Receptors

Question 1

Which receptors bind to hydrophilic and hydrophobic molecules?

Answer 1

Hydrophilic- Cell Surface Receptor

Hydrophobic- Intracellular Receptor

Question 2

Define ‘receptor’

Answer 2

A receptor is a molecule that recognises
specifically a second molecule (ligand) or
family of molecules and which in response to
ligand binding brings about regulation of a
cellular process

Question 3

What is a ligand?

Answer 3

A ligand is any molecule that binds specifically to a receptor site

Ligand binding may produce activation of a
receptor. In this case the ligand is termed an agonist

A ligand may combine with a receptor site without causing activation. This type of ligand is termed an antagonist because it would oppose the actions of an agonist.

Question 4

Describe the affinity of ligands to receptors

Answer 4

Affinity of ligand binding at receptor sites is generally much higher than binding of substrates and allosteric regulators to enzyme
sites

Kd is much lower than Km.

Question 5

How are receptors classified?

Answer 5

Classified according to:

Specific physiological signalling molecule (agonist) recognised

Sub-classification:

Affinity (tightness of binding) of a series of antagonists

Question 6

What are the two types of acetylcholine receptors?

Answer 6

• Nicotine

- Muscarine

Question 7

What is the difference between a receptor and and an acceptor?

Answer 7

Receptor is silent at rest and agonist binding stimulates a biological response, whereas an acceptor operates in absence of ligand and ligand binding alone produces no response

Question 8

Give four ways in which signals are transduced in a cell

Answer 8

1. Membrane-bound receptors with integral ion
   channels
2. Membrane-bound receptors with integral
   enzyme activity
3. Membrane-bound receptors which couple to
   effectors through transducing proteins
4. Intracellular receptors

Question 9

Describe the structure of the nicotinic acetylcholine receptor

Answer 9

• Pentameric
• alpha subunits binds ACh and opens channel
• ring of negatively charged residues at both ends that confer anion selectivity

Question 10

How do Membrane-bound receptors with integral enzyme activity work?

Answer 10

• dimers

- ligand binding to binding domain causes catalytic domain to be revealed

Question 11

Describe signalling via tyrosine kinase-linked receptors

Answer 11

• Dimers
• Activation causes autophosphorylation (receptors phosphorylate themselves)
• Phosphotyrosine recognition site becomes active, and enzymes can bind or transducing proteins can bind to phosphotyrosine receptor and this protein can bind to several enzymes

Question 12

Describe membrane-bound receptors that signal through transducing proteins (Seven transmembrane domain (7TMD) receptors)

Answer 12

-Coupled through GTP-binding regulatory
proteins (G-proteins) to enzymes or channels

-thousands of these

Question 13

What is the structure of G-protein coupled receptors?

Answer 13

-7 transmembrane domains which form cleft in membrane where ligand binds

Question 14

What is integrated signalling via G-protein coupled receptors?

Answer 14

• stimulatory receptor and inhibitory receptor could both be present in a cell, that both affect same enzyme
• integrated response based on signalling molecules present

Question 15

Describe the structure of intracellular receptors

Answer 15

• DNA binding domain (blocked at rest) and Binding domain

- cytoplasmic or nuclear

Question 16

How do intracellular receptors work

Answer 16

• DNA binding domain blocked at rest via inhibitory protein complex
• On ligand binding, conformational change, DNA binding site revealed and can go on to bind DNA

Question 17

Describe amplification in cellular signalling

Answer 17

• One receptor can activate multiple G-proteins whilst a ligand is bound to it
• Effector enzyme can convert a lot of substrate for further amplification
• Second messenger molecules could activate protein kinases, introducing further steps of amplification

Question 18

What is the difference between receptor activation and inhibition?

Answer 18

Responses to receptor activation can lead to cellular activation or inhibition depending on the receptor activated

E.g.1) cardiac pacemaker cells

– Noradrenaline -> beta1-adrenoceptors -> increased heart rate
-Acetylcholine -> M2 Muscarinic receptors -> slowing of heart rate

E.g.2) Hepatocytes

• Insulin -> stimulates glycogen synthesis from glucose
• Glucagon -> stimulates glycogen breakdown to glucose