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8/3/2019 3120 Lecture 2
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Lecture Outline
Homeostasis Negative Feedback Systems
Body Fluid Compartments and ionic compositions
Cell Membrane
Membrane Transport Mechanisms Simple diffusion
Diffusion through lipid bilayer
Diffusion through protein lined pore/channel
Facilitated diffusion
Active transport
Tom Stavraky 661-3474
MS 206
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Terry Fox
Terry Fox Run
for Cancer Research
Sunday, September 18th
at
UWO and Springbank
Gardens
Terryfox.org
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Internal and External Environments
External Environment
Internal Environment
Its important tomaintain this internal
environment so the
cells can function
properly .
Homeostasis
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Body Fluid Compartments
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Chemical Composition Inside and
Outside a Cell
Substance Plasma Interstitial Intracellular
Sodium ions 144 140 14
Potassium 4.8 5.0 150
Calcium 2.5 2.0 10-4
Chloride 102 125 10
Bicarbonate 22 24 12
Proteins 1.2 0.2 4
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Cell Membrane
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Membrane Transport Mechanisms
1. Endocytosis/Exocytosis
2. Diffusion
Simple diffusion
Through cell membrane/lipid bilayer
Through protein-lined pore
3. Facilitated diffusion
4. Active transport
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Simple Diffusion
The movement of molecules due to theirrandom thermalmotion
- Water moves at 2,500 kph
- Glucose moves at 850 kph
Molecules move from an area ofhigh concentration to lowconcentration (down theirconcentration gradient)
Until chemical (dynamic) equilibrium is reached
(no net movement)
High
Conc.
Low
Conc.
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Diffusion Distance
Diffusion is not efficientover long distances
Glucose traveling 10
takes 3.5 sec at 38oC
Glucose traveling 10 cm
takes 11 years
The time for diffusion
increases with the
square of the distance
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Diffusion Through Cell Membrane
Substances must be non polar (lipid soluble) inorder to penetrate the lipid (fatty acid tail) region of
the lipid bilayer.
non polar molecules include: O2, CO2, fatty acids, steroids
and some alcohols
Driving force is the concentration gradient
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Ficks First Law of Diffusion
J = - kT
x
dc
x
A
6r dxWhere:
J = net rate of diffusion in moles or grams per unit time
k = Boltzmann constant
T = absolute temperature
r= molecular radius = viscosity of the medium
The 4 values above (K, T, r, ) are sometimes all summarized into thediffusion coefficient, D.
A = total surface area of the membrane for diffusiondc = concentration gradient of the solute
dx
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Ficks First Law of Diffusion
J = - kT x dc x A
6r dx
Questions:
1. How would you decrease the rate of diffusion?
2.Why is there a - before the kT?
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Membrane Transport Mechanisms
Diffusion Simple diffusion
Through cell membrane/lipid bilayer
Through protein-lined channel/pore
Facilitated diffusion
Active transport
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Diffusion Through Protein
Channels/Pores (pg EC-16)
Polarmolecules (ions andother water-solublemolecules) cannot diffusedirectly through the cellmembrane due to thehydrophobicfatty acidregion.
They require a proteinpore/channel (leak channel)
Water moves through porescalled aquaporins
Driving force is theconcentration gradient
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Factors affecting the rate of diffusion
through protein channel (EC-17)
1. Size of the molecule (< 0.8 nm)
2. Charge on the molecule and
channel (+, -)
3. Electrochemical gradient
4. Pressure gradient
( kinetic energy)
5. Hydration energy (water
shell)
- Hilles theory of closest fit
-Water shell must be removed by the
channel without the water
knowing it so ion remains
energetically comfortable
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Some Ion Charges and Diameters
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Factors affecting the rate of movement
through protein leak channel
1. Size*
2. Charge*
3. Electrochemical
4. Pressure gradient5. Hydration energy (water shell)*
Some of these factors act as *filters
preventing one ion from passingthrough another ions channel this is
NOT chemical specificity, as we will
see in a moment.
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Membrane Transport Mechanisms
Diffusion Simple diffusion
Through cell membrane/lipid bilayer
Through protein-lined channel/pore
Facilitated Diffusion
Active transport
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Facilitated Diffusion
Some large molecules (>0.8 nm) cross the membrane fasterthan Ficks law predicts
Attachment of a molecule to an integral membrane protein
will cause a conformational change in that protein moving the
molecule across the membrane
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Facilitated Diffusion
This is a form ofcarrier
mediated transport
Driving force is the
concentration gradient
Characteristics:
Chemical Specificity
Competitively inhibited
Saturation Kinetics
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Facilitated Diffusion
Saturation Kinetics Transport rate is
limited by the number
of carriers and thespeed of the
conformational
change..
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Membrane Transport Mechanisms
Diffusion Simple diffusion
Through cell membrane/lipid bilayer
Through protein-lined channel/pore
Facilitated Diffusion
Active transport
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Active Transport
A form ofcarrier mediated transport Chemical Specificity
Competitively inhibited
Saturation Kinetics
*Moves substances against the conc. grad.
- Requires energy (ATP)
Eg. Na+/K+ pump..
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Active Transport
Sodium/Potassium
Pump (ATPase)
Pumps 3 Na+ out and
2 K+ in (against their
conc. gradients) for
every ATP split
Extracellular
fluid
Intracellular
fluid
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Sequence of events in Na+/K+ pump
At rest all binding sites empty, ATP attached but not split
Step 1. Three Na+ bind to their intracellular binding sites
Step 1 to 2. ATP is hydrolyzed, ADP is released causing conformation
change of protein
Steps 2 and 3. Spontaneous conf. change Na+ is shuttled across
membrane (protein now has low affinity for Na+)
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Sequence of events in Na+/K+ pump
Step 4. K+ ions attach to
extracellular binding sites
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Sequence of events in Na+/K+ pump
Step 4 to 5. Inorganic Phosphate (Pi) is released from protein protein changes shape
Step 5 to 6. New ATP binds to protein causing conformation change
K+ is shuttled across membrane into the cell
Step 6. Protein returns to resting configuration and sequence
repeats
Metabolic inhibitors such as ouabain and digoxin can inhibit the pump by
binding to extracellular side (usually between steps 3 and 4)
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Functions of the Na+/K+ pump
Helps maintain the concentration gradients forNa+ and K+ across the cell membrane
Causes slight increased negativity inside the cell(more positive charge is being removed thanreplaced)
Keeps the cell from swelling and bursting due toosmosis
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Secondary Active TransportEC-24
The Na+/K+ pumpmaintains largeconcentration gradientfor Na+ high conc.outside and low inside
These concentrationgradients can be usedto power other
transport mechanisms
Indirectly requiresATP