Flashcards in MR 6-9 Deck (63)
Define a partial agonist
Cannot create a full response with maximal binding.
Difference between a receptor and acceptor
Receptors are functionally silent without agonist, acceptors are normally active and activity is effected by binding of ligands
What are the differences between rectors and ligands
Kd< Km, so higher binding affinity of ligands to receptors -9 to -6 compared with -6 to -3
Ligand is unchanged at receptor but changed by active site.
What is the structure of a classical integral ion channel?
Consists of 5 subunits. Each subunit has 4 transmembrane domains, one of which forms the channel lining.
Typical structure of G protein coupled receptors?
7 transmembrane domains.
Describe membrane bound receptors with integral enzyme activity
Tyrosine kinase linked receptors autophosphorylate. This can then allosterically activate an enzyme or be recognised by a transducin protein which in turn activates an enzyme.
Also make be linked to guanylyl cyclase.
Describe intracellular receptors for hydrophobic ligands.
Ligand binds, and receptor dissociates from chaperone or heat shock protein and interacts with DNA control regions to regulate gene expression .
What is the difference between phagocytosis, pinocytosis and RME
Phagocytosis is in response to the binding of a ligand to a receptors, pseudopods are extended which also bind to ligands (normally attached to another cell) and engulf it.
Pinocytosis is a non specific invagination of particles from outside the cell- does not involve receptors.
RME involves invagination, brought about by spontaneous formation of vesicles by triskelions (May be pinocytosis also) of specific ly receptor dense areas/ coated pits. Bonding of ligand can trigger membrane coating. RME is the selective internalisation of molecules into the cell through binding to specific receptors.
What is the triskelion made out of?
3 Cathrin chains and 3 light chains
Describe uptake of cholesterol
Apoprotein b binds to LDL receptor
Endocytosed and fuses with CURL/ endo some.
Low pH so dissociation.
Receptor back to membrane (via golgi?) sequestered to specific region.
LDL goes to lysosome.
Give mutations effecting LDL receptor
Deficiency so not present.
Non functional so apoprotein cannot bind
Binding normal but cannot trigger coat.
Describe the uptake of fe3+
Free fe3+ binds to apotransferrin twice to form transferrin.
Binds to transferrin receptor.
Endocytosed and fuses with curl/ endosome.
Fe dissociates at pH but apotransferrin stays bound.
Receptor sent to membrane where apotransferrin dissociates.
Give an example of the passage of large molecules across cells
Transcytosis. Receptor and ligand (e.g. IgA (maternal immunoglobulins to foetus) Endocytosed and in vesicle receptor is cleaved so that IgA with part of receptor is released other side.
Insulin control of receptor number?
Insulin binds to receptor, conformational change so the receptor can be targeted to coated regions.
Insulin and receptor degraded.
Entry of membrane enveloped viruses
Enter via REM, in endosome, low pH is favorable and so the viruses fuse their membrane and their DNA is sent into cell.
How to G protein coupled receptors work?
GDP swapped for GTP on alpha subunit -(receptor acts as a guanine nucleotide exchange factor (GEF))
Alpha and beta/gamma subunits dissociate.
Subunits activate/inhibit other enzymes
Intrinsic GTPase dephosphorylates GTP to GDP and unit re associate with receptor.
Name 4 G proteins and their effectors
Gs - stimulates adenylyl cyclase
Gi - inhibits adenylyl clclase
Gq - stimulates phospholipases C to convert PIP2 to IP3 and DAG
Gt - stimulates cyclic GMP phosphodiesterase (light)
Name some toxins aimed at G protein cascades.
Pertussis toxin prevents the GDP/GTP exchange in Gi proteins.
Cholera prevents the GTPase in Gs so effect lasts longer.
The ability of a drug, once bound to a receptor to cause a response after binding. Depends on its ability to activate the receptor once bound (intrinsic efficacy) and cellular factors. It is measured in relative terms not absolute.
What is IC50
The amount of inhibitor needed to give 50% inhibition.
Why is EC50 often less than KD
Because often binding less than 100% of receptors produces maximal response as there are spare receptors. This allows greater sensitivity.
Give a cause of drug tolerance/ tachyplaxis
Receptor number is not sufficient for a maximal response
Give an example of how a partial agonist can prevent a full response in the present of a full agonist.
Partial agonist must have higher affinity so that it out competes full agonist. E.g. Buprenorphine relieves the effects of morphine.
How does a competitive reversible antagonist effect the agonist concentration response curve?
Causes a parallel shift to the right (is surmountable)
How does a non-competitive reversible antagonist effect the agonist concentration response curve? (Same as competitive)
Shift curve to right but at higher concentrations there will no longer be a maximal response. Non surmountable
What is kB?
Kd (affinity) / 50%) when derived pharmacologically.
Who is pharmaceutical process, pharmacokinetics, pharmacodynamics and what does this produce?
Pharmaceutical process is putting the drug into the patient.
Pharmacokinetics is what the body does to the drug
Pharmacodynamics is what the drug does to the body.
This produces a therapeutic effect.
Describe the methods of administering drugs and what is first pass metabolism?
Enteral - sublingual, renal, oral
Parental - intramuscular, subcutaneous, intravenous, transdermal, inhalation
First pass metabolism is everything but oral as it bypasses the portal system from gut to liver.
Define volume of distribution, how can it be calculated?
The theoretical volume in which a drug spreads into assuming it occurred instantaneously = amount given/ plasma concentration at time 0 (found by plotting a graph of plasm conc vs time and extrapolating backwards)