Cell Signaling III

Question 1

What are ionotropic receptors?

Answer 1

Ion channels - signals directly bind to the ion channel

Question 2

What are metabotropic receptors?

Answer 2

GPCRs - signal binding to GPCR results in increase in 2nd messenger levels

Question 3

What is an example of a neurotransmitter that is both ionotropic and metabotropic?

Answer 3

ACh - binds to ionotropic receptors in skeletal muscle, but to metabotropic receptors in the heart

Question 4

How do the beta cells of the pancrease release insulin?

Answer 4

1. Blood glucose levels increase
2. Cytoplasmic ATP levels increase from cellular respiration
3. ATP-sensitive K+ channels close, depolarizing cell
4. Voltage-gated Ca2+ channels open, causing Ca2+ influx
5. Ca2+ activates insulin gene expression via CREB
6. Exocytosis of insulin into blood increases

Question 5

What happens when sulfonyl ureas bind and close K+ channels in the beta cells of pancreas?

Answer 5

Membrane potential moves closer to threshold, making it easier to depolarize the cell so more insulin can be released

Question 6

How does signaling by insulin primarily occur?

Answer 6

Enzyme-linked receptor

Question 7

What type of receptor is the insulin receptor?

Answer 7

Tyrosine kinase

Question 8

Describe the insulin/IRS family mechanism.

Answer 8

1. Insulin binds to inactive tyrosine kinase receptor, which phosphorylates itself and the IRS family.
2. 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.

Question 9

How does insulin stimulate glycogen synthase? Defects in this system lead to what disease?

Answer 9

Inhibits a deactivating kinase

Type 2 diabetes mellitus (insulin resistance)

Question 10

How does insulin regulate metabolism of major nutrients including transport of glucose into cells?

Answer 10

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.

Question 11

Name three insulin-sensitive tissues. What type of GLUT transporter do they have?

Answer 11

Adipose, skeletal muscle, cardiac muscle

GLUT 4

Question 12

Name 3 anabolic (cell division/growth) processes insulin causes.

Answer 12

1. Increases protein, glycogen, lipid, and ATP synthesis
2. Decreases protein, glycogen, lipid degradation
3. Activates glucose, AA, Na+/K+ ATPase transporters

Question 13

Describe insulin’s effect on the MAP kinase cascade. How can a mutation in this mechanism lead to cancer?

Answer 13

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).

Question 14

What are normal blood glucose levels? How is blood glucose concentration regulated?

Answer 14

70-110 mg/dL or 5 mM

Insulin decreases blood glucose concentration.
Glucagon, GH, cortisol, epinephrine increase blood glucose concentration.

Question 15

What is the function of IRS (insulin receptor substrate)

Answer 15

Act as a docking site for other proteins/kinases

Question 16

How is insulin signaling terminated? Name two ways.

Answer 16

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.

Question 17

What are 3 shared features of the following signals: cortisol, prednisone, aldosterone, vitamin D, thyroxin

Answer 17

Readily enter cells, related to cholesterol, alter gene transcription

Question 18

Name two examples gene transcription alteration that can decrease inflammation.

Answer 18

1) Increase synthesis of inhibitory IkBa

2) Decrease synthesis of cytokines like IL-1, IL-2, TNF-alpha

Question 19

Synthesis of what molecules increases during inflammation?

Answer 19

NFkB, TNF-alpha, IL-1, IL-2

Question 20

What hormone do we produce more of to cope with stress?

Answer 20

Cortisol

Question 21

What are some of the effects of increased cortisol levels?

Answer 21

Increased eating, fluid retention - edema, hyperglycemia, lipidemia, prone to infections

Question 22

What drug is a modified cortisol used for treating asthma that has many expected side effects?

Answer 22

Prednisone

Question 23

What drug should you use for a child with an acute asthma attack?

Answer 23

Albuterol - faster acting than Prednisone

Question 24

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.

Answer 24

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