Session 6

Question 1

What is a receptor?

Answer 1

A molecule that recognises specifically a second molecule or family of molecules and responds to binding by bringing about changes.

Question 2

How are receptors classified?

Answer 2

By their specificity to a ligand.

Then by their affinity to a series of agonists.

Question 3

Why is the affinity of ligands binding to receptor sites so high?

Answer 3

Because the ligand may be present in very small concentrations.

Question 4

What are some of the roles of receptors?

Answer 4

Signalling via hormones

Neurotransmittion

Question 5

What is it called when a molecule operates in absence of its ligand?

Answer 5

An acceptor

Question 6

What is a ligand?

Answer 6

Any molecule that binds specifically to a receptor site.

Question 7

What is an agonist?

Answer 7

Where binding of the ligand activates the receptor.

Question 8

What is an antagonist?

Answer 8

Where binding of the ligand doesn’t cause activation. It blocks the receptor.

Question 9

What molecule can bind to receptors inside the cell?

Answer 9

Small hydrophobic molecules as they can pass through the membrane.

Question 10

How can hydrophillic signalling molecules cause a reaction?

Answer 10

They bind to receptors at the cell surface which then transmit a signal into the cell and causes signal transduction.

Question 11

What is signal transduction?

Answer 11

A mechanism that converts a mechanical/chemical signal into a cellular response.

Question 12

How can membrane bound receptors cause cellular responses?

Answer 12

Integral ion channels
Integral enzyme activity
Coupling to effectors through transducing proteins

Question 13

How do membrane bound receptors with integral ion channels cause a cellular response?

Answer 13

The agonist binds, causing a conformational change and the opening of the ion channel. This then allows ions to flow down an electrochemical gradient.

Question 14

What is the classical ligand gated ion channel family structure?

Answer 14

Pentameric subunit structures with four transmembrane domains. eg Nicotinic Ach receptors.

Question 15

What is an example of a non classical ligand gated ion channel?

Answer 15

Ryanodine receptor

Question 16

How do membrane bound receptors with integral enzyme activity cause a cellular response?

Answer 16

An agonist will bind to the extracellular domain of the receptor. Causes a conformational change. Then activates an intrinsic enzyme activity contained within the protein structure of the receptor. eg PDGF linked to Tyrosine Kinase.

Question 17

What happens when the ligand binds to Tyrosine Kinase Linked receptors?

Answer 17

There is autophosphorylation. The phosphorylated receptor tyrosine residues are recognised by transducing proteins or enzymes with phosphotyrosine recognition sites.

Question 18

What happens when there is an association the receptor or transducing protein and phosphotyrosine?

Answer 18

Effector enzymes become activated allosterically/by receptor kinase. This transduces the message into an intracellular chemical event eg Insulin receptors.

Question 19

How can membrane bound receptors with transducing proteins cause a cellular response?

Answer 19

Transmembrane domain (7) receptors couple to effector molecules via a transducing molecule (GTP binding regulatory protein - G protein)

Question 20

What can be the effectors of G proteins?

Answer 20

Enzymes or ion channels. There are often many different types of G protein receptors for a particular agonist.

Question 21

What is integrated signalling?

Answer 21

Where separate G protein coupled receptors will act simultaneously to stimulate/inhibit the effector so they combine and produce a measured effect.

Question 22

Intracellular receptors in their resting state are bound to what?

Answer 22

Heat shock or chaperone proteins which stabilise it.

Question 23

What happens when an intracellular receptor is activated?

Answer 23

The activated receptor dissociates from the stabilising protein and translocates to the nucleus. Here it binds to control regions of DNA.

Question 24

Are intracellular receptors fast or slow compared to extracellular receptors?
Extra point - How do they work?

Answer 24

They are relatively slow.

Extra point - They depend on transcription and translation.

Question 25

What are 2 examples of signal amplification?

Answer 25

Binding of a chemical signal molecule to one receptor can cause modification of 100s/1000s of substrate molecules. Enzymatic cascade.

Question 26

What does binding of Noradrenaline in cardiac pacemaker cells cause? Extra point - Where do they bind?

Answer 26

Increased heart rate | Extra point - Beta 1 adrenoceptors.

