Classification of Receptors Flashcards
intracellular receptors are…
lipid soluble messengers: function in the nucleus as transcription factors or suppressors to alter the rate of transcription of particular genes
plasma membrane receptors are
water soluble receptors
state what the 4 water soluble messengers are
- ligand-gated ion channels
- receptors that function as enzymes (eg - tyrosine kinases)
- receptors bound to and which activate cytoplasmic janus kinases
- G-protein coupled receptors that activate G protein, which in turn acts upon effector proteins (either ion channels or enzymes) in the PM
explain the process of: Receptors that are ligand-gated ion channels (3 things)
- activation of receptor by first messenger = conformational change in shape receptor forming open ion channel
- inc^ net diffusion of specific ion across PM
- causes change in membrane potential - contributes to cell response
explain the first portion of: G-Protein coupled reactions (4 things)
- G-Protein sub-units bound to inactive receptor on cytosolic surface PM
- first messenger binding to receptor = conformational change
- activated receptor inc^ affinity for alpha sub and alpha sub dissociates from Trimeric G-Protein
- dissociation allows activated alpha sub to link with another PM protein (ion channel/enzyme) - G-Protein-Coupled-Repectors
explain the second portion of: G-Protein coupled reactions (3 things)
- G-Protein causes ion gate open and change in membrane potential
- alternatively, activate/deactivate PM enzyme
- enzyme, when activated, can cause generation of second messengers in the cell
explain the third (and final) portion of: G-Protein coupled reactions
- once alpha sub activates effector, GTPase actively inherent in subunit cleaves GTP –> GDP + Pi
- cleavage leaves alpha sub inactive allowing it to recombine to beta + gamma
state what the alpha, beta and gamma sub-units roles are in the G-Protein coupled reaction
- alpha - can bind GDP and GTP
2. gamma/beta - help anchor alpha sub-unit in the plasma membrane
state 2 primary facts in: Receptors which function as enzymes
- the receptors have intrinsic enzyme activity which are protein kinases
- these receptors are known as ‘Receptor Tyrosine Kinases’
explain the process of: Receptors which function as enzymes
- binding of specific first messenger = conformational change so enzymatic portion is activated
- results in autophosphrylation of receptor
- formed phosphotyrosines = docking sites for cytoplasmic proteins
- bound docking proteins activate other proteins which activate one or more signalling pathway within the cell
what is the only exception to Receptors which function as enzymes (3 things)
- receptor act as receptor and Guanylyl Cyclase to catalyse formation of Cyclic GMP (cGMP)
- cGMP acts as 2nd messenger which activates cGMP-dependent protein kinase
- this kinase phosphorylates proteins which mediate cells response to 1st messenger
state 3 primary facts to: Receptors which interact with cytoplasmic Janus Kinases
- receptor has intrinsic enzyme activity (tyrosine kinase activity)
- doesn’t reside in receptor but separate cytoplasmic kinases (janus kinases - JAKs) associate with the receptor
- receptor and associated JAKs function as a unit
explain the process of: Receptors which interact with cytoplasmic Janus Kinases
- binding of 1st messenger = conformational shape change to receptor leading to Janus Kinase activation
- different receptors associate with different JAKs
- different JAKs phosphorylate different target proteins - many of which are transcription factors
- result in these pathways are synthesis ofd new proteins which mediate cells response ton 1st messenger
explain the first part of the process: Adenylyl Cyclase and Cyclic AMP (4 things)
- activation of receptor via 1st messenger allows receptor to activate G protein
- G protein activates effector protein in PM called adenylyl cyclase
- activated adenylyl cyclase catalyses cytosolic AMP –> Cyclic AMP (cAMP)
- cAMP acts as 2nd messenger + diffuses throughout cell leading to events to respond to 1st messenger
explain the second part of the process: Adenylyl Cyclase and Cyclic AMP
action of cAMP eventually terminates + broken down by cAMP phosphodiesterase
