1. The basic structural unit of biomembranes is the phos-pholipid bilayer. Acetic acid and ethanol are composed each of two carbons, hydrogen and oxygen, and both enter cells by passive diffusion. At pH 7, one is much more membrane permeant than the other. Which is the more permeable, and why? Predict how the permeability of each is altered when pH is reduced to 1.0, a value typical of the stomach.
2. Uniporters and ion channels support facilitated diffusion across biomembranes. Although both are examples of facilitated diffusion, the rates of ion movement via a channel are roughly 104- to 105-fold faster than that of molecules via a uniporter. What key mechanistic difference results in this large difference in transport rate?
3. Name the three classes of transporters. Explain which of these classes is able to move glucose or bicarbonate (HCO3~), for example, against an electrochemical gradient. In the case of bicarbonate, but not glucose, the AG of the transport process has two terms. What are these two terms, and why does the second not apply to glucose? Why are cotransporters often referred to as examples of secondary active transport?
4. GLUT1, found in the plasma membrane of erythrocytes, is a classic example of a uniporter. Design a set of experiments to prove that GLUT1 is indeed a glucose-specific uniporter rather than a galactose- or mannose-specific uniporter. Glucose is a 6-carbon sugar while ribose is a 5-carbon sugar. Despite this smaller size, ribose is not efficiently transported by GLUT1. How can this be explained?
5. Name the four classes of ATP-powered pumps that produce active transport of ions and molecules. Indicate which of these classes transport ions only and which transport primarily small molecules. In the case of one class of these ATP-powered pumps, the initial discovery of the class came from studying not the transport of a natural substrate but rather artificial substrates used as cancer chemotherapy drugs. What do investigators now think are common examples of the natural substrates of this particular class of ATP-powered pumps?
6. Genome sequencing projects continue, and for an increasing number of organisms the complete genome sequence of that organism is known. How does this information allow us to state the total number of transporters or pumps of a given type in either mice or humans? Many of the sequence-identified transporters or pumps are "orphan" proteins, in the sense that their natural substrate or physiological role is not known. How can this be, and how might one establish the physiological role of an orphan protein?
7. As cited in the section Perspectives for the Future, specific inhibitors or activators of channels, pumps, and transporters constitute the largest single class of drugs produced by the pharmaceutical industry. Skeletal muscle contraction is caused by elevation of Ca2+ concentration in the cytosol. What is the expected effect on muscle contraction of selective drug inhibition of sarcoplasmic reticulum (SR) P-class Ca2 + ATPase?
8. The membrane potential in animal cells, but not in plants, depends largely on resting K+ channels. How do these channels contribute to the resting potential? Why are these channels considered to be nongated channels? How do these channels achieve selectivity for K+ versus Na+?
9. Patch clamping can be used to measure the conductance properties of individual ion channels. Describe how patch clamping can be used to determine whether or not the gene coding for a putative K+ channel actually codes for a K+ or Na+ channel.
10. Plants use the proton electrochemical gradient across the vacuole membrane to power the accumulation of salts and sugars in the organelle. This creates a hypertonic situation. Why does this not result in the plant cell bursting? How does the plasma membrane Na+/K+ ATPase allow animal cells to avoid osmotic lysis even under isotonic conditions?
11. Movement of glucose from one side to the other side of the intestinal epithelium is a major example of transcellular transport. How does the Na+/K+ ATPase power the process? Why are tight junctions essential for the process? Rehydration supplements such as sport drinks include a sugar and a salt. Why are both important to rehydration?
12. Name the three phases of an action potential. Describe for each the underlying molecular basis and the ion involved. Why is the term voltage-gated channel applied to Na+ channels involved in the generation of an action potential?
13. Myelination increases the velocity of action potential propagation along an axon. What is myelination? Myelination causes clustering of voltage-gated Na+ channels and Na+/K+ pumps at nodes of Ranvier along the axon. Predict the consequences to action potential propagation of increasing the spacing between nodes of Ranvier by a factor of 10.
14. Compare the role of H+-linked antiporters in the accumulation of neurotransmitters in synaptic vesicles and sucrose in the plant vacuole. Acetylcholine is a common neurotrans-mitter released at the synapse. Predict the consequences for muscle activation of decreased acetylcholine esterase activity at nerve-muscle synapses.
15. Neurons, particularly those in the brain, receive multiple excitatory and inhibitory signals. What is the name of the extension of the neuron at which such signals are received? How does the neuron integrate these signals to determine whether or not to generate an action potential?
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