Adrenaline Signalling Flashcards
Describe the structure of adenylyl cyclase
What two G proteins interact with adenylyl cyclase?
What are the 3 other inputs of adenylyl cyclase?
What does adenylyl cyclase do to ATP to form 3’5’cAMP? 2 things
What does phosphodiesterase to do cAMP to form 5’AMP?
12 transmembrane domain with domain linker between both 6-transmembrane domains and a C-terminus domain at the end
Gi & Gs
PKC, calcium/calmodulin receptors, beta-gamma subunits
- Removes gamma & beta phosphate of ATP
- Alpha phosphate cyclised into structure
Hydrolyses bond between 3’C of purine and O of phosphate
What are the 5 steps to the activation of adenylyl cyclase and PKA by adrenergic receptors?
4 steps for suppressing activation of PKA by adenylyl cyclase & adrenergic receptors?
Is alpha-i a competitive inhibitor?
- Ligand binds so helices twist in adrenergic receptor - changes of intracellular surface of helix bundle & loops & C-terminal tail
- GDP dissociates & GTP binds such that Gs subunits break up
- GTP-alpha-s subunit binds to adenylyl cyclase - activating catalytic site
- ATP converted to cAMP - diffuses across cell & binds to regulatory binding sites of PKA
- Catalytic subunits of PKA released (effectors) and also mediate beta adrenergic receptor
o - When Prostaglandin E1 & Extracellular Adenosine bind to their respective GPCRs, cause the release of a Gi alpha subunit
- Gi alpha binds to adenylyl cyclase at a different binding site to suppress its activity
- Low [cAMP] allows for phosphodiesterases to break them down after their spontaneous dissociation from the regulatory PKA subunits
- Therefore the PKA heterotetramer is reformed and PKA activity decreases
no it binds to a different site on the adenylyl cyclase
How is glucose converted into ATP?
What are the 4 steps of catabolism/glucose increase?
What are the 4 steps of anabolism/glucose decrease?
What is the main symptom of diabetes insipidus?
Why is this?
What happens to patients with diabetes mellitus in type 1 and type 2?
Oxidative phosphorylation
- Pancreatic receptors on the beta cells recognise high levels of glucose
- Beta cells produce and secrete insulin
- Liver contains insulin receptors in order to recognise this and convert glucose into glycogen
- ## Glucose levels lowered
- Pancreatic receptors on alpha cells recognise low levels of glucose
- Alpha cells produce and secrete glucagon
- Liver contains glucagon receptors that recognise this and convert glycogen into glucose
- Glucose levels increase
Large volumes excess urine
Patients do not response to vasopressin which promotes the scavenging of water not retained by the kidneys
Type 1 = can’t produce enough insulin
Type 2 = can’t respond to insulin signal
What is the structural difference between adrenaline & noradrenaline?
Does adrenaline or noradrenaline contribute to the signalling pathway?
What are the 3 steps to the adrenaline pathway?
What happens when adrenaline is sent to the following target cells:
Skeletal muscle
Liver
Adipose tissue
What 3 substances increase in the plasma?
Methyl CH3 in adrenaline is replaced by H in nora
There is more adrenaline than noradrenaline present but adrenaline is the main cause of the symptoms (increased heart rate etc)
- Fight/flight response causes plasma glucose levels decrease
- Signals sent to adrenal medulla (part of adrenal glands) causing secretion of adrenaline & noradrenaline into blood stream
- Adrenaline circulates in blood plasma to target cells
Stores of glycogen are hydrolysed (glycogenolysis) to release glucose for ATP
Glycogenolysis and gluconeogenesis (making new glucose) for ATP
Lipolysis of triglycerides & fatty acids pumped into blood to make ATP
Glucose, glycerol and fatty acids
For the following receptors, what is the response and effects?
- Bronchi beta adrenergic
- Heart beta adrenergic
- Veins alpha adrenergic
- Arteries alpha & beta adrenergic
- Skeletal muscle beta adrenergic
- Liver beta adrenergic
- Adipose tissue beta adrenergic
What is the end goal of these co-ordinated receptors?
- Dilation resulting in double flow of blood & increased ventilation to remove carbon dioxide
- Increased heart rate (chronotropic effect), increased contraction/ejection volume (ionotropic effect) & as a result cardiac output from both of these
- Constriction to return blood back to heart for increased blood flow to muscle heart & brain
- Constriction/dilation
- Increased twitch & formation of blood lactate to fuel muscles & heart
- Increase glycogenolysis to increase blood glucose levels
- Increase lipolysis to increase fatty acid & glycerol levels
Increased oxygen and fuel to the muscle, heart and brain for glucose and triglyceride metabolism to ATP
What happens to initial ATP reserves in stress conditions less than 10 seconds?
What happens if the stress lasts longer than 10 seconds?
What are the different classes of adrenergic receptors?
In which receptors are the metabolic effects of catecholamines mediated?
What are the 8 steps for the formation of glucose from glycogen through beta adrenergic signalling?
Instantaneously replaced by phosphocreatine as ADP is phosphorylated
Glucose is required
Beta 1 & 2 and alpha 1 & 2
Beta
- Adrenaline/noradrenaline activates beta adrenergic receptor causing release of activated G-alpha-s subunit
- Alpha-s binds to adenylyl cyclase increasing its ATP -> cAMP activity
- cAMP binds to the regulatory domains of PKA causing the release of its regulatory dimer and two kinase subunits
- PKA phosphorylates glycogen phosphorylase kinase for its activation
- Glycogen phosphorylase kinase glycogen phosphorylase for its activation
- Glycogen phosphorylase phosphorylates glycogen into Glucose-1-P
- Glucose-1-P monomers isomerise into glucose-6-phosphate
- Glucose-6-phosphate enters the glycolytic pathway to generate ATP by glycolysis
How is the production of glycogen regulated?
What are the 7 steps that occurs when adrenaline levels fall?
Why does adrenaline generate different responses in different tissues?
PKA phosphorylates glycogen synthase to reduce its rate of synthesis
- Beta adrenergic receptors are no longer activated
- G-alpha-s hydrolyses its GTP into GDP and reassociates with its beta-gamma subunits
- Adenylyl cyclase activity falls so [cAMP] levels fall
- Protein kinase subunits recombine to enter its inactive state
- Protein phosphatases dephosphorylate glycogen synthase to increase [glycogen]
- Phosphatases dephosphorylate glycogen phosphorylase kinase so it can no longer phosphorylate glycogen phosphorylase
- Therefore conversion of glycogen into glu-1-phosphate stops but increase in glycogen production
Different final phosphorylation targets are expressed in different tissues
