Biochem, Lecture 37 - G-Protein Coupled Receptors

Front 1

In g-protein coupled receptors, what are the four main components?

Back 1

1. A receptor (inactive until binding)
2. A G-protein
3. An effector
4. A secondary messenger

Front 2

How many subunits does a G-protein have and what are they?

Back 2

G-proteins are tri-meric - have an alpha, beta and gamma subunits.

Front 3

In g-protein coupled receptors, how is a signal detected and how does it activate the g-protein? What happens to the g-protein?

Back 3

Binding of a hormone causes a conformational change in the receptor, which then binds to the ALPHA subunit of G-protein. Alpha subunit changes conformation, looses GDP and gains a GTP

Front 4

After binding the the active receptor and exchanging GDP for GTP, what happens to the G-protein?

Back 4

GTP causes alpha subunit to disassociate from beta/gamma, then interacts with the EFFECTOR, activating it. Hydrolysis causes GTP-GDP change, alpha subunit then disassociates from effector, binds back with beta/gamma

Front 5

What is the most common type of effector, and what does an activated effector do most commonly? How are its effects carried through the cell?

Back 5

Most common = adenylyl cyclase. This catalyzes the creation of CYCLIC AMP (cAMP). cAMP = secondary messenger.

cAMP's effects are mediated through pKA (protein kinase A).

Front 6

How do inhibitory signals work? What are some examples of inhibitory hormones?

Back 6

there can be inhibitory signals picked up and transmitted with inhibitory receptors/g proteins. Adenosine is one example.

Alpha-i subunit inhibits, same way as a normal alpha activates. Lowers production of cAMP.

Front 7

Name 4 secondary messengers and the mediator that transmits their signal through the cell

Back 7

cAMP = pKA

cGMP = pKG

DAG = pKC

IP3 = opens Ca++ channels in ER

Front 8

pKA - what subunits does it have, and what happens to them?

Back 8

pKA has 2 subunits - a regulatory and catalytic. cAMP binds regulatory, displacing it, allowing catalytic to go to work.

Catalytic subunit goes through NUCLEAR MEMBRANE.

Front 9

Once the catalytic subunit translocates into the nucleus, what does it bind? How are genes turned on, and what are the DNA regions called that respond?

Back 9

Catalytic subunit binds CREB (cAMP response element biding protein), that binds to a CRE area of DNA (cAMP response element) - a CBP coactivator binds, helping to induce basal transcription.

Front 10

What kind of receptor detects epinephrine, and what secondary messenger is used?

Back 10

Epi is picked up by the Beta-Andrenergic receptor and uses cAMP as a secondary messenger. pKA phosphorylates, ups heart rate, glycogen metabolism, constricts vessels

Front 11

Acetycholine receptor - How is it different? How is cAMP involved? What's the secondary messenger?

Back 11

Acetycholine uses the muscarinic receptor. Binding of hormone causes alpha I subunit to GDP-GTP, disassociate. NOTE - beta/gamma subunit is business end - interacts with K+ channel, opens, REDUCES heart rate. GTP-GDP re-associates, turns off.

cAMP has NO ROLE. K++ channel is the secondary messenger.

Front 12

Aside from the heart, what other organ should we think of with muscarinic acetycholine recptors?

Back 12

Overactive bladders - binding of acetycholine causes bladder contraction

Front 13

Heart failure and g-protein coupled receptors - what's the receptor used and what's the mechanism?

Back 13

B-andrenergic receptors, responsive to chatecholamines (adrenaline) - use cAMP, results in release of sarcoplasmic reticulum Ca+. Need to have difference in [Ca+] in cytosol vs. SR for normal heart function. Too much activation = weak heart.

Front 14

What drug can we use to fight heart failure?

Back 14

Beta blockers - stop the Beta-andronergic receptor, decrease cAMP production, keep Ca+ in the SR and lower [Ca+] in the cytosol = better heart function.

Front 15

If you use phospholipase C as an effector, what's the effect on the cell?

Back 15

Think Ca+ release from ER. Phospholipase C releases IP3 which opens CA+ channels. Phospholipase C also activates DAG, a protein the PM. Ca+ tells pKC to associate with DAG in the membrane and get activated.

Front 16

When i hear calcium/calmodulin regulation, what should i think of?

Back 16

think relaxation of smooth muscle and dilation of blood vessels.

Acetycholine can bind + activate Phospholipase C, which activates IP3 to release Ca+ from ER. Ca+ binds with CALMODULIN to activate nitric oxide, which diffuses.

NO receptor on smooth muscles activated, turns on cGMP to pKG relaxes muscles = DILATION OF BLOOD VESSLES.

Front 17

How is cholera related to G-proteins?

Back 17

Cholera toxin activates G-alpha unit, keeping it stimulated = up cAMP = up Cl- channel

Front 18

How is whooping cough related to g-proteins?

Back 18

Bortella pertussis - modifies G-alpha-I (inhibitory) - can't displace GDP for GTP, so inhibition never activated = hyperactivation, up cAMP, up fluid loss into lungs.