Signaling

Question 1

___________________ is a 51 amino acid peptide that is released by pancreatic beta cells of the islets of Langerhans when the concentration of blood glucose is high.

Answer 1

Insulin

Question 2

______________________ is a 29 amino acid peptide hormone that is released when the concentration of glucose in the blood drops below 5 mM.

Answer 2

Glucagon

Question 3

Where are receptors for glucagon located in the body?

Answer 3

In the liver and fat cells; there are no glucagon receptors on muscle cells

Question 4

_______________________ is a catecholamine hormone that signals fight or flight; it is produced in the adrenal glands.

Answer 4

Epinephrine

Question 5

Both _____________ and ____________ act upon G-protein coupled receptors.

Answer 5

Glucagon

Epinephrine

Question 6

____________ ________________ ____________ _____________ are a key component of a signaling pathway - a pathway that transduces a signal that converts information (i.e., a hormonal signal) into a chemical change. Signal transduction pathways are characterized by having highly specific interacts between ligands and receptors in the nM k_d range and amplified signals.

Answer 6

G-protein coupled receptors

Question 7

What are the three essential components of G-protein coupled receptors?

Answer 7

1. Plasma membrane receptor with 7 transmembrane helical segments
2. An effector enzyme in the pasma membrane that generates an intracellular second messenger
3. A guanine nucleotide binding protein (“G-protein”)

Question 8

What are the seven steps of the GPCR stimulatory pathway?

Answer 8

1. Ligand binds to receptor
2. Occupied receptor causes replacement of the GDP bound to Gs by GTP, activating Gs
3. Gs (alpha subunit) moves to adenylyl cyclase and activates it
4. Adenylyl cyclase catalyzes the formation of cAMP
5. cAMP activates PKA
6. PKA phosphorylates cellular proteins that causes response to ligand
7. cAMP is degraded, reversing the activation of PKA

Question 9

What are three ways to stop a signal?

Answer 9

1. Degrade secondary messenger (cAMP)
2. Replace GTP with GDP on G-protein (intrinsic GTPase activity)
3. Receptor endocytosis

Question 10

What degrades the secondary messenger cAMP?

Answer 10

Cyclic nucleotide phosphodiesterase

Question 11

______ _____________ is a heterotrimeric protein that consists of three subunits (alpha, beta, gamma). Upon hormone binding to receptor, GDP is replaced by GTP, activating the alpha subunit and releasing it from the beta-gamma complex. The alpha subunit moves in the membrane to an effector protein and activates it. This protein contains intrinsic GTPase activity that limits its time in the active GTP bound state.

Answer 11

G-protein

Question 12

_____________ _______________ is an integral membrane protein that is activated by association with Gsalpha-GTP and catalyzes the formation of the secondary messenger, cAMP.

Answer 12

Adenylyl cyclase

Question 13

___________ is a common secondary messenger, an intracelullar mediator of an extracellular hormonal signal.

Answer 13

cAMP

Question 14

Adenylyl cyclase catalyzes the conversion of ATP to _____________, a 3’ –> 5’ cyclic structure.

Answer 14

Cyclic AMP

Question 15

___________________ phosphorylates multiple targets at specific sites containing serine or threonin residues; it is inactive when its regulatory and catalytic subunits are bound together and active when cAMP binds its regulatory subunits, freeing its catalytic subunits.

Answer 15

Protein kinase A

Question 16

In the liver, what is the net effect of glucagon signaling?

Answer 16

Increased blood glucose levels; therefore, gluconeogenesis should be on

Question 17

When glucagon binds its GPCR on a liver cell, what signaling pathway is stimulated?

Answer 17

PKA is activated; PKA phosphorylates PFK2/FBPase2, which activates the FBPase2 domain

When FBPase2 is activated, the concentration of fructose-2,6-bisphophate decreases, which activates FBPase1 and gluconeogenesis

Question 18

When glucagon binds its receptor in the liver, what is the effect on PFK-2/FBPase-2?

Answer 18

PFK-2/FBPase-2 is phosphorylated, which deactivates PFK-2 activity and activates FBPase-2 activity

Question 19

What happens to the concentration of fructose-2,6-bisphosphate when PFK-2/FBPase-2 is phosphorylated?

Answer 19

It decreases because FBPase-2 domain is active

Question 20

When PFK-2/FBPase-2 is phosphorylated, the concentration of fructose-2,6-bisphosphate decreases. What effect does this have on PFK-1?

Answer 20

PFK-1 is deactivated and glycolysis is inhibited

Question 21

When PFK-2/FBPase-2 is phosphorylated, the concentration of fructose-2,6-bisphosphate decreases. What effect does this have on FBPase-1?

Answer 21

FBPase-1 is activated and gluconeogenesis is stimulated

Question 22

When PKA is activated by the glucagon signal in the liver, two targets are phosphorylated: PFK-2/FBPase-2 and _______________ ______________.

Answer 22

Pyruvate kinase

Question 23

Phosphorylation of pyruvate kinase by PKA ___________________ the enzyme.

Answer 23

Inactivates

Question 24

Glucagon acts on both liver and ______ cells.

Answer 24

Fat

Question 25

In the liver, the effect of epinephrine is the same as that of glucagon; epinephrine can also act on muscle cells, but its effects are different there. Why?

Answer 25

In muscle, epinephrine stimulates the break down of glycogen; therefore glycolysis is operational

Question 26

Glucagon and epinephrine stimulate gluconeogenesis in the liver, but in the muscle cells, epinephrine stimulates what process?

Answer 26

Glycogenolysis

Question 27

What type of receptor is the insulin receptor?

Answer 27

A tyrosine kinase receptor (RTK)

Question 28

\_\_\_\_\_\_\_\_\_\_\_\_\_\_ __________________ \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ function as binding sites for hormones on the extracellular face of the plasma membrane with enzymatic active sites on the cytoplasmic face; enzymatic activity is a protein kinase that phosphorlyates tyrosine residues in target proteins, and insulin receptor substrate (IRS-1) is phosphorylated upon insulin binding.

Answer 28

Receptor tyrosine kinase

Question 29

Insulin stimulates three major cellular responses. What are they?

Answer 29

1. Movement of glucose transporters to the membrane 2. Increase in the transcription rates of glycolytic enzymes (PK, glucokinase, PFK-1) 3. Decrease in the transcription rates of gluconeogenesis enzymes (PEPCK, G6Pase, FBPase-1)

Question 30

What do glucose transporters facilitate?

Answer 30

The diffusion of glucose across the plasma membrane

Question 31

What glucose transporter is found in the liver and remains embedded within the plasma membrane?

Answer 31

GLUT2

Question 32

What glucose transporter is located in the brain and resides within the plasma membrane?

Answer 32

GLUT3

Question 33

What glucose transporte is found in cardiac and skeletal muscle tissues and adipose tissues and moves from intracellular vesicles to the plasma membrane upon insulin signaling?

Answer 33

GLUT4

Question 34

What is the net result of insulin signaling?

Answer 34

Increase in glycolytic flux

Question 35

How does insulin stimulate glycolytic flux?

Answer 35

Insulin binding results in phosphorylation of phosphoprotein phosphatase, which dephosphorylates PFK-2/FBPase-2; this activates PFK-2 and deactivates FBPase-2, leading to increased concentrations of F26BP; increased concentrations of F26BP stimulate the activity of PFK-1 and inhibit the activity of FBPase-1, thereby turning glycolysis on and gluconeogenesis off