Chapter 10 Membrane Transport Chapter 10 Membrane Transport Biochemistry I Dr. Loren Williams...
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Transcript of Chapter 10 Membrane Transport Chapter 10 Membrane Transport Biochemistry I Dr. Loren Williams...
Chapter 10Membrane Transport
Biochemistry IDr. Loren Williams
Revised 03/11/2013
Thermodynamics of Transport
Mammalian Cell
inside 12 mM Na+
140 mM K+
outside150 mM Na+
4 mM K+
Passive TransportMovement of molecules across membranes driven by electochemical potentialMechanism is either simple diffusion or facilitated (mediated) diffusionNot thermodynamically linked to other processesNo ATP hydrolysis
Mediation of transport across membranesrequired for charged, polar or large molecules
1) Ionophoreslipid-soluble molecules synthesized by microorganisms facilitate transport of ions across membrane.
Valinomycin a potassium-specific passive transporter a dodecadepsipeptide antibioticproduced by several Streptomyces strains highly selective for potassium ions over sodium and other
ionsKd for potassium is 106
Kd for sodium is 10.facilitates transport of K+ down the electrochemical
potential gradient.Deadly
Figure 10-1
Sodium (Na+)Oxidation state: +1Ionic radius: 0.95 ÅPreferred ligands: ONumber of ligands: 6-7Preferred geometry: octahedral (not a strong preference)
Potassium (K+)Oxidation state: +1Ionic radius: 1.33 ÅPreferred ligands: ONumber of ligands: 4-7Preferred geometry: variable, octahedral
Calcium (Ca2+)Oxidation state: +2Ionic radius: 0.99 ÅPreferred ligands: ONumber of ligands: 6-10Preferred geometry: variable
Passive Transport
2) Ion Channelsintegral membrane proteins found in the membranes of all cells (necessary to keep cells from
exploding)highly selective for specific ions (K+ vs Na+ vs Ca2+ etc)fast: rate of transport is close to the diffusion limit very tightly regulatedgated: flow of ions across the cell membrane is turned off or no in
response to stimuliSensors: pH, ligands, voltage, etcK+ channels and anion channels hyperpolarize cells (cause
the membrane potential to become more negative), Na+ and Ca2+ channels and non-selective cation channels depolarize
cells (cause the membrane potential to become more positive).
Ion channels form pores that permit the flux of ions down their electrochemical gradient.
Mammalian Cell
outside (high Na+)150 mM Na+
4 mM K+
inside (high K+) 12 mM Na+
140 mM K+
Ion channels form pores that permit the flux of ions down their electrochemical gradient.
KcsA K+ channel
KcsA K+ Ion Channel10,000-fold selectivity of K+ over Na+
homo tetramerfour identical protein subunits
two transmembrane helices, central pore
three parts: a selectivity filter
(extracellular side), a dilated water-filled cavity
(center),gate
(cytoplasmic side, proton-activated,
opens at acidic pH)
How does ion selectivity work? How is K+ distinguished from Na+?
Ion Dehydration: disrupts favorable molecular interactions (DH>0)Ion Coordination: forms favorable molecular interactions (DH<0)
To enter the selectivity channel the ions must dehydrate. The enthalpy of ion coordination by the selectivity channel has to offset the unfavorable dehydration enthalpy.
Na+ is smaller (ionic radius 0.95 Å) than K+ (ionic radius 1.33 Å). The coordination geometry in the selectivity channel is bad for Na+: The O-Na+ distances are too long. The O-K+ distances are just right.
Optimum O - Na+ distance = 2.4 Å (0.95 + 1.5)Optimum O - K+ distance = 2.8 Å (1.33 + 1.5)
K+ is about the same size as water, Na+ is smaller than water.
Free energy landscape for K+ is featureless throughout the channel.
Channels are gated (they open and close)
Mechanics (touch, sound, etc): Channels open and close in response to membrane deformation.
Ligands (neurotransmitters…): Channels open and close in response to ligand binding
Signals (Ca2+…): Channels open and close in response to Ca2+ binding
Voltage (changes in membrane potential): Channels open and close in response to Ca2+ binding
Voltage Gating (Kv Channel): Gate # 1S4 helix (+++++ charged)
At the resting potential (-60mV), the gate is closed. Depolarization moves S4 toward the outside (extracelluar side) of the membrane, and opens the channel.
Voltage Gating (Kv Channel): Gate # 2inactivation ball
Closes the channel a few msec after the S4 helix opens it. The channel does not reopen until the potential is reset,
Figure 10-9
Outside
Inside
openclosed
Figure 10-9a
Outside
Figure 10-9b,c
Action Potential
o stimulation of a neurono open Na+ channelo depolarizeo close Na+ channelo open K+ channelo hyperpolarizeo close K+ channel
(refractory)o Slow reset to resting
potential by ionpumps
10 m/sec
Figure 10-3
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Figure 10-6b
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Figure 10-10
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Figure 10-11a
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Figure 10-11b
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Figure 10-12
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Glucose Transporter: has two exclusive conformational statesis specific for glucoseis driven by chemical potential (concentration)is the basis of selectivity is indicatedis similar to systems of amino acid transport, etc
Box 10-1a
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Box 10-1b
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Box 10-2
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Figure 10-14
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Figure 10-15
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Figure 10-16
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The Na+/K+ pump (ATPase)
maintains resting potentialregulates cell volume,signal transducer/integrator
20% of cell's energy expenditure.50-70% cell's energy expenditure for neurons
Pumps 3 Na+ out for every 2 K+ in (hydrolyzes 1 ATP in the process).
o unphosphorylated pump binds 3 intracellular Na+ and an ATP,o phosphate is transfered from ATP to aspartate of the pump, release of ADP o conformational change exposes the Na+ ions to the outside, all Na+ are released outside o pump binds 2 extracellular K+ ions. o dephosphorylation of the pump, o both K+ are released on the insideo cycle completed
start
Box 10-3
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Figure 10-18
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Figure 10-19
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Figure 10-21a
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Figure 10-23
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Figure 10-23b
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