Week 2 - Role of membranes as permeability barriers Flashcards

1
Q

What is the relative permeability of a synthetic lipid bilayer to different classes of molecules?

A
  • Hydrophobic molecules (O2, CO2, N2 and benzene) can diffuse
  • Small, uncharged polar molecules (H2O, urea and glycerol) can diffuse
  • Large, uncharged polar molecules and ions cannot diffuse through the phospholipid bilayer-
    The permeability coefficients for most ions and hydrophilic molecules are very low (the transverse movement would require a large free energy change)
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2
Q

What does passive transport depend on?

A
  • Permeability
  • Concentration gradient
  • The rate of passive transport increases linearly with increasing concentration gradient
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3
Q

How does water move across membranes?

A

By osmosis

- Most membranes are relatively permeable to water

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4
Q

What are the roles of transport processes?

A
  • Maintenance of ionic composition
  • Maintenance of intracellular pH
  • Regulation of cell volume
  • Concentration of metabolic fuels and building blocks
  • The extrusion of waste products of metabolism and toxic substances
  • The generation of gradients necessary for the electrical excitability of nerve and muscle
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5
Q

What models are there for facilitated transport?

A
  • Protein pores (channels, may be opened in response to a stimulus)
  • Carrier molecules (ping-pong, may be gated: ligand or voltage)
  • Protein flip-flop (unlikely thermodynamically)
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6
Q

What is responsible for the transport of Cl- across the lipid bilayer?

A

Band 3 protein: it carries out a specific exchange of Cl-

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7
Q

What can increase the permeability of the lipid bilayer for polar substances?

A

The presence of specific proteins in the bilayer

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8
Q

Why is facilitated diffusion a saturable process?

A
  • Each carrier can interact with only 1 or a few ions/molecules at any time
  • There are a finite number of transporters present in the membrane
    As the concentration gradient increases, a maximum rate of transport will be measured when all the transporters are busy
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9
Q

What determines where the transport of an ion/molecule is passive or active?

A

By the free energy change of the transported species

  • This is determined by the concentration gradient for the transported species and/or by the electrical potential across the membrane bilayer when the transported species is charged
  • Passive transport occurs spontaneously (e.g. simple and facilitated diffusion)
  • Active transport requires energy
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10
Q

What is active transport?

A

Transport that allows the transport of ions/molecules against an unfavourable concentration and/or electrical gradient

  • Energy directly/indirectly from ATP hydrolysis, electron transport or light is used
  • Movement must be coupled with a thermodynamically favourable reaction
  • Sometimes the transport of 1 substance is linked to the concentration gradient for another via a cotransporter (secondary active transport)
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11
Q

How can membrane transporters be driven?

A

By:

  • Gradients of ATP
  • Phosphoenolpyruvate
  • Protons and sodium ions
  • Light
  • High-potential electrons
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12
Q

What are some co-transport systems?

A

Na+ - glucose:
- Symport
- Used in the small intestine and kidney
- Entry of sodium provides energy for the entry of glucose
Na+ - Ca2+ exchange:
- Inward flow of sodium down its concentration gradient drives outward flow of Ca2+ up its concentration gradient
- Antiport
Na+ - H+ exchange:
- Inward flow of sodium down its concentration gradient leads to cell alkalisation by removing H+
- Antiport

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13
Q

What is a uniport?

A

When 1 solute molecule species is transported from 1 side of the membrane to the other

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14
Q

What is a symport?

A

When the transfer of 1 solute molecule depends on the simultaneous or sequential transfer of a second solute in the same direction

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15
Q

What is an antiport?

A

When the transfer of 1 solute molecule depends on the simultaneous/sequential transfer of a second solute in the OPPOSITE direction

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16
Q

What is the free ion distribution of Na+ across the cell?

A

Intracellular conc = 12 mM

Extracellular conc = 145 mM

17
Q

What is the free ion distribution of Cl- across the cell?

A

Intracellular conc = 4.2 mM

Extracellular conc = 123 mM

18
Q

What is the free ion distribution of Ca2+ across the cell?

A

Intracellular conc = 10^-7 mM

Extracellular conc = 1.5 mM

19
Q

What is the free ion distribution of K+ across the cell?

A

Intracellular conc = 155 mM

Extracellular conc = 4 mM

20
Q

What is the sodium-potassium ATPase?

A

A pump

  • Forms Na+ and K+ gradient
  • Drives many secondary active transport process
  • Uses ATP to pump ions
  • 25% of the basal metabolic rate is used for the pump
  • 3 Na+ out, 2 K+ in
21
Q

What is the role sodium-potassium ATPase?

