Ahern's Biochemistry #20 Signaling and Metabolic Energy

• published: 15 Nov 2014
• views: 78

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://oregonstate.edu/dept/biochem/ahern/123.html 7. Check out my Metabolic Melodies at http://www.davincipress.com/ 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 1. A receptor related to and that can dimerize with the EGF receptor is called HER. HER, when dimerized with EGF, stimulates cell division. Normally HER is made (expressed) at very low levels in cells and doesn't play a big role in cell division. Mutation in the promoter of HER that causes it to be made in large amounts converts it into an oncogene. Thus, overexpression of HER can cause cells to divide uncontrollably. HER-caused tumors are treated with a monoclonal antibody called herceptin that binds to HER and stops it from stimulating cell division. 2. One type of leukemia (CML) arises from DNA rearrangement that joins together two genes known as BCR and ABL. ABL is a tyrosine kinase that plays an important role in controlling when cells divide. When BCR is joined to ABL (making BCR-ABL), the fusion that arises is made in greater quantities than ABL itself and it still contains the tyrosine kinase activity. Thus, the overexpressed fusion stimulates cells to divide uncontrollably. 3. BCR-ABL tumors are successfully treated with a tyrosine kinase inhibitor known as Gleevec, that was advocated and advanced by Dr. Brian Druker, a research scientist at OHSU. Highlights Metabolic Energy 1. The body must manage metabolic energy through the breakdown of complex substances to simpler ones (catabolism) and the reverse of that process, the synthesis of complex substances from simpler ones (anabolism). Catabolic processes tend to release energy, 2. To understand chemical reactions in cells, we must understand the thermodynamics (energy) of the reactions. 3. The free energy of a process is the energy available to do useful work. The free energy of a process is called the Gibbs Free Energy. 4. Most commonly, we are concerned with the change in free energy for a system. For example, for an enzymatically catalyzed reaction, we are interested in the change in free energy between the reactants and the products. The change in free energy ( G) indicates the favorability of a process. a. If the G for a process is negative, the forward process is favored. b. If the G for a process is positive, the forward process is not favored and the reverse of the process is favored). c. If the G for a process is zero, the process is at equilibrium. Example: For A (=) B - (=) means reaction, (Capitol D below = DELTA) if DG is negative, A to B is favored. if DG is positive, B to A is favored. if DG is 0, B to A and A to B are equally favored. The system is at equilibrium. 5. DG = DG0' + RTln[Products/Reactants] or, for the above reaction, DG = DG0' + RTln[B/A] Students should be able to predict the effects of increasing/decreasing amounts of product/reactant on the direction of reactions. They should also understand how DG0' plays a role in determining the direction. 6. Phosphates "store" energy in molecules. Resonant structures of phosphates allow shifting of electrons and stabilization of adjacent phosphates. 7. ATP is a source of energy in cells because the G of the hydrolysis reaction is very negative. Hydrolysis of ATP directly to yield energy (like burning of wood to heat a house) is not the mechanism used by cells to drive reactions. Instead, hydrolysis of ATP (energetically favorable) is coupled to energetically unfavorable reactions to make them proceed. We will discuss examples of this later in the term. 8. High energy phosphates, such as on creatine phosphate, allow molecules containing them to transfer phosphate directly onto ADP, forming ATP. This is known as substrate level phosphorylation and is a relatively minor contributor to the amount of ATP in the body. The other types of phosphorylation that occur in cells are oxidative phosphorylation (in mitochondria) and photophosphorylation (in photosynthetic organisms). 9. Cells must have ATP to accomplish work (muscular action), transmit information (nerve signals), signal each other (cellular signaling), and synthesize important biochemicals.