Chemical Signalling 1 Flashcards
Describe the general steps of cell communication by extracellular signals
- Synthesis and release of signalling molecule by signalling cell
- Transport of signal to target cell
- Detection of incoming signal by a receptor on target cell/organelle
- Binding of signal to receptor = biological response
- Removal of signal = termination of response
Give three examples of hormones and growth factors
Any from:
Oestradiol Progesterone Growth hormone Nerve growth factor Epidermal growth factor
Give three examples of metabolic regulators
Any from:
Insulin
Glucagon
Adrenaline
Cortisol
Give three examples of neurotransmitter
Any from:
Glutamate Acetylcholine Dopamine GABA Opioids
Give three examples of inflammatory mediators
Prostaglandins
Thromboxanes
Cytokines
What are the four types of signalling molecules?
Hormones/growth factors
Metabolic regulators
Neurotransmitters
Inflammatory mediators
What are the three main types of signalling and what is this classification based on?
Endocrine
Paracrine
Autocrine
Based on distance over which the signals act
What is endocrine signalling?
Secretion of hormones into bloodstream
What type of organs/glands are involved in endocrine signalling?
Endocrine organs/glands
How far are the target cells from site of signalling molecule synthesis in endocrine signalling?
Up to a few metres
What are the steps of endocrine signalling?
- Stimulation of endocrine gland to synthesise and secrete hormone
- Hormone carried in bloodstream to target cells
- Hormone binds to and activates receptor to stimulate a biological response
What is paracrine signalling?
Signalling to adjacent cells
What is an example of paracrine signalling?
Transmission at neuromuscular junctions
How far apart are the cells involved in paracrine signalling?
A few microns/micrometres
What is autocrine signalling?
Signalling back onto the same cell
What is an example of autocrine signalling?
Any from:
Tumour cells
Certain growth factors
Autoreceptors (neurotransmitter release)
What are cell surface receptors?
Integral proteins which bind signalling molecules with high selectivity and high affinity
What are the three major classes of receptors?
Ionotropic
Metabotropic
Catalytic
Give an example of an ionotropic receptor
Nicotinic cholinergic receptor
Ionotropic glutamate receptor
What is another name for ionotropic receptors
Ligand-gated ion channels
What is another term for metabotropic receptors?
7 transmembrane spanning G-protein coupled receptors
Give an example of a metabotropic receptor
Glucagon receptor
Adrenaline receptor
(Beta adrenergic receptors)
What does RTK stand for?
Receptor tyrosine kinase
What kind of receptor is RTK?
Catalytic
Give an example of a catalytic receptor
Insulin receptor
Nerve growth receptor
What are the two types of intracellular signalling pathways?
Signalling cascades/adaptor protein scaffolds
Secondary messengers
Which receptor uses signalling cascades/adaptor protein scaffolds?
RTK
What type of receptor uses secondary messengers?
GPCR
Give an example of an effector enzyme
Adenylyl cyclase
Phospholipase C
Give an example of a second messenger molecule
cAMP cGMP Arachidonic acid Nitric oxide IP3 DAG
What second messenger does adenylyl cyclase produce?
cAMP
What second messenger does phospholipase C produce?
IP3 (inositol 1,4,5-triphosphate)
OR
DAG (1,2-diacylglycerol)
Where is the G-protein interaction domain on a 7TMGPCR?
Between the 5th and 6th transmembrane protein
What is the main type of secondary protein structure present in a 7TMGPCR?
Alpha helix
Where is the N-terminal of a 7TMGPCR?
Outside the cell
Where is the C-terminal of a 7TMGPCR?
Inside the cell
When is a G-protein active?
When bound to GTP
What is a G-protein?
Molecular “switch” that carries information from receptors to effector enzymes
How many subunits is the G-protein (involved in GPCR signalling) made up of?
3 (heterotrimeric)
What are the steps in GPCR signalling?
- Hormone binds to receptor
- Inactive G-protein associates with receptor
- GTP is exchanged for the GDP (activation of G-protein)
- G-protein dissociates into alpha-GTP and beta-gamma subunits
- Alpha-GTP activates effector enzyme
- Effector enzyme produces second messenger
- GTP hydrolysed to GDP and G-protein complex reassociates; signalling ends
What G-protein is associated with beta-adrenergic receptors?
Gs
What G-protein is associated with cannabinoid (CB1) receptors?
Gi
What G-protein is associated with M1 muscarinic (ACh/alpha-1 adrenergic) receptors?
Gq
What effector enzyme is associated with beta-adrenergic receptors? What is the effect?
Adenylyl cyclase
Increase cAMP production
What effector enzyme is associated with cannabinoid (CB1) receptors? What is the effect?
Adenylyl cyclase
Decrease cAMP production
What effector enzyme is associated with M1 muscarinic (ACh/alpha-1 adrenergic) receptors? What is the effect?
Phospholipase C
Produce IP3 (release calcium from stores)
Produce DAG (activates PKC)
What does IP3 trigger?
Release of calcium from stores
What is the function of DAG?
Activate PKC
What is the structure of PKA?
4 sub-units: 2 catalytic, 2 regulatory
What does PKA stand for?
cAMP dependent protein kinase A
What happens when cAMP and PKA bind?
PKA falls apart releasing catalytic subunits
What occurs after the PKA catalytic subunits are released?
Serine/threonine phosphorylation
What is the result of serine/threonine phosphorylation? (2)
Short term signalling actions (metabolic)
Phosphorylation of CREB
What is CREB?
cAMP response element binding protein (transcription factor)
What does CREB phosphorylation affect?
Affects glucose/glutamate transporters (regulating gene expression)
What enzyme converts cAMP to 5’AMP?
Phosphodiesterase
What is the function of phosphodiesterase?
Convert cAMP to 5’AMP
No binding to PKA therefore terminates response
What type of receptor is stimulated in the “fight or flight” response?
Beta adrenergic
What is the point in the “fight or flight” response?
Liberates glucose for respiration (more energy released)
More cAMP to stimulate more PKA
What enzymes are stimulated in the “fight or flight” response?
(Adenylyl cyclase and PKA)
Glycogen phosphorylase kinase
Glycogen phosphorylase
What enzyme is inhibited in the “fight or flight” response?
Glycogen synthase
What does the stimulation of glycogen phosphorylase cause?
Increased glycogen degradation
What does the inhibition of glycogen synthase cause?
Decreased glycogen synthesis