Intracellular Signalling Pathways Flashcards
Can effectors be Enzymes?
Yes
What are two examples of effectors that are enzymes ?
Adenylyl cyclise and phospholipase C
Describe how an agonist can stimulate adenylyl cyclase ?
- adrenaline / noradrenaline can bind to G protein coupled receptors called B2/adrenoreceptors.
- this would cause a conformational change in the G protein coupled receptor. This would activate the G protein.
- activation of the G protein would cause GDP to be exchanged for GTP on the Alpha (s) subunit. Leaving the alpha (s) subunit free to interact.
- Alpha subunit (s) then interacts with the adenylyl cyclase effector which then in turn causes ATP to be converted to cyclic AMP ( which is a second messenger)
- Cyclic AMP then attaches to the regulatory sites on Protein Kinase A enzyme. This then causes the release of catalytic subunits on protein kinase A.
- the catalytic subunits are responsible for phosphorylation of proteins ( not just any protein - typically linked to one of the three amino acids that have an -OH group eg serine , tyrosine , threonine). This would cause a protein to become more or less active.
What are three tamino acids protein Kinase A catalytic subunits target and why ?
- tyrosine
- serine
- threonine
- they target these specific amino acids because they have an -OH group attached.
Give an example of how the enzyme effector phospholipase C can be activated ?
1) adrenaline would bind to a1-adrenoreceptors which would eventually activate G(q) proteins causing GDP exchange for GTP to occur on the Alpha(q) subunit.
2) this causes the G protein to dissemble
3) alpha (q) subunit then goes off to interact with phospholipase C enzyme.
4) Phospholipase C enzyme then catalyses the cleavage of the membrane phospholipid PIP2 into two second messengers - IP3 and DAG.
5) IP3 causes the release of calcium from an intracellular store (SR).
6) the calciums then play a role in activating protein kinase C
What molecule can be responsible for the amplification of a signal ?
Company cyclic AMP which then go off to activate many protein kinases.
What is an inotrope?
A class of drug that works to alter the force or energy of muscular contractions.
What is an example of an endogenous inotrope?
Adrenaline
Give an example of inotropy in the heart ?
Adrenaline and nor adrenaline can both bind to b1-adrenoreceptors in the ventricular walls in the heart which can increase the force of contraction - this is called +ve inotropy.
- when they bind to the G protein coupled receptors , they cause GDP to be exchanged for GTP on the alpha ( s) subunit - this dissosiates alpha (s) subunit from the rest. Alpha (s) then goes off to interact with Adenylyl cylase which catalyses the formation of cyclic AMP from ATP. Cyclic AMP then interacts with the regulatory sites of protein kinase.
- protein kinase phosphorylates the voltage operated Ca2+ channels increasing Ca2+ concentration in cardiac cells as the voltage operated Ca2+ channels are open for longer.
- this then causes Ca2+ induced receptors( ryanodine ) to open and allow even more Ca2+ to leave the SR/ER into the cytoplasm»_space; more forceful contraction.
Sympathetically released noradrenaline can interact with what receptor and what does it cause ? And what type of GPCR is it
- a1- adrenoreceptprs which cause vasoconstriction in smooth muscle.
- these receptors utilise the Gq - phospholipase C pathway
Parasympathetically released ACH can interact with what type of smooth muscle and receptor ? And what pathway does it take
- gq-phospholipase C pathway
- causes bronchoconstriction on the bronchiolar smooth muscle M3 Muscarinic receptors
In the CNS and PNS what is neurotransmitter release modulated by ?
- pre-synapticG protein coupled receptors
- for example morphine one will bind to u-opioid receptor , this causes alpha GTP and beta gamma to dissosiate. The beta gamma then binds to VOCC , but not completely. As a result , less Ca2+ enter cell at depolarisation therefore less vesicles - less NT.
