Biology 2382B Lecture Notes - Lecture 4: Adenylyl Cyclase, Glycogen Phosphorylase, Glycogen Synthase

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5 May 2018

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Functions of GCPR

1) GCPRs that Regulate K+ Channels in the Heart

- Muscarinic Acetylcholine Receptors found in heart cells involved in contraction of heart.

- GCPR binds acetylcholine (ligand), causing trimeric G-protein complex to move along the PM and bind

to the receptor. Alpha subunit releases GDP, binds GTP, but the Gβ subunit dissociates from the receptor

and the other subunits and binds the effector protein.

- The effector protein is a K+ protein channel and when Gβ binds to and activates it, potassium is

released into exterior of heart cell, leading to a slower rate of heart contraction.

2) GCPRs that Regulate Adenylyl Cyclase

- GCPR and adenylyl cyclase (effector protein that makes cAMP) in intestinal epithelial cells

- Epinephrine = stimulatory ligand

- PGE1 and Adenosine = inhibitory ligands

- When epinephrine eventually activates adenylyl cyclase, it makes cAMP (a 2nd messenger).

- Cholera toxin can enter directly into intestinal epithelial cell (no ligand required) and binds/activates

the stimulatory Gαs which activates adenylyl cyclase leading to lot of cAMP which activates protein

kinase A (PKA) which phosphorylates and activates CFTR (Cl-, Na+, + H2O pumped out).

- Pertussis toxin can enter the lung cells and binds/inhibits the inhibitory Gαi which leads to mass

activation of Adenylyl Cyclase leading to lots of cAMP which activates PKA which activates CFTR ion

pumps, and water accumulates in lungs...leads to whooping cough.

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How does cAMP activate PKA?

- cAMP = second messenger (amplifies activity of an enzyme).

- When cAMP is present, it binds to the B domain on the regulatory subunit which allows (increases

affinity/lowers Kd) another cAMP molecule to bind to the A (cooperative fashion). This causes the

catalytic subunits to dissociate so they can go onto phosphorylate things.

4 Common Intracellular 2nd Messengers

1. cAMP (activates PKA)

2. cGMP (activates PKG)

3. DAG (activates PKC)

4. IP3 (opens calcium channels in SR)

2nd Messengers  Signal Amplification

How does cAMP regulate glycogen metabolism?

Epinephrine  high [cAMP]  PKA activated

No Epinephrine  low [cAMP]  PP activated

PKA  2 regulatory subunits (where

cAMP regulates PKA) and 2 catalytic

subunits.

- epinephrine = ligand (steroid hormone)  not a lot of it

- adenylyl cyclase (effector) is eventually activated

- many cAMP molecules produced

- lots of PKA produced

- PKA phosphorylate proteins

- leads to adealie ush  speeds up heart rate, liberates

glucose from glycogen, vasoconstriction

- do’t eed a lot of hooe to eliit stog ad uik

response b/c amplified amount of cAMP is produced

Glycogen Metabolism is Activated

- PKA phosphorylates/activates GPK

- GPK phosphorylate/activates GP (glycogen phosphorylase)

- GP phosphorylates/breaks down glycogen

Glycogen Synthesis is Inhibited

- PKA phosphorylates/inactivates GS (glycogen synthase)

- PKA phosphorylates/activates inhibitor of PP

Glycogen Synthesis is Activated

- PP dephosphorylates/activates GS

Glycogen Metabolism is Inhibited

- PP dephosphorylates/inactivates GPK and GP

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3) GPCRs that Regulate Adenylyl Cyclase + CREB

- activates gene expression

- long-lasting

- Ligand binds GPCR

- Adenylyl Cyclase is activated

- [cAMP] increases

- PKA is atiated ad it’s atalti doai etes

nucleus and phosphorylates CREB (transcription factor)

- CREB dimer binds to CRE sequences in DNA

- leads to activation or repression of genes

4) GPCRs that Activate Phospholipase C

- Ligand binds GPCR

- Gα is activated

- Phospholipase C (effector) is activated

- Phospholipase C (PLC) cleaves PIP2  DAG and IP3

(2nd messengers)

- DAG stays near PM

- IP3 shuttles to ER membrane and opens Ca2+ channels

- [Ca2+] in cytosol increase and binds PKC

- PKC goes to PM and interacts w/DAG (PKC now active)

- Active PKC phosphorylates substrates including activators of MAPK

In Smooth Muscle Cells...

- Increase in cytosolic Ca2+ leads to production of NO gas

- NO gas diffuses into smooth muscle cells and binds/activates NO receptor

- NO receptors activate Guanylyl Cyclase which synthesizes cGMP

- cGMP activates PKG

- PKG triggers a pathway resulting in muscle relaxation and vasodilation

Viagra...

- PDE inhibitor

- PDE-5 converts cGMP to GMP

- If PDE-5 is inhibited, cGMP accumulates which continually activates PKG which continually allows

increased blood flow in the corpus caversonum of penis.

