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CORE Block 4 > Membrane Transport > Flashcards

Membrane Transport Flashcards

1
Q

What are the two general ways to pass the cell membrane?

A
  • dissolve (not many do this)
  • cross with the aid of a transmembrane protein
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2
Q

Which molecules can easily pass the cell membrane without help?

A
  • gases (O2, N2, CO2)
  • small polar molecules (ethanol)
  • small nonpolar molecules (diethylurea)
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3
Q

Which molecules need help getting through the cell membrane?

A
  • too polar (ions, ATP, amino acids)
  • too large (glucose)
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4
Q

What gets through tight junctions?

A

Nothing

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5
Q

What intercellular junctions link cells into a wall?

A

Tight junctions

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6
Q

How are tight junctions formed?

A

Made from proteins. Fusion of parallel layers of proteins residing in the outer leaflets of membranes. `

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7
Q

What do tight junctions do?

A
  1. barriers
  2. selective gates (some are leaky, some are tight, protein type dictates permeability(
  3. fences (apical/basolateral polarisation of cells)
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8
Q

What process facilitates the transport of substances between membranes of two cells?

A

facilitated by gap junctions, hollow tubes made up of proteins called connexins (holes between cells)

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9
Q

What limits transport through gap junctions?

A

Limited by size of molecule, less than 1 kD (ions, amino acids, sugars, nucleotides). probably not proteins

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10
Q

What does it mean for diffusion to be thermally-driven?

A

It means that there is no energy input required.

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11
Q

What does the rate of diffusion depend on?

A

It depends on the frequency of collisions with the membrane, which is proportional to concentration.

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12
Q

What is diffusion measured as?

A

FLUX

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13
Q

What does it mean that the flux of diffusion is unidirectional?

A

It means that thing diffuse in both directions, but eventually even out if let to.

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14
Q

What is Fick’s law?

A

The net diffusion of uncharged solutes through a membrane. This is the measurement of flux

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15
Q

What is a partition coefficient?

A

It relates membrane concentration to known aqueous concentration (e.g. dissolving something in lipid vs water will have different parition coefficient, K)

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16
Q

Describe the partition coefficient equation.

A

K=C(oil)/C(water). So, when K > 1, C of membrane is more than C of aqueous environment and the molecule must be hydrophobic to get through.

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17
Q

What does Overton’s law tell us?

A

The higher the lipid solubility, the higher the permeability.

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18
Q

What does Overton’s law predict?

A
  • predicts hydrophobic molecules will cross membrane better
  • crossing is dependent on linear concentration
  • “interesting” molecules have low flux without help from carriers or transporters
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19
Q

What are the five types of membrane transport?

A
  1. simple diffusion
  2. simple: ion channels
  3. facilitated diffusion: insulin regulated glucose transport
  4. primary active: Na pump
  5. secondary active: Na/Ca exchange
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20
Q

What do secondary active pumps reqauire for energy?

A

The energy made by primary active pumps in the form of concentration gradients

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21
Q

Describe transporters.

A
  • it is a slow mechanism becasue there are rate limiting steps
  • uniports (facilitated diffusion)
  • symports/cotransporters (active transport)
  • antiports/exchangers (active transport)
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22
Q

Describe channels

A

Simple diffusion

  • much faster
  • based on fick’s law
  • concentration-dependent
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23
Q

Describe ATP-driven pumps

A

-not as fast as simple diffusion, but not as slow as facilitated diffusion

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24
Q

what type of protein is a permease?

A

It is a carrier protein. It catches a molecule (rate limiting), and then moves it, though it is concentration-dependent. It is a type of uniporter.

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25
Q

Describe the rocking banana model for uniporters.

A

No energy is used, it is reliant on concentration, but only one side of the cell at a time can access the binding portions of the carrier or uniporter. This is a form of facilitated diffusion.

26
Q

In which direction does facilitated diffusion work?

A

It can work both ways, as it is only dependent on concentration.

27
Q

What type of transporter protein is GLUT1, and how does it work?

A

It is a uniporter (can go either way, but is concentration dependent facilitated diffusion). It is the glucose carrier of red blood cells.

  • has high substrate specificity
  • has low affinity for glucose, and this is why concentration is important, so it can later be released easily on the side of the cell membrane where concentration is lower
28
Q

Describe the facilitated diffusion mechanism.

A
  • carriers have two conformations
  • it is a catalytic cycle allowing alternating access of binding sites on either side of the cell membrane
  • there are open and occluded protein conformations
  • the two enzyme conformations have high and low affinities (need to be able to grab substrate and also let it go)
29
Q

How do facilitated diffusion kinetics differ from simple diffusion kinetics?

A
  • simple: rate of diffusion increases proportionally with concentration of substrate
  • for facilitated diffusion, rate of diffision reaches a Vmax because there is a rate-limiting step: grabbing onto the substrate
30
Q

How do symporters/cotransporters function?

