Lecture 27 Flashcards

1
Q

GPCRs

A
  • largest family of cell surface receptors
  • can bind to hormones, local mediators and neurotransmitters
  • composed of a single polypeptide chain that spans the lipid bilayer 7 times
  • ancient, can be found in prokaryotes
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2
Q

activation of a GPCR

A
  • binding of an extracellular signal molecule to a GCPR causes it to change conformation causing the associated G-protein to decrease affinity for GDP
  • GDP dissociates and is exchanged for GTP
  • sometimes g-protein subunits dissociate (this doesn’t always happen) and are switched on
  • this in turns activates trimeric G-protein which results in transmission of a signal
  • g-protein then interact with target enzymes or ion channels
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3
Q

describe the structure of a G-protein

A
  • composed of a, y, b subunits
  • a and y are tethered to the plasma membrane by a short lipid tail
  • when unstimulated, a is bound to GDP
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4
Q

what dictates the length of the response

A
  • the amount of time the g-protein subunits are switched on
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5
Q

explain the switching off process

A
  • the a subunit contain a GTPase activity which can hydrolyze GTP to for GDP
  • the a subunits reassembles with the by complex and the protein returns to its original, inactive state
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6
Q

G-proteins and ion channels

A

Example: regulation of the heart
- acetylcholine binding to GCPRs of heart pacemaker cells activate G-protein Gi
- then the by subunit binds to K+ ion channels causing it to open
- channel closes when GTP is cleaved and the subunits reassembles with one another

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7
Q

the two most common enzyme targets include

A
  • adenylyl cyclase which produces cAMP
  • phosphlipase C which produces inositol triphosphate (IP3) and diacylglycerol (DAG)
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8
Q

Give examples of second messengers

A
  • cAMP
  • IP3
  • DAG
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9
Q

cAMP signalling pathway

A
  • the g-protein Gs is responsible for the activation of adenylyl cyclase which generates cAMP from ATP, releasing PPi
  • cAMP phosphodiesterase converts cAMP into AMP using water
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10
Q

what role does caffeine play in cAMP signalling pathway

A
  • it inhibit cAMP phosphodiesterase keeping cAMP levels high
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11
Q

cAMP- glycogen breakdown

A
  • cAMP activate protein kinase A (PKA)
  • PKA is normally inactivated by regulatory proteins
  • when cAMP binds to PKA it releases regulatory proteins
  • PKA can then phosphorylate other proteins (like glycogen phosphorylase in skeletal muscle)
  • glycogen breakdown is an example of a relatively quick response
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12
Q

cAMP slow responses

A
  • cAMP can also cause activation of gene expression - a relatively slow response
  • PKA phosphorylates transcriptional regulators which can initiate transcription
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13
Q

what is cholera toxin

A
  • a bacterial toxin that modifies the a subunit of the g-protein so that it can no longer hydrolyze GTP therefore the g-protein is always active
  • result: in the intestine this can result in a prolonged outflow of Cl- and water (dehydration)
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14
Q

Inositol phospholipid pathway

A
  • phospholipase C converts membrane phospholipids into diacylglycerol (DAG) which stays in the membrane and IP3 which is released into the cytosol
  • IP3 binds to and opens Ca2+ channels embedded in the ER and free Ca2+ is released into the cytosol
  • DAG recruits protein kinase C (PKC)
  • activation of PKC requires the binding of Ca2+
  • PKC phosphorylates many intracellular protein
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15
Q

Ca2+ signalling

A
  • it is important in muscle contraction and secretion
  • when Ca2+ channels open, Ca2+ rushes down its electrochemical gradient
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16
Q

What is the most common protein Ca2+ binds to

A

calmodulin

17
Q

Calmodulin

A
  • binds to four Ca2+ ions, inducing a conformational change allowing it to interact with proteins like Ca2+ / calmodulin dependent-protein kinases (CaM-kinases)
18
Q

GPCR signalling- photoreceptors

A
  • light activates GCPR known as rhodopsin
  • rhodopsin activates g-protein known as transducin
  • transducin activates cyclic GMP phosphodiesterase which reduces cGMP levels by converting it to GMP
  • signalling is very fast despite the multiple steps
19
Q

is vision possible in dim light? why?

A
  • yes because photoreceptors can amplify signal so that vision is possible even in dim light
20
Q

What does it mean when we say “photoreceptors are capable of adaption?”

A
  • the adjustment of sensitivity
  • allows you to see in bright sunlight
  • strong light reduces Ca2+ concentrations which is required by signal amplification enzyme