Biochemical basis for Therapy: Receptors and Signaling

Question 1

Autocrine signals:

Answer 1

cell to its own receptors

Question 2

Paracrine signals:

Answer 2

produced by cell, targets nearby cells

Question 3

Endocrine signals:

Answer 3

targes specific cells far away from source (hormones)

Question 4

hydrophilic ligand

Answer 4

signals move freely through ECM, bind to surface receptors on cell

Question 4

hydrophobic ligand

Answer 4

cannot freely stay in ECM, brought into cells via carrier proteins

Question 5

stage in cell signalling reception:

Answer 5

Receptor binds to ligand

Question 6

stage in cell signalling reception transduction

Answer 6

Receptor protein changes, activates intracellular molecules (2nd messengers)

Question 7

what is the third stage in cell signalling

Answer 7

cell responses

Question 8

Classes of signalling pathway

Answer 8

• G-protein coupled receptors
• Enzyme coupled receptors
• Ion channel receptors

Question 9

what is the response like for ligand-gated ion channels

Answer 9

response in milliseconds

Question 10

step 1 in ligand gated ion channel

Answer 10

Ligand binds to the receptor, channel opens

Question 11

step 2 in ligand gated ion channelin

Answer 11

Ions (Ca2+, Na+, K+) flow through passively

Question 12

step 3 in in ligand gated ion channel

Answer 12

Triggers signalling pathway

Question 13

LGCI sequence of action

Answer 13

1. Agonist binds - conformational change
2. Channel opens - conduction pathway for ions
3. Ions flow down electrochemical gradient
   
   1. Nicotinic ACh receptor → Na+ out + K+ in → membrane depolarization and excitation

Question 14

what quick is the response for G-protein couples receptors

Answer 14

Response happens in seconds

Question 15

G-Protein Coupled Receptors (GPCRs)

Answer 15

• 1 pathway activated
• signal travels far (larger tissue response) due to singal amplification

Question 16

G protein:

Answer 16

• Peripheral membrane protein, 3 polypeptide subunits (⍺, β, 𝛾)
• ⍺ subunit holds GTP or GDP

Question 17

Receptor:

Answer 17

7-pass membrane receptors

Question 18

Turning signal on:

Answer 18

1. Agonist (ligand) activates G-coupled receptor
2. ⍺ subunit leaves G-protein
3. GDP exchanged for GTP (guanine nucleotide exchange)
4. Triggers other proteins in signaling pathway

Question 19

Turning signal off:

Answer 19

1. ⍺ subunit hydrolyses GTP → GDP
2. disactivating G-protein
3. ⍺ subunit recombines with β𝛾 subunit

Question 20

No signaling:

Answer 20

⍺ subunit binding site occupied by GDP

Question 21

what is the response like for Enzyme coupled (kinase-linked) receptors

Answer 21

Response occurs in hours

Question 22

Enzyme coupled (kinase-linked) receptors

Answer 22

• Single pass transmembrane proteins
• multiple pathways activated

Question 23

Enzyme domainis kinase=

Answer 23

phosphorylates other molecules

Question 24

Receptor tyrosine kinases

Answer 24

- Can’t phosphorylate their own tyrosine side chains - → they dimerise and cross-phosphorylate (inc affinity for their binding sites)

Question 25

what is the response time for nuclear receptors

Answer 25

Response occurs in hours/days

Question 26

Nuclear receptors

Answer 26

- Found in nucleus of target cell, bound by steroid hormones - 2 domains: ligand-binding domain, DNA-binding domain

Question 27

Activation:

Answer 27

causes transcription of key proteins

Question 29

what are some examples of G-protein coupled receptors

Answer 29

adreno-receptors eg. α1 α2 β1 β2 β3

Question 30

what is the 4 main targets of drugs

Answer 30

- receptors - enzymes - ion channels - carrier proteins