Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacy Year 2 > Cell signalling inc GPCR > Flashcards

Cell signalling inc GPCR Flashcards

1
Q

How do G proteins work?

A

The G-protein coupled receptor has 7-transmembrane domains.
1. Initially Gα has GDP bound, and α, β, & γ subunits are complexed
together.
2. Activation of a 7-helix receptor (GPCR) causes a conformational
change that is transmitted to the G protein. The nucleotide-binding
site on Gα becomes more accessible to the cytosol, where [GTP] >
[GDP].
3. Gα releases GDP & binds GTP (GDP-GTP exchange).
4. Substitution of GDP for GTP causes another conformational change
in Gα.
5. Gα-GTP dissociates from the βγ complex & can now bind to and
activate their respective downstream effectors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What do Gi, Gs and Gq proteins do?

A

Gs (Activates adenylate cyclase)
Gi (Inhibits adenylate cyclase activation)
Gq (Activates PLC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which receptors do noradrenaline/adrenaline bind to?

A

Noradrenaline/adrenaline activates adrenergic receptors. Specifically
α1 Linked to Gq β1, β2 and β3 are all Gs
α2 Linked to Gi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which receptors do acetylcholine bind to?

A

Acetylcholine activates cholinergic receptors. Specifically
M1 Linked to Gq
M2 Linked to Gi
M3 Linked to Gq

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the Gs signalling pathway?

A

Activation of adenylate cyclase results in ATP consumption resulting in
cAMP and PPI production.
cAMP activates Protein Kinase A, which catalyzes phosphorylation of
various cellular proteins, altering their activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the Gi signalling pathway?

A

Gi:
Inhibition of adenylate cyclase reduces availability of cAMP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the Gq signalling pathway?

A

Gq:
Activation of PLC results in membrane bound PIP2 hydrolysis, resulting in
the production of DAG and IP3.
IP3 releases Ca2+ from the endoplasmic or sarcoplasmic reticulum via IP3
receptors.
DAG activates Protein kinase C (PKC).
PKC catalyses phosphorylation of intracellular proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is a cascade and what is the process of one?

A

Events often occur in a relay chain, sometimes called a cascade.
A first messenger – extracellular molecule (signal), binds to a receptor.
Binding activates the receptor protein, which then activates relay protein.
Relay protein stimulates some other membrane protein which acts as an
effector (effects changes in cell) and usually produces a second
messenger.
Things to rem

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is a first messenger? and what do they activate?

A

First messenger – extracellular molecule (signal), binds to a receptor. Binding activates receptor protein, which then activates relay protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is a relay protein?

A

Relay protein stimulates another membrane protein which acts as an effector (effects changes in cell).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is an effector protein?

A

Effector protein – enzyme that produces a secondary messenger (cytoplasmic molecule that triggers metabolic and/or structural responses within cell).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are second messengers?

A

Intracellular signalling molecule whose concentration changes in response to binding of extracellular hormone (the first messenger) to cell-surface receptor
Include:
cAMP (3´,5´-cyclic AMP)
cGMP (3´,5´-cyclic GMP)
DAG (1,2-diacylglycerol)
IP3 (inositol 1,4,5-trisphosphate)
Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is a protein kinase?

A

Protein kinase
A kinase is an enzyme that phosphorylates another protein (or, in the case of a tyrosine-kinase receptor, also themselves).
ATP supplies the phosphate group.
A tyrosine kinase is therefore an enzyme that phosphorylates tyrosine amino acids found on target proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is a protein phosphatase?

A

Protein phosphatase
A protein phosphatase catalyzes the reverse reaction of the one catalyzed by a protein kinase, i.e., the hydrolytic removal of a phosphate added to a protein.
Protein phosphatases allow reversibility to the protein-kinase-mediated phosphorylation of a protein, thus contributing to the dynamic nature of a cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does a protein kinase do? how is it activated?

A

A protein kinase transfers the terminal phosphate of ATP to a hydroxyl group on a protein.

PKC phosphorylates proteins on the serine and threonine residues
PKC impt in cellular growth and division

PKC inactive without DAG or Ca2+ and is soluble in cytoplasm
binding of DAG and Ca2+ activates PKC and moves it to membrane (translocation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is a protein phosphatase?

A

A protein phosphatase catalyzes removal of the Pi by hydrolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How are protein kinases activated?

A

Ca2+-calmodulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How are Protein kinase A activated?

