Download 4.2 How to get other molecules across membranes

Chapter 5
Membrane Transport Mechanisms
Membrane Permeability
1) lipid soluble solutes go
through faster
1)
smaller molecules go faster
1) uncharged & weakly charged
go faster

2) Channels or pores may
also exist in membrane to
allow transport
1
2
How to get other molecules across
membranes
There are two ways that the molecules typically move
through the membrane:
passive transport and active transport
•Active transport requires that the cell use energy
that it has obtained from food to move the molecules
(or larger particles) through the cell membrane.
•Passive transport does not require such an energy
expenditure, and occurs spontaneously.
1 Passive Transport

Net movement of material from hi to
lo concentration
• Diffusion
• Osmosis
• Facilitated Diffusion
concentration gradient
Passive Transport
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Simple Diffusion- simple movement
from regions of high concentration to
low concentration
Osmosis- diffusion of water across a
semi-permeable membrane
Facilitated diffusion协助扩散- protein
transporters which assist in diffusion
Passive Transport
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Unaided movement through the
phospholipid bilayer in response to
concentration gradients.
Large or charged molecules are
unable to pass through the bilayer
unassisted.
Diffusion
Movement generated by random
motion of particles. Caused by
internal thermal energy.
Movement always from region of high
free energy(high concentration) to
regions of low free energy (low
conc.)
Diffusion

If a concentration gradient exists, there
will be a net flow of material across the
membrane
Osmosis
Movement of water
across a semipermeable barrier.
Example: Salt in
water, cell
membrane is
barrier. Salt will
NOT move across
membrane, water
will.
Text pg 87
Osmosis
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Refers to movement of water
Across a semipermeable membrane
• Permeable to water
• Impermeable to dissolved materials

Water always moves from lo to high
solute
• Hypotonic  Hypertonic
cell
Osmosis in
Hypertonic
medium
Hypertonic
solutionsshrink cells
Osmosis in
Hypotonic
medium
Hypotonic solutions- swell cells
Osmosis
Hypotonic
Hypertonic
简单扩散与协助扩散的比较
Osmotic pressure =
Weight of water column
Plant Turgor
Hypertonic
Hypotonic
Central
vacuole
Water pressure inside cell lends
support to plant structure
Plasmolysis due to water
deprivation
Charged particle cloaked with water
molecules, can not get through
Na+
ClK+
H+
+
Large molecules, also cloaked with water
molecules, can not get through
Nucleotides
Sugars
Amino acids
Large molecules can not get through
Facilitated Diffusion
Sugars
Transport Protein
Channel
Shape change resulting from
solute interaction with transport
protein
Types of Protein
Transporters
A. Facilitated Diffusion
Assist in diffusion
process.
Solutes go from High
conc
to Low conc.
Examples: Glucose
transporters
Text pg 88
http://bio.winona.msus.edu/berg/ANIMTNS/FacDiff.htm
A Transport Proteins
Facilitated Diffusion
& Active Transport

move solutes
faster across
membrane

highly specific to
specific solutes

can be inhibited
by drugs
Transport Proteins are specific
glucose
Na+
Cell Controls Movement by
Number of Transport Proteins in
Membrane
High
Moderate
No transport
Gated Channels
Chemical
messenger, e.g.
insulin
glucose
Voltage Dependent K+ channel
Model of protein shape change in response to change in
voltage across a membrane
Roderick MacKinnon, M.D., Howard Hughes Medical Institute Investigator, Youxing Jiang, Ph.D.
Cystinuria

Defective transport
protein in urinary
tract unable to
absorb cystine
from urine
cysteine
cystine
Cystine
crystal
Facilitated Diffusion
The Glucose Transporters
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Transport of glucose into cells mediated by
proteins in the GLUT (GLUcose Transport)
family of transporters. There are 7 different,
but related, proteins. But, only four (GLUT1-4)
are known to be involved in glucose transport.
All GLUT proteins share a set of similar
structural features and are all about 500
amino acids in length (giving them a predicted
molecular weight of about 55,000 Daltons)
Glucose uptake shows saturation and glucose
uptake can be inhibited by drugs
A classic Membrane Transport protein
Glucose Transporter
Characteristics:
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integral protein: spans the
membrane
12 alpha helices woven into
membrane
55,000 mol. wt.
Text pg. 88
Glucose Transporter:
How it works..
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glucose binds to
outside of transporter
(exterior side with
higher glucose conc.)
glucose binding causes
a conform. change in
protein
glucose drops off inside
cell
protein reassumes 1st
configuration
Types of Protein Transporters:
Ion Channels
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work by facilitated diffusion No E!
deal with small molecules... ions
open pores are “gated”- Can
change shape.
• How?
• How much gets in?

important in cell communication
B Ion Channels

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Work fast: No conform. changes
needed
Not simple pores in membrane:
• specific to different ions (Na, K,
Ca...)
• gates control opening
• Toxins, drugs may affect channels
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saxitoxin, tetrodotoxin
cystic fibrosis
Toxins…how they work
Cystic Fibrosis
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Fatal genetic disorder
Mucus build-up results in lung and
liver failure
Patients die between 4 and 30 yrs.
Single gene defect
1 in 25 Caucasians carry 1 bad
gene copy
1 in 2500 kids has it in Canada
Testing
CF Cont…
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~Proteins for diffusion of salt
into the airways don't work.
~Less salt in the airways
means less water in the
airways.
~ Less water in the airways
means mucus layer is very
sticky (viscous).
~Sticky mucus cannot be
easily moved to clear particles
from the lungs.
~Sticky mucus traps bacteria
and causes more lung
infections.
http://www.the-aps.org/education/lot/cell/HotT.htm
2 Active Transport