Side Effects of continually inhibiting PDE-5

- priapism (persistent erection)

- heart attack, stroke

- sudden hearing loss

- cyanopsia

- angina = chest pains

- angina results from ischemia (lack

of blood/oxygen to heart cells)

- nitroglycerin used to treat angina

b/c it decomposes into NO,

allowing relaxation of blood vessels

and blood flows back into heart.

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Related Questions

7 A) Which of the following steps amplify the epinephrine signal response in cells?

1. receptor activation of G protein

2. G protein activation of adenylyl cyclase

3. cAMP activation of PKA

4. PKA phosphorylation of glycogen phosphorylase kinase (GPK)

2, 3, and 4

1, 3, and 4

1 and 3

1 and 4

7 B) Which of the following statements regarding ion channel regulation by GPCRs is FALSE?

Activation of GPCRs in rod cells leads to increased neurotransmitter release.

The muscarinic acetylcholine receptor activates a K+ channel via the G-beta/gamma subunit.

The G-alpha subunit is responsible for activation of PDE in the membrane of rod cells.

Activation of GPCRs in rod cells causes the closing of nonselective cation channels in the membrane.

harlequinhound34

QUESTION 1

Which of the following is an example of an extracellular signal molecule?

	a.	IP₃
	b.	cAMP
	c.	Insulin
	d.	Diacylglycerol

2 points

QUESTION 2

Nuclear hormone receptors _____

	a.	Bind to water soluble ligands
	b.	Activate second messengers
	c.	Regulate transcription in response to ligand binding
	d.	Are normally located on the plasma membrane

2 points

QUESTION 3

Which of the following does not occur when a receptor tyrosine kinase is bound by ligand?

	a.	Phosphorylation of the RTK
	b.	Cytoplasmic proteins bind the phosphorylated RTK
	c.	Dimerization of the RTK
	d.	The RTK binds to DNA to regulate transcription

2 points

QUESTION 4

Which of these is a logical signal-transduction pathway?

	a.	An intracellular receptor activates phospholipase C, which cleaves a membrane protein to form IP₃, which then activates the opening of an ER channel protein, which releases cyclic AMP into the cytoplasm, where it binds to an intracellular enzyme that carries out a response.
	b.	A G-protein-linked receptor activates G protein, which activates phospholipase C, which cleaves a membrane lipid to form IP₃, which binds to a calcium channel on the ER, which opens to release calcium ions into the cytoplasm, which bind to an intracellular enzyme that carries out a response.
	c.	An ion-channel receptor opens, allowing a steroid hormone to enter the cell; the steroid hormone then activates protein kinases that convert GTP to GDP, which binds to an intracellular enzyme that carries out a response.
	d.	A tyrosine-kinase receptor activates adenylyl cyclase, which activates phospholipase C, which converts ATP into cyclic AMP, which binds to an intracellular enzyme that carries out a response.

2 points

QUESTION 5

Which of the following is an example of signal amplification?

	a.	activation of an enzyme molecule
	b.	activation of a specific gene by a growth factor
	c.	Breakdown of many cAMP molecules
	d.	activation of 100 molecules by a single signal binding event

2 points

QUESTION 6

Consider a signal transduction pathway that utilizes cAMP as a second messenger to activate PKA (Protein Kinase A). Which of the following situations will result in the cellular response?

		The G protein releases GDP and binds to GTP
		The target protein (adenylyl cyclase) is inactive
		The regulatory subunits of PKA (Protein Kinase A) are bound to the catalytic subunits
		The appropriate G protein is bound to GDP

2 points

QUESTION 7

Which of the following is found in only some signal transduction pathways? [In other words, which is not found in all signal transduction pathways?]

		Receptor protein
		Extracellular signal molecule
		Intracellular signaling molecule
		Cellular response
		Effector protein

2 points

QUESTION 8

The enzyme that specifically catalyzes the conversion of ATP to cAMP is:

		Adenylyl phosphatase
		Adenylyl kinase
		Adenylyl dehydrogenase
		Adenylyl cyclase

2 points

QUESTION 9

If an animal cell suddenly lost the ability to produce GTP, what might happen to its signaling system?

		It would use ATP instead of GTP to activate and inactivate the G protein on the cytoplasmic side of the plasma membrane.
		It would not be able to activate and inactivate the G protein on the cytoplasmic side of the plasma membrane.
		It would employ a transduction pathway directly from an external messenger.
		It would be able to carry out reception and transduction but would not be able to respond to a signal.

2 points

QUESTION 10

A hormone signal is sent from the brain to other parts of the body via the bloodstream. Why do only certain cells respond to this signal?

		Hormones do not last long enough in the bloodstream to stimulate a cellular response
		Only cells that have a specific transcription factor gene will be able to respond to the signal
		Only cells in the immediate vicinity of the cell sending the signal will respond
		Only cells that have a receptor for the specific signal will be able to respond to it

cerisehedgehog846

Tetraethylammonium (TEA) is a drug that blocks voltage-gated potassium channels. What effect would this have on an action potential?

