1. How Do Water Soluble (Protein Based) Hormones Work?

2. Problems with water soluble (protein based) Hormones They cannot diffuse through the lipid by-layer of a cell due to differences in polarity They need to bind to receptors in the surface of the membrane These receptors are called first messengers, which in turn will lead to the production of a second messenger The second messenger is often Cylic-AMP or a neurotransmitter that will do the work of the hormone in the cell.

3. Step 1 The hormone diffuses from the blood plasma and binds to a receptor on the external surface of the cell If the cell lacks the proper receptor, the hormone keeps on going in search of one that has it.

4. Step 2 The receptor will activate a G-Protein The G-Protein will activate adenylate cyclase

5. Steps 3, 4, and 5 Adenylate Cyclase will convert ATP into Cyclic AMP in the cytosol of the cell C-AMP will activate a protein kinase (Enzymes the phosphorylates cellular proteins)‏ This converts ATP to ADP Activated protein kinases phosphorylate one or several enzymes so they can work.

6. Step 6 The enzymes will catalyze reactions that produce the response the hormone instructs it to.

8. Step 7 After a brief period of time PHOSPHDIESTERASE will inactive C- AMP

9. Step 8 This de-activation turns off the cells ability to respond to the hormone As a result the effects of the hormone will wear off over time, unless more hormone has been released To prevent over stimulation via hormones, each cell has many different protein kinases, each specific to a particular hormone.

10. Mechanism of Action of Water- soluble Hormones Process Diagrams Step-by-Step Copyright © 2007 by John Wiley & Sons, Inc.

11. Water-soluble hormone Receptor G protein Blood capillary Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Adenylate cyclase Target cell 1

12. Water-soluble hormone Receptor G protein cAMP Second messenger Activated adenylate cyclase converts ATP to cAMP Blood capillary Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Adenylate cyclase Target cell ATP 1 2

13. Water-soluble hormone Receptor cAMP serves as a second messenger to activate protein kinases G protein Protein kinases cAMP Second messenger Activated adenylate cyclase converts ATP to cAMP Blood capillary Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Adenylate cyclase Target cell ATP 1 2 3 Activated protein kinases

14. Water-soluble hormone Receptor cAMP serves as a second messenger to activate protein kinases G protein Protein kinases cAMP Activated protein kinases Second messenger Activated adenylate cyclase converts ATP to cAMP Activated protein kinases phosphorylate cellular proteins Blood capillary Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Adenylate cyclase Target cell ATP 1 2 4 3 Protein— P ADP Protein ATP

15. Water-soluble hormone Receptor cAMP serves as a second messenger to activate protein kinases G protein Protein kinases cAMP Activated protein kinases Protein— Second messenger Activated adenylate cyclase converts ATP to cAMP Activated protein kinases phosphorylate cellular proteins Millions of phosphorylated proteins cause reactions that produce physiological responses Blood capillary Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Adenylate cyclase Target cell P ADP Protein ATP 1 2 4 3 5

16. Water-soluble hormone Receptor cAMP serves as a second messenger to activate protein kinases G protein Protein kinases cAMP Activated protein kinases Protein— Second messenger Phosphodiesterase inactivates cAMP Activated adenylate cyclase converts ATP to cAMP Activated protein kinases phosphorylate cellular proteins Millions of phosphorylated proteins cause reactions that produce physiological responses Blood capillary Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Adenylate cyclase Target cell P ADP Protein ATP 1 2 6 4 3 5