Notes for Chapter 12,  Biosignaling

How many of the signals listed in Table 12-1 are familiar to you?

Terms you should be able to define and describe with examples:

• specificity
• amplification by enzyme cascades
• desensitization
• integration

Scatchard analysis is a wonderful tool.  This type of analysis is used to determine K_d and the number of ligand binding sites.  Everyone needs to know what K_d  is.

What are the general features of all signal transduction systems?  Figure 12-2 has examples of each of the basic types of signaling mechanisms.

The discussion of gated ion channels is very similar to what you read in chapter 11.   The transmembrane potential is Vm (aka ).   Use this equation to work problem #6.

It was interesting to note that the number of sodium, potassium and chloride ions that come rushing in to change a membrane potential are miniscule when compared to the total ion concentration.  Calcium ion concentrations are kept very low inside the cytosol, so the Ca⁺² levels are significantly altered when a calcium channel is opened.

Acetylcholine receptor.

The discussion of acetylcholine receptor should also look familiar.  You should now be able to fully describe the acetylcholine receptor.  How does acetylcholine bind?  What happens when it does?  What does acetylcholinesterase do?  What happens if the acetylcholinesterase isn't functioning properly?

Voltage-gated and ligand-gated channels.

For the voltage gated channels in neurons, Ca⁺² enters the cell and acts as a "second messenger" that triggers the fusion of acetylcholine containing vesicles with the membrane.  This releases acetylcholine into the synaptic cleft.   Note: usually "second messenger" is used to refer to chemicals that are inside the cell, these "second messengers" relay the signal that a molecule on the outside of the cell sends.  In this case, Ca⁺² was outside the cell, but it is relaying the "message of the polarized membrane. 

• How does the voltage-gated Ca⁺² channel and the acetylcholine-gated channel work to send a neuronal signal?
• How are cation channels specific for cations?  How are anion channels specific for anions?

Receptor Enzymes

The insulin receptor is a tyrosine kinase.   Be able to describe how the binding of insulin activates a target protein (figure 12-7).  Figure 12-6 shows how insulin activates a cascade of protein activation.  It is not necessary to memorize this cascade, but do walk yourself through it. 

• What  are the advantages of a catalyst activating a catalyst? (One advantage is given in the text, can you come up with another?)

Figure 12-8 shows how insulin triggers the activation of glycogen synthase via  phosphorylation of IRS-1.  You should be able to describe this pathway, and its relationship with the GluT4 receptor (Box 11-2). 

• What are two other enzyme receptors that are similar to the insulin receptor?

Guanyl cyclase generates cGMP.  You should be able to draw the structure for this.

• What are the effects of cGMP in the kidney?  intestine? cardiac smooth muscle? brain?
• What is guanyl cyclase activated by in the kidney?  What is the net effect of this activation?  What happens to vascular smooth muscle when this samw hormone binds to the guanyl cyclase receptor?
• How do some gram negative bacteria cause diarhea?
• How do nitrogycerin tablets bring about relief from angina?