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Question 1

What can signalling occur between?What are three types of chemical signal classification?

Answer 1

Between secreted molecules and between plasma membrane bound molecules Endocrine - HormoneSynaptic - NeutransmissionParacrine - Chemical Mediators

Question 2

What is hormonal signalling?

Answer 2

Signalling between cells in different tissues via the circulation

Question 3

What kind of signalling do neurotransmitters do?

Answer 3

Signalling at specialised cell junctions in the nervous system at synapses

Question 4

Define paracrine signalling

Answer 4

Signalling where the target tissue is close to the cell releasing the hormone xc- local chemical mediators

Question 5

Define ligand

Answer 5

Any small molecule that binds specifically to a receptor site

Question 6

What kind of action does an agonist ligand bring about?

Answer 6

Agonist activate receptors

Question 7

What action does an antagonist ligand bring about?

Answer 7

In binds with a receptor without causing activation– opposes the agonist

Question 8

What is the name for an agonist that stimulates a receptor but does not elicit a maximum cell response?

Answer 8

Partial agonist

Question 9

Define receptorWhat occurs when the receptor is in an unbound state

Answer 9

A molecule that recognises specifically a ligand or family of ligands. In response to ligand binding. It brings about regulation of a cellular process Unbound state = functionally silent

Question 10

What does the binding of adrenaline to a B-adrenergic receptor activate?

Answer 10

It activates adenylyl cyclase which activates a cascade of events inside the cell.

Question 11

Which has a higher affinity: ligand binding at a receptor or substrates and allosteric regulators to enzyme sites?

Answer 11

Ligand binding at receptor sites

Question 12

Give some examples of the roles that receptors have? (8)

Answer 12

• Signalling by hormones/local chemical mediators• Neurotransmission• Cellular delivery• Control of gene expression• Cell adhesion• Modulation of the immune response• Sorting of intracellular proteins• Release of intracellular calcium stores

Question 13

How are receptors classified?

Answer 13

By which signal molecule they recognise before being subclassed in to their affinity for certain antagonistse.g. ACh receptors can be nicotinic or muscarinic but both will bind to nicotine and muscarine.

Question 14

What are the differences between receptors and acceptors?

Answer 14

Receptors – are silent at rest and agonist binding stimulates a biological responseAcceptors – can operate in absence of ligand.

Question 15

How has evolution solved the problem of transducing extracellular into intracellular signals?

Answer 15

The receptor and the effector molecules are on separate proteins but are coupled by a transducing protein.

Question 16

What are the four methods of signal transduction?What are the relative speeds of change for each process?

Answer 16

1. Membrane-bound receptors with integral ion channels2. Membrane-bound receptors with integral enzyme activity3. Membrane-bound receptors which couple to effectors through transducing proteins4. Intracellular receptorsFast to slow – 1 to 4

Question 17

What is an acceptor?

Answer 17

A molecule which can carry out its basic function without the binding of a ligand

Question 18

Give some examples of membrane-bound receptors with integral ion channels

Answer 18

• Nicotinic acetylcholine receptor (nAChR)• Gamma amino butyric acid (GABA) receptor • Glycine receptor- gated chloride channel• Glutamate receptors - Gated Ca2+ entry• Inositol 1,4,5-trisphosphate (IP3) receptor - gated release of Ca2+ from the ER

Question 19

Why is signal transduction necessary?

Answer 19

Hydrophillic signal molecules cannot pass through the cell membrane – must bind to an extracellular receptor to transmit the signal into the cell. All signal need a receptor in order for the cell to recognise a specific signal and be able to coordinate a response.

Question 20

Describe ligand gated ion channels and the method of signal transduction

Answer 20

Agonist binding to a ligand gated channel causes a conformational change in the receptor, opening the channel and allowing the flow of ions down and electrochemical gradient, stimulating an electrical response in the cell.

Question 21

What is the classical subunit structure of a logan gated ion channel and give an example of one of these receptors.

