Chapter 32

Compare and contrast the features and physiological advantages of each of the major classes of hormones, including the steroid hormones, polypeptide hormones, and the amino acid-derived hormones.

Compare and contrast the features and physiological advantages of each of the known classes of second messengers.

Nitric oxide may be merely the first of a new class of gaseous second messenger/neurotransmitter molecules. Based on your knowledge of the molecular action of nitric oxide, suggest another gaseous molecule that might act as a second messenger and propose a molecular function for it.

Herbimycin A is an antibiotic that inhibits tyrosine kinase activity by binding to SH groups of cysteine in the sre gene tyrosine kinase and other similar tyrosine kinases. What effect might it have on normal rat kidney cells that have been transformed by Rous sarcoma virus? Can you think of other effects you might expect for this interesting antibiotic?

Monoclonal antibodies that recognize phosphotyrosine are commercially available. How could such an antibody be used in studies of cell signaling pathways and mechanisms?

Fxplain and comment on this statement: The main function of hormone receptors is that of signal amplification.

GTP \(\gamma\) S is a nonhydrolyzable analog of GTP. Experiments with squid giant axon synapses reveal that injection of GTyS into the presynaptic end (terminal) of the neuron inhibits neurotransmitter release (slowly and irreversibly). The calcium signals produced by presynaptic action potentials and the number of synaptic vesicles docking on the presynaptic membrane are unchanged by GTP \(\gamma\) S. Propose a model for neurotransmitter release that accounts for all of these observations.

A typical hormone binds to its receptor with an affinity \(\left(K_{\mathrm{D}}\right)\) of approximately \(1 \times 10^{-9} M\). Consider an in vitro (test-tube) system in which the total hormone concentration is approximately 1 n \(M\) and the total concentration of receptor sites is \(0.1 \mathrm{n} M\). What fraction of the receptor sites is bound with hormone? If the concentration of receptors is decreased to \(0.033 \mathrm{n} M\), what fraction of receptor is bound with the hormone?

(Integrates with Chapter 24 .) All steroid hormones are synthesized in the human body from cholesterol. What is the consequence for steroid hormones and their action from taking a "statin" drug, such as Zocor, which blocks the synthesis of cholesterol in the body? Are steroid hormone functions compromised by statin action?

Given that \(\beta\) -strands provide a more genetically economical way for a polypeptide to cross a membrane, why has nature chosen \(\alpha\) -helices as the membrane-spanning motif for G-protein-coupled receptors? That is, what other reasons can you imagine to justify the use of \(\alpha\) -hclices?