L3 - How Drugs Work - Part 2 Flashcards
how does direct opening of ion channels work?
- in this case receptor protein is an ion channel
- protein that forms a pore in plasma membrane through which a specific type of ion can pass
- open/closed depending of the presence of the specific agonist
- binding of agonist results in a conformation change in the protein, which then opens
- ions flow through channel down conc gradient
for the agonist acetylcholine, what is the recptor and the channel
- receptor
- nicotinic chlonergic
- channel
- opens cation channels
- mainly Na+
How do enzyme receptors work
- mainly transmembrane proteins which often psses enzyme activity
- they have a ligand binding domain on the outer face of the plasma membrane
- also have a catalytic or enzymatic domain of the inner face of the plasma membrane
- strimulation of this type of receptor by an agonist increases the receptors catalytic activity
domain
a distinct region of a complex molecule or structure
tyrosine kinase receptors
- class of enzyme-linked receptors
- activation of the recptor by the agonist causes the trasnfer of a phosphate group onto specifc amino acids in the recptor itself
- this results in the recruitment of proteins from the cytosol
- become ‘scaffolded’ to the receptor
- this scaffold transmits the signalling information to the cell
what type of recptor is the insulin receptor, what is the agonist, what physiological effects does it have, what disease does it treat
- tyrosine kinase receptor
- agonist is insulin
- physiological effect is glucose uptake
- disease is diabetes
What are the 3 protein components of G protein-coupled receptor signalling
- 7 transmembrane receptor
- G portein (‘switch)
- GTP bound = active/on
- GDP bound= inactive/off
What are GTP and GDP
- GTP
- guanosine triphosphate
- GDO
- guanosin diposphate
G protein-coupled receptor singalling
what do components 1 and 2 do
- component 1
- each receptor (GPCR) binds its specific agonist
- e.g. glucagon binds to glucagon receptors
- component 2
- the G-protein (guanine nucleotide-binding regulatory protein) acts as a molecular switch
- the G-protein is associated with GTP, off when associated with GDP
- swithches itself and the system off
G-protein
guanine nucleotide-binding regulatory protein
what is the third component
- effector enzymes
- produce secondary messengers
secondary messengers
- bind to specific target proteins within the cell to change the cell’s physiology
- usually protein kinases or IP3 receptors
adenyl cyclase
- catalyses conversion of ATP (adenosine triphosphate) to cAMP (cyclic edenosine monophosphate)
phospholipase C
- cuts the plasma membrane lipid phosphatidylinositol bisphosphate into DAG (diacylglycerol) and IP3 (inositol trisphosphate)
cGMP phosphodiesterase
- effector enzyme
- breaks down cGMP (cyclic GMP, cyclic guanosine monophosphate)
How does GPCR signalling work (GG protein-coupled receptor signalling)
ACTIVATION
- agonist activation of receptor induces its 3d or conformational shape
- enabling it to interact with a G protein
- the G protein loses GDP and gains GTP
- G protein becomes switched on
- activated G protein interacts with the effector enzyme and increases its catalytic activity
- the effector enzyme produces specific ‘second messenger’ molecules
- these alter the biochemical machinery inside the cell by interacting with their specific target molecules
- which either phosphorylate other specific protein or releases intracellular stores of Ca2+
How GPCR signlaling works
deactivation
- agonist dissociates from receptor
- G protein’s own GTPase activity convers the bound GTP and GDP and the G protein becomes switched off
- G protein interaction with the effector enzyme ceases and the effector enzyme activity returns to normal
- the ‘second messenger’ molecules are broken down and their target proteins are no longer activatied