Question 27

What does binding of Acetylcholine in cardiac pacemaker cells cause? Extra point - Where do they bind?

Answer 27

Slows heart rate | Extra point - M2 Muscarinic receptors

Question 28

What does binding of insulin cause in hepatocyes?

Answer 28

Stimulates Glycogen synthesis from glucose.

Question 29

What does binding of Glucagon cause in hepatocytes?

Answer 29

Stimulates Glycogen breakdown to glucose.

Question 30

Describe the process of Phagocytosis.

Answer 30

In response to binding of a particle (to receptors in the plasma membrane) the cell extends Pseudopods that permit further receptor interactions and membrane invagination of the particle (via membrane zippering mechanism) Phagolysosomes degrade the particle material.

Question 31

What is Pinocytosis?

Answer 31

The invagination of the plasma membrane to form a lipid vesicle. Allows uptake of impermeable extracellilar solutes and retrieval of plasma membrane.

Question 32

What are the 2 forms of Pinocytosis?

Answer 32

Fluid phase | Receptor mediated endocytosis.

Question 33

What is receptor mediated endocytosis?

Answer 33

Specific binding of molecules to cell surface receptors permits the selective uptake of substances into the cell.

Question 34

How is uptake of cholesterol and example of receptor mediated endocytosis?

Answer 34

Cells synthesise surface LDL receptors that recognise specifically apoprotein B (On the outside of LDLs) These receptors are localised to clusters over Clathrin Coated Pits that form spontaneously. These pits invaginate to form coated vesicles when LDL binds to the receptors.

Question 35

How can a non functioning receptor cause Hypercholesterolaemia?

Answer 35

There is a mutation in the LDL binding site of the LDL receptor so there is a prevention of binding and uptake of LDL meaning there are higher levels in the blood.

Question 36

How can there be Hypercholesterolaemia if the receptor binding is normal?

Answer 36

A mutation leading to the deletion of the C terminal cytoplasmic domain prevents the interaction between the receptor and Clathrin coat so the receptors are distributed over the entire cell surface instead of being concentrated in 2% of it.

Question 37

How can receptor deficiency cause Hypercholeserolaemia?

Answer 37

A deficiency caused by a mutation prevents expression of the LDL receptor so there are high levels of LDLs in the blood.

Question 38

What is Transcytosis?

Answer 38

Ligands that remain bound to their receptors may be transported across a cell.

Question 39

What is an example of transcytosis?

Answer 39

Maternal immunoglobulins in the foetus via the placenta. Transfer of immunoglobulin A from the circulation to bile in the liver - During transport the receptor is cleaved so the immunoglobulin with a bound secretory component (derived from the receptor) is released.

Question 40

What are the properties of receptor mediated endocytosis mode 1?

Answer 40

The receptor is recycled, ligand degrasded. Eg LDL. Function of it is metabolite uptake.

Question 41

What are the properties of receptor mediated endocytosis mode 2?

Answer 41

The receptor is recycled, the ligand is recycled eg transferring. Function is metabolite uptake.

Question 42

What are the properties of receptor mediated endocytosis mode 3?

Answer 42

The receptor is Degraded, ligand is degraded eg Insulin, EGF. The function is receptor down regulation and removal from circulation.

Question 43

What are the properties of receptor mediated endocytosis mode 4?

Answer 43

The receptor is transported, the ligand is transported, eg maternal IgG. Function is transfer of large molecules across cell.

Question 44

How can receptor mediated endocytosis mode 3 be a model for the development of type II diabetes?

Answer 44

When there is hyperglycaemia there becomes low levels of insulin which bind to receptors that are constantly taken up and down regulated as in mode 3 the receptor and ligand is degraded.

Question 45

How can viruses and toxins take advantage of Receptor Mediated Endocytosis to gain entry to the cell? Extra point - Give an example of a virus that does this.

Answer 45

Membrane enveloped viruses bind to receptors in the plasma membrane and once in the endosome the acidic pH allows the viral membrane to fuse with the endosomal membrane and release viral RNA into the cell. Then it can be translated and replicated by the host cells machinery to form new viral particles. Extra point - Cholera toxin does this.