Cellular Physiology & Pathology

Question 1

What are the 3 stages of signal transduction?

Answer 1

1) Extracellular signal molecule binds to receptor (first messenger)
2) Transduced via certain pathway (secondary messenger system)
3) Cellular response

Question 2

What are ligand-gated ion channels?

Answer 2

Ionotropic receptors, that open in response to binding of a extracellular molecule (eg. Neurotransmitter)

Question 3

What are metabotropic receptors?

Answer 3

Receptors that initiates a number of metabolic steps resulting in a cellular response (transduction)

Question 4

Give examples of ionotropic receptors.

Answer 4

~Nictotinic acetylcholine receptors (neurone synapses Na+, Ca2+)
~Gaba A in neurones allowing Cl- to hyperpolarise neurone, inhibiting action potential

Question 5

Give examples of metabotropic receptors.

Answer 5

~Muscarinic receptors (Gq, Gi)
~Gaba B receptors on neurones allow K+ out of neurone hyperpolarising neurone and inhibiting action potential

Both are G-protein couple receptors

Question 6

How do Gs-protein coupled receptors produce a cellular response?

Answer 6

1) First messenger binds to GCPR; conformational change and GCPR attaches to GP
2) GP a-GDP exchanges GDP w/ GTP; a-GTP has low affinity for beta-gamma complex; dissociates from complex
3) a-GTP binds to adenyl cylase (AC); activated AC converts ATP to cAMP
4) cAMP binds to regulatory subunits(2) on PKA causing catalytic subunits(2) to be released (activated PKA)
5) Active PKA activates specific enzymes via phosphorylation which causes a cellular response via a cascade of reactions

Question 7

How does activated PKA stimulate transcription of genes?

Answer 7

1) PKA activates transcription factors via phosphorylation
2) Transcription factors bind to promoter region initiating transcription

Question 8

How is signal transduction terminated in a metabotropic cellular response?

Answer 8

Phosphodiesterases hydrolyse cAMP causing termination; PKA remains inactive

Question 9

What do phosphatases do?

Answer 9

Convert phosphorylated proteins (by PKA) back into inactive form via hydrolysis

Question 10

How can does Cholera toxin cause diarrhoea?

Answer 10

Prevents hyrdrolysis of alpha(s)-GTP

• AC activated indefinitely
• influx of chloride and water into the gut

Question 11

Name the 4 main types of receptors.

Answer 11

~ Ligand-gated ion channels
~ G-protein coupled receptors
~ Enzyme-linked receptors
~ Nuclear receptors

Question 12

How do Gq-proteins cause a cellular response?

Answer 12

1) Ligand binds to GPCR, causing a-GTP to release and activate phospholipase-C (PLC)
2) PLC cleaves PIP2 into IP3 and DAG
3) IP3 binds to receptors on ER releasing Ca2+ (cellular response)
4) Ca2+ and DAG together activate Protein Kinase C which activate target proteins

Question 13

What protein mediates Ca2+ in the Gq-protein cycle?

Answer 13

Calmodullin (CaM) binds to 4 Ca2+

Question 14

Effects of DAG?

Answer 14

~Activates Protein Kinase C
~Regulates cell shape and proliferation

Question 15

How does Pertussis toxin work?

Answer 15

Prevents activation of alpha(i) subunit; no inhibition of adenyl cyclase

Question 16

Name 5 types of Enzyme-linked receptors.

Answer 16

~ Guanylyl Cyclase
~ Serine/Threonine Kinases
~ Tyrosine Kinases
~ Tyrosine Kinase associated
~ Trysine Phosphatases

Question 17

How does Guanylyl Cyclase recpetor produce cellular response?

Answer 17

1) ANP binds to receptor causing conformational change and dimerisation
2) Guanylyl cyclase activity converts GTP into cGMP
3) cGMP cascade

Question 18

Serine/Threonine receptor mechanism?

Answer 18

1) 1st messenger binds to Type 2 receptor; dimerisation
2) Type 2 receptor phosphorylates Type 1 and Ser/Thr activity causes Ser/Thr Kinases to phosphorylate target proteins

Question 19

What is important about ligands that bind to nuclear receptors?

Answer 19

~ Lipophillic
~ small

Because they must be able to pass plasma membrane

Question 20

What’s the difference between steroid and non-steroid hormones?

Answer 20

Steroid are chemically derived from cholesterol but generally these are the differences;

Steroid:
~ lipophillic
~ small
~ intracellular receptors
~ slow acting

Non-steroid:
~ hydrophilic
~ cell membrane receptors
~ fast acting
~ transduction pathway therefore amplified

Question 21

Where are the sex hormone receptors found?

Answer 21

Nucleus

Question 22

Where are corticosteroid receptors found?

Answer 22

Both glucocorticoid and mineralocorticoid receptors are cytoplasmic

Others are all Nuclear

Question 23

What are the two types of nuclear receptors?

Answer 23

Cytoplasmic and nuclear

Question 24

What’s the difference in dimerisation between steroid hormone receptors and non-steroid receptors?

Answer 24

~Steroid hormone receptors form homodimers

~Non-steroid hormone receptors form heterodimers

Question 25

How do hormones that bind to nuclear receptors produce a cellular response?

Answer 25

1) Hormone enters cell and binds to receptor either in the cytoplasm or nucleus.

2) Binding of hormone causes regulatory protein to be released, activating the Zn fingers on the DNA binding region

3) The hormone-receptor complex migrates to the DNA and binds to the hormone response element acting as a TF

4) Gene expression is either promoted or inhibited. Causing mRNA and therefore protein production

Question 26

Describe the structure of nuclear-receptors.

Answer 26

~ Transactivation domain allows transcription
~ DNA-binding domain (two Zn fingers)
~ Hormone-binding domain
~ Nuclear localisation domain, allows receptor to migrate to nucleus
~ Regulatory protein