GPCR And cAMP Flashcards
What do g protiens help with
Help activate specific effector molecules
What type of signalling is GPCR
Second messenger
How can GTP binding protiens (g protiens) act as switches to regulate signal events
They exact as both active (when GTP is bound) or inactive (gdp it bound)
This change happens through hydrolysis and nucleotide exchange
What do GPCRs work together with to relay signals
Work with heterotrimic g protiens
What are heterotrimeric g protiens
How are they linked to the membrane
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
Describe the process of receptor mediated activation of effectors via heterotrimeric g protiens
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
How does termination of receptor mediated activation of effectors via heterotrimeric g protiens happen
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
What else does arrestin do
Facilitates the degredation of the second messengers
How does cyclic amp get made and how is it broken down
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
What are the three ligands that activate adenylyl cyclase through three different receptors
ACTH
epinephrine
Glucagon
What does acth do to adenylyl cyclase
Adrenocorticotopic hormone from the pituitary gland (so this is endocrine signalling)
Through endocrine signalling, It controls cortisol production
What does glucagon do to adenylyl cyclase
In the pancreas it increase blood glucose levels
What does epinephrine do to adenylyl cyclase
It’s in the adrenals and is the fight or flight hormone
What happens if you add all three ligand with all three of their receptors in the same cell
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
What is glucose and how is it stored
What is glucagon
A source of energy that gives cells atp
Excess is stored as glycogen (linked glucoses)
Glucagon is a hormone that breaks down glycogen
What is insulin
It stimulates the uptake of glucose and storage of glycogen
What happens if a liver cell is introduced to glucagon or epinephrine
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)
if a liver cell is introduced to glucagon or epinephrine what happens after PKA goes into the cytoplasm
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
if a liver cell is introduced to glucagon or epinephrine what happens when pka goes into the nucleus instead of just cytoplasm
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
Which types of tissues give diffeeent responses to the same signalling pathway?
Liver
Skeletal muscle
Cardiac muscle
Camp is made in all of these by all different types of ligands
In the liver, what hormone activate the pathway and what is the response
Epinephrine and glucagon
Glycogen breakdown, gluconeogensis (formation of glucose) inhibition of glycogen synthesis
In the skeletal muscle, what hormone activate the pathway and what is the response
Epinephrine
glycogen breakdown, inhibition of glycogen synthesis
In the cardiac muscle, what hormone activate the pathway and what is the response
Epinephine
Increase contractility
Cards 1-13 check with liaba
Okay
