Lecture 14 Flashcards
What does the ability of a molecule to cross a membrane depend on?
- the membrane permeability to the molecule
- - the presence of appropriate transporter and an energy source
True or False, for uncharge membrane permeable molecules, chemical concentration gradient determines spontaneous movement across membranes
True
True or False, for charged molecules, one needs to consider an additional electrical potential term
True
For an uncharged molecule what equation determines spontaneity of diffusion?
deltaGtrans = RTln(c2/c1) R: gas constant, T: temperature
For charged molecules what equation determines spontaneity of diffusion?
deltaGtrans = RTln(c2/c1) + ZFdeltaV
Z: charge of the molecule
F: Faraday constant
deltaV: charge gradient (potential for all ions)
True or False; deltaGtrans indicates if the transport is passive (deltaGtrans <0) or if it requires energy input (e.g. ATP) and is thus active (deltaGtrans > 0)
True; basically if deltaGtrans is negative it is passive; and if it is positive or greater than 0 it is active
How are lipid bilayers are barriers to diffusion?
- low permeability to ions (need desolvation to go through the membrane directly)
- low permeability to polar molecules (except H2O, small and uncharged; however this is slow)
- High selective permeability barriers to ions, using proteins pumps and channels
True or False, for lipid bilayers, ions need to have H2O molecules removed b4 movement occurs aka desolnation
True
T or F, the high selective permeability barriers to ions that lipid bilayers have contributes to the maintenance of different ion conc. on each side of the membrane
True; this is important for membrane potential
What are the 3 classes of proteins for transports across
– membrane carriers/membrane channels
– membrane pumps
– membrane cotransporters
What is the function of membrane carriers/membrane channels?
- for passive transport or facilitated diffusion
- provide a selective pore through which ion can flow rapidly
- when deltaGtrans < 0 (negative)
- NO USE OF ATP
- can be sensitive to membrane polarization
What is the function of membrane pumps?
- for primary active transport
- ATP often source of energy for this process
- when deltaGtrans > 0 (positive)
- drive thermodynamic uphill reactions with ATP as free energy source
- different pumps use different strategy for transport and use of ATP
– pumps have ATPase activity (hydrolyze ATP) to transfer phosphate group to their own residues
What is the function of Membrane cotransporters? aka cariers
– for secondary active transport when deltaGtrans > 0 (positive)
– coupling a thermodynamically unfavorable reaction (e.g. transport against conc. gradient) with a favorable one (e.g. transport with conc. gradient)
– No use of ATP –> use concentration gradient instead
T or F, no energy is required for membrane channels but charged molecules are allowed to move across the lipid bilayer
True
T or F, membrane channels permit movement more readily across lipid bilayers and molecules will move from high concentration to low
True
Describe an aquaporin as a membrane channel.
- they are channels that specialize in H2O transport
- 6 alpha helices forming hydrophilic channel –> span membrane
- 10^6 H2O molecule/sec
- important for rapid H2O transport (e.g. reabsorption of water in kidney, tears) –> also when cells are trying to get flooded with water
What are membrane ion channels?
- fastest transporters: 1000 fold faster than pumps
- close to diffusion rates of ions
- different ion channels use similar transport mechanisms yet are highly selective for specific ions
- channels can work because of ion concentration gradients generated by membrane pumps in live cells
True or False. Na+ and K+ ion channels are particularly important for signal communication in the nervous systems
True
True or False; sequential triggering of Na+ and K+ ion channels generates action potential (nerve impulse)
True
Describe the structure of a K+ channel
– tetramer (4 identical subunits) forming pore through lipid membranes
– peptidic backbone of 5 aa: TVGYG from 2 subunits provides polar interactions with K+ as a replacement for H2O
– polar interaction compensate the energy cost of desolvation for K+ but not for other ions (e.g. Na+)
– size of the pore and position of TVGYG aa optimal for the K+ ion only (tight binding)
Describe the structure of a K+ channel
– tetramer (4 identical subunits) forming pore through lipid membranes
– peptidic backbone of 5 aa: TVGYG from 2 subunits provides polar interactions with K+ as a replacement for H2O
- polar interaction compensate the energy cost of desolvation for K+ but not for other ions (e.g. Na+)
- —-> Ex: sodium can’t come in; too small on it’s own too big w/ water
- polar interaction compensate the energy cost of desolvation for K+ but not for other ions (e.g. Na+)
– size of the pore and position of TVGYG aa optimal for the K+ ion only (tight binding)
T or F, electrostatic repulsions between K+ ion in channel allows for rapid flow
True
How does the K+ ion interact with K+ channels?
– desolvated K+ ion (water must be removed) interacts with a specific aa sequence (binds tightly to carbonyl) along the channel that provides high selectivity for K+
What is a gated-ion channel?
– passive transport system
– gated pores that respond to highly-specific signals
– most important are those for Na+, Ca2+, and K+
– passage of ions goes down concentration gradient thus they are much faster (1000x) than transport by Na+/K+ ATPase pump
i.e. Nerve impulse signals
Describe voltage gating in K+ channels.
