Lecture 4 Flashcards
(16 cards)
Briefly explain the adenylyl cyclase/epinephrine/GPCR pathway for increasing blood sugar
1) Epinephrine binds to the GPCR which causes the alpha-G protein to exchange GDP for GTP (activating the alpha g-protein)
2) The alpha-GTP subunit dissociates from the beta/gamma subunits and binds to adenylyl cyclase (activating it)
3) Adenylyl cyclase will produce a secondary messenger called cAMP from ATP and activated protein kinase A.
4) PKA will phosphorylate phosphorylase kinase b (activating it)
5) Phosphorylase kinase b will phosphorylate glycogen phosphorylase (activating it)) and allows for the degradation of glycogen.
6) This obtains glucose which is sent into the bloodstream so blood sugar levels will be increased.
7) Protein kinase A will phosphorylate glycogen synthase and inhibit it. (reciprocal regulation - don’t want glycogen synthesis active while glycogen degradation is active)
Where do cells receive signals that causes changes in cell composition and function? What’s an example of this?
Cells receive signals from their environment. The kind of signals that a cell may receive might be antigens or hormones, causing the cell to produce antibodies or begin cell growth/division.
For fight or flight, what hormone is released? Where is it released from? Where does it bind? What are the results of binding to these regions?
Epinephrine is released by the adrenal glands and binds to receptors in the muscles/liver, adipose tissue, and heart cells.
Binding of epinephrine to receptors in muscle and liver cells induces breakdown of stored glycogen. (glycogen breakdown for energy) Binding to adipose/fat cells induces lipid hydrolysis. (for energy) Binding to receptors in the heart increased heart rate. (faster delivery of oxygen to the muscles)
How do g-proteins become activated?
When GTP binds ot the GTP binding region of the Ras g-protein, the unstructured loops of the protein will help move and change the g-protein to activate it.
How is the second messenger cAMP degraded in the epinephrine/adenylyl cyclase/GPCR pathway? What affect does this have on the rest of the pathway?
The second messenger cAMP is degraded if you have a bunch of cAMP. This utilizes a phosphodiesterase enzyme to decyclize the cAMP to produce AMP. This reverse the activity of PKA (no more cAMP to activate PKA.) As a result, phosphorylation steps and cleaving of glucose from glycogen stop.
What are hormone agonists vs antagonists?
Hormone agonists are the ones that mimic the hormone and bind to the same receptor as a specific hormone and elicit a similar response. Hormone antagonists are ones that bind to the same receptor and do nothing.
What are the different types of signals that a cell can receive? What are the two major forms of these signals?
They can receive chemical signals (hormones and neurotransmitters), physical signals (pressure, temperature, light), or biological (differentiation, apoptosis)
The 2 major forms are those carried by nerve cells (neuronal signaling), and those carried by soluble molecules (hormonal/endocrine signaling)
What are the four features of signal-transducing systems? Explain.
1) Specificity: receptors bind specific ligands - receptors are only specific to some ligands and not others
2) Amplification: binding of single molecule to one enzyme leads to the activation of more enzymes, leading to the activation of even more enzymes
3) Desensitization/adaptation: If a hormone is bound to a receptor, it won’t over amplify or overdo a response if it does not need to be. (good example to growing immunity to Tylenol and needing to take higher dosage)
4) Integration: 2 different signals that activate 2 different receptors and those can come together to create a single response.
What is binding affinity? How do we measure the affinity of a signaling molecule and its receptor?
Binding affinity is how much the ligand wants to be with the receptor. A common measure is the dissociation constant. The lower the value of the dissociation constant, the more likely the ligand and receptor are.
What is reciprocal regulation?
It’s the process which prevents 2 pathways from occurring simultaneously. Glycolysis will be stimulated and gluconeogenesis is stopped.
What is signal transduction?
It is the process by which a cell converts a signal or stimulus into a metabolic activity.
Why is signal amplification important?
It makes processes in the cell occur faster, and to make an all or nothing cellular response.
How does self-inactivation in g-protein signaling work? Why is this important?
Inactivation of g-protein signaling occurs through hydrolysis of GTP to GDP, thus inactivating the alpha g-protein. The g-protein has the ability to hydrolyze the GTP to GDP. The addition of helper proteins will make this process occur much faster in the alpha-GTP subunit. You will have cAMP being broken down by the phosphodiesterase after this as well.
This is important because epinephrine is meant to be a short acting signal, it must be able to stop glucose synthesis if there is no need for it.
How do a large number of GPCRs mediate their effects?
cAMP
How can a bunch of different receptors all use cAMP as a secondary messenger, yet still have the correct response?
Different cells may use cAMP as the same secondary messenger, but they contain different enzymes/proteins which respond differently to the effects of cAMP. This causes different effects to occur within different cells.
In the beta-adrenergic receptor, the alpha subunit dissociates from the beta/gamma subunits as soon as the alpha subunit swaps out the bound GDP for GTP. What do the beta/gamma subunits do after dissociation of the alpha-GTP? Why are they important?
As soon as epinephrine binds to the beta-adrenergic receptor, the alpha subunit exchanges its bound GDP for a GTP molecule, thus causing it to dissociate from beta-gamma g-proteins. After this occurs, the beta-gamma subunits become responsible for the desensitization of the beta-adrenergic receptor. This is a result of overstimulation/continued stimulation by a ligand. After the alpha-GTP subunit dissociates, the beta-gamma subunits will recruit beta-adrenergic receptor kinase, which will phosphorylate serine residues on the c-terminus of the receptor. This allows for the recruitment of another protein called beta-arrestin, which stops the receptor from continuing to work. Binding of the beta-arrestin to the phosphorylation site of the c-terminus will cause endocytosis of the portion of the cell membrane which contains the beta-adrenergic receptor and c-terminus bound beta-arrestin. The receptor becomes engulfed on the inside of the cell in a tiny vesicle. Once the beta-arrestin dissociates, the phosphates on the c-terminus domain of the receptor become hydrolyzed off, and the receptor can go back to the plasma membrane to prepare for another signal.
This is important because endocytosis of the receptor through activity of the Gαβ/βARK/βarr prevents the receptor from binding another epinephrine again.
If continued stimulation by a ligand occurs, desensitization will occur to prevents receptor being present on the cell membrane such that no more responses to hormones occur down the road.
