Net water movements across an epithelium are
dependent on net solute movement
I.
II.
e.g. Na is the solute
Na into cellLow
osmolarity in the lumen
 water flow from
lumen to cell
Diffusion
A. Magnitude and direction of diffusion
B. Diffusion through cell membranes
1. Diffusion through the lipid bilayer
g protein
p
channels
2. Diffusion of ions through
Mediated transport
A. Difference between mediated transport and diffusion
B. Passive mediated transport (facilitated diffusion)
C. Active transport
a y active
act ve transport
t a spo t
1.. Primary
2. Secondary (gradient-driven) active transport
Question: Is it diffusion, facilitated diffusion, or active
transport?
III. Osmosis
IV. Endocytosis and exocytosis
A. Kinds of endocytosis
B. Fate of endocytotic vesicles
C. Functions of exocytosis
V.
Epithelial transport
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