Week 2 - Role of membranes as permeability barriers Flashcards
What is the relative permeability of a synthetic lipid bilayer to different classes of molecules?
- 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)
What does passive transport depend on?
- Permeability
- Concentration gradient
- The rate of passive transport increases linearly with increasing concentration gradient
How does water move across membranes?
By osmosis
- Most membranes are relatively permeable to water
What are the roles of transport processes?
- 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
What models are there for facilitated transport?
- 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)
What is responsible for the transport of Cl- across the lipid bilayer?
Band 3 protein: it carries out a specific exchange of Cl-
What can increase the permeability of the lipid bilayer for polar substances?
The presence of specific proteins in the bilayer
Why is facilitated diffusion a saturable process?
- 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
What determines where the transport of an ion/molecule is passive or active?
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
What is active transport?
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)
How can membrane transporters be driven?
By:
- Gradients of ATP
- Phosphoenolpyruvate
- Protons and sodium ions
- Light
- High-potential electrons
What are some co-transport systems?
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
What is a uniport?
When 1 solute molecule species is transported from 1 side of the membrane to the other
What is a symport?
When the transfer of 1 solute molecule depends on the simultaneous or sequential transfer of a second solute in the same direction
What is an antiport?
When the transfer of 1 solute molecule depends on the simultaneous/sequential transfer of a second solute in the OPPOSITE direction
What is the free ion distribution of Na+ across the cell?
Intracellular conc = 12 mM
Extracellular conc = 145 mM
What is the free ion distribution of Cl- across the cell?
Intracellular conc = 4.2 mM
Extracellular conc = 123 mM
What is the free ion distribution of Ca2+ across the cell?
Intracellular conc = 10^-7 mM
Extracellular conc = 1.5 mM
What is the free ion distribution of K+ across the cell?
Intracellular conc = 155 mM
Extracellular conc = 4 mM
What is the sodium-potassium ATPase?
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
What is the role sodium-potassium ATPase?
Drives many secondary active transport process:
- Ion homeostasis
- Intracellular Ca2+ ion concentration
- Intracellular pH
- Cell volume
- Ion gradients
- Nutrient uptake
What is the plasma membrane Ca2+ ATPase?
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
What is the sarco(end) plasmic reitculum ATPase?
SERCA
- Accumulates Ca2+ into the SR/ER
- High affinity, low capacity
- Removes residual calcium
What is the sodium-calcium exchanger?
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
