M And R Flashcards
Name the four ways that phospholipids can move in the plasma membrane
Flexing, rotation, lateral movement and flip flop
Why can proteins not do flip flop?
There would be too large of a disruption to the plasma membrane which would probably result in rupture
How can we test if a protein sits on the inner membrane or outer membrane of the phospholipid bilayer?
Freeze fracture
Which two proteins are important for maintaining the cytoskeleton of the cell?
Actin and spectrin
Name two hereditary deficiencies to spectrin protein
Spherocytosis and elliptocytosis
Which two sites are important for protein integration into the plasma membrane?
The signal recognition particle (SRP) on the protein and the docking protein on the membrane
What properties must be displayed for a substance to diffuse through the plasma membrane?
Hydrophobic, small and uncharged
Name the four ways that membrane proteins can aid in transport of charged or large substances across a membrane
Facilitated diffusion
Ping pong
Ligand binding (e.g. nicotinic receptors)
Voltage sensitivity
Define equilibrium potential
The concentration at which there is no net movement of an ion in or out of the cell
What does the Goldman-Hodgkin-Katz equation tell us?
This is the overall equilibrium potential of the cell including all of the ions. Opening an ion specific channel in the cell will change the overall charge of the cell toward the equilibrium potential of that ion
What is the significance of a negative equilibrium potential of an ion?
The opening of these ion specific channels will hyperpolarise the cell. (Chloride and potassium)
How many transmembrane regions are in the voltage gated sodium channel? And how many subunits?
6 transmembrane regions and 4 subunits
In the voltage gated sodium channel, where is the pore located?
Between the fifth and sixth transmembrane region in all four of the subunits
Lidocaine is a use-dependent blocker of which channel?
Voltage gated sodium channel. This means that the channel must first open before being blocked
Describe the basis of neural accommodation
Depolarisation of the membrane allows sodium influx, further activating other voltage gated sodium channels. These take time to inactivate and so many impulses in quick succession makes the threshold incrementally higher with each impulse until threshold cannot be reached and an impulse is not conducted
Give the five subunits of the nicotinic receptor
2 alpha, 1 beta, 1 delta and 1 gamma
Acetylcholine binds to which subunit of the nicotinic receptor?
The two alpha subunits, causing the central pore to open and allow sodium influx
What is the local current theory of conduction?
Immediate local change to an axonal polarisation that is not propagated
Why is myelin used to surround axons?
It is a good conductor of impulses
At what diameter is myelination detrimental to conduction velocity?
1 micrometre
What is saltatory conduction?
Propagation of a signal down an axon jumping between the nodes on Ranvier
How is acetylcholine released into the synapse?
It is held within a vesicle, which binds to the presynaptic membrane by a snare complex and synaptotagmin. When the impulse arrives, calcium influx binds to the snare complex and create a fusion pore for the ACh to be released into the synapse
Define affinity
The tendency of a receptor to bind to a ligand
Define efficacy
The intrinsic response that occurs within a cell as a result of binding to a receptor
Give the unit of measurement of affinity
Kd - the concentration of substrate at which half of the receptors are occupied. Low Kd means a high affinity
Explain the difference between a receptor and an acceptor
A receptor binds the ligand and initiates a response internally whereas an acceptor only binds the ligand and has no associated response
Define drug potency
The concentration at which the drug is required to induce a specific response. This is affinity + efficacy
How do we measure efficacy of a drug?
Give the highest possible concentration of the drug so that all receptors are occupied and only internal response is measured. This is the Emax
Give the unit of measurement for drug potency
EC50 - the concentration at which half Emax is elicited
What structure of clathrin coated pits allows for receptor mediated endocytosis (RME)?
The triskelion
Once the ligand and receptor are taken up by a cell in RME, what structure do they enter?
The compartment of uncoupling of receptor and ligand (CURL)
What is the fate of the ligand and receptor in RME for ferric ions?
Both recycled
What is the fate of the ligand and receptor of insulin in RME?
Ligand recycled, receptor degraded
What is the fate of the receptor and ligand of LDL in RME?
Receptor recycled and ligand degraded
How many transmembrane domains are there in a G protein coupled receptor?
Seven
Give the two subunits associated with a GPCR
Alpha and beta-gamma
How do the alpha and beta-gamma subunits dissociate and associate in GPCRs?
Alpha subunit is initially bound to GDP
Stimulation of GPCR causes GTP to displace GDP
Beta-gamma subunit freed and exerts effects in the cell
Alpha unit slowly hydrolyses GTP to GDP by GTPase enzyme
GDP presence increases affinity for beta-gamma again
Give the three forms that an alpha subunit of a GPCR can take
S, i and q
Which enzyme do Gas and Gai act on?
Adenylyl cyclase
What is the function of adenylyl cyclase?
Convert ATP to cAMP. cAMP will stimulate protein kinase A and cause a signal amplification
Give the process occurring after Gaq stimulation
Stimulates phospholipase C to convert PIP2 into DAG and IP3. IP3 binds to sarcoplasmic reticulum to release calcium into the cytosol. The released calcium and DAG activate protein kinase C to cause signal amplification. The calcium is often utilised in muscle contractility
How does calcium enter a cardiac myocyte?
Depolarisation of the membrane causes the voltage operated calcium channel to open
Describe calcium induced calcium release
Voltage operated calcium channels open to allow calcium into the cell. This binds to a ryanodine receptor on the sarcoplasmic reticulum and allows calcium to be released from the sarcoplasmic reticulum.
Give the role of calcium in myocyte contraction
Binds to the troponin complex to move the tropomyosin away from the myosin binding site, allowing the myosin head to bind
Which calcium channel is important for the maintenance of the resting membrane potential?
Sodium calcium exchanger (NCX). Extrudes calcium for sodium influx
Which portion of the spine has sympathetic outflow?
Thoracolumbar (T1-L2)
Which portion of the spine has parasympathetic outflow?
Sacral and cervical
Where in the autonomic system are nicotinic receptors found?
The pre-ganglionic synapses of both the parasympathetic and sympathetic fibres
Where are muscarinic receptors (using ACh) found in the autonomic nervous system?
Post-ganglionic synapses of the parasympathetic division
Where are adrenoceptors (using noradrenaline) found in the autonomic nervous system?
Post-ganglionic synapses of the sympathetic division
How is acetylcholine removed from the synapse space?
By acetylcholinesterase enzyme breaking it down to acetate and choline
How is acetylcholine made in the pre-synaptic bulb?
Made using choline acetyltransferase (CAT) and packed into vesicles using vacuolar ATPase
How is noradrenaline removed from the synaptic space?
It is taken back up into the pre-synaptic bulb and broken down by monoamine oxidase (MAO)
What is the mechanism of action of AChE inhibitors and what conditions are they used for?
These block acetylcholinesterase activity and keep the acetylcholine concentration high. Used for Parkinson’s disease and myasthenia gravis
What is the mechanism of action of MAO inhibitors and what conditions are they used for?
These block monoamine oxidase enzyme and so noradrenaline is not degraded and so more persists in the synapse. This is used for depressive or anxious patients.
Why is salbutamol favoured over salmeterol for asthmatics?
Salbutamol is a selective beta 2 agonist whereas salmeterol is not and so may induce tachycardia
Between which two values is the therapeutic value found?
LD50 and ED50
What is a precipitant (class II) drug?
One that displaces the original drug from binding blood proteins so that the first has a higher circulating concentration
Describe first order drug metabolism kinetics
The rise in drug concentration is met by a proportional increase in product concentration
Describe zero order drug metabolism kinetics
All of the enzymes are saturated and so a rise in drug concentration will not affect the rate at which product is made