what 2 things can control the cell concentration of Cyclic AMP (cAMP)
- altering the rate of it’s messenger mediated synthesis
2. altering the rate of it’s phosphodiesterase-mediated breakdown
what are the effects of caffeine and theophylline on phosphodiesterase activity
caffeine and theophylline inhibit phosphodiesterase activity, thereby prolonging the actions of cAMP within cells
what does cAMP actually do within cells (2 things)
- binds + activates Protein Kinase A (enzyme)
- protein kinases phosphorylate other proteins (often enzymes) to bring about cells responses (contraction, secretion etc…)
in essence, the activation of adenylyl cyclase by a G protein initiates a…
‘amplification cascade’ of events that converts proteins from inactive to active forms
in addition, what can activated Protein Kinase A do (3 points)
- diffuse into nucleus + phosphorylate a protein which can bind to specific regulatory sites on genes
- such genes are said to be ‘cAMP responsive’
- effects of cAMP can be rapid and independent of changes in gene activity
Gs and Gi - what do they mean (3 points)
- Gs = stimulatory for Adenylyl Cyclase
- Gi = inhibitory for Adenylyl Cyclase
- most PM have both Gs and Gi in PM to tightly regulate cAMP conc^
explain the system: Phospholipase C, Diacylglycerol and Inositol Triphosphate (4 things)
- Gq activated by receptor bound to 1st messenger
- activated Gq activates PM effector enzyme Phospholipase C
- catalyses breakdown of Phosphatidylinostiol Bisphosphate (PIP2) to Diacylglycerol (DAG) and Inositol Triphosphate (IP3)
- both DAG and IP3 function as 2nd messengers but in different ways
what is the function of DAG (2 things)
- DAG activates Protein Kinase C
2. this phosphorylates a large number of proteins leading to the cells response
what is the function of IP3 (3 things)
- doesn’t exert 2nd messenger by directly activating a protein. kinase - contrast to DAG
- binds to ligand gated CA2+ channels (receptors) on ER which open
- CA2+ diffuses out organelle down conc^ grad which then continues sequence leading to cells response
state 3 summary points of the mechanisms by which receptor activation influences ion channels
- the ion channel is part of the receptor
- a G protein can directly gate the channel
- a G protein can indirectly gate the channel via a second messenger
state what it is meant by the key term ‘eicosanoids’
eicosanoids are a family of molecules produced by the polyunsaturated fatty acid ‘arachidonic acid’ which is present in plasma membrane phospholipids
state 2 basic facts about eicosanoids
- include a variety of growth factors, immune defence molecules and more eicosanoids
- eicosanoids may act as both extracellular and intracellular messengers - depending on the cell type
what is the first step of eicosanoid synthesis
an appropriate stimulus (hormone, neurotransmitter, pan ccrine substance, drug) binds to it’s receptor and activates Phospholipase A2 - an enzyme localised to the PM of the cell
what is the second step of eicosanoid synthesis
Phospholipase A2 off arachidonic acid from phospholipid and arachidonic can then ben metabolised by 2 pathway
what are the two pathways in which arachidonic acid can be metabolised
- pathway initiated by cyclooxygenase (enzyme)
2. pathway initiated by lipoxygenase (enzyme)
once eicosanoids have been synthesised in response to a stimulus, what do they do (2 things)
- can act as intracellular messengers
2. can be released and act locally
after eicosanoids act, what happens
quickly metabolised by local enzymes to there inactive forms
what 3 eicosanoids does cyclooxygenase lead to the production of
- cyclic endoperoxides
- prostaglandins
- thromboxans
what eicosanoid does lipoxygenase lead to the production of
produces the leukotrienes
what is the effect of Aspirin on eicosanoids
aspirin inhibits cyclooxygenase and therefore blocks the production of cyclic endoperoxides, prostaglandins and thromboxans
state the 4 ways in which cessation of activity in signal transduction pathways occur
- reduction of first messenger conc^ in receptor region
- receptor becomes chemically altered reducing affinity for 1st messenger (usually phosphorylated)
- phosphorylation of receptor may prevent further G protein binding to the receptor
- PM receptors removed via endocytosis
