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BIOC3560 > Transport across membranes > Flashcards

Transport across membranes Flashcards

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1
Q

Membrane Permeability: ions and polar molecules

A

cannot cross - impermeable

Na+, Cl-, sugars, a.a.

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2
Q

Membrane permeability: small, uncharged, somewhat polar

A

molecules can cross

glycerol, ethanol

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3
Q

Membrane permeability: hydrophobic molecules, gases

A

cross quickly

O2, CO2, N2, cholesterol based steroid hormones, hydrophobic (most drugs)

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4
Q

What is the permeability of morphine?

A

somewhat, polar therefore can cross the membrane

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5
Q

Heroin permeability across membrane?

A

crosses fast cuz its acetylated morphine and hydrophobic

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6
Q

Where and why are there ion concentration gradients?

A
  • PM and organelle membranes

- ionic composition differs in cytosol and extracellular environment

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7
Q

Simple diffusion occurs in what direction?

A

From high to low concentration gradient

- spontaneously therefore delta G is negative when moving from high to low

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8
Q

The energy required to maintain the chemical gradient is delta G (+ve or -ve)

A

to maintain therefore +ve.

when moving down gradient = -ve

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9
Q

What is the equation for free energy?

A

delta g = RT ln c

c being c2/c1

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10
Q

If you were to transport hydrophillic solutes across the membrane without aid, how is this down and what is the velocity?

A
  • slowly
  • very few solutes have enough activation energy to overcome the barrier
  • it must break the solvent-solute (h20) bonds first, pass, then reform
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11
Q

If you were to transport hydrophillic solutes across the membrane with a transporter, how fast would this be?

A
  • with transporter
  • reaches same equilibrium but
  • FASTer
  • lower activation energy needed
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12
Q

Membrane Channels vs Membrane Transporters? Difference in flux, saturation, gated?

A 
Channels:
very fast
not saturable
gated open/close to stimuli
Transporters:
slow
saturable
no gate
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13
Q

Membrane Channels

A
  • solutes flow through rapidly
  • via diffusion
  • not saturable (rate of transport is dependent on the concentration of the substrate) - down the gradient
  • gated: open and close in response to stimuli
  • highly selective - many types of channels
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14
Q

Passive Transporters

A
  • facilitated diffusion
  • down a concentration gradient
  • highly selective - sterospecific (D vs L a.a.)
  • transport one molecule at a time; saturable binding sites
  • not a continuous pore, changes open/close
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15
Q

How do you increase the velocity of passive transporters?

A
  • increase number of transporters since one transporter transports one set of molecules at a time
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16
Q

Are aquaporins channels or transporters?

A

Water channels

very fast

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17
Q

How do transporters work?

A
  • substrate binds on one side
  • conformational change
  • other side opens
  • substrate released
  • conformational change to original side open
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18
Q

What are GLUT1, GLUT2, GLUT4 transporters and where are they expressed/roles, respectively?

A
  • Glucose transporters
  • GLUT1: ubiquitous - RBC and brain; basal glucose uptake (imports glucose)
  • GLUT2: liver - removal of excess glucose in the blood; pancreas - regulation of insulin release; intestines; (exports glucose)
  • GLUT4: muscle, fat, heart - activity increased by insulin; insulin sensitive and critical for diabetes to increase glucose uptake
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19
Q

Explain the GLUT4- total body glucose uptake graph with time.

A
  • GLUT4 uptakes total body glucose
  • insulin regulates GLUT4 uptake
  • if normal, GLUT4 transporter will follow the concentration gradient and be selective to glucose
  • as you give insulin (without resistance) with time, the glucose uptake increases significantly
  • if you take away insulin, there is not a lot of glucose uptake (glut4 decreased) and you are left with lots of glucose in the blood
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20
Q

Active transporter

A
  • transports agains concentration gradient
  • pumps
  • poweredby ATP hydrolysis
  • ion gradients generated across membrane
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21
Q

How are cells kept from swelling?

A

Water association with Na+. 3 Na+ pumped out due to Na/K ATPase

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22
Q

Ion gradients: Na+, Cl-, K+, Ca2+. Which ones have high concentraton outside of the cell.

A

Na+, Cl-, Ca2+ - high outside

K+ high inside

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23
Q

What are the 3 classes of membrane transporters:

A
  • Uniporter (one, one direction)
  • Symporter (2 same direction, co transport)
  • Antiporter (bidirectional, co transport)
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24
Q

Membrane potential is measured in what units? What is the definition?