A

Protein Kinase A is activated by cyclic-AMP (cAMP).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is PLC? what is it linked to? and what does it produce, where are the products located?

A

phospholipase C (PLC) is an enzyme linked to receptor by Gq protein (stimulatory)
from the membrane phospholipid PLC produces the second messengers:
inositol trisphosphate (IP3) (moves into cytosol)
diacylglycerol (DAG) (stays in membrane)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the steps for DAG/IP3 signalling?

A
  1. Initially Gα has bound GDP, and α, β, & γ subunits are complexed together.
  2. Activation of a 7-helix receptor (GPCR) causes a conformational change that is transmitted to the G protein. The nucleotide-binding site on Ga becomes more accessible to the cytosol, where [GTP] > [GDP].
    Ga releases GDP & binds GTP (GDP-GTP exchange).
  3. Substitution of GTP for GDP causes another conformational change in Ga.
    Ga-GTP dissociates from the inhibitory bg complex & can now bind to and activate PLC.
  4. Membrane bound PIP2, hydrolysed by PLC forms DAG and IP3
  5. IP3 releases Ca2+ from SR IP3 receptors
    DAG activates PKC
  6. Protein Kinase C catalyzes phosphorylation of various cellular proteins, altering their activity.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is IP3 function and how does it do it?

A

IP3’s main functions are to mobilize Ca2+ from storage organelles and to regulate cell proliferation and other cellular reactions that require free calcium. In smooth muscle cells, for example, an increase in concentration of cytoplasmic Ca2+ results in the contraction of the muscle cell.

P3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does DAG do?

A

DAG helps activate protein kinase C (PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses.

23
Q

What happens when Ca2+ binds directly?

A

DIRECTLY can activate enzymes, ion channels, cytoskeletal proteins

24
Q

What happens when Ca2+ binds indirectly?

A

INDIRECTLY via calcium-binding proteins (e.g. calmodulin, CaM)) which activate protein kinases (CaM-protein kinases)

25
Q

what are tyrosine kinase receptors?

A

these receptors traverse the membrane only once
receptor has intrinsic enzyme activty
i.e. the receptor itself is an enzyme
respond exclusively to protein stimuli
cytokines
mitogenic growth factors:
platelet derived growth factor
epidermal growth factor

26
Q

What do kinase enzymes do?

A

Add phosphate groups (Pi) this changes shape of protein and alters its function.

27
Q

What do phosphatases do?

A

Remove phosphates

28
Q

What is an agonist?

A

Agonist - a chemical substance which binds to a receptor and activates it, thereby producing a cell’s response.acetylcholine

29
Q

What is an antagonist?

A

Antagonist - a drug which binds to a receptor, thereby preventing the binding of agonist and blocking its biological response
Tubocurarine

30
Q

What is competitive antagonism?

A

Competitive antagonism: Both agonist and antagonist compete for binding to the same receptor.

31
Q

What is reversible binding?

A

Reversible Binding: Increasing [agonist] reverses antagonist effect

32
Q

What is irreversible binding?

A

Irreversible Binding: Increasing [agonist] does not reverse antagonist effect.

33
Q

What is non competitive antagonism?

A

Non-competitive antagonism: Antagonist block response by inhibiting at some point other than the agonist receptor. e.g. Effect of tetrodotoxin inhibiting acetylcholine response.

34
Q

What is chemical antagonism?

A

Chemical antagonism: Not common. Chemical reaction inactivating the agonist. e.g. Dimercaprol reversing the enzyme inhibition of mercury

35
Q

What is pharmacokinetic?

A

Pharmacokinetic: Affects the pharmacokinetics of the agonist by reducing absorption, increasing excretion or degradation of the agonist. e.g. The effect of phenobarbitone on warfarin

36
Q

What is physiological?

A

Physiological: Has opposite effect by affecting different system/receptor. e.g. Histamine and Salbutomol.

37
Q

What is nitric oxide?

A

Nitric oxide is a free radical gas (NO). Formed in atmosphere during electrical storms.

ALSO formed in an enzyme catalysed reaction between molecular oxygen and L-arginine.

NO is a key signalling molecule in cardiovascular and nervous systems.

38
Q

How does cyclic GMP induce smooth muscle relaxation?

