Chapter 20

Caffeine is an inhibitor of cyclic AMP phosphodiesterase. How would drinking several cups of coffee affect muscle function? How might it affect lipid metabolism?

List two or three factors that make it advantageous for peptide hormones to be synthesized as inactive prohormones that are activated by proteolytic cleavage.

Signaling molecules interact with cells through specific macromolecular receptors. For each of the four receptors identified below, list all characteristics, by number, which accurately describe that receptor. (a) An adrenergic receptor (b) A steroid receptor (c) The LDL receptor (d) The insulin receptor (1) Located at the cell surface (2) Associated with the protein clathrin (3) Ligand binding stimulates the activity of phospholipase \(C\) (4) A transmembrane protein (5) A DNA-binding protein (6) Located in the cell interior (7) Receptor-ligand complex moves to the lysosome (8) Receptor-ligand complex becomes concentrated in the nucleus (9) Receptor activation can inhibit the synthesis of glycogen (10) The hormone-receptor complex activates specific gene transcription (11) Internalization decreases the synthesis of cholesterol esters (12) Action of this receptor diminishes the synthesis and activity of \(\beta\) hydroxy- \(\beta\)-methylglutaryl-CoA reductase (HMG-CoA reductase) (13) This receptor activates its own synthesis (14) Biological activity of this receptor involves interaction with guanine nucleotide-binding proteins (15) This receptor has a protein kinase activity (16) Not known to act through a second messenger

Upon activation by a receptor, a G protein exchanges bound GDP for GTP, rather than phosphorylating GDP that is already bound. Similarly, the \(\alpha\) subunit-GTP complex has a slow GTPase activity that hydrolyzes bound GTP, rather than exchanging it for GDP. Describe experimental evidence that would be consistent with these conclusions.

Write a balanced equation for the hydrolysis of cGMP, catalyzed by cGMP phosphodiesterase. Would you expect an inhibitor of this enzyme to potentiate or antagonize the action of Viagra? Explain.

Suppose that you measured binding to the isolated EGF receptor of EGF at various concentrations. Would you expect the binding curve to be hyperbolic? Explain your answer.

Describe two features of insulin signaling that affect glucose utilization. A \(\beta\)-adrenergic response can be modulated through the actions of a receptor kinase and arrestin because phosphorylation by the kinase desensitizes the receptor. How might signaling by a tyrosine receptor kinase, such as the insulin receptor, be modulated?

Suppose that a G protein undergoes a mutation that allows the exchange of bound GTP for GDP to occur in the absence of G protein binding to a receptor. How might this mutation affect signaling involving a GPCR? Which subunit of the G protein is most likely affected by the mutation?

Bisphenol \(\mathrm{A}\) is widely used as a building block in polymer synthesis and is found in the polycarbonate hard plastics of reusable drink containers, DVDs, cell phones, and other consumer goods. Bisphenol A is reported to have estrogenic activity, and its widespread occurrence in our environment is a potential concern. Describe one or two biochemical experiments that could be done to compare the activity of bisphenol A with that of its estradiol, its structural relative. CC(C)(c1ccc(O)cc1)c1ccc(O)cc1 Bisphenol A

In early studies of adrenergic signaling, it was thought that the epinephrine receptor and adenylate cyclase were one and the same protein. What kind of evidence would prove otherwise?

Mutations that inactivate p53 have a recessive phenotype, whereas mutations affecting Ras are dominant. Explain the difference.

GTP \(\gamma \mathrm{S}\) is a nonhydrolyzable analog of GTP. Suppose this compound were added to a cell-free system containing active components of an adrenergic signaling system. What consequences would you expect? What would be the effects on cAMP levels? GTP \(\gamma \mathbf{S}\)

\(\beta\)-adrenergic receptors are subject to phosphorylation at several serine residues by \(\boldsymbol{\beta}\)-adrenergic receptor kinase, and this is followed by binding to the phosphorylated sites by a protein called arrestin. What do you think might be the purpose of these modifications?

Herceptin is an antibody that is used to treat certain forms of breast cancer by binding to a class of estrogen receptors. What is the basis for its effectiveness in treating certain forms of breast cancer?