Signal transduction

Question 1

What is a ligand?

Answer 1

Something that binds to cell surface receptors to stimulate or inhibit pathways

Question 2

What is the difference between agonists and antagonists?

Answer 2

Agonists = stimulate
Antagonist = inhibit

Question 3

Is signalling highly specific?

Answer 3

Yes it is, it has a high affinity

Question 4

What does a receptor + a ligand make?

Answer 4

A receptor-ligand complex

Question 5

What is the equation for the association rate?

Answer 5

Association rate = k+ [R][L]
R = conc. of receptor
L = conc. of ligand

Question 6

What are low affinity interactions?

Answer 6

Less specific, therefore a lot of material is needed for binding

Question 7

What is desensitisation?

Answer 7

The signal is continuous so no pathway is desensitised

Question 8

What is cross-talk?

Answer 8

Where pathways share common components so they communicate

Question 9

What is integration?

Answer 9

If there are multiple signals, the cell produces a unified response

Question 10

Name all the classes of ligands (5)

Answer 10

• Direct contact
• Gap junction
• Autocrine
• Paracrine
• Endocrine

Question 11

What level should blood glucose be at?

Answer 11

4.5 mM

Question 12

What are the two pancreatic molecules responsible for blood sugar and what do they do?

Answer 12

Insulin: decrease blood sugar
Glucagon: increase blood sugar

Question 13

What are the two adrenal molecules responsible for blood sugar and what do they do?

Answer 13

Epinephrine: increase blood sugar
Cortisol: increase blood sugar

Question 14

How are insulin receptors activated?

Answer 14

They are activated by insulin binding which causes an allosteric change which leads to auto-phosphorylation which causes activation

Question 15

Describe the pathway of insulin signalling

Answer 15

• activated IR activate IRS-1
• IRS-1 is bound by adaptor molecules Grb2 and Sos
• Sos activates inactive Ras to active Ras
• Ras recruits Raf kinase and activated protein kinase activity
  RAF phosphorylates MEK kinase
  MEK phosphorylates MAPK
• activated ERK migrates to nucleus to modulate expression of insulin and cyclins/CDK’s

Question 16

Describe the pathway of glucose regulation

Answer 16

• IRS-1 is bifunctional and recruits PI-3K
• PI-3K phosphorylates PIP2 to produce PIP3
• PIP3 recruits PDK1
• PDK1 activates PKB

Question 17

What 2 things is insulin?

Answer 17

• growth factor
• blood glucose regulation

Question 18

What did Lim et al (2011) do?

Answer 18

Found the reversal of Type II diabetes through increased exercise levels and a restricted diet for 2 months

Question 19

What is the Lipostat Theory?

Answer 19

Eating behaviour is inhibited when body weight exceeds a certain point

Question 20

Define obesity

Answer 20

More calories eaten than burned off

Question 21

Who created the BMI?

Answer 21

Lambert Jaques Quetlet (1853)

Question 22

How does leptin work?

Answer 22

• Leptin is released into the bloodstream by adipose tissue and binds to receptors in the hypothalamus
• Endocrine signalling occurs which is released when adipose tissue says fat reserves are sufficient

Question 23

What is the endocrine signalling of leptin?

Answer 23

• Binds to a TM domain
• This dimerises Lep R
• This generates sites for the recruitment of JAK

Question 24

What unusual thing does leptin do?

Answer 24

Signals to liver and muscle cells, making them more sensitive to insulin
(cross talk)

Question 25

Where is erythropoietin found?

Answer 25

In bone marrow

Question 26

What does erythropoietin do?

Answer 26

Controls the development of red blood cells from precursor cells

Question 27

In what two cases can erythropoietin be used?

Answer 27

- women in chemo for ovarian cancer for haemoglobin level below 8g/100ml - people with severe anaemia and cannot have a blood transfusion

Question 28

What is the basic structure of a G-protein coupled receptor?

Answer 28

- Extracellular domains - Trans-membrane domains - Cytosolic domains

Question 29

What structure do GPCRs fold to and how many transmembrane helices does it have?

Answer 29

Tertiary structure like a barrel, 7 helices

Question 30

What does a ligand binding to a GCPR do?

Answer 30

- changes shape so it activates heterotrimeric G-protein - G-protein dissociates from receptor to make G∞-GTP monomer and Gβγ dimer

Question 31

What is the definition of the fight or flight response?

Answer 31

Acute stress response to a harmful event, attack or a threat to survival

Question 32

What are the 2 types of fight or flight responses?

Answer 32

Type I = believing a falsehood Type II = rejecting a truth

Question 33

What do epinephrine and cortisol do for the fight or flight response?

Answer 33

Increase glucose and fatty acids for energy production

Question 34

When GTP stimulates adenylate cyclase what happens?

Answer 34

A very rapid response

Question 35

What is the secondary messenger in the fight or flight response?

Answer 35

cAMP

Question 36

What is the peak absorbance or rhodopsin?

Answer 36

500nm

Question 37

What is rhodopsin?

Answer 37

A visual pigment specialised GPCR

Question 38

What does light absorption do to GPCR?

Answer 38

Light absorption alters the conformation of GPCR so inactive rhodopsin becomes activated metarhodopsin II, this stimulates nucleotide exchange on the alpha-subunit in transducin.

Question 39

What does it mean if humans are trichromats?

Answer 39

We can see 3 pigments (blue, green and red)

Question 40

How would you describe someone who is colourblind?

Answer 40

Dichromat

Question 41

Why does sildenafil citrate cause blue tinged vision?

Answer 41

It has a similar structure to cGMP so acts as a competitive inhibitor

Question 42

How is angina treated today and how does it work?

Answer 42

Treated by nitroglycerine which increases the volume of blood vessels and lowering blood pressure

Question 43

What does nitric oxide activate?

Answer 43

Activates guanylate cyclase which converts GTP to cGMP which is a secondary messanger

Question 44

What does nitric oxide do?

Answer 44

Lowers blood pressure

Question 45

What does oestrogen act as?

Answer 45

A transcription factor

Question 46

Name some roles of oestrogen (5)

Answer 46

- Reproduction - Cardiovascular system - Immune system - Central nervous system - Skeletal system