1. Nitric oxide (NO) is a gaseous molecule with lipid solubility similar to that of O₂ and CO₂. Endothelial cells lining arteries use NO to signal surrounding smooth muscle cells to relax, thereby increasing blood flow. What mechanism or mechanisms would transport NO from where it is produced in the cytoplasm of an endothelial cell into the cytoplasm of a smooth muscle cell, where it acts?

2. Acetic acid (a weak acid with a pK_a of 4.75) and ethanol (an alcohol) are each composed of two carbons, hydrogen, and oxygen, and both enter cells by passive diffusion. At pH 7, one is much more able to permeate a cellular membrane than the other. Which is more membrane permeable, and why? Predict how the membrane permeability of each is altered when the extracellular pH is reduced to 1.0, a value typical of the stomach.

3. Uniporters and ion channels support facilitated transport across cellular membranes. Although both are examples of facilitated transport, the rates of ion movement via an ion channel are roughly 10⁴- to 10⁵-fold faster than the rates of molecule movement via a uniporter. What key mechanistic difference results in this large difference in transport rate? What contribution to free energy (ΔG) determines the direction of transport?

4. Name the three classes of membrane transport proteins. Explain which one or ones of these classes is able to move glucose and which can move bicarbonate (HCO₃⁻) against an electrochemical gradient. In the case of bicarbonate, but not glucose, the ΔG 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?

5. An H⁺ ion is smaller than an H₂O molecule, and a glycerol molecule, a three-carbon alcohol, is much larger. Both readily dissolve in H₂O. Why do aquaporins fail to transport H⁺ whereas some can transport glycerol?

6. GLUT1, found in the plasma membrane of erythrocytes, is a classic example of a uniporter.

7. 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 organic molecules. The initial discovery of one class of these ATP-powered pumps came from studying the transport not of a natural substrate, but rather of 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?

8. Explain why the coupled reaction ATP → ADP + P_i in the P-class ion pump mechanism does not involve direct hydrolysis of the phosphoanhydride bond.

9. Describe a negative feedback mechanism for controlling a rising cytosolic Ca²⁺ concentration in cells that require rapid changes in Ca²⁺ concentration for normal functioning. How would a drug that inhibits calmodulin activity affect cytosolic Ca²⁺ concentration regulation by this mechanism? What would be the effect on the function of, for example, a skeletal muscle cell?

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10. Certain proton pump inhibitors that inhibit secretion of stomach acid are among the most widely sold drugs in the world today. What pump does this type of drug inhibit, and where is this pump located?

11. The membrane potential in animal cells, but not in plants, depends largely on resting K⁺ channels. How do these channels contribute to the resting membrane potential? Why are these channels considered to be nongated channels? How do these channels achieve selectivity for K⁺ versus Na⁺, which is smaller than K⁺?

12. 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 a Na⁺ channel.

13. Plants use the proton electrochemical gradient across the vacuole membrane to power the accumulation of salts and sugars in the organelle. This accumulation creates hypertonic conditions in the vacuole. Why does this not result in the plant cell swelling and bursting? Even under isotonic conditions, there is a slow leakage of ions into animal cells. How does the plasma-membrane Na⁺/K⁺ ATPase enable animal cells to avoid osmotic lysis under isotonic conditions?

14. In the case of the bacterial two-Na⁺/one-leucine symporter, what is the key distinguishing feature of the bound Na⁺ ions that ensures that other ions, particularly K⁺, do not bind?

15. Describe the symport process by which cells lining the small intestine import glucose. What ion is responsible for the transport, and what two particular features facilitate the energetically favored movement of this ion across the plasma membrane?

16. 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? Why is localization of the transporters specifically in the apical or basolateral membrane crucial for transcellular transport? Rehydration supplements such as sport drinks include a sugar and a salt. Why are both important to rehydration?