02-11-21 - Molecular Movement Across Membranes Flashcards
Learning outcomes
- Explain the key role that the lipid bilayer plays in determining trans-membrane diffusion and maintaining a concentration gradient.
- Compare and contrast passive, carrier mediated of facilitated transport and active transport
- Identify molecules crossing the membrane by passive diffusion, facilitated transport and active transport
- Describe the role played by the permeability constant in determining trans-membrane diffusion and the anomalous permeability of water
- Describe the structure and membrane organisation of aquaporin water channels and their contribution to the trans epithelial movement of water.
- Describe the sodium pump as an example of active transport and how it maintains an intracellular steady state of sodium and potassium ions
What are the 2 types of transport across the membrane?
What are the 2 types of each?
- Uniport transport – Movement of one molecule across the membranes
- Broken down into:
- Passive transport
- This is the movement of one molecule across the membrane, which does not require energy, and is with the concentration gradient.
- Can be broken down into:
- Simple diffusion – Lipid-soluble molecule move through space in the bilayer
- Facilitated diffusion – Movement of molecule through a transmembrane protein, such as a carrier or channel;
- Active transport (primary or secondary)
- This is the movement of one molecule across the membrane, which requires energy (ATP), and is against the concentration gradient
- Active transport involves a protein carrier
- Cotransport – Movement of 2 molecules across the membrane
- Can be broken down into:
- Symport – 2 molecules in the same direction
- Antiport – 2 molecules in opposite directions
What is the formula for concentration gradient?
What is net diffusion proportional to?
When will diffusion stop?
What is the formula for rate of diffusion into a cell?
What is the permeability coefficient?
What are 2 factors that affect the permeability coefficient?
- Concentration gradient formula:
- ΔS = [S]outside – [S]inside
- Net diffusion is proportional to Co-Ci
- Diffusion will stop until particles reach an equilibrium
- The permeability is a constant for a particular system, and is different for every membrane and substrate
- Factors that can affect the permeability co-efficient:
- Thickness/viscosity of membrane
- Substrate size, shape, polarity and solubility in membrane
What is the partition coefficient (K) a measure of?
What does it give information on?
What 2 steps is the partition co-efficient measured in?
What is the formula for the partition coefficient?
- The partition coefficient gives a measure of how well a substances dissolves in lipid or aqueous phase of the membrane
- This gives information about the permeability coefficient
- Measuring partition coefficient:
- Shake the substance with a mixture of oil and water
- Measure the concentration of substance in the oil and the water
What characteristics of a molecule affect its rate of transport through the lipid area of the membrane?
What are 2 examples?
How does partition coefficient (K) correlate with rate of diffusion in lipids?
- Diffusion through the lipid area of the membrane can be affected by the molecules:
- Size
- Shape
- Polarity
- Solubility in the membrane
- E.g Diethyl urea diffuses faster than urea, as it is less polar, making it more lipid soluble
- Though very polar, methanol has a very high rate of diffusion across the membrane due to its size
- An increase in partition coefficient causes molecules to have a higher rate of diffusion across lipids in the membrane
What are aquaporins?
What do aquaporins consist of?
What do the subunits form?
What does this allow?
How narrow is each channel/pore?
What does this allow?
Up to how many molecules of water can pass through some AQP?
What kind of diffusion is associated with aquaporins?
- Aquaporins are intrinsic protein channels that transport water
- Aquaporins consist of 4 subunits consisting of 6 alpha helices each
- The subunits form a tetramer, with each subunit/monomer acting as a water channel
- This means a relatively small number of aquaporins can give a massive increase in water that can pass through a particular membrane
- A tetramer is an oligomer formed from four monomers or subunits
- Each channel is 2.8Å (angstrom – 10^-10m) at its narrowest point
- This is wide enough for the continuous passage of one water molecule at a time – this is known as single file permeation
- Up to 3x10^9 molecules of water per seconds can pass through some aquaporins e.g AQP 1, 2, 4, and 5
- Water movement through Aquaporins is an example of water-selective facilitated diffusion
How do substances diffuse through aqueous membrane channels?
Do membrane channels transport any molecule?
How do these channel proteins affect rates of diffusion in a particular substance?
- Substances stay in the aqueous solution and pass-through hydrophilic channels in transmembrane proteins
- These membrane channels are usually highly specific to a particular molecule
- Due to this specificity, rates of diffusion can be very high, with few pores needed to make a big difference in membrane permeability for a particular substance
How many molecules can fit through an aquaporin channel at once?
What can aquaporins channels not fit?
How many different aquaporins are there?
What areas are aquaporins particularly permeable in?
What is this?
- Aquaporin channels are 1x water molecule wide
- Aquaporins are too narrow to permit any of the hydrated ions to pass through
- There are 13 different aquaporins found in different tissues all over the body
- AQPs are particularly common in certain areas, such as red blood cells and kidneys
- This is because these tissues/cells require the ability to move water through their cell membranes very quickly
What does ADH regulate in the kidneys?
How does it do this?
Where does this occur?
What is the purpose of this?
Where else re there AQP in the kidney?
How do these differ?
- ADH regulates AQP-2 in the kidneys
- It stimulates the movement of AQP-2 to the luminal side of the renal cell membrane
- This occurs in distal tubules, collecting tubules and collecting ducts
- This is in order to increase water absorption
- There are other AQPs on the basolateral membranes, probably not regulated by ADH?
What effects the passage of other molecules through aqueous membrane channels?
What is an example of this?
