My Dog is Broken!Maria Chiaffarano and Julia Burton

Signal Transduction Process by which an extracellular signal

molecule activates a membrane receptor that in turn alters intracellular molecules to create a response

Transmembrane receptors span the cell membrane (part of the membrane is inside, part is outside the cell)

A chemical signal binds to the extracellular part of the receptor causing a conformational change in the receptor (shape change)

Signal Transduction (cont) The conformational change in the

receptor also changes the part of the enzyme inside the cell

There is a cascade of signals within the cell once activated

With each step, the signal is amplified, a small signal can lead to a large response

The signal causes a change in the cell

Email 1

Email 1 (cont) Nitric Oxide is the first messenger and binds to the

extracellular domain of the receptor Guanylyl Cyclase is the second messenger inside

the cell. The Nitric Oxide enters the cell and activates the messenger. The input of GTP makes cyclic GMP

GMP and the addition of ATP is an input of energy into the cascade and activates PKG (protein kinase)

Activated PKG activates the Phospho-Proteins which then lowers the amount of Calcium in the blood

Email 1 (cont) The lowering of Calcium desensitizes

the cell to Calcium and increases blood flow

Increased blow flow leads to relaxation 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

Email 1 (cont) The receptor in this cell is an enzyme-

linked receptor Has two important domains

Intracellular Extracellular

Email 2

Email 2 Ginseng

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.

Viagra 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.

Email 2 (cont) Ginseng is known to increase NO2 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

Ginseng would increase blood flow by increasing the signal

Email 2 (cont) Phosphodiesterase (PDE5) is any enzyme that

breaks a phosphodiester bond It functions to remove cGMP once a signaling

molecule, such as nitric oxide, is no longer present

This turns off the function of the signal molecule Viagra inhibits phosphodiesterase so that it does

not get turned off This leads to increased blood flow and relaxation

Email 2 (cont) If neither chemical works, PKG is suspected to be

dysfunctional PKG activates the proteins and the lowering of

calcium; it is activated by the cGMP PKG affects other parts of the “cascade” in the cell

IP3 P Lamban Myosin light chain phosphotase

Email 2 (cont) Inositol trisphosphate receptor (IP3)

Membrane glycoprotein complex that acts as a calcium channel

When activated, it releases calcium into the cytoplasm

If PKG is dysfunctional, too much calcium will be released which would then raise calcium levels and decrease blood flow

Email 2 (cont) Phospholamban (P Lamban)

52-amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle and skeletal muscle cells

Cardiac muscle is also smooth muscle (same as the muscle in this case study)

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

Email 2 (cont) Myosin-light-chain phosphotase is an

enzyme that catalyzes a chemical reaction It is important for regulating contraction in

smooth muscle It is inhibited by calcium pathways for

maintaining muscle contraction If PKG is not working properly, the myosin

light chain will contain too much calcium and muscle contraction will not function properly