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BIOC3560 > Transport across membranes > Flashcards

Transport across membranes Flashcards

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
Q

What is the inside of a plasma membrane at rest?

A

= - 60mV (between -50 to -70)

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26
Q

What is the equation for an electro chemical gradient?

A

delta G = RTlnc2/c1 + zFdeltaV

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27
Q

Na+K+ ATPase. What are the 4 points that it does?

A
  • 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)
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28
Q

What is the tertiary structure of the Na+K+ ATPase?

A

tetramer of a2b2

- a performs the transport

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29
Q

What is the net charge generated by the Na+K+ ATPase?

A
  • +ve net charge OUT

- membrane potential cuz -ve inside

30
Q

What is the power stroke of this transporter?

A
  • conformational change due to phosphorylation
31
Q

ATPase transport cycle: Step One

A

bind 3 Na+ cytoplasmic to inside of cell

32
Q

ATPase transport cycle: Step Two

A

Na+ binding stimulates the phosphorylation by ATP on the cytosolic side
- ATP adds a phosphate to the enzyme, ADP released

33
Q

ATPase transport cycle: Step Three

A

Phosphorylation causes a conformational change

  • release Na+ to extracellular outside
  • affinity of Na+ decreased
34
Q

ATPase transport cycle: Step Four

A

K+ binds the extracellular side

  • this triggers the release of the phosphate group
  • dephosphorylation
35
Q

ATPase transport cycle: Step Five

A
  • dephosphorylation causes conformational change and restore to original shape of the enzyme
36
Q

ATPase transport cycle: Step Six

A
  • 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
Q

What is a secondary active transporter?

A

The transport of ion DOWN its GRADIENT can transport another isolute UP its gradient

38
Q

What is an example of a secondary active transporter?

A

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
Q

Where is the Na+-glucose symporter located in the body?

A
  • microvilli - intestinal lumen to epithelial cells (between intestine and blood)
  • Na+ and glucose are brought into the epithelial cell
40
Q

What drives the Na+- glucose symporter? How many molecules are needed?

A

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
Q

What mechanisms are involved with Na+/K+/Glucose between the epithelial cell and blood?

A
  • 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
Q

GLUT2 is what type of transporter?

A
  • passive transporter
  • uniporter
  • downhill efflux
43
Q

How are ion channels gated?

A
  • ligand gated

- voltage gated

44
Q

How do ion gated channels affect neurons?

A
  • presynaptic (ligand - Ach receptor ion channel)

- post synaptic - action potential response to change in voltage - Na+/K+ (de)polarize

45
Q

Explain the first step to a nerve impulse?

A
  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
Q

In the graph, the second part to change in membrane potential is?

A
  • depolarization
  • occurs because of Na+ in = depolarize
  • a full Na+ influx
47
Q

In the graph the 3rd part of the change in membrane potential is?

A
  • K+ efflux (out) = repolarization

- establish potential again

48
Q

Where does an action potential occur and what does this mean?

A
  • 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
Q

What is the ionic composition/gradients in neurons?

A

high K+ cytosol

low Na+ cytosol

50
Q

What transmits a nerve impulse?

A
  • action potential

- neurotransmitter

51
Q

What does the action potential do in a neurotransmitter?

A
  • it carries the electrical signal down the axon
52
Q

What does the neurotransmitter do in a neuron?

A
  • it carries a signal molecule to the next cell
53
Q

The Na+K+ ATPase in a neuron causes the _____. Ion voltage gated channels causes the _____.

A
  • electro-chemical gradient

- action potential

54
Q

What is the structure of the voltage gated K+ channel.

A
  • 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
Q

What causes the channel to be closed?

A

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
Q

How is K+ stabilized in the channel/selective?

A
  • 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
Q

How is K+ channel selective?

A
  • size
  • partial negative charges of C=O
  • consensus sequence for K+ = gly-tyr-gly-val-thr
58
Q

How does the K+ pass through?

A

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
Q

What is the structure of voltage gated Na+ channels?

A
  • 4 domains

- 6 transmembrane helices (S1-S6) each

60
Q

Which helices of the voltage gated Na+ channel forms the central channel?

A

S5 and S6

61
Q

What helix is the voltage sensor?

A

S4

62
Q

What happens to the Na+ channel when the membrane is depolarized?

A
  • voltage change induces conformational S4 (less +ve outside)
  • S4 moves up.out of membrane
  • channel opens
63
Q

What helix is the activation/inactivation gate?

A

S6

64
Q

How is the Na+ channel blocked?

A
  • 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
Q

At what membrane potential is the channel fully open?

A
  • 70 mV to +30 mV

- must pass threshold

66
Q

What causes the S4 to pop up initially in order to open the channel and depolarize?

A

the neurotransmitter release
- depolarize at cell body to decrease repulsion
S4 pops up

67
Q

What is the inactivation gate. Fast/slow?

A
  • it occurs quickly

- if u increase the tether u increase the time to close and vice versa

68
Q

What does the selectivity filter do?

A
  • the part of the pore region that only allows Na+ in
69
Q

How does the activation gate work?

A

S5 and S6 helices
form the channel
S6 is the activation gate and allows for the open/close

70
Q

What are two defective ion channels and their result?

A

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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