- Passage of other molecules through aqueous membrane proteins is possible, though decreases rapidly with size
- Urea diameter is 20% larger than water, but urea transfer occurs 1000 times less than water
What can protein channels be specific to?
What might they be opened or closed by?
What are the 2 types of Gated channels?
How long do channels stay open?
How can membrane potential affect opening of channels?
- Many protein channels are highly specific to a particular ion e.g Na+, Cl-, K+
- These protein channels may be opened or closed by a gate, or they can always be open
- The 2 types of gated channels are:
- Voltage gated
* A potential difference inside/outside the cell causes a confirmation change in the gate - Ligand gates
* Binding of a chemical ligand (e.g acetyl choline) causes conformational change
- Channel are all or nothing (either open or closed) and stay open for less than a few milliseconds at a time
- At particular membrane potential (mp), channels may be open or closed all of the time/most of the time
What is an example of a voltage gated channel?
How does this channel allow sodium to move through?
How does it prevent potassium from moving through?
How do potassium channels allow only potassium and not sodium to move through?
- The sodium channel is an example of a voltage gated channel
- Free sodium ions are associated with water, and are too large to fit through the channel
- Negatively charged amino acids lining the sodium channel pull the sodium ion away from its water shell
- This smaller unhydrated sodium ion can then diffuse through the channel
- Unhydrated potassium ions are too large, so K+ has to use another channel
- Carbonyl oxygens (C=O) in the potassium channel strip water molecules from potassium ions, but not from sodium ions
- This means only sodium will be allowed to move through the channel
What 2 things can carrier mediated transport (aka facilitated diffusion?) be?
How does the process occur in both cases?
What 3 reasons can this process saturate?
What does this mean for Vmax of this reaction?
- Carrier mediated transport can be:
- Active transport – against concentration gradient
- Facilitated diffusion – down a concentration gradient
- In both cases, a substance binds onto a specific receptor on a carrier protein, resulting in a conformational shape change that transports the substance to the other side of the membrane
- This transport can saturate as:
- There is limited binding sites available on carrier protein and
- It takes time for transport to occur and
- It takes time for the carrier protein to revert to its original ready state
- This means the carrier protein reaction will reach a Vmax – the maximum velocity of the reaction
What does the rate of carrier mediated transport (aka facilitate diffusion?) and simple diffusion look like on a graph as substrate concentration increases?
- Simple diffusion – the progress of rate of transport is linear, and does not saturate
- Carrier mediated transport – Rate of transport increases, but tapers off as it reaches Vmax
What can active transport do?
What 2 times is active transport important?
What can active transport involve?
How can active transport be inhibited?
What are the 2 types of active transport?
- Active transport can push a substance against its concentration gradient
- Active transport is important when a concentration gradient must be maintained e.g Na+ or K+ between ECF and ICF
- Can also be important for maintaining or changing concentration gradients during an action potential
- Active transport can involve the movement of more than 1 substance
- Active transport can be competitively inhibited by substances that bind to active sites e.g during carrier-mediated transport
- 2 types of active transport:
- Primary active transport – energy obtained directly from energy source e.g ATP
- Secondary active transport – energy stored as a concentration difference
What is a widespread example of primary active transport?
How does it change shape and obtain energy?
- The Na+/K+ ATPase is an example of primary transport, which transports both sodium and potassium
- A conformational shape change and energy is produced through the binding and breakdown of ATP to ADP + Pi
Describe how Primary active transport and secondary active transport can be linked
- Primary active transport
* H+ ions moved from low to high concentration using energy from ATP - Secondary active transport
- H+ at high concentration outside the cell passes back into the cell, which doesn’t require energy due to the electrochemical gradient (chemical and electrical gradient)
- This process is exergonic (releases energy)
- The energy from the movement of H+ ions used to simultaneously cotransport S against the concentration into the cell
- This is an example of symport transport
What are the 2 protein cotransporters?
What do symporters do?
What is the typical driver ion for symporters?
What do symporters use?
What occur when both substances bind?
What are 3 examples of symporters?
- The 2 protein cotransporters are symporters and antiporters
- Symporters transport substances in the same direction as the driver ion
- Typically, the driver ion used is Sodium
- Symporters use electrochemical gradients (often for sodium)
- When both substances bind to the symporter, this results in a conformational shape change, which allows for transport
- 3 examples of symporters:
- Sodium – amino acid co-transporter
- Sodium – glucose co-transporter
- Sodium Bi-carbonate ion co-transporter (2 bicarbonate ions)
What do antiporters do?
What is the typical driver ion used?
What occurs when both molecules bind to the anti-porter?
What are 3 examples of antiporters?
- Antiporters transport substances in the opposite direction from the driver ion
- Typically, the driver ion used is sodium
- When both molecules bind to the anti-porter, it will cause a conformational shape change, and the electrochemical energy will transport a substance in and a substance out
- 3 examples of antiporters:
- Na+ in Ca2+ out antiporter
- Na+ in H+ out antiporter
- Na+/HCO3- in Cl-/H+ put antiporter
What is the secondary structure of AQPs like?
What is the tertiary structure of AQPs like?
What is the quaternary structure of AQPs like?
- The secondary structure of aquaporins contains 6 alpha helices connected by 3 extracellular loops and 2 intracellular loops, with both N and C termini being intracellular
- The 6 alpha helices exist in a tight tertiary monomer structure with a central transmembrane pore through the 3D barrel structure that allows the passage of water
- 4 AQP monomers homotermerize to create a 5-pore quaternary structure
- The function of the central pore isn’t known
