Download August 24, 2010 Dr. Cynthia Smas Distinguish the major kinetic

August 24, 2010
Dr. Cynthia Smas
1. Distinguish the major kinetic difference(s) between simple and facilitated diffusion
a. Facilitated diffusion through transport-specific carriers acts to accelerate a
reaction that is already thermodynamically favorable
b. Facilitated diffusion (carrier- or ion channel-mediated) is much faster than
simple diffusion and occurs at a limited number of carrier proteins
2. Compare the ion concentrations in the ECF and ICF and discuss the role of these
gradients in membrane transport
a. Sodium: [ECF] >> [ICF]
b. Potassium: [ICF] >> [ECF]
c. Gradients, caused by the membrane’s selective permeability, act as driving
forces for membrane transport (passive diffusion and secondary active
transport)
3. Describe the mechanism of action of GLUT 4 in insulin-responsive glucose uptake
a. GLUT receptors are examples of carrier-mediated facilitated diffusion
b. GLUT 4, expressed on fat and muscle cells, is the major insulin-responsive
glucose transporter
c. Upon insulin binding to its receptor, a signal transduction cascade causes
GLUT 4 vesicles to fuse with plasma membrane, resulting in increased
GLUT 4 expression
d. As glucose bonds to GLUT 4, the carrier protein undergoes
thermodynamically favorable structural changes, leading to glucose being
deposited into the ICF
e. Glucose must be immediately modified to preserve its electrochemical
gradient. Increased GLUT 4 expression leads to rapid glucose uptake via
carrier-mediated facilitated diffusion
4. Describe how the Na/K ATPase primary active transporter functions to drive secondary
active transport of glucose. Understand the concept of symporters and antiporters
a. Cells must maintain electrochemical gradients to function
b. Na/K ATPase pumps use ATP to pump Na and K each against their
established electrochemical gradients (high [Na] in ECF; high [K] in ICF)
c. The Na/K ATPase pump establishes/maintains the gradient’s potential
energy, which is then used (via symporters) to drive flow of a second type of
transport (Ex. Na-Glucose symporter)
i. Antiporters: pumps one molecule alongs its gradient and the other
coupled with another molecule in the opposite direction
ii. Symporters: pump one molecule down its concentration gradient
coupled with another molecule in the same direction
5. Explain the mechanism of cardiotonic steroids on the Na/K ATPase pump.
a. Cardiotonic steroids increase heart contraction w/o increasing heart rate
b. They inhibit dephosphorylation of pump, locking the pump in a nonfunctional state
c. This leads to increased [Ca] in the cell (action of the Na/Ca transporter)
d. Calcium mediated signals increase heart contraction strength
6. Explain the structural basis of the ion selectivity of the voltage-gated K+ channel
a. Ion channels use specialized structure to “selectively filter” ions
b. All ions exist in hydrated form physiologically
August 24, 2010
Dr. Cynthia Smas
c. As ion enters progressively smaller channel, it must shed its hydration shell
d. Shell-shedding must be thermodynamically favorable, i.e. shell must be
replaced by more-favorable non-covalent interaction between the channel/ion
e. Shell-shedding is only thermodynamically favorable at channels for specific
ions (it is favorable for K at K channel, but not for Na at K-channel)
7. Describe the involvement of ABC-type ATP-powered pumps in cystic fibrosis and
multi-drug resistance.
a. ATP-Binding Cassette-type (ABC-type) ATP-powered pumps couple ATP
hydrolysis to solute movement
b. Binding of solute particle to transport increases transporter’s ATP affinity
c. ATP binding causes release of ligand, and hydrolysis causes resetting of
transporter
i. Multiple Drug Resistance – MDR1 (ABC-type Pump)
1. Pumps small, planar molecules (such as those to treat cancer,
malaria) from cytosol before drug can be effective
2. Chemo-resistance results
3. Often amplified in tumor cells, but normally expressed in liver
ii. Cystic Fibrosis – CFTR
1. CFTR pumps chloride out of cell
2. Mutant CFTR (as in cystic fibrosis) fails to reach cell surface
(deltaF508CFTR)
3. Cl- accumulates in cytosol, creating EC difference which
drives H2O into cell, dehydrating mucous and increasing
respiratory infection likeliness/ineffective cilia
8. Describe the role of the acetylcholine receptor in channelopathy
a. Ligand bonding induces conformation change in ligand-gated ion channels
b. Acetylcholine receptor
i. 2 ACH molecules bind, causing opening of channel to Na/K
ii. Myasthenia Gravis is an autoimmune disorder wherein the body
produces antibodies against ACh receptor.
iii. Symptoms: skeletal muscle weakness (particularly in face) which
resolves upon rest
iv. Treatment: AChase inhibitor, immunosuppresion