Membranes

Small Molecule Transport

II. TRAFFIC OF SMALL MOLECULES

General Features of Small Molecule Transport
1. Selective permeability = Property of biological membranes which allows some substances to cross more easily than others.
2. The selectively permeable plasma membrane regulates the type and rate of molecular traffic into and out of the cell.
3. The selective permeability of a membrane depends upon
  1. membrane solubility characteristics of the phospholipid bilayer and
  2. presence of specific integral transport proteins.
4. Transport Proteins
  1. Water, carbon dioxide and nonpolar molecules rapidly pass through the plasma membrane as they do an artificial membrane.
  2. Unlike artificial membranes, however, biological membranes are permeable to specific ions and certain polar molecules of moderate size (e.g. sugars). These hydrophilic substances avoid the hydrophobic core of the bilayer by passing through transport proteins.
  3. Transport proteins
    1. Integral membrane proteins that transport specific molecules or ions across biological membranes. (Figure 8.10)
    2. May provide a hydrophilic tunnel through the membrane.
    3. May bind to a substance and physically move it across the membrane.
    4. Are specific for the substance they translocate.
  4. Types of Transport Proteins:
    1. Uniport - carries a single solute across the membrane.
    2. Symport - translocates two different solutes simultaneously in the same direction. Both solutes must bind to the protein for transport to occur.
    3. Antiport - exchanges two solutes by transporting them in opposite directions.
Diffusion and Passive Transport
1. Concentration Gradient = Regular, graded concentration change over a distance in a particular direction.
2. Net Directional Movement = Overall movement away from the center of concentration, which results from random molecular movement in all directions.
3. Diffusion = The net movement of a substance down a concentration gradient.
  1. Results from the intrinsic kinetic energy of molecules and atoms (also called thermal motion, or heat).
  2. Results from random molecular motion, even though the net movement may be directional.
  3. Diffusion continues until a dynamic equilibrium is reached.
  4. Much of the traffic across cell membranes occurs by diffusion.
  5. In the absence of other forces, a substance will diffuse from where it is more concentrated to where it is less concentrated. A substance diffuses down its concentration gradient.
  6. Because it decreases free energy, diffusion is a spontaneous process. It increases entropy of a system by producing a more random mixture of molecules.
  7. A substance diffuses down its own concentration gradient and is not affected by the gradients of other substances.
4. Passive transport
  1. Diffusion of a substance across a biological membrane.
  2. Spontaneous process which is a function of a concentration gradient when a substance is more concentrated on one side of the membrane.
  3. Passive process which does not require the cell to expend energy.
  4. Rate of diffusion is regulated by the permeability of the membrane.
  5. Water diffuses freely across most cell membranes.
Osmosis: A Special Case of Passive Transport
1. Definitions
  1. Hyperosmotic solution = A solution with a greater solute concentration compared to another solution.
  2. Hypoosmotic solution = A solution with a lower solute concentration compared to another solution.
  3. Isoosmotic solution = A solution with an equal solute concentration compared to another solution.
2. Osmosis
  1. Diffusion of water across a selectively permeable membrane.
  2. Water diffuses down its concentration gradient, from a hypoosmotic solution to a hyperosmotic solution.
    1. For example, if two solutions of different concentrations are separated by a selectively permeable membrane that is permeable to water but not the solute, water will diffuse from the hypoosmotic solution to the hypertonic solution.
  3. Solute molecules can reduce the proportion of water molecules that can freely diffuse. Some water molecules form a hydration shell around hydrophilic solute molecules. This bound water cannot freely diffuse across a membrane.
  4. In dilute solutions including most biological fluids, it is the difference in the proportion of unbound water that causes osmosis, rather than the actual difference in water concentration.
  5. Direction of osmosis is determined by the difference in total solute concentration, regardless of the type or diversity of solutes in the solutions.
  6. If two isoosmotic solutions are separated by a selectively permeable membrane, water molecules diffuse across the membrane in both directions at any equal rate. There is no net movement of water.
  7. Osmotic concentration = Total solute concentration of a solution.
  8. Osmotic pressure
    1. Measure of the tendency for a solution to take up water when separated from pure water by a selectively permeable membrane.
    2. Osmotic pressure of pure water is zero.
    3. Osmotic pressure of a solution is proportional to its osmotic concentration. (The greater the solute concentration, the greater the osmotic pressure.)
    4. Osmotic pressure can be measured by an osmometer:
      - In one type of osmometer, pure water is separated from a solution by a selectively permeable membrane that is permeable to water by not solute.
      - The tendency for water to move into the solution by osmosis is counteracted by applying enough pressure with a piston so the solution's volume will stay the same.
      - The amount of pressure required to prevent net movement of water into the solution is the osmotic pressure.
Water Balance of Cell Without Walls
1. In an isoosmotic environment, the volume of an animal cell will remain stable with no net movement of water across the plasma membrane.
2. In a hyperosmotic environment, an animal cell will lose water by osmosis and crenate (shrivel).
3. In a hypoosmotic environment, an animal cell will gain water by osmosis, swell and perhaps lyse (cell destruction).
4. Organisms without cell walls prevent excessive loss or uptake of water by:
  1. Living in an isoosmotic environment (e.g. many marine invertebrates are isoosmotic with sea water).
  2. Osmoregulating in a hypo- or hyperosmotic environment. Organisms can regulate water balance by removing water in a hypoosmotic environment (e.g. Amoeba with contractile vacuoles in fresh water) or conserving water and pumping out salts in a hyperosmotic environment (e.g. bony fish in seawater).
Water Balance of Cells with Walls