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Active transport- proteins which
transport against concentration
gradient.
Requires energy input
T
Types of Protein Transporters:
Active Transport
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carrier proteins
go against the concentration
gradients Low to High
require Energy to function (ATP,
PEP, light energy, electron
transport)
Membrane Transport Active
Transport

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Move materials from lo to high
concentration
Requires cell to expend energy
Equivalent to running diffusion in
reverse
Simulation 1- how can you put the
particles back into the box?
http://lewis.eeb.uconn.edu/lewishome/applets/Diffusion/diffusion.html

Active Transport
Sodium-Potassium Pump
CA-ATP Pump
proton Pump
p- proton Pump
v -proton Pump
H- ATP Pump
Cotransport symport
aniport
Active Transport:
Sodium-Potassium Pump
ATP-direct depend
Na+
high
Na+
low
K+
low
K+
high
Balance of the two ions goes hand-in-hand
ATP required for maintenance of the pump
Electrochemical Gradient
negative
positive
K+
Na+
Na+
Na+
K+
Na+
Na+
K+
Na+
ADP
ATP
Na+ K+
Na+
Na+
Na+
Na+
K+
pump
Na+
K+
Na+
Na+
Na+
Na+
This gradient powers conduction of signals along nerves
Stored Energy for Cotransport
sucrose
H+
H+
H+
H+
H+
sucrose
H+
sucrose
sucrose
H+
H+
sucrose
ATP
sucrose
H+
proton
H+
H+
H+
H+
sucrose
sucrose
H+
ADP
H+
pump
H+
H+
H+
H+
H+
Voltage difference or membrane potential
The sodium/potassium pump
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All nerve and muscle cells have a high internal
potassium ion concentration and a low internal
sodium ion concentration. [Ki=166 mM; Ko=5 mM;
Nai=18 mM; Nao=135 mM].
Early on, it was thought that the nerve and muscle
membranes were relatively impermeable to these
ions and that the difference in ionic concentration
was set up in early development of the cells. The
membrane then became impermeable.
The later availability and use of radioactive Na and
K ions showed that this was not true and that there
was a metabolic pump that pumped Na out of the
cell and K in; the ratio being 3 Na pumped out of
the cell for every 2 K pumped into the cell.
Is a Protein Involved ?
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Experiments showed a dependency
of both Na and K ions for pump to
work
Pump was inhibited by ouabain (a
drug)
1957: an ATPase enzyme was
found to be associated with Na/K
pumping
Studies showed this ATPase
capable of pumping Na/K ions
Sodium/Potassium
ATPase Protein
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Made of 2 large and 2 small subunits
2 large units span membrane
• inside region: contains ATP binding site
• inside: binding sites for Na
• outside: binding site for K
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How does it work??
Sodium-Potassium Pump
http://www.cat.cc.md.us/courses/bio141/lecguide/unit1/eustruct/sppump.html
Na-K Pump Model: Part I
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3 Na+ bind to inner region of protein
Na+ binding triggers phosphorylation
of protein. ATP
ADP + Pi
Phosphorylation causes conformation
change and Na+ binding site faces
outside
3 Na+ released to outside
Na-K Active Pump: Part II
2 K+ ions on outside are able to
bind
 K+ binding causes
dephosphorylation and new
conformation change
 2K+ ions exposed to inside and
released
Cyclic process uses ATP energy to
drive Na & K ion transport against
conc. Gradient
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钙泵
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Ca++浓度：胞外约10-3M，胞质小于或等
于10-7M（自由Ca++）
肌质网的Ca++泵
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Transmembrane transport and
membrane potential
静息电位
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静息电位
动作电位
阳离子通道
突触前膜，突触后膜
乙酰胆碱受体（配体控制的闸门）
3 Transport of Macromolecules
active transport

Exocytosis & Endocytosis
• Formation of vesicles around large molecules
Receptor mediated
Receptor proteins
Coat proteins
Endocytosis
Pinocytosis
phagocytosis

Endocytosis
Receptor –mediated endocytosis
No-special endocytosis
LDL endocytosis movie
Low Density Lipoprotein
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/LDL_F.01/atherosclerosis.html
Endocytosis
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Transports macromolecules and large
particles into the cell.
Part of the membrane engulfs the
particle and folds inward to “bud off.”
• Fig. 5.16
Endocytosis
Putting Out the Garbage
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Vesicles (lysosomes, other secretory
vesicles) can fuse with the
membrane and open up the the
outside…
Exocytosis
(Cellular Secretion)

Exocytosis
Constitutive exocytosis
pathway(default pathway)
regulated exocytosis pathway
Cellular Membranes
REVIEW
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Importance of Membranes
Membrane Structure
Proteins
Fluid Mosaic model
Permeability
Types of Transport
• Passive and Active
Assignment

What is the role of NAD+ and the
electron transport chain in extracting
useful energy from food?