Cell signalling

Question 1

What is the function of extracellular signals in metabolic pathways ?

Answer 1

• help to preserve homeostasis
• coordinate cellular activity throughout the whole organism

Question 2

What is the most important mechanism of intercellular communication in metabolism ?

Answer 2

The endocrine system

Question 3

What are the 4 mechanisms of intercellular communication ?

Answer 3

• juxtrine : direct contact
• paracrine : the signal released will affect cells in close proximity
• autocrine : it is a type of paracrine mechanism but the sender of the signal and target cell is the same
• endocrine : signalling between cells over a short or long distance

Question 4

Describe the general sequence of events that happen in an intercellular communication mechanism

Answer 4

1) synthesis of the signal molecule
2) release of the signal molecule
3) transport of the signal molecule to the target tissue
4) detection of the signal molecule (binding to the receptor)
5) effect
6) removal of the signal molecule

Question 5

What is the endocrine system ?

Answer 5

• endocrine organs produce hormones which have effects beyond their tissue of origin
• examples of endocrine organs include the adrenal glands and pancreas
• the release of these hormones will affect other chemicals and regulate a metabolic pathway

Question 6

What are the 2 types of receptors involved in the endocrine system ?

Answer 6

• nuclear receptors : they alter the rate of DNA transcription and therefore protein synthesis
• cell surface receptors : they are coupled to a variety of intracellular reactions called signal transduction cascades

Question 7

Which types of hormones bind to nuclear receptors ?

Answer 7

• hydrophobic hormones bind to nuclear receptors
• they alter gene expression
• effects may take minutes to hours

Question 8

Which types of hormones bind to cell surface receptors ?

Answer 8

• hydrophilic hormones bind to cell surface receptors
• cause downstream effects
• insulin, glucagon and adrenaline will bind to cell surface receptors

Question 9

What is glucagon ?

Answer 9

glucagon is a peptide hormone (29 amino acids long) which is secreted by the alpha cells of the pancreas

Question 10

When is glucagon secreted ?

Answer 10

it is secreted when blood glucose levels drop

Question 11

What is the role of glucagon ?

Answer 11

• it promotes the mobilisation of fuel reserves
• it inhibits the the utilisation of glucose

Question 12

What is the main target tissues of glucagon ?

Answer 12

• liver
• adipocytes (fat cells)

Question 13

What is adrenaline ?

Answer 13

it is a derivative of the amino acid tyrosine and it is synthesised in the adrenal glands

Question 14

How is the secretion of adrenaline controlled ?

Answer 14

secretion is controlled directly by the brain through the nervous system

Question 15

What is the role of adrenaline ?

Answer 15

• promotes the mobilisation of fuel reserves
• inhibits storage pathways
• affects circulation

Question 16

What is the main target tissues of adrenaline ?

Answer 16

most tissues are a target

Question 17

What is insulin ?

Answer 17

• it is generated as a polypeptide of ~ 103 amino acids and called proinsulin
• it is then modified into an active form ~ 51 amino acids long

Question 18

When is insulin secreted ?

Answer 18

• secreted by the beta cells of the pancreas
• in response to increased levels of glucose in the blood

Question 19

What is the role of insulin ?

Answer 19

• promotes an anabolic state by channelling metabolism towards the storage of carbohydrates and lipids

Question 20

What is the main target tissues of insulin ?

Answer 20

• liver
• muscle
• adipose (fat)

Question 21

What happens when glucagon, insulin and adrenaline bind to cell surface receptors ?

Answer 21

• the structure of the protein will change
• this leads to an event : generation of a secondary messenger or change in membrane potential
• this will activate enzymatic cascades

Question 22

What are the different types of cell surface receptors ?

Answer 22

• ligand gated ion channel receptor
• cytokine receptors
• enzyme linked receptors
• G protein coupled receptors

Question 23

Which types of receptors do glucagon, adrenaline and insulin bind to ?

Answer 23

• insulin binds to enzyme linked receptors
• glucagon and adrenaline binds to G protein coupled receptors

Question 24

Describe the general signalling events that happen in the endocrine system

Answer 24

1) a signal will be released by a hormone due to a change in the environment
2) the signal is transported around the body by the blood
3) it will reach a receptor and bind
4) the signal will be relayed from the outside of the cell to the inside
5) there is amplification of the signal by enzyme activation
6) there will be an increase in the concentration of 2nd messenger
7) this leads to a cellular effect

Question 25

Which types of G protein coupled receptors does adrenaline bind to ?

Answer 25

- α adrenergic receptors - β adrenergic receptors

Question 26

Where are G protein coupled receptors located ?

Answer 26

- they sit across the surface of the membrane - the receptor proteins are located in the plasma membrane and have 7 transmembrane spanning regions

Question 27

Describe G protein coupled receptors

Answer 27

- they are guanosine binding proteins - when GDP is bound they are inactive - when GTP is bound they are active - there are 2 types : monomeric and trimeric - trimeric receptors have 3 subunits and the guanosine nucleotide will bind to the α subunit

Question 28

Describe signal transduction by glucagon and adrenaline

Answer 28

1) binding of the hormone to the receptor will induce a conformational change in the receptor 2) the activated receptor will bind to the alpha subunit of the G protein 3) the activated receptor will cause a conformational change in the alpha subunit triggering the dissociation of GDP 4) GTP will bind to the alpha subunit causing dissociation of the alpha subunit from the receptor and from the other 2 subunits of the G protein 5) the hormone will dissociate from the receptor and the alpha subunit will bind to the effector activating it 6) hydrolysis of GTP to GDP will cause the alpha subunit to dissociate from the effector and reassociate with the other 2 subunits

Question 29

How is the signal transduction of glucagon and adrenaline amplified ?

Answer 29

- glucagon receptors and β adrenergic receptors initiate a cascade of events via the secondary messenger cAMP which will amplify the signal of the hormone - the effector involved in the signal transduction is adenyl cyclase and this takes ATP and turns it into cAMP

Question 30

Describe the structure and function of protein kinase A

Answer 30

- it has 4 subunits : 2 catalytic and 2 regulatory - it is a key enzyme in the modulation of metabolic enzymes - it phosphorylates proteins - cAMP binds to the regulatory subunits leading to a conformational change

Question 31

Describe the control of adenylate cyclase

Answer 31

- it can be upregulated or downregulated by the action of different hormones - the alpha subunit has hydrolytic activity which rapidly converts GTP to GDP

Question 32

Describe how the cellular response is terminated

Answer 32

cell signalling requires a rapid termination once hormone levels decrease - if something is switched on it needs to be switched off again

Question 33

List some diseases associated with defective cell signalling

Answer 33

excessive signalling : - cholera - cancer - hypertension deficient signalling : - night blindness - pertussis

Question 34

Summarise cholera

Answer 34

- caused by Vibrio cholerae - affects intestinal epithelial cells - an increase in cAMP leads to chloride transport into the lumen and absorption of Na+ leading to water loss

Question 35

What are some alternative secondary messengers ?

Answer 35

α adrenergic receptors involve the secondary messengers DAG and Ca 2+

Question 36

Describe signal transduction by insulin

Answer 36

1) insulin binds to an enzyme linked receptor 2) the receptor undergoes autophosphorylation on its tyrosine residues 3) the insulin receptor will phosphorylate IRS-1 4) IRS-1 activates other kinase enzymes leading to downstream effects 5) it also activates phosphatases which cause dephosphorylation 6) insulin signal transduction is downregulated by endocytosis