1. Cells of prokaryotes, some protists, fungi and plants have cell walls outside the plasma membrane.
2. In a hyperosmotic environment, walled cells will lose water by osmosis and will plasmolyze, which is usually lethal.
  1. Plasmolysis = Phenomenon where a walled cell shrivels and the plasma membrane pulls away from the cell wall as the cell loses water to a hypertonic environment.
3. In a hypoosmotic environment, water moves by osmosis into the plant cell, causing it to swell until internal pressure against the cell wall equals the osmotic pressure of the cytoplasm. A dynamic equilibrium is established (water enters and leaves the cell at the same rate and the cell becomes turgid).
  1. Turgid = Firmness or tension such as found in walled cells that are in a hypoosmotic environment where water enters the cell by osmosis.
    1. Ideal state for most plant cells.
    2. Turgid cells provide mechanical support for plants.
    3. Requires cells to be hyperosmotic to their environment.
4. In an isoosmotic environment, there is no net movement of water into or out of the cell. Plant cells become flaccid or limp. Loss of structural support from turgor pressure causes plants to wilt.
Facilitated Diffusion
1. General Features
  1. Diffusion of solutes across a membrane, with the help of transport proteins.
  2. Passive transport because solute is moved down its concentration gradient.
  3. Helps the diffusion of many polar molecules and ions that are impeded by the membrane's phospholipid bilayer.
2. Transport proteins:
  1. Share some properties of enzymes:
    1. Transport proteins are specific for the solutes they transport.
    2. There is probably a specific binding site analogous to an enzyme's active site.
    3. Transport proteins can be saturated with solute, so the maximum transport rate occurs when all binding sites are occupied with solute.
    4. Transport proteins can be inhibited by molecules that resemble the solute normally carried by the protein (similar to competitive inhibition in enzymes).
  2. Differ from enzymes in they do not usually catalyze chemical reactions.
3. One Model for Facilitated Diffusion:
  1. Transport protein most likely remains in place in the membrane and translocates solute by alternating between two conformations.
  2. Transport protein might bind to solute in one conformation and deposit it on the other side of the membrane in another conformation.
  3. The solute's binding and release may trigger the transport protein's conformational change.
  4. In some inherited disorders, transport proteins are missing or are defective (e.g. cystinuria, a kidney disease where the carriers are missing for cystine and other amino acids).
Active Transport
1. Energy requiring process where a transport protein pumps a molecule across a membrane, against its concentration gradient.
2. Is energetically uphill (+ delta G) and requires the cell to expend energy.
3. Helps cells maintain steep ionic gradients across the cell membrane (e.g. Na⁺, K⁺, Mg⁺⁺, Ca++ and Cl-).
4. Transport proteins involved in active transport harness energy from ATP to pump molecules against their concentration gradients.
5. An example of an active transport system that translocates ions against steep concentration gradients is the sodium-potassium pump. Major features of the pump are:
  1. The transport protein oscillates between two conformations:
    1. High affinity for Na⁺ with binding sites oriented towards the cytoplasm.
    2. High affinity for K⁺ with binding sites oriented towards the cell's exterior.
  2. ATP phosphorylates the transport protein and powers the conformational change from Na+ receptive to K⁺ receptive.
  3. As the transport protein changes conformation, it translocates bound solutes across the membrane.
  4. Na⁺K⁺-pump translocates three Na+ ions out of the cell for every two K+ ions pumped into the cell.
The Special Case of Ion Transport
1. Because anions and cations are unequally distributed across the plasma membrane, all cells have voltages across their plasma membranes.
2. Membrane potential = Voltage across membranes.
  1. Ranges from -50 to -200 mv. As indicated by the negative sign, the cell's inside is negatively charged with respect to the outside.
  2. Affects traffic of charged substances across the membrane.
  3. Favors diffusion of cations into cell and anions out of the cell (because of electrostatic attractions).
3. Two forces drive passive transport of ions across membranes:
  1. Concentration gradient of the ion.
  2. Effect of membrane potential on the ion.
4. Electrochemical gradient = Diffusion gradient resulting from the combined effects of membrane potential and concentration gradient.
  1. Ions always diffuse down their electrochemical gradient.
  2. Ions may not always diffuse down their concentration gradients.
  3. At equilibrium, the distribution of ions on either side of the membrane may be different from the expected distribution when charge is not a factor.
  4. Unaffected by membrane potential, uncharged solutes diffuse down concentration gradients.
5. Factors which contribute to a cell's membrane potential (net negative charge on the inside):
  1. Negatively charged proteins in the cell's interior.
  2. Plasma membrane's selective permeability to various ions. For example, there is a net loss of positive charges as K⁺ leaks out of the cell faster than Na+ diffuses in.
  3. The sodium-potassium pump. This electrogenic pump translocates 3 Na⁺ out for every 2 K⁺ in - a net loss of one positive charge per cycle.
6. Electrogenic Pump
  1. A transport protein that generates voltage across a membrane.
  2. Na⁺/K⁺ - ATPase is the major electrogenic pump in animal cells.
  3. A proton pump is the major electrogenic pump in plants, bacteria and fungi. Mitochondria and chloroplasts use a proton pump to drive ATP synthesis.
  4. Voltages created by electrogenic pumps are sources of potential energy available to do cellular work.
Cotransport
1. Process where a single ATP-powered pump actively transports one solute and indirectly drives the transport of other solutes against their concentration gradients.
2. One mechanism of cotransport involves two transport proteins:
  1. ATP-powered pump actively transports one solute and creates potential energy in the gradient it creates.
  2. Another transport protein couples the solute's downhill diffusion as it leaks back across the membrane with a second solute's uphill transport against its concentration gradient.
  3. For example, plants use a proton pump coupled with sucrose-H⁺ symport.