Exam 2 GPCR and TKR

Question 1

Signal molecule fits binding site on its complimentary receptor; other signals do not fit

Answer 1

Specificity

Question 2

When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade

Answer 2

Amplification

Question 3

Proteins with multivalent affinities form diverse signaling complexes from interchangeable parts. Phosphorylation provides reversible points of interaction

Answer 3

Modularity

Question 4

Receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell

Answer 4

Desnsitization/Adaptation

Question 5

When two signals have opposite effects on a metabolic characteristic such as the concentration of a second messenger, X, or the membrane potential, Vm, the regulatory outcome results from the integrated input from both receptors (net response)

Answer 5

Integration

Question 6

Signaling where external ligand (L) binds to receptor (R) and activates an intracellular GTP-binding protein (G), which regulates an enzyme that generates an intracellular second messenger (X)

Answer 6

G protein-coupled receptor

Question 7

Signaling where ligand binding activates tyrosine kinase activity by autophosphorylation. Kinase activates transcription factor that then alternates gene expression

Answer 7

Receptor tyrosine kinase

Question 8

Ligand binding to extracellular domain stimulates formation of a second messenger cGMP (Viagra)

Answer 8

Receptor guanylyl cyclase

Question 9

Opens or closes in response to concentration of signal ligand or membrane potential

Answer 9

Gated-ion channel

Question 10

Hormone binding allows the receptor to regulate the expression of specific genes (Group 1 signaling androgens)

Answer 10

Nuclear receptor

Question 11

Three essential elements of G-protein coupled receptors

Answer 11

1. Plasma membrane receptor with seven transmembrane segments
2. G protein that cycles between GTP bound (active) and GDP bound (inactive) forms
3. An effector enzyme/ion channel that is regulated by GPCR and generates secondary messengers that effect downstream intracellular targets

Question 12

Approximately how many drugs (%) bind to GPCRs?

Answer 12

50%

Question 13

What are the three different subunits of GPCRs, and what is the classification?

Answer 13

a, b, y

Heterotrimeric

Question 14

What does the alpha subunit do?

Answer 14

Binds to GDP (off) or GTP (on) and transmits signal to effector protein

Question 15

What are alpha subunits that transfer a signal?

Answer 15

Stimulatory G proteins (Gs)

Question 16

What happens when a GPCR is active?

Answer 16

B and Y subunits dissociate from the A subunit as a BY dimer and Gs moves to its effector protein

Question 17

What happens when GPCR is inactive?

Answer 17

B and Y subunits are bound to the A subunit

Question 18

What are two enzymes that converts Gs (GTP) to the inactive form?

Answer 18

GAP, RGS

Question 19

A GPCR that has seven transmembrane spanning domains

Answer 19

Beta-adrenergic receptor

Question 20

What does the Beta-adrenergic receptor usually bind to?

Answer 20

Epinephrine

Question 21

This receptor binds agonists that inhibit the release of norepinephrine and contraction of the anal sphincter

Answer 21

Alpha-2

Question 22

This receptor causes vasodilation, bronchodilation, and smooth muscle relaxation

Answer 22

Beta-2

Question 23

The receptor causes increased heart rate and force of contraction

Answer 23

Beta-1

Question 24

This receptor binds agonists that effect smooth muscle contraction and vasoconstriction of the skin

Answer 24

Alpha-1

Question 25

Agonist of the beta-adrenergic receptor

Answer 25

Isoproterenol

Question 26

Antagonist of the beta-adrenergic receptor that is a non-selective beta-blocker

Answer 26

Propranolol

Question 27

Describe the 7 steps of a typical G-protein coupled receptor

Answer 27

1. Epinephrine binds to receptor
2. Hormone-receptor complex causes GDP to be replaced by GTP and activate Gsa
3. Activated Gsa seperates from Gsby and moves to adenylyl cyclase to activate it
4. Adenylyl cyclase catalyzes the formation of cAMP
5. cAMP activates PKA
6. Phosphorylation of cellular proteins by PKA causes the cellular response to epinephrine (second messenger)
7. cAMP is degraded and shuts off PKA

Question 28

Describe how Gsa-GTP is turned off

Answer 28

GTP is hydrolyzed by Gsa’s intrinsic GTPase, and the Gsa subunit reforms with the Gsby subunit

Question 29

Four methods of terminating the beta-adrenergic receptor response

Answer 29

1. Epinephrine concentration drops below Kd for the receptor, the hormone dissociates and Gsa is inactive
2. Hydrolysis of GTP bound to Gsa leads to reformation of complex with Gsby
3. Cyclic nucleotide phosphodiesterase hydrolyzes cAMP which lowers [cAMP]
4. Phosphoprotein phosphatases remove phosphates from activated PKA

Question 30

How does the beta-adrenergic receptor undergo desensitization?

Answer 30

Binds to beta-adrenergic receptor kinase (BARK) and beta-arrestin (Barr). Binding of Barr results in receptor sequestration via endocytosis

Question 31

Steps of binding beta-arrestin (Barr)

Answer 31

1. Epinephrine binds to beta-adrenergic receptor. Gsby dissociates from Gsa
2. Gsby recruits BARK to the membrane, where it phosphorylates Ser residues at the carboxyl terminus of the receptor
3. Beta-arrestin (Barr) binds to the phosphorylated carboxyl-terminal domain of the receptor
4. Receptor-arrestin complex enters the cell by endocytosis
5. In an endocytotic vesicle, arrestin dissociates; the receptor is dephosphorylated and returns to the cell surface

Question 32

cAMP is a secondary messenger for when the cell is in a (low / high) energy state

Answer 32

Low energy state

Question 33

Binding of epinephrine to the beta adrenergic receptor results in mobilization of ________ stores to release glucose-1-phosphate

Answer 33

Glycogen stores

Question 34

What hormone stimulates adenylyl cyclase?

Answer 34

Glucagon when it binds to its receptors

Question 35

What affect does adenylyl cyclase have on [cAMP]?

Answer 35

Increases

Question 36

Increase [cAMP] leads to _____ activating proteins that result in the metabolism of ________ _______

Answer 36

PKA activating proteins that metabolize fatty acids

Question 37

PKA can also enter the nucleus and interact with what protein, which changes the expression of genes affected by cAMP?

Answer 37

cAMP response element binding protein (CREB)

Question 38

If a hormone inhibits adenylyl cyclase, this will then (raise / lower) [cAMP], and (stimulate / inhibit) protein phosphorylation

Answer 38

lower [cAMP]; inhibit protein phosphorylation

Question 39

What happens when prostaglandin E1 binds to adipocytes?

Answer 39

Slows mobilization of fatty acids, and counteracts the stimulatory binding of epinephrine

Question 40

Describe the steps involving a hormone binding to a Gq receptor protein

Answer 40

1. Hormone binds to receptor
2. Occupied receptor exchanges GDP for GTP and activates
3. Gq-GTP moves to PLC and activates it
4. Active PLC cleaves PIP2 to IP3 and diacylglycerol
5. IP3 binds to receptor-gated Ca++ channel which releases Ca++
6. The presence of diacylglycerol and Ca++ in the cytosol activates surface protein kinase C (PKC)
7. PKC phosphorylates cellular proteins to give cellular response to hormone

Question 41

An integral subunit of Ca++/calmodulin-dependent protein kinases

Answer 41

Calmodulin