My Dog is Broken!<br />Maria Chiaffarano and Julia Burton<br />
Signal Transduction<br />Process by which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response<br />Transmembrane receptors span the cell membrane (part of the membrane is inside, part is outside the cell)<br />A chemical signal binds to the extracellular part of the receptor causing a conformational change in the receptor (shape change) <br />
Signal Transduction (cont)<br />The conformational change in the receptor also changes the part of the enzyme inside the cell <br />There is a cascade of signals within the cell once activated <br />With each step, the signal is amplified, a small signal can lead to a large response<br />The signal causes a change in the cell <br />
Email 1 (cont) <br />Nitric Oxide is the first messenger and binds to the extracellular domain of the receptor<br />GuanylylCyclase is the second messenger inside the cell. The Nitric Oxide enters the cell and activates the messenger. The input of GTP makes cyclic GMP<br />GMP and the addition of ATP is an input of energy into the cascade and activates PKG (protein kinase) <br />Activated PKG activates the Phospho-Proteins which then lowers the amount of Calcium in the blood <br />
Email 1 (cont) <br />The lowering of Calcium desensitizes the cell to Calcium and increases blood flow<br />Increased blow flow leads to relaxation<br />The arrows in this diagram become increasingly larger because cell signals are amplified throughout the cell so that a small signal can trigger a large response<br />
Email 1 (cont) <br />The receptor in this cell is an enzyme-linked receptor<br />Has two important domains<br />Intracellular <br />Extracellular <br />
Email 2 <br />Ginseng <br />Ginseng is shown to increase locally produced nitric oxide (NO), all over the body. The mechanism is not completely understood, but the outcome is enhancement of erection in males.<br />Viagra<br />Muscle relaxation is countered by the activity of PDE breaking down cGMP. Viagra increases erection by blocking the activity of the PDE; by slowing the break-down of cGMP, erection is enhanced.<br />
Email 2 (cont) <br />Ginseng is known to increase NO2<br />If Ginseng was used for the dog, the amount of NO2 would be in greater supply. More NO2 would enter the cell and trigger the cell signal and response<br />Ginseng would increase blood flow by increasing the signal <br />
Email 2 (cont) <br />Phosphodiesterase (PDE5) is any enzyme that breaks a phosphodiester bond<br />It functions to remove cGMP once a signaling molecule, such as nitric oxide, is no longer present<br />This turns off the function of the signal molecule<br />Viagra inhibits phosphodiesterase so that it does not get turned off<br />This leads to increased blood flow and relaxation<br />
Email 2 (cont) <br />If neither chemical works, PKG is suspected to be dysfunctional <br />PKG activates the proteins and the lowering of calcium; it is activated by the cGMP<br />PKG affects other parts of the “cascade” in the cell <br />IP3 <br />P Lamban<br />Myosin light chain phosphotase<br />
Email 2 (cont) <br />Inositol trisphosphate receptor (IP3) <br />Membrane glycoprotein complex that acts as a calcium channel<br />When activated, it releases calcium into the cytoplasm<br />If PKG is dysfunctional, too much calcium will be released which would then raise calcium levels and decrease blood flow <br />
Email 2 (cont) <br />Phospholamban (P Lamban) <br />52-amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle and skeletal muscle cells<br />Cardiac muscle is also smooth muscle (same as the muscle in this case study) <br />If PKG is dysfunctional, it will not be able to control P Lamban. Therefore, the calcium pumps would not work properly and create a build up of calcium <br />
Email 2 (cont) <br />Myosin-light-chain phosphotase is an enzyme that catalyzes a chemical reaction<br />It is important for regulating contraction in smooth muscle <br />It is inhibited by calcium pathways for maintaining muscle contraction <br />If PKG is not working properly, the myosin light chain will contain too much calcium and muscle contraction will not function properly <br />
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