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ESA 2 > M&R 6.1 - Signal Transduction > Flashcards

M&R 6.1 - Signal Transduction Flashcards

1
Q

Describe paracrine signalling

A

A signalling molecule is produced by one cell and secreted into the tissue fluid where it can then act upon adjacent cells with the appropriate receptor

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2
Q

Describe endocrine signalling

A

A hormone is produced by an endocrine organ and travels in the circulation to a distant site where it acts upon its target cell

  • Long distance
  • Slower
  • Specific
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3
Q

Describe synaptic signalling

A
  • The release of a neurotransmitter by a nerve cell when stimulated to give a targeted response
  • Signals are quick and long distance to specific target cells
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4
Q

Give an example of molecules that use paracrine signalling

A
  • Local mediators e.g. growth factors

- Fibroblast Growth Factor (stimulate fibroblast proliferation and granulation tissue formation)

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5
Q

Give an example of a molecule that uses endocrine signalling

A
  • Insulin
  • Promotes glucose uptake in skeletal muscle/fat
  • Inhibits glucose production by the liver
  • Causes fat to be stored rather than used
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6
Q

Give an example of a molecule that uses synaptic transmission

A
  • Acetylcholine

- Has many functions depending on which receptor is activated

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7
Q

Where are the receptors that are used by hydrophilic molecules located? Why are they here?

A
  • On the cell surface membrane

- Hydrophilic molecules are unable to readily pass through the membrane

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8
Q

Where are the receptors that are used by hydrophobic molecules located? Why are they here?

A
  • Intracellular receptors are used

- Hydrophobic molecules can readily pass through the membrane

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9
Q

What is the definition of a receptor?

A

A molecule that recognises a ligand/family of molecules and brings about the regulation of a cellular process in response

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10
Q

What is the definition of a ligand?

A

A molecule that binds specifically to a receptor site

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11
Q

What are the two types of ligand and what are their functions?

A
  • Agonist = Activates receptor by causing a conformational change
  • Antagonist = Combines to the receptor but doesn’t activate it therefore preventing binding of the agonist
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12
Q

Describe the affinity of receptors. What is the definition of Kd?

A
  • Affinity of receptors is very high (higher than that of enzymes)
  • Kd = Half of the concentration required to fill half of the receptors
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13
Q

What is the significance of a ligand binding to a receptor?

A

Brings about a change in response therefore controlling cellular processes

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14
Q

How are receptors classified?

A
  • Initially into the type of agonist recognised

- Sub-classification = their affinity to antagonists (which is the most potent)

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15
Q

What is an acceptor?

A

A receptor like molecule that doesn’t need ligand binding to bring about a response

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16
Q

Describe the activity of a receptor when an agonist is not bound

A
  • Functionally silent

- Doesn’t work

17
Q

What are the four ‘super families’ of receptor? Rank them in order of speed of signal transduction

A

1) Membrane bound receptors with integral ion channel e.g. Na+ channels for depolarisation
2) Membrane bound receptors with integral enzymes e.g. PDGF receptor which activate Tyrosine Kinases
3) Membrane bound receptors that couple to effectors by transducing proteins e.g. any type of G proteins
4) Intracellular receptors for hydrophobic molecules e.g. Nuclear receptors for gene transcription

18
Q

Give an example of a classical ligand gated ion channel and describe its structure

A
  • Nicotinic Acetylcholine Receptor (opens cation channels for depolarisation)
  • Pentameric (5 subunits) with 2 alpha subunits for the binding of Acetylcholine
  • 4 Transmembrane domains that make up the ion channel
19
Q

Give three other examples of classical ligand gated ion channels and their functions

A
  • GABA receptor = opens gated Cl- channels (hyperpolarisation)
  • Glycine receptor = opens gated Cl- channels (hyperpolarisation)
  • Glutamate receptors = gated entry of Ca2+
20
Q

Give 3 examples of non-classical ligand gated ion channels and their functions

A
  • IP3 Receptor = Gated release of Ca2+
  • ATP sensitive K+ Channel = Ligand binding means closure of the ion channel
  • Ryanodine Receptor = Opens Ca2+ channel
21
Q

Describe the structure of a membrane-bound receptor with integral enzyme activity and give an example

A
  • Binding site is extracellular
  • Catalytic site is intracellular
  • Dimers - one subunit moves relative to the other the bring about the conformational change upon agonist binding
22
Q

Give an example of a MBR with integral enzyme activity

A
  • Platelet Derived Growth Factor Receptor

- Direct link to Tyrosine Kinase

23
Q

Describe how the binding of PDGF to its receptor brings about an intracellular event

A
  • Agonist binding = autophosphorylation of tyrosine residues on the receptors
  • Phosphorylated tyrosine residues are recognised by transducing proteins/other enzymes with phosphotyrosine receptor sites
  • Activates effector enzymes either allosterically or by tyrosine phosphorylation
24
Q

What is the function of PDGF? Why is it significant?

A
  • Regulation of cell growth and division

- Significant in angiogenesis

25
Q

Describe the structure of G-protein coupled receptors

A
  • 7 transmembrane domain receptors that couple to effector molecules via G-proteins
  • Binding site is within the membrane
  • C terminal is for the binding of G proteins
26
Q

Give an example of a stimulatory G-protein pathway

A
  • Adrenaline binds to Beta-Adrenoreceptors in pacemaker cells
  • Beta-Adrenoreceptors activates Gs protein
  • Gs protein activates Adenylyl Cyclase (effector = enzyme)
27
Q

Give an example of an inhibitory G-protein pathway

A
  • Acetylcholine binds to M2 muscarinic receptor
  • M2 muscarinic receptor activates Gi protein
  • Gi protein opens K+ channel (effector = ion channel)
28
Q

Describe the structure of intracellular receptors

A
  • 1 protein
  • Ligand binding domain = C-terminal
  • DNA binding domain
29
Q

What blocks the intracellular receptors at rest?

A
  • Heat shock proteins

OR

  • Chaperone proteins
30
Q

What happens as a result of agonist binding to intracellular receptors?

A
  • Conformational change
  • Inhibitory protein is released which exposes the DNA binding site
  • Able to regulate transcription
31
Q

What is amplification in cellular signalling?

A
  • Receptor remains activated which means that another g protein can bind
  • Enzymes are then able to amplify the signal further
32
Q

What is the significance of amplification signalling?

A

A lot of substrates can be modified from the activation of only one signal

33
Q

Give the receptor that noradrenaline binds to in cardiac pacemaker cells and the effect

A
  • Beta 1-Adrenoreceptors

- Increased heart rate

34
Q

Give the receptor that acetylcholine binds to in cardiac pacemaker cells and the effect

A
  • M2-Muscarinic Receptors

- Decreased heart rate

ESA 2 (63 decks)

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