Answer 21

pentameric subunit structures with four transmembrane domains. The M2 domain lines the channel pore. – nicotinic ACh receptor

Question 22

What type of residues are present in nACh receptors which give it selectivity?

Answer 22

Acidic residues which are negative therefore give the pore cationic attraction

Question 23

What other type of ligand gated ion channels can you get?

Answer 23

Non-classical ligand gated ion channelse.g ATP sensitive K+ channel, Ryanodine receptors and P2x purinoceptors

Question 24

Descibe the series of events that occur when an agonist binds with membrane bound receptors with integral enzyme activity

Answer 24

Agonist binding to these receptors causes a conformational change, which activates an intrinsic enzyme activity which is contained within the protein structure of the receptor

Question 25

Give some examples of membrane bound receptors with integral enzyme activity

Answer 25

1. Atrial natriuretic peptide receptros which is coupled to guanylyl cyclase2. Insulin receptors -- tyrosine kinase3. Epidermal growth factor-- tyrosine kinase4. Platelet derived growth factor -- tyrosine kinase

Question 26

What happens when an agonist binds to a tyrosine kinase linked receptor?

Answer 26

Protein kinase activated whic autophosphorylate tyrosine residues on the receptors. They are the recognised by other transducing proteinsor enzymes with phosphotyrosine recognition sites (Src-homology-2 domains)This allosterically activates effector enzymes and transduces the message into an intracellular chemical event.

Question 27

What is the most common mechanism for transducing signals?

Answer 27

Using membrane-bound receptors that signalthrough transducing proteins-- Seven transmembrane domain (7TMD) receptors

Question 28

What are membrane bounds receptors that signal throught ransducing proteins also called?

Answer 28

G-protein coupled receptor family

Question 29

What type of effectors are present in the G-protein coupled receptor family?

Answer 29

enzymes (adenylyl cyclase)ion channels

Question 30

Give a couple of examples of signalling molecules that have he seven transmembrane structure

Answer 30

muscarinic ACh receptorsDopamine receptorslight, smell and taste receptorsB-adrenoceptors -- adrenaline binding

Question 31

How do G-proteins work?

Answer 31

Receptor binding results in a conformational change which activates GDP/GTP exchange in GTP-binding regulatory proteins, which transduce the message on to an enzyme or channel in the membrane. The subunits then dissociates and GTP binding to an enzyme or channel and activates it.

Question 32

What do the different G-proteins do?

Answer 32

Gs = stimulatoryGi = inhibitory

Question 33

What are the different enzymes that can be activated by G-proteins?

Answer 33

Adenylyl cyclase --> convert ATP to cAMPIon channels e.g. K+ or Ca2+ channels

Question 34

When do intracellular responses take place?

Answer 34

When there is a hydrophobic ligand (steroid hormones) which can bind to nucleic receptors or monomeric receptors in the cytoplasm.

Question 35

How are intracellular receptors stabilised in the cell?

Answer 35

By association with heat shock or chaperone proteins.

Question 36

How are the intracellular signal activated?

Answer 36

The DNA binding domain is blocked by an inhibitory protein. Hormone binding causes a conformational change, which exposes the binding site. Gene transcription is changed.

Question 37

What is a particular characteristic of intracellular receptors?

Answer 37

They have a very similar structure

Question 38

Describe integrated signalling

Answer 38

Occurs when separate G-protein coupled receptirs act simultaneaously to stimulate and inhibit the effector. The two inputs combine to produce a measured effort.

Question 39

What is amplification?

Answer 39

The process by which the concentration of a substrate molecule increases exponentially.-- One active ligand can stimulate 4 G-proteins-- Activation increases exponentiallyA single receptor can cause the modification of hundreds or thousands of substrate molecules.

Question 40

What can the binding of a molecule to a receptor do?

Answer 40

Can activate or inhibit actions inside the cell e.g. B-adrenoceptors in the heart increase the rate while ACh muscarinic receptors decrease the ratehepatocytes -- insulin stimulates synthesis of glycogen and glucagon stimulate glycogen breakdown