A

Cyclic GMP induces smooth muscle relaxation by multiple mechanisms including
1. increased intracellular cGMP, which inhibits calcium entry into the cell, and
decreases intracellular calcium concentrations.
2. activates K+ channels, which leads to hyperpolarization and relaxation.
3. stimulates a cGMP-dependent protein kinase that activates myosin light chain
phosphatase, the enzyme that dephosphorylates myosin light chains, which leads
to smooth muscle relaxation.

39
Q

How is ASTHMA TREATED?

A

Salbutamol - beta adrenergic receptor
Asthma is an inflammatory immure response which causes airways to constrict and increase mucus
Inc contractility decrease diameter of airways which makes it harder to breathe
salbutamol
↳drugs act on receptor classes to allow muscle airways to relax mimics adrenaline. Adrenaline stimulate beta adrenergic receptors. These are G protein couple receptors when activated the diameter increases + muscles relax

40
Q

What are ACE inhibitors used for?

A

High BP,

ACE inhibitors prevents the change from Angiotensin I to Angiotensin II allowing vasodilation. Angiotensin II causes vasoconstriction.

41
Q

Example of a Ca2+ blocker?

A

Nifedipine for hypertension
Lignocaine - Local Anaesthetic
tetrodotoxin - irreversible blocks CA channel DEAD before unblocks snake venom.

42
Q

Give an example of drug inhibiting enzymes

A

ACE inhibitor prevents angiotensin I to Angiotensin II prevents vasoconstriction
Drug - Captopril hypertension

Viagra (sildenafil) - erectile dysfunction
Prevents enzyme which normally degrade cyclic GMP the preventation helps cyclic GMP to promote smooth muscle relaxation overcomes erectil dysfunction.

Digitoxin - congestive heart failure (build up of fluid)
Digitoxin increases force of cardiac contraction it inhibits Na/K pump inc force of contraction of cardiomyocytes (heart) overcoming symptoms (tired, inc fluid legs/arms, not able to get enough blood to maintain normal O2 around body) of disease. It inhibits enzyme that ATP pase in NA/K ATPase pump.

43
Q

What is a muscle relaxant drug?

A

In surgical procedures Atracurium - blocks nicotinic receptors - blocks ligand gated sodium channels in skeletal muscle

44
Q

What drugs used for stomach acid - process?

A

Stomach acid irritates lining and can cause stomach ulcers. Cimetidine (drug) binds to histamine acts as an antagonist. This blocks the signalling pathway reduces protons and acidity present reducing stomach secretions.

45
Q

Example of K+ opening channels

A

Nicorandil and the K+ channel opener allowing vasodilation. Activate K channels - relaxation of muscle inc blood vessel diameter improve blood flow.

46
Q

What is the signalling pathway associated with b-adrenoreceptor activation in VASCULAR SMOOTH MUSCLE?

A

The beta receptor in smooth muscle is B2, this is G2 linked so will activate adenylate cyclase which dephosphorylates ATP giving the 2nd messenger cAMP which will activate protein kinase A (PKA).

47
Q

How does actin and myosin interact to cause a contraction in a muscle cell?

A

ATP binds to sites on the myosin head, this causes the head to detach from the actin filament. When ATP binds to the myosin head it activates ATPase and results in ADP + Pi, this is a conformational change which happens in the myosin head which can bind to the adjacent actin monomer of the filament. ADP dissociates and results in the POWER STROKE and actin is pulled across (ratchet effect). ATP binds to the myosin head and process repeats.

48
Q

What is the regulatory protein for Smooth muscle?

A

Calmodium

49
Q

What is the regulatory protein for cardiac?

A

Troponin (tropomyosin regulates access to myosin binding sites on the actin filament.

50
Q

What is the regulatory protein for skeletal muscle?

A

Troponin (tropomyosin regulates access to myosin binding sites on the actin filament.

51
Q

Describe mechanism regulating the interaction between actin and myosin in smooth muscle?

A

There is an increase in Calcium in smooth muscle which binds to calmodulin which activates myosin-light chain kinase. This allows ATP binding.

52
Q

Describe mechanism regulating the interaction between actin and myosin in Skeletal and Cardiac?

A

Inc in calcium binds to troponin. This results in a conformational change moving tropomyosin, exposing the myosin binding sites on the actin filaments. ATP regulates actin/myosin interactions.

53
Q

What causes contraction?

A

Actin myosin interaction - calcium binds to troponin which blocks tropomyosin allowing actin/myosin interaction

54
Q

What blocks contraction?

A

tropomyosin

Pharmacy Year 2 (33 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions