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Membranes and Receptors > Session 6 > Flashcards

Session 6 Flashcards

1
Q

What is a receptor?

A

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

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2
Q

How are receptors classified?

A

By their specificity to a ligand.

Then by their affinity to a series of agonists.

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3
Q

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

A

Because the ligand may be present in very small concentrations.

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4
Q

What are some of the roles of receptors?

A

Signalling via hormones

Neurotransmittion

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5
Q

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

A

An acceptor

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6
Q

What is a ligand?

A

Any molecule that binds specifically to a receptor site.

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7
Q

What is an agonist?

A

Where binding of the ligand activates the receptor.

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8
Q

What is an antagonist?

A

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

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9
Q

What molecule can bind to receptors inside the cell?

A

Small hydrophobic molecules as they can pass through the membrane.

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10
Q

How can hydrophillic signalling molecules cause a reaction?

A

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

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11
Q

What is signal transduction?

A

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

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12
Q

How can membrane bound receptors cause cellular responses?

A

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

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13
Q

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

A

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

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14
Q

What is the classical ligand gated ion channel family structure?

A

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

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15
Q

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

A

Ryanodine receptor

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16
Q

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

A

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.

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17
Q

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

A

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

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18
Q

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

A

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

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19
Q

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

A

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

20
Q

What can be the effectors of G proteins?

A

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

21
Q

What is integrated signalling?

A

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

22
Q

Intracellular receptors in their resting state are bound to what?

A

Heat shock or chaperone proteins which stabilise it.

23
Q

What happens when an intracellular receptor is activated?

A

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

24
Q

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

A

They are relatively slow.

Extra point - They depend on transcription and translation.

25
Q

What are 2 examples of signal amplification?

A

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

26
Q

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

A

Increased heart rate

Extra point - Beta 1 adrenoceptors.

27
Q

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

A

Slows heart rate

Extra point - M2 Muscarinic receptors

28
Q

What does binding of insulin cause in hepatocyes?

A

Stimulates Glycogen synthesis from glucose.

29
Q

What does binding of Glucagon cause in hepatocytes?

A

Stimulates Glycogen breakdown to glucose.

30
Q

Describe the process of Phagocytosis.

A

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.

31
Q

What is Pinocytosis?

A

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

32
Q

What are the 2 forms of Pinocytosis?

A

Fluid phase

Receptor mediated endocytosis.

33
Q

What is receptor mediated endocytosis?

A

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

34
Q

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

A

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.

35
Q

How can a non functioning receptor cause Hypercholesterolaemia?

A

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.

36
Q

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

A

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.

37
Q

How can receptor deficiency cause Hypercholeserolaemia?

A

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

38
Q

What is Transcytosis?

A

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

39
Q

What is an example of transcytosis?

A

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.

40
Q

What are the properties of receptor mediated endocytosis mode 1?

A

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

41
Q

What are the properties of receptor mediated endocytosis mode 2?

A

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

42
Q

What are the properties of receptor mediated endocytosis mode 3?

A

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

43
Q

What are the properties of receptor mediated endocytosis mode 4?

A

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

44
Q

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

A

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.

45
Q

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.

A

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.

Membranes and Receptors (10 decks)

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