Cell Signaling III Flashcards
What are ionotropic receptors?
Ion channels - signals directly bind to the ion channel
What are metabotropic receptors?
GPCRs - signal binding to GPCR results in increase in 2nd messenger levels
What is an example of a neurotransmitter that is both ionotropic and metabotropic?
ACh - binds to ionotropic receptors in skeletal muscle, but to metabotropic receptors in the heart
How do the beta cells of the pancrease release insulin?
- Blood glucose levels increase
- Cytoplasmic ATP levels increase from cellular respiration
- ATP-sensitive K+ channels close, depolarizing cell
- Voltage-gated Ca2+ channels open, causing Ca2+ influx
- Ca2+ activates insulin gene expression via CREB
- Exocytosis of insulin into blood increases
What happens when sulfonyl ureas bind and close K+ channels in the beta cells of pancreas?
Membrane potential moves closer to threshold, making it easier to depolarize the cell so more insulin can be released
How does signaling by insulin primarily occur?
Enzyme-linked receptor
What type of receptor is the insulin receptor?
Tyrosine kinase
Describe the insulin/IRS family mechanism.
- Insulin binds to inactive tyrosine kinase receptor, which phosphorylates itself and the IRS family.
- IRS 1-4 bind to various cytosolic proteins through the IRS phosphorylated Tyr groups and activate them so they can phosphorylate or dephosphorylate other proteins.
How does insulin stimulate glycogen synthase? Defects in this system lead to what disease?
Inhibits a deactivating kinase
Type 2 diabetes mellitus (insulin resistance)
How does insulin regulate metabolism of major nutrients including transport of glucose into cells?
Initiates phosphorylation rxns in cell that send signal to glucose receptors located on an intracellular endosome to tell them to migrate to the cell membrane so they can boost glucose uptake into cell.
Name three insulin-sensitive tissues. What type of GLUT transporter do they have?
Adipose, skeletal muscle, cardiac muscle
GLUT 4
Name 3 anabolic (cell division/growth) processes insulin causes.
- Increases protein, glycogen, lipid, and ATP synthesis
- Decreases protein, glycogen, lipid degradation
- Activates glucose, AA, Na+/K+ ATPase transporters
Describe insulin’s effect on the MAP kinase cascade. How can a mutation in this mechanism lead to cancer?
Activates Ras, which activates MAP kinases, resulting in cell division.
Ras has an intrinsic GTPase activity, so if mutation leads to loss of this function, there will be constant signaling to divide cells (cancer).
What are normal blood glucose levels? How is blood glucose concentration regulated?
70-110 mg/dL or 5 mM
Insulin decreases blood glucose concentration.
Glucagon, GH, cortisol, epinephrine increase blood glucose concentration.
What is the function of IRS (insulin receptor substrate)
Act as a docking site for other proteins/kinases
How is insulin signaling terminated? Name two ways.
1) Low glucose levels decreases insulin secretion. Leftover insulin is then degraded in liver and kidney by insulinase and other proteases.
2) Phosphatases dephosphorylate insulin-dependent kinases.
What are 3 shared features of the following signals: cortisol, prednisone, aldosterone, vitamin D, thyroxin
Readily enter cells, related to cholesterol, alter gene transcription
Name two examples gene transcription alteration that can decrease inflammation.
1) Increase synthesis of inhibitory IkBa
2) Decrease synthesis of cytokines like IL-1, IL-2, TNF-alpha
Synthesis of what molecules increases during inflammation?
NFkB, TNF-alpha, IL-1, IL-2
What hormone do we produce more of to cope with stress?
Cortisol
What are some of the effects of increased cortisol levels?
Increased eating, fluid retention - edema, hyperglycemia, lipidemia, prone to infections
What drug is a modified cortisol used for treating asthma that has many expected side effects?
Prednisone
What drug should you use for a child with an acute asthma attack?
Albuterol - faster acting than Prednisone
Patient presents with hyperkalemia with K+ levels > 6mM. Abnormal blood K+ levels can lead to cardiac arrhythmias. Normal K+ levels are 3.5 - 5 mM. What infusion of IV will you use to quickly lower serum K+ levels.
Insulin and glucose - insulin will increase transport of nutrients/ions and glucose into cells so giving patient glucose will keep their blood glucose levels normal