A
  • rely on active transport
  • couples downward movement of one substrate down its concentration gradient to move another substrate in the same direction against its concentration gradient.
  • almost always uses Na as the downhill substrate
31
Q

On which side of the cell membrane is Na higher?

A

It is always higher on the outside than it is on the inside.

32
Q

What type of active transport do symporters/co-transporters use?

A

Secondary active transport

33
Q

What is vSGLT?

A
  • It is a glucose transporter.
  • prokaryotic homolog
  • family of LeuT family of Na+-dependent cotransporters
34
Q

What is the structure of vSGLT?

A

Consists of two mirror images that act in the rocking banana mechanism (same as facilitated diffusion mechanism). The closing of the structure on the one side contributes to the rate-limiting step.

35
Q

How are antiports/exchangers similar to symports/co-transporters?

A

They function in the same way, but the substrate moving against its concentration gradient moves in the opposite direction to the substrate moving downhill. (uses rocking banana)

36
Q

How does the Na/Ca exchanger work?

A

It reduces intracellular Ca (because it is used as a signal, we dont want levels high in the cell) in cardiac myocytes to lead to relaxation

37
Q

Describe the Na/H antiporter.

A

Helps maintain cellular pH and volume homeostasis by pushing protons out of the cell.

38
Q

Describe the Cl/HCO3 exchanger.

A

Transports CO2 from tissues to blood and to lungs. Uses gradient energy from Cl= to move CO2 out of cells.

39
Q

What type of active transport is used by ATP-driven pumps?

A

Primary active transport (direct use of ATP)

40
Q

What do ATP-driven pumps do?

A

directly couple ATP hydrolysis with movement of a substrate against its concentration gradient.

41
Q

What type of intermediate do all P-class pumps have?

A

E-P

42
Q

What type of pump is Na/K, and what is it used for?

A

It is a P-class ATP pump that is used to set up ion gradients

43
Q

What does Ca ATPase do and what class of pump is it?

A

It is P-class pump, and it is used to maintain low intracellular Ca++

44
Q

What does it mean that the Na/K ATPase is electrogenic?

A

It means that there is a net change in charge across the membrane. (more charge is going out of the membrane than in)

45
Q

Why is so much of the cell’s energy devoted to the Na/K ATPase?

A

Because many other processes are dependent on the gradients set up from the pump.

46
Q

Describe the movement of the Na/K ATPase.

A

3 Na+ move out of the cell and 2 K+ move into the cell.

47
Q

Describe the mechanism of the Na/K ATPase.

A
  • There are two confromations of the pump with alternating access: open and occluded
  • there is high/low affinity binding
  • E1 binds Na and ATP with high affinity on the inside of cell (Na is low here) and K with low.
  • E2 binds K with high affinity and Na with low on the outside of the cell
48
Q

What is the SERCA pump responsible for?

A

Building up calcium stores in the cell

49
Q

What is SERCA and what does it do?

A

It is a Ca pump (primary active transport) that removes Ca from the cytosol and moves it into the SR/ER. The crystal structure of SERCA has been determined and allows us to examine various stages of the catalytic cycle.

50
Q

Describe F-class pumps.

A

Primary active transport

  • bacteria, mito, chloroplasts
  • run backward to make ATP from downward movement of H+
51
Q

Describe V-class pumps.

A

Primary active transport.

-used to acidify internal compartments such as lysosomes

52
Q

How are F- and V-class pumps similar?

A

They are very similar in structure and mechanism, and there is no phosphorylated “E” intermediate

53
Q

Describe mito F1 ATPase.

A

It generates ATP through proton movements using a molecular motor. We know this because we can attach a fluorescent bead to that protein domain and we see it moving around like a motor, and if you give the protein ATP, it will hydrolyze it and move the fluorescence in the opposite direction.

54
Q

What compounds are transported by ABC transporters, and how many of them are there?

A

There are more than 100 known ABC transporters. They transport toxins, mainly metabolites, lipids, sterols, and xenobiotics.

55
Q

How does the eukaryotic ABC transporter work in general?

A

Has two ATPase domains which each bind and hydrolyze ATP on one side in order to move a small molecule to the other side of the cell.

56
Q

What is P-glycoprotein?

A

It is an ABC transporter that moves large, hydrophobic molecules

57
Q

How do ABC transporters contribute to multidrug resistance?

A

They can push out beneficial drugs as well, including anti-malarial drugs and other small hydrophobic molecules. This is due to the similarity of the drugs to normal substrates of the transporters

58
Q

Why is it hard to get drugs through the blood brain barrier?

A

There are a lot of ABC transporters moving the drugs right back out of the cells where they are needed.

59
Q

Describe the ABC superfamily CFTR.

A

Cystic fibrosis transmembrane regulator:

  • it is a cAMP-dependent Cl- channel that uses ATP to move Cl-
  • movement of Cl- helps move water across epithelial cells
60
Q

What can defects in the CFTR superfamily result in?

A

Defect in Cl- transport results in reduced H2O movement, leading to viscous mucous or secretions.

CORE Block 4 (8 decks)

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