Signal Transduction Pathways - Chapter 13 Flashcards
What are the key steps to signal-transduction pathways?
- Release of the primary messenger
- Reception of the primary messenger; membrane receptors transfer information from the environment to the cell’s interior
- Relay of information by the second messenger concentration change
- Activation of effectors that alter the physiological response
- Termination of the signal
What are second messengers? How do they relay information?
Second messengers are small molecules used to relay information from the receptor-ligand complex. Their concentration changes.
They can diffuse to other parts of the cell and influence other processes. They can also amplify the signal in response to a low concentration of signal molecules.
What happens if signals are not terminated?
Cells lose their responsiveness to new signals; also increases vulnerability to uncontrolled cell growth and cancer.
What does the structure of cyclic AMP or cyclic GMP look like?
What structure is this?
Cyclic AMP/Cyclic GMP
What structure is this?
Calcium ion
What does the structure of calcium look like?
What does the structure of inositol 1,4,5-triphosphate (IP3) look like?
What structure is this?
Inositol 1, 4, 5-triphosphate (IP3)
What structure is this?
Diacylglycerol (DAG)
What does the structure of diacylglycerol (DAG) look like?
What do Seven-Transmembrane-Helix receptors do in response to ligand binding?
Change conformation and activate G proteins
What kind of receptor is the B-adrenergic receptor? What does it bind?
7TM (seven-transmembrane-helix)/G protein complex receptor
Binds epinephrine (adrenaline)
Which hormone is responsible for the fight-or-flight response? Which receptor binds it?
Epinephrine and the B-adrenergic receptor
Describe the process of ligand binding to 7TM/GPCR receptors.
- Ligand binds to the receptor
- Conformational change in the7TM receptor
- Activation of G proteins
What is a G protein?
A GTP-binding protein
When activated, it stimulates adenylate cyclase, which then increases the concentration of cAMP
What does adenylate cyclase do? How is it activated?
Adenylate cyclase is an enzyme that increases the concentration of the second messenger cAMP by forming it from ATP. It is stimulated by an activated G protein.
Which guanyl nucleotide is bound to the G protein in its unactivated state? Describe its structure.
GDP
G protein exists as a heterotrimer with alpha, beta, and gamma subunits. The alpha subunit binds the nucleotide; the alpha and gamma subunits are anchored to the membrane by covalently attaching fatty acids.
What catalyzes the exchange of bound GDP for GTP?
ligand-bound receptor interacts with heterotrimeric G protein and opens the nucleotide bindng site so GDP can leave and GTP can bind; the alpha subunit dissociates from the beta-gamma dimer and transmit signal that receptor has bound its ligand
What transmits the signal the 7TM receptor bound its ligand?
Dissociation of the G-protein heterotrimer into G-alpha and G-beta-gamma
What does protein kinase A do?
Kinases phosphorylate a substrate at the expense of a molecule of ATP. It mediates the impact of cAMP in eukaryotic cells.
Describe the structure of PKA and how it responds to cAMP.
2 regulatory subunits and 2 catalytic subunits
Binding of cAMP to the regulatory subunits releases the catalytic subunits, which are enzymatically active alone. Then, specific serine and threonine residues in targets are phosphorylated.
Which residues are phosphorylated by PKA in the presence of cAMP?
serine and threonine
What does cAMP phosphodiesterase do?
Turns off the cAMP cascade by converting cAMP into AMP, which cannot activate PKA
What converts cAMP to AMP?
cAMP phosphodiesterase
How is the signaling pathway started by 7TM receptors turned off?
G-alpha subunits have GPTAse activitiy and can hydrolyze bound GTP to GDP and Pi, deactivating itself.
It acts as a built in clock that resets the G-alpha subunit after a short time period.
What influences the likelihood that a receptor will remain unbounded?
concentration of ligand in the environment