A
  • a charge imbalance as a result of a charged molecule moved across a membrane
  • free energy is different on sides of membrane
  • measured in volts
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25
What is the inside of a plasma membrane at rest?
= - 60mV (between -50 to -70)
26
What is the equation for an electro chemical gradient?
delta G = RTlnc2/c1 + zFdeltaV
27
Na+K+ ATPase. What are the 4 points that it does?
- generates gradients of Na+ and K+ - controls cell volume (pump out water) - drives active transport of other species (i.e. secondary active transport of Na+/Glucose) - electrically excitable (nerve cells)
28
What is the tertiary structure of the Na+K+ ATPase?
tetramer of a2b2 | - a performs the transport
29
What is the net charge generated by the Na+K+ ATPase?
- +ve net charge OUT | - membrane potential cuz -ve inside
30
What is the power stroke of this transporter?
- conformational change due to phosphorylation
31
ATPase transport cycle: Step One
bind 3 Na+ cytoplasmic to inside of cell
32
ATPase transport cycle: Step Two
Na+ binding stimulates the phosphorylation by ATP on the cytosolic side - ATP adds a phosphate to the enzyme, ADP released
33
ATPase transport cycle: Step Three
Phosphorylation causes a conformational change - release Na+ to extracellular outside - affinity of Na+ decreased
34
ATPase transport cycle: Step Four
K+ binds the extracellular side - this triggers the release of the phosphate group - dephosphorylation
35
ATPase transport cycle: Step Five
- dephosphorylation causes conformational change and restore to original shape of the enzyme
36
ATPase transport cycle: Step Six
- 2 K+ released affinity decreases without P - and cycle repeats - this step works agains the concentration gradient but favours the electrical gradient cuz more negative interior and adding more positive
37
What is a secondary active transporter?
The transport of ion DOWN its GRADIENT can transport another isolute UP its gradient
38
What is an example of a secondary active transporter?
Na+ glucose symporter. - Na+ is pumped out of the cell via Na+K+ ATPase - Na+ is brought back into the cell by going DOWN the gradient - glucose is brought into the cell in this symporter going UP the gradient - going UP gradient so its an active transporter
39
Where is the Na+-glucose symporter located in the body?
- microvilli - intestinal lumen to epithelial cells (between intestine and blood) - Na+ and glucose are brought into the epithelial cell
40
What drives the Na+- glucose symporter? How many molecules are needed?
high Na+ gradient outside, needs to go down gradient - 2 Na+ are needed to drive glucose UP the gradient (vs 3+ Na+ out for sodiumpotassium pump)
41
What mechanisms are involved with Na+/K+/Glucose between the epithelial cell and blood?
- NA+ K+ ATPase active transporter - Na+ is brought out of the epithelial (opposing gradient) - K+ is brought in - glucose is brought out via glucose uniporter
42
GLUT2 is what type of transporter?
- passive transporter - uniporter - downhill efflux
43
How are ion channels gated?
- ligand gated | - voltage gated
44
How do ion gated channels affect neurons?
- presynaptic (ligand - Ach receptor ion channel) | - post synaptic - action potential response to change in voltage - Na+/K+ (de)polarize
45
Explain the first step to a nerve impulse?
1. Ach is the ligand that causes a small Na+ influx and slight depolarization - this occurs in the cell body - nerve impulse sends the Ach as a signal
46
In the graph, the second part to change in membrane potential is?
- depolarization - occurs because of Na+ in = depolarize - a full Na+ influx
47
In the graph the 3rd part of the change in membrane potential is?
- K+ efflux (out) = repolarization | - establish potential again
48
Where does an action potential occur and what does this mean?
- action potential occurs at the top +3-mV - means the nerve has been fired = reaction - action potentials are all or none, it must reach the threshold for a fire
49
What is the ionic composition/gradients in neurons?
high K+ cytosol | low Na+ cytosol
50
What transmits a nerve impulse?
- action potential | - neurotransmitter
51
What does the action potential do in a neurotransmitter?
- it carries the electrical signal down the axon
52
What does the neurotransmitter do in a neuron?
- it carries a signal molecule to the next cell
53
The Na+K+ ATPase in a neuron causes the _____. Ion voltage gated channels causes the _____.
- electro-chemical gradient | - action potential
54
What is the structure of the voltage gated K+ channel.
- tetramer - each subunit with 2 transmembrane helices and a shorter helix - selectivity filter - 2 outer helices in each subunit interacts with bilyayer - inner helices contribute to inner pore
55
What causes the channel to be closed?
The +ve extracellular space interact with the +ve helix dipole from 4 Arg/Lys +ve residues - electrostatic repulsion pushes down transmembrane helix to pinch off the channel
56
How is K+ stabilized in the channel/selective?
- K+ interacts with the carbonyl oxygens (O coordinates with unhydrated K+) - it forms a cage precisely - stabilizes it and replaces stabilizing interactions with O from water sphere and water molecules
57
How is K+ channel selective?
- size - partial negative charges of C=O - consensus sequence for K+ = gly-tyr-gly-val-thr
58
How does the K+ pass through?
the gate is opened when the membrane potential changes - the depolarization causes the outside environment to become more negative and the +ve helices shift up - open gate and release K+
59
What is the structure of voltage gated Na+ channels?
- 4 domains | - 6 transmembrane helices (S1-S6) each
60
Which helices of the voltage gated Na+ channel forms the central channel?
S5 and S6
61
What helix is the voltage sensor?
S4
62
What happens to the Na+ channel when the membrane is depolarized?
- voltage change induces conformational S4 (less +ve outside) - S4 moves up.out of membrane - channel opens
63
What helix is the activation/inactivation gate?
S6
64
How is the Na+ channel blocked?
- S4 voltage sensor helix has 4 Arg/Lys that repel the +ve exterior - this pushes down on the channel/closed when at resting potential
65
At what membrane potential is the channel fully open?
- 70 mV to +30 mV | - must pass threshold
66
What causes the S4 to pop up initially in order to open the channel and depolarize?
the neurotransmitter release - depolarize at cell body to decrease repulsion S4 pops up
67
What is the inactivation gate. Fast/slow?
- it occurs quickly | - if u increase the tether u increase the time to close and vice versa
68
What does the selectivity filter do?
- the part of the pore region that only allows Na+ in
69
How does the activation gate work?
S5 and S6 helices form the channel S6 is the activation gate and allows for the open/close
70
What are two defective ion channels and their result?
Na+ channels in muscle - causes paralysis Na+ channels in neurons - stop action potentials i.e. terodotoxin binds Na+ channels of neurons Na+ channels also inhibited by anaesthetics like lidocaine and cocain to dapen down CNS (anti-epileptic, anti-arrythmic drugs)

BIOC3560 (6 decks)

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