(a)Prevent the rising phase

(b)Prevent the cell from reaching the threshold to trigger an action potential

(c)Prevent or prolong the falling phase

(d)None of the above

The hyperpolarization phase of the action potential is due to:

(a)The opening of voltage-gated Cl- channels

(b)Prolonged opening of voltage gated K+ channels

(c)The closure of resting Na+ channels

(d)Rapid inactivation of voltage-gated K+ channels

The period when it is difficult to initiate another action potential for several milliseconds due to voltage-gated sodium channel inactivation is referred to as the:

(a)Relative refractory period

(b)Absolute refractory period

(c)Resting period

(d)Hyperpolarization period

In the human central nervous system, Gap junctions are found:

(a)Only between neurons

(b)Only between astrocytes

(c)In both neurons and astrocytes

(d)In all cells

Small molecule transmitters such as acetylcholine are synthesized in:

(a)The nerve terminal

B) The cell body and transported to the nerve terminal

C) Synaptic vesicles

D) Endoplasmic reticulum

Prior to Otto Loewiâs classical experiment, which of the following was not known:

(a)stimulation of the vagus nerve slows the heart

(b)extracts of frog heart, made following vagal nerve stimulation, slow the heart

(c)some acetylcholine effects are similar to those produced by muscarine

(d)vagal nerve stimulation releases a substance which slows the heart

Which of the following is most important in determining if neurotransmission is excitatory or inhibitory?

(a)The structure of the synapse

(b)The neurotransmitter released by the presynaptic neuron

(c)The neurotransmitter receptor

(d)The strength of the stimulus

Benzodiazepines such as Valium allosterically regulate GABA receptors by:

(a)Binding at receptor sites other than the transmitter binding site

(b)Binding at the transmitter (GABA) binding site on the receptor

(c)Blocking the action of the endogenous transmitter

(d)Mimicking the action of the endogenous transmitter

GABA-A receptors are ligand-gated Cl- channels. The equilibrium potential of Cl- is -65 mV. At the neuronal resting membrane potential of -65 mV, GABA binding to the GABA-A receptor would result in the opening the Cl- channel, resulting in:

(a)no net flow of Cl- ions

(b)Cl- inflow and hyperpolarization

(c)Cl- outflow and depolarization

(d)Cl- outflow and hyperpolarization

At the mammalian neuromuscular junction, the released neurotransmitter acts on:

(a)muscarinic receptors

(b)nicotinic receptors

(c)adrenergic receptors

(d)Beta receptors

Neurotransmitters are packaged into synaptic vesicles by:

(a)endocytosis following transmitter release

(b)presynaptic membrane transporters

(c)vesicular transporters

(d)all of the above

. Which of the following are NOT types of ion channels?

Voltage-gated

(a)Ligand-gated

(b)G protein coupled receptor (GPCR)-gated

(c)Leak channels

(d)NONE of the above

NMDA receptors are unique in that their ion channel is:

(a)Ligand-gated

(b)Voltage-gated

(c)Ligand- and voltage-gated ion channels

(d)GPCR-gated

. Which of the following is INCORRECT regarding Catecholamine neurotransmitters

(a)Includes Dopamine, Norepinerphrine, and Epinephrine

(b)Contain a Catechol Ring

(c)Synthesized from Tryptophan

(d)Are produced by neurons whose cell bodies are located in the upper brainstem

The largest and most diverse group of receptors in eukaryotes is:

(a)Ligand gated receptors

(b)Glutamate receptors

(c)G-Protein coupled receptors

(d)Allosteric receptors

The most abundant G-protein coupled receptor in the brain is:

(a)Glutamate receptors

(b)Acetylcholine receptors

(c)Cannabinoid receptors

(d)Dopamine receptors

Which of the following drugs DOES NOT block voltage-gated Na+ channels

(a)Lidocaine

(b)Riluzole

(c)Reserpine

(d)Tetrodotoxin

Sarin, a nerve gas, exerts its toxicity by:

(a)blocking nicotinic receptors

(b)inhibiting choline acetyltransferase

(c)inhibiting acetylcholinesterase

(d)inhibiting voltage-gated Na+ channels

Botulinum Toxin (BoTox) interferes with transmitter release by:

(a)cleaving protein(s) involved in transmitter release

(b)blocking voltage-gated Ca2+ channels

(c)blocking voltage-gated Na+ channels

(d)blocking voltage-gated K+ channels

Atropine is:

(a)An agonist of the acetylcholine ionotropic receptor

(b)An antagonist of the acetylcholine ionotropic receptor

(c)An agonist of the acetylcholine metabotropic receptor

(d)An antagonist of the acetylcholine metabotropic receptor

Biology 2382B Lecture Notes - Lecture 4: Adenylyl Cyclase, Glycogen Phosphorylase, Glycogen Synthase

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