Small Molecule Transport
II. TRAFFIC OF SMALL MOLECULES
- General Features of Small Molecule Transport
- Selective permeability = Property of biological
membranes which allows some substances to cross more easily
- The selectively permeable plasma membrane regulates the
type and rate of molecular traffic into and out of the
- The selective permeability of a membrane depends upon
- membrane solubility characteristics of the
phospholipid bilayer and
- presence of specific integral transport proteins.
- Transport Proteins
- Water, carbon dioxide and nonpolar molecules
rapidly pass through the plasma membrane as they do an
- 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.
- Transport proteins
- Integral membrane proteins that transport
specific molecules or ions across biological membranes.
- May provide a hydrophilic tunnel through the
- May bind to a substance and physically move it across
- Are specific for the substance they translocate.
- Types of Transport Proteins:
- Uniport - carries a single solute across the
- Symport - translocates two different solutes
simultaneously in the same direction. Both solutes must
bind to the protein for transport to occur.
- Antiport - exchanges two solutes by transporting them
in opposite directions.
- Diffusion and Passive Transport
- Concentration Gradient = Regular, graded
concentration change over a distance in a particular
- Net Directional Movement = Overall movement away from the
center of concentration, which results from random molecular
movement in all directions.
- Diffusion = The net movement of a substance down a
- Results from the intrinsic kinetic energy of
molecules and atoms (also called thermal motion, or
- Results from random molecular motion, even though the
net movement may be directional.
- Diffusion continues until a dynamic equilibrium is
- Much of the traffic across cell membranes occurs by
- 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
- Because it decreases free energy, diffusion is a
spontaneous process. It increases entropy of a system by
producing a more random mixture of molecules.
- A substance diffuses down its own concentration gradient
and is not affected by the gradients of other
- Passive transport
- Diffusion of a substance across a biological
- Spontaneous process which is a function of a
concentration gradient when a substance is more concentrated
on one side of the membrane.
- Passive process which does not require the cell to
- Rate of diffusion is regulated by the permeability of
- Water diffuses freely across most cell membranes.
- Osmosis: A Special Case of Passive Transport
- Hyperosmotic solution = A solution with a
greater solute concentration compared to another
- Hypoosmotic solution = A solution with a lower solute
concentration compared to another solution.
- Isoosmotic solution = A solution with an equal solute
concentration compared to another solution.
- Diffusion of water across a selectively
- Water diffuses down its concentration gradient, from a
hypoosmotic solution to a hyperosmotic solution.
- 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
- 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.
- 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
- Direction of osmosis is determined by the difference in
total solute concentration, regardless of the type or
diversity of solutes in the solutions.
- 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.
- Osmotic concentration = Total solute concentration of a
- Osmotic pressure
- Measure of the tendency for a solution to
take up water when separated from pure water by a
selectively permeable membrane.
- Osmotic pressure of pure water is zero.
- Osmotic pressure of a solution is proportional to its
osmotic concentration. (The greater the solute
concentration, the greater the osmotic pressure.)
- 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
- The amount of pressure required to prevent net
movement of water into the solution is the osmotic
- Water Balance of Cell Without Walls
- In an isoosmotic environment, the volume of an
animal cell will remain stable with no net movement of water
across the plasma membrane.
- In a hyperosmotic environment, an animal cell will lose
water by osmosis and crenate (shrivel).
- In a hypoosmotic environment, an animal cell will gain
water by osmosis, swell and perhaps lyse (cell
- Organisms without cell walls prevent excessive loss or
uptake of water by:
- Living in an isoosmotic environment (e.g. many
marine invertebrates are isoosmotic with sea water).
- 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
- Water Balance of Cells with Walls
- Cells of prokaryotes, some protists, fungi and
plants have cell walls outside the plasma membrane.
- In a hyperosmotic environment, walled cells will lose water
by osmosis and will plasmolyze, which is usually lethal.
- 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
- 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 = Firmness or tension such as found in
walled cells that are in a hypoosmotic environment where
water enters the cell by osmosis.
- Ideal state for most plant cells.
- Turgid cells provide mechanical support for
- Requires cells to be hyperosmotic to their
- 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
- General Features
- Diffusion of solutes across a membrane, with
the help of transport proteins.
- Passive transport because solute is moved down its
- Helps the diffusion of many polar molecules and ions
that are impeded by the membrane's phospholipid
- Transport proteins:
- Share some properties of enzymes:
- Transport proteins are specific for the
solutes they transport.
- There is probably a specific binding site analogous
to an enzyme's active site.
- Transport proteins can be saturated with solute, so
the maximum transport rate occurs when all binding sites
are occupied with solute.
- Transport proteins can be inhibited by molecules that
resemble the solute normally carried by the protein
(similar to competitive inhibition in enzymes).
- Differ from enzymes in they do not usually catalyze
- One Model for Facilitated Diffusion:
- Transport protein most likely remains in place
in the membrane and translocates solute by alternating
between two conformations.
- Transport protein might bind to solute in one
conformation and deposit it on the other side of the
membrane in another conformation.
- The solute's binding and release may trigger the
transport protein's conformational change.
- 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
- Active Transport
- Energy requiring process where a transport protein
pumps a molecule across a membrane, against its concentration
- Is energetically uphill (+ delta G) and requires the cell
to expend energy.
- Helps cells maintain steep ionic gradients across the cell
membrane (e.g. Na+, K+, Mg++,
Ca++ and Cl-).
- Transport proteins involved in active transport harness
energy from ATP to pump molecules against their concentration
- 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:
- The transport protein oscillates between two
- High affinity for Na+ with
binding sites oriented towards the cytoplasm.
- High affinity for K+ with binding sites
oriented towards the cell's exterior.
- ATP phosphorylates the transport protein and powers the
conformational change from Na+ receptive to K+
- As the transport protein changes conformation, it
translocates bound solutes across the membrane.
- Na+K+-pump translocates three Na+
ions out of the cell for every two K+ ions pumped into the
- The Special Case of Ion Transport
- Because anions and cations are unequally
distributed across the plasma membrane, all cells have voltages
across their plasma membranes.
- Membrane potential = Voltage across membranes.
- Ranges from -50 to -200 mv. As indicated by the
negative sign, the cell's inside is negatively charged with
respect to the outside.
- Affects traffic of charged substances across the
- Favors diffusion of cations into cell and anions out of
the cell (because of electrostatic attractions).
- Two forces drive passive transport of ions across
- Concentration gradient of the ion.
- Effect of membrane potential on the ion.
- Electrochemical gradient = Diffusion gradient resulting
from the combined effects of membrane potential and
- Ions always diffuse down their electrochemical
- Ions may not always diffuse down their concentration
- 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.
- Unaffected by membrane potential, uncharged solutes
diffuse down concentration gradients.
- Factors which contribute to a cell's membrane potential
(net negative charge on the inside):
- Negatively charged proteins in the cell's
- 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+
- 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.
- Electrogenic Pump
- A transport protein that generates voltage
across a membrane.
- Na+/K+ - ATPase is the major
electrogenic pump in animal cells.
- A proton pump is the major electrogenic pump in plants,
bacteria and fungi. Mitochondria and chloroplasts use a
proton pump to drive ATP synthesis.
- Voltages created by electrogenic pumps are sources of
potential energy available to do cellular work.
- Process where a single ATP-powered pump actively
transports one solute and indirectly drives the transport of
other solutes against their concentration gradients.
- One mechanism of cotransport involves two transport
- ATP-powered pump actively transports one solute
and creates potential energy in the gradient it
- 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
- For example, plants use a proton pump coupled with