A

Drives many secondary active transport process:

  • Ion homeostasis
  • Intracellular Ca2+ ion concentration
  • Intracellular pH
  • Cell volume
  • Ion gradients
  • Nutrient uptake
22
Q

What is the plasma membrane Ca2+ ATPase?

A

PMCA

  • A primary active transporter
  • Expels Ca2+ out of the cell
  • Requires magnesium for ATP hydrolysis
  • Transports H+ into the cell
  • High intracellular calcium concentration is toxic cells
23
Q

What is the sarco(end) plasmic reitculum ATPase?

A

SERCA

  • Accumulates Ca2+ into the SR/ER
  • High affinity, low capacity
  • Removes residual calcium
24
Q

What is the sodium-calcium exchanger?

A

NCX

  • Secondary active transporter
  • Low affinity, high capacity
  • Removes most Ca2+
  • Electrogenic (current flows in the direction of the Na+ gradient)
  • Role in expelling intracellular Ca2+ during cell recovery
  • Possible role in cell toxicity during ischaemia/reperfusion (reverses!)
  • 3 Na+ in, 1 Ca2+ out
25
Q

What is the sodium-hydrogen exchanger?

A

NHE

  • Extrudes H+
  • Involved in control of cell pH
  • Exchanges extracellular Na+ for intracellular H+
  • Electroneutral
  • Regulates cell volume (Na+ has an osmotic influence)
  • Activated by growth factors
  • Inhibited by amiloride
26
Q

What is the anion exchanger?

A

Cl-

  • HCO3- exchanger
  • Acidifies cell
  • Removes base from cell
  • Involved in cell volume regulation
27
Q

Why do ion transporters work together in cell physiology?

A

By working together, they can achieve biological endpoints that would not be possible if they worked in isolation

28
Q

How is the resting intracellular Ca2+ concentration controlled?

A
High intracellular Ca2+ concentration is toxic to cells so needs to be controlled:
Primary active transport:
- PMCA expels Ca2+ out of the cell
- SERCA accumulates Ca2+ into the SR/ER
Secondary active transport:
- NCX expels Ca2+
Facilitated transport:
- Mitochondrial Ca2+ uniparts (operate at high intracellular Ca2+ concentration to buffer potentially damaging Ca2+)
29
Q

How is cellular pH controlled?

A

By the activity of a variety of plasma membrane transporters (after cellular buffering capacity has been exceeded)

  • Acidification can be opposed by: expelling H+ ions, inward movement of bicarbonate ions
  • Alkalisation can be opposed by: expelling bicarbonate via the anion exchanger
  • Different ion transporters can also be used:
  • – Acid extruders: Na+/H+ exchanger, Na+ dependent Cl-/HCO3- exchanger
  • – Base extruders: anion exchanger
30
Q

How is cell volume regulated?

A

Cells extrude ions in response to cell swelling and influx ions in response to cell shrinkage

  • Water follows the ions
  • Different cell types use particular combinations of transporters to achieve the regulation they need
31
Q

What mechanisms are there to resist cell swelling?

A
  • K+ and Cl- extruded via ion channels, so water moves out
  • K+ and Cl- cotransported out, amino acids are moved out via sodium-potassium pump, so water moves out
  • Anion exchanger moves Cl- in and HCO3- out, K+ is moved out in exchange for H+, H+ and HCO3- are combined to form H2CO3, CO2 is then released and water moves out
32
Q

What mechanisms are there to resist cell shrinking?

A
  • Na+ and Ca2+ move in via ion channels, so water moves in
  • Na+ and Cl- move in together, Na+ and organic osmolytes move in together and K+, 2Cl- and Na+ move in together, so water moves in
  • H2CO3 moves in via CO2 and is split into HCO3- and H+, HCO3- is moved out in exchange for Cl-, H+ is moved out in exchange for Na+
33
Q

Describe renal bicarbonate reabsorption

A

Under normal circumstances, the kidney reabsorbs all of the bicarbonate filtered into the proximal tubule

  • To retain base for pH buffers- Na+/K+ pump drives other channels by keeping intracellular Na+ concentration low, so NHE can pump H+ ions into the proximal tubule lumen
  • H+ goes into the lumen to ‘pick up’ bicarbonate with HCO3 (as H2O and CO2) and bring it back into the cell
34
Q

What is the goal of renal anti-hypertensive therapy?

A

To reduce the reuptake of Na+ and other molecules

  • So less water is absorbed by osmosis
  • Blood volume and therefore blood pressure falls
  • Use diuretics to treat oedema or hypertension