GPCR And cAMP

Question 1

What do g protiens help with

Answer 1

Help activate specific effector molecules

Question 2

What type of signalling is GPCR

Answer 2

Second messenger

Question 3

How can GTP binding protiens (g protiens) act as switches to regulate signal events

Answer 3

They exact as both active (when GTP is bound) or inactive (gdp it bound)

This change happens through hydrolysis and nucleotide exchange

Question 4

What do GPCRs work together with to relay signals

Answer 4

Work with heterotrimic g protiens

Question 5

What are heterotrimeric g protiens

How are they linked to the membrane

Answer 5

They are protiens with three different polypeptide units

Alpha beta and gamma

They relay signals from the ligand bound active receptor to the cytoplasm or nucleus through an effector protien

The alpha and gamma subunits are linked to the membrane by lipid groups

Question 6

Describe the process of receptor mediated activation of effectors via heterotrimeric g protiens

Answer 6

First inactive gdp version of trimetic protien is near receptor

Ligand binds and alters the confirmation of the receptor and increases affinity of it for g protiens

The GTP binding site on the alpha subunit of the trimeric prtion is attached to receptor (still inactive)

Galpha removes gdp and gets GTP

The nucleotide exchange results in a conformational change in the galpha subint (attached to the effector since less affinity for gamma and beta)

The effector (which is adenylyl cyclase) produces cAMP as a second messenger and second messengers activate one or more signalling protiens in a cascade effect

GTP hydrolysis of alpha subint occurs and induced a confirmational change

Question 7

How does termination of receptor mediated activation of effectors via heterotrimeric g protiens happen

Answer 7

The g aplha conformation change lets it leave the effector and go back to gbetagamma to make the inactive heterotrimeric g protien and inactive effector

The receptor (with ligand) gets phosphorylated by Grk (g protien coupled receptor kinase)

The conformational change from the ligand that causes GPCRS to activate g protiens make them good substrates for GRK

The phosphylated receptor gets bound by arrestin which stops it from activating more g protiens

The receptor is then taken up by endocytosis

Question 8

What else does arrestin do

Answer 8

Facilitates the degredation of the second messengers

Question 9

How does cyclic amp get made and how is it broken down

Answer 9

For example, in glucose mobilization

The heterotrimeric g protiens activate an effector called adenylyl cyclase

Adenylyl cyclase is a integral membrane protien that has it catalytic domain on the inner surface of the plasma membrane

This effector then makes cAMP from atp

Camp is broken down by phosphodiesterase

Question 10

What are the three ligands that activate adenylyl cyclase through three different receptors

Answer 10

ACTH

epinephrine

Glucagon

Question 11

What does acth do to adenylyl cyclase

Answer 11

Adrenocorticotopic hormone from the pituitary gland (so this is endocrine signalling)

Through endocrine signalling, It controls cortisol production

Question 12

What does glucagon do to adenylyl cyclase

Answer 12

In the pancreas it increase blood glucose levels

Question 13

What does epinephrine do to adenylyl cyclase

Answer 13

It’s in the adrenals and is the fight or flight hormone

Question 14

What happens if you add all three ligand with all three of their receptors in the same cell

Answer 14

It’s assumed that their effect on adenylyl cyclase activity would be additive but that’s not the case

They’re are having to share and stimulate the same population of adenylyl cyclase molecules

Question 15

What is glucose and how is it stored

What is glucagon

Answer 15

A source of energy that gives cells atp

Excess is stored as glycogen (linked glucoses)

Glucagon is a hormone that breaks down glycogen

Question 16

What is insulin

Answer 16

It stimulates the uptake of glucose and storage of glycogen

Question 17

What happens if a liver cell is introduced to glucagon or epinephrine

Answer 17

A cAMP induced response

First g alpha activated adenylyl cyclase (effector) like normal

Then cAMP (second messenger) are formed like normal

The camp molecules diffuse into cytoplasm and bind to a camp dependent kinase called protein kinase a (PKA)

Question 18

if a liver cell is introduced to glucagon or epinephrine what happens after PKA goes into the cytoplasm

Answer 18

Goes into the cytoplasm where it phosphorylated glycogen phosphorylase which then phosphorylates glycogen to make glucose

Also can inhibit glycogen
Synthase by phosphorylating it

Or goes in the nucleus

Question 19

if a liver cell is introduced to glucagon or epinephrine what happens when pka goes into the nucleus instead of just cytoplasm

Answer 19

It phosphorylates the transcription factor CREB (camp response element binding protien)

The phosphorylated CREB binds as a dimer to CRE (CAMP response elements) in the dna sequence

In the liver this helps the enzymes carry out gluconeogenesis to form glucose

Question 20

Which types of tissues give diffeeent responses to the same signalling pathway?

Answer 20

Liver

Skeletal muscle

Cardiac muscle

Camp is made in all of these by all different types of ligands

Question 21

In the liver, what hormone activate the pathway and what is the response

Answer 21

Epinephrine and glucagon

Glycogen breakdown, gluconeogensis (formation of glucose) inhibition of glycogen synthesis

Question 22

In the skeletal muscle, what hormone activate the pathway and what is the response

Answer 22

Epinephrine

glycogen breakdown, inhibition of glycogen synthesis

Question 23

In the cardiac muscle, what hormone activate the pathway and what is the response

Answer 23

Epinephine

Increase contractility

Question 24

Cards 1-13 check with liaba

Answer 24

Okay