– voltage gating is provided by a positively charged domain at the bottom of the channel structure (usually filled w/ positively charged amino acids)
– S4++ domain form voltage sensing paddles that can occlude (close) the channel
– close channel: S4++ domain “down position”
– on membrane depolarization inside become +++, electrostatic repulsion of S4++ paddles upward: channel opens
———————–> this is because repulsion occurs by charge inside cell because they are already positive
True or False, free energy of ATP induces large conformational changes in pumps
True; both phosphorylation and dephosphorylation
True or False; the interconversion between 2 conformations (open/close) provides unidirectional pumping of ions
True
True or False, pumps are important to maintain steady state concentration of ions in cells
True
What is the importance of the regulation of Calcium concentration and Na+/K+ concentration by membrane channels?
- Regulation of Ca2+: important for cell signaling
- - Regulation of Na+/K+: important for membrane potential
Describe the active membrane transport of Na/K+ of ATPase.
- requires work, usually provided by hydrolysis of ATP
- necessary to move substances across concentration gradient
#1.) Protein (4 subunits) is open to interior of cell and binds Na+ ATP phosphorylates protein #2.) conformational change. Open to outside, doesn't bind Na+, but does bind K+. P is hydrolyzed, giving Pi #3.) Goes back to original form, no longer binds K+, which enters the cell. More Na+ can now bind
– pumps Na+ out despite low concentration inside cell; pumping K+ in despite high concentration inside cell
T or F, Na+/K+ ATPase pumps against the gradient and there for each cycle uses one ATP that is able to move 3 Na+ out and 2 K+ in
True
Describe the structure of ATP-Binding Cassette (ABC) transporter pumps
- also uses ATP to move things against their gradient
- 1 transmembrane domain and 2 ABC
- 1 molecule transported for 2 ATP hydrolyzed
– binding of specific substrate induces steric fit that enhances affinity for ATP
T or F, ATP binding induces strong interaction between ABC
True
Describe the function of ATP-Binding Cassette proteins (ABC)
– multi-domain transport proteins
– have 2 cytosolic ATP-binding sites (cassette)
– small molecules, like drugs, can be transported across the membrane
– drug efflux pumps involved in multidrug resistance of cancer cells
What is an example of ABC in eukaryotes?
– multi-drug resistance protein (MDR) ejects pharmacological agents, such as those used in cancer treatments
What happens when there are mutations in the CTFR gene?
CTFR = Cystic Fibrosis Transmembrane Regulator
– mutations in CFTR gene (usually in NBD 1) cause Cystic Fibrosis
– the channel normally transports Cl- across cell membrane
– non-functional, Cl- secretion is decreased, leaders to formation of viscous mucus
What is the difference between an antipoter and symporter?
- Antiporter = transport of 2 solutes in opposite directions (1 moving in and 1 moving out)
- -Symporter = transport of 2 soluetes in same direction (both moving in or both out )
What is a uniporter?
– transport of single solutes following concentration gradients
Describe cotransport systems.
- uses ion gradient that forms from a uniport system
- the flow of ions down a gradient can be used to perform work
– high concentration of Na+ from outside the cell can flow back inside and bring glucose along with it when BOTH are present in lumen of intestine (concentration is high in lumen so it’s unfavorable); it can transport glucose against concentration gradient by using potential energy of Na+ gradient
Note = bringing in glucose is unfavorable;
What is nerve-impulse transmission?
– neurons have specialized projections, called dendrites and axons that act as the wires of the system
– signals must be conducted over long distances very quickly
– it accomplished this by waves in the membrane electrical potential on the membrane surface
– basic idea is that we want to move a signal from where it’s received and transmit it along a pathway
T or F, ion gradient established across membranes can be used by cells that have gated ion channels in their membranes
True
T or F, Na+/K+, Na+ only, K+ only, and Ca2+ are used in nerve conduction
True
T or F, signal is transmitted by a neurotransmitter across the synapse
True
How does activation of voltage-gated channels work?
– influx of Na+ results in a change in voltage and activates voltage-gated channels along the axon
– and finally activate voltage-gated Ca2+ channel to release neurotransmitter at presynaptic terminal
What is an example of a ligand gated ion channel? Describe how it works.
– acetylcholine receptors
– responsible for electrochemical signal transduction at synapses
– expressed at postsynaptic membrane. Respond to acetylcholine released by massive vesicle fusion at the presynaptic membrane
– binding of acetylcholine triggers opening of this non-selective channel (let both Na+ and K+ ions through)
What is an action potential and describe how it works.
– generated in neurons by membrane depolarization involving Na+ and K+ ion channels
What is resting membrane potential?
– 60 mV
What are the two types of gates? and describe them,
– voltage gating: a channel will open given a specific change in membrane potential
– ligand gating: a channel will open upon binding of a specific ligand
– for both types of gates, stimulus (voltage or ligand) induces a change in channel conformation that leads to opening
What leads to the opening of voltage-gated Na+ channels?
- sudden rise in Na+ ion influx
- - 40 mV
Describe action potential propagation in neurons.
1- Steady state membrane potential (-60 mV)
achieved and maintained by Na+ and K+ ion pumps
(with ATP)
2- Firing of neuron leads to acetylcholine release
in synaptic cleft
3- Binding to acetylcholine receptors and opening
of ligand gated channels
4- Entry of Na+ and exit of K+ ions (chemical
gradient) towards ~ -20 mV (Veq)
5- At ~ -40 mV voltage gated Na+ channels open
and depolarization accelerates with high Na+ influx
6- After a few ms Na+ channels inactivate, and K+
channel open. Action potential reach its max.
7- With efflux of K+ action potential decrease
rapidly, until K+ inactivate.
8- Slight overshoot in K+ (resting potential below
-60mV) is slowly corrected by active pumping of
Na+ and K+
