1. Contact me at kgahern@davincipress.com / Friend me on Facebook (kevin.g.ahern) 2. Download my free biochemistry book at http://biochem.science.oregonstate.edu/biochemistry-free-and-easy 3. Take my free iTunes U course at https://itunes.apple.com/us/course/biochemistry/id556410409 4. Check out my free book for pre-meds at http://biochem.science.oregonstate.edu/biochemistry-free-and-easy 5. Course video channel at http://www.youtube.com/user/oharow/videos?view=1 6. Check out all of my free workshops at http://www.youtube.com/playlist?list=PLlnFrNM93wqyTiCLZKehU1Tp8rNmnOWYB&feature;=view_all 7. Check out my Metabolic Melodies at http://www.davincipress.com/metabmelodies.html 8. My courses can be taken for credit (wherever you live) via OSU's ecampus. For details, see http://ecampus.oregonstate.edu/soc/ecatalog/ecourselist.htm?termcode=all&subject;=BB 9. Course materials at http://oregonstate.edu/instruct/bb450 Signaling Highlights 1. Signaling involves a signaling molecule (first messenger) released on one part of the body that travels to a protein receptor found in the membrane of target cells in another part of the body. The protein receptor's shape is changed as a result of binding of the first messenger and that causes changes internal to the cell that results in a cellular response. 2. The signal transduction process involves amplification of the message -- one signal molecule can result in the production of many signal molecules inside of the cell (these are different molecules on the inside compared to outside). Changes brought about by the signaling process may include modification of enzyme activities, genes expressed that weren't being made before, or stimulating cell division. 3. Second messengers are molecules made on the inside of the target cell in response to binding of a signaling molecule outside the cell (first messenger). 4. Second messengers include cAMP, cGMP, calcium, IP3, and DAG. 5. Second messengers spread throughout the cell and cause a cellular response. 6. 7TM receptors are a class of receptors that are involved in a variety of bodily functions. 7. 7TM refers to the fact that the protein crosses the cell membrane 7 times. 8. Rhodopsin is a 7TM that is involved sensing light and vision. 9. 7TM receptors have a protein partner on the inside of the cell that helps them to transmit the signal. This partner is known as a G-protein. 10. G-proteins can bind guanine nucleotides - GTP or GDP. G-proteins interact with the carboxy tail of the beta-adrenergic receptor. 11. G-proteins have three subunts - alpha, beta, and gamma. When there is no signal present, alpha has GDP bound to it. 12. Binding of the beta-adrenergic receptor of a signal (epinephrine here) causes the G-protein to change in response. This causes the alpha subunit to bind GTP and lose GDP. GTP is SWAPPED for the GDP. 13. When the alpha subunit has GTP bound, it separates from the beta and gamma subunits and moves to a membrane-bound enzyme known as adenylate cyclase. This enzyme catalyzes the conversion of ATP to cAMP. 14. Thus, a second messenger has been created. cAMP can move in the cytoplasm and interact with and activate protein kinase A, as described earlier in the class. 15. Action of protein kinase involves phosphorylation other proteins (enzymes). These may result in activation or inactivation of the target protein depending on the enzyme 16. For example, ephinephrine is released to release glucose. 17. In the liver and muscles, glycogen (glucose polymer) is available. Binding of epinephrine to the receptors in those cells stimulates protein kinase A, which phosphorylates target enzymes. Phosphorylation of glycogen breakdown enzymes results in making them active. Conversely, enzymes which synthesize glycogen are inactivated when phosphorylated by protein kinase A. 18. Turning on of the signaling pathway can be problematic if left on continuously. 19. The system can be turned off in several ways. One way is that GTP gets converted back to GDP by the alpha subunit hydrolyzing the GTP to GDP. This takes a minute or two. When that happens, the alpha subunit re-binds to the beta and gamma units and no longer associates with adenylate cyclase. 20. Another step of turning off of the signal include dissociation of the epinephrine from the receptor. 21. An alternative to dissociation of epinephrine is for an enzyme called receptor kinase to phosphorylate the carboxy tail of the beta-adrenergic receptor. The phosphorylated tail is a target for a protein called beta-arrestin which can stop the signaling. 22. Another step of turning off the signal is by breaking down cAMP with an enzyme called phosphodiesterase. 23. Another system is the angiotensin receptor, which binds to angiotensin (regulates blood pressure) that binds to a different 7TM, which activates a G-protein, which activates an enzyme called phospholipase C, which breaks down PIP2 to form two new second messengers - DAG and IP3.

• published: 12 Nov 2013
• views: 454