Chapter 15

What might be the effect on liver function of a mutation in a gene that encodes a cAMP phosphodiesterase? of a mutation in a gene encoding a glucagon receptor? of a mutation in a gene encoding phosphorylase kinase? of a mutation that altered the active site of the GTPase of a G. subunit? (Assume in all cases that the mutation causes a loss of function of the gene product.)

\(\mathrm{Ca}^{2+}, \mathrm{IP}_{3},\) and \(\mathrm{cAMP}\) have all been described as second messengers. In what ways are their mechanisms of action similar? In what ways are they different?

Suppose that epinephrine and norepinephrine could initiate a similar response in a particular target cell. How could you determine whether or not the two compounds act by binding to the same cell-surface receptor?

One of the key experiments to show that gap junctions (page 262 ) allowed the passage of small molecules was carried out by allowing cardiac muscle cells (which respond to norepinephrine by contraction) to form gap junctions with ovarian granulosa cells (which respond to FSH by undergoing various metabolic changes). The researchers then added FSH to the mixed cell culture and observed the contraction of the muscle cells. How could muscle cells respond to \(\mathrm{FSH}\), and what does this tell you about the structure and function of gap junctions?

Because calmodulin activates many different effectors (e.g., protein kinases, phosphodiesterases, calcium transport proteins), a calmodulin molecule must have many different binding sites on its surface. Would you agree with this statement? Why or why not?

Diabetes mellitus is a disease that can result from a number of different defects involving insulin function. Describe three different molecular abnormalities in a liver cell that could cause different patients to exhibit a similar clinical picture, including, for ecample, high concentrations of glucose in the blood and urine.

Would you expect a mutation in Ras to act dominantly or recessively as a cause of cancer? Why? (A dominant mutation causes its effect when only one of the homologous alleles is mutated, whereas a recessive mutation requires that both alleles of the gene are mutated.)

One of the genes of the cowpox virus encodes a protein called CrmA that is a potent inhibitor of caspases. What effect would you expect this inhibitor to have on an infected cell? Why is this advantageous to the infecting virus?

Why do you suppose that some people find a compound called PROP to have a bitter taste, whereas others do not report this perception?

The inhibition of a specific protein kinase often leads to an increased phosphorylation of many cellular proteins. How can you explain this observation?