deck_782667

Question 1

What are G protein coupled receptors?

Answer 1

A family of receptors that act by altering the activity of effectors

Question 2

What do G-proteins activate in order to interact with effectors?

Answer 2

Gunaine nucleotide binding proteins

Question 3

What is the the word to describe G-proteins?

Answer 3

Heterotrimeric

Question 4

How can G-proteins be described as heterotrimeric?

Answer 4

The consist of three different subunits - alpha, beta and gamma- Beta and gamma bind tightly together and form single unit- Alpha has a GTP binding site which has GTPase activity (slowly hydrolyses bound GTP to GDP)

Question 5

Where is the G-protein usually present in the cell, and in what form?

Answer 5

at the inner face of the plasma membrane

Question 6

Describe what occurs when G-protein coupled receptor binds an agonist

Answer 6

Agonist binds receptorProtein-Protein interaction releases GDP, binds GTP to alpha subunita-GTP and bg released and interact with effectorsGTP hydrolysed to GDPa-GDP and bg reform heterotrimer

Question 7

What is the interaction of G proteins with effectors inhibited by?

Answer 7

Intrinsic GTPase activity of alpha subunit. Once bound GTP hydrolysed to GDP, the affinity of alpha subunit for bg increases, and the hetertotrimer reforms

Question 8

How g proteins be thought of a switches and timers?

Answer 8

The on switch is receptor-facilitated GDP/GTP exchangethe timer/off switch is governed by the length of time taken for GTP hydrolysis.

Question 9

What is the role of stimulatory G (Gs) proteins?

Answer 9

Plays an intermediate role - stimulate adenylyl cyclase to produce cAMP

Question 10

What is the role of inhibitory G protein (Gi) paths?

Answer 10

Inhibit adenylyl cyclase, reducing cAMP Also effect ion channels and signalling pathways involved in growth and differntiation

Question 11

What do Gq proteins interact with?

Answer 11

Activate phospholipase C, which hydrolyses PIP2 to IP3

Question 12

What is the name of the light sensing receptor in the eye, and what does it activate?

Answer 12

Rhodopsin, activates Gt whichin turn activates a phosphodiesterase enzyme that hydrolyses cyclic GMP to 5’-GMP

Question 13

What does adrenaline activate when activating b adrenoreceptors? Receptor, G protein, effects, physiological response

Answer 13

b-AdrenoceptorGsStimulates Adenylyl CyclaseGlycogenolysis, lipolysis

Question 14

What does acetylcholine activate when interacting with M3?

Answer 14

GqStimulates Phospholipase CSmooth Muscle Contraction

Question 15

What does Ach activate when interacting with M2?

Answer 15

GiInhibits Adenylyl CyclaseStimulates K+ ChannelSlowing of Cardiac Pacemaker

Question 16

What does light do?

Answer 16

RhodopsinGtStimulates Cyclic GMP PhosphodiesteraseVisual Excitation

Question 17

What G protein and effector do the following use?a1a2

Answer 17

a1 - Gq, stimulate phospholipase Ca2 - Gi, inhibit adenylyl cyclase

Question 18

What G protein and effector do the following use?b1b2

Answer 18

b - Gs, stimulate adenylyl cylase

Question 19

What G protein and effector do the following use?M1M2M3

Answer 19

M1 + M3 - Gq, stimulate phospholipase C,M2 - Gi, inhibit adenylyl cyclase

Question 20

How many Ga, Gb and Gg exist?

Answer 20

20 Ga, 5Gb and 12+ Gg proteins.

Question 21

How may possible Ga, Gb and Gg combinations are there?

Answer 21

over 1,000

Question 22

How many receptor types are there, and what do they interact with?

Answer 22

800 receptor types, which can interact with different G subtypes to activate/inhibit 10 or more enzyme/ion channel effectors.

Question 23

What do Cholera (CTx) and Petussis (PTx) toxin do the G protein cycle?

Answer 23

enzymes that ADP-Ribosylate specific G-Proteins

Question 24

What does CTx do?

Answer 24

Eliminates the GTPase activity of Gsa, leading it to become irreversibly activated (opening chloride ion channels!)

Question 25

What does PTx do?

Answer 25

PTx interferes with the GDP/GTP exchange on Gia. This leads Gia to become irreversibly inactivated.

Question 26

What can genetic changes to GPCRs cause?

Answer 26

loss-of-function or gain-of-function mutations

Question 27

How is retinitis Pigmentosa caused?

Answer 27

By a loss-of-function mutation to Rhodopsin

Question 28

What are the symptoms of retinitis pigmentosa?

Answer 28

Severe visual impairment

Question 29

How is nephrogenic diabetes insipidus cause?

Answer 29

By a loss-of-function mutation to V2 Vasopressin receptor

Question 30

What are the symptoms of nephrogenic diabetes insipidus?

Answer 30

improper response of the kidney to ADH, leading to a decrease in the ability of the kidney to concentrate the urine by removing free water

Question 31

What is Familial Male Precocious Puberty caused by?

Answer 31

a gain-of-function mutation (Receptor active without ligand) to the Luteinising Hormone (LH) Receptor

Question 32

What are the symptoms of amilial Male Precocious Puberty?

Answer 32

Early onset puberty?

Question 33

Name three diseases caused by mutations to G-protein coupled receptors

Answer 33

Retinitis Pigmentosa Nephrogenic Diabetes InsipidusFamilial Male Precocious Puberty

Question 34

What is the mechanism of adenylyl cyclase?

Answer 34

This enzyme hydrolyses cellular ATP to generate cyclic AMP. Cyclic AMP interacts with a specific protein kinase (PKA) which phosphorylates a variety of proteins to affect cell activity

Question 35

What does adenylyl cylcase cause to happen in cells?

Answer 35

-increased Glycogenolysis and gluconeogenesis in the liver- increased lipolysis in adipose tissue- relaxation of a variety of types of smooth muscle- positive inotropic and chronotropic effects in the heart.

Question 36

What is the mechanism of phospholipase C?

Answer 36

Activates by Gq and hydrolses PIP2 to IP3IP3 exerts effects by interacting with receptors on ER to allow calcium to enter cytoplasm

Question 37

How does Cyclic GMP phosphodiesterase work?

Answer 37

It regulates the breakdown of the second messenger cyclic GMP phosphodiesterase by Gt

Question 38

How are G-protein coupled receptor pathways deactivated

Answer 38

- When activated, receptor vunerable to variety of protein kinases that phosphorylate the receptor and prevent it activating further G proteins- The active lifetime of a GTP may be limited by cellular factors that stimulate intrinsic GTPase activity of Ga subunit- Cells contain high activity enzymes that metabolise second messengers, rapidly returning their levels to the basal (favoured state)- Enzymatic cascades activated downstream of second messenger/protein kinase activation act to oppose their effect.

Question 39

How is chronotrophy in the heart regulated?

Answer 39

- Rate at which SA node fires affect by Ach release by parasympathetic nerves- Activation of M2 receptors increases oen probability of K+ channels via Gi- Increasing membrane permeability to K+ causes hperpolarisation, slowing intrinsic firing rate- This causs negative chronotrophic effect

Question 40

How is intotrophy in heart regulated?

Answer 40

- Sympathetic innervation of cardiac ventricles can influence force of contraction- Activation of B adreno receptors increases open probability of voltage operated calcium channels via Gs- Gs both interact directly with VOCCs and indirectly via cyclic AMP --> PKA --> phosphorylation and activation VOCCs- Influx of Ca2+ brings about postive inotropic effect

Question 41

How is arteriolart vasoconstriction regulated?

Answer 41

Sympathetic release of noradrenaline acts on 1-adrenoceptors to stimulate phospholipase C and IP3 production via Gq. The IP3 releases ER Ca2+ (See above) and initiates a contractile response.

Question 42

How is neutransmitter release modulated?

Answer 42

-Pre-synaptic G-Protein-Coupled Receptors - pre-synaptic u-opiod receptors can be stimulated, either by endogenous opiods or by analgesics such as morphine to couple to GaI proteins.- The G subunits liberated from the heterotrimer interact with VOCCs to reduce Ca2+ entry, thus reducing neurotransmitter release.