Transport Across Membrane
• Most of the substances that move across
membranes are dissolved ions and small organic
molecules- Solutes
– Not macromolecules and fluids
• Ions
– Na+, K+, Ca2+, Cl-, H+
• Organic molecules
– metabolites: sugars, amino acids, nucleotides
• 20% of gene in E. coli- Transport
A membrane’s molecular organization
results in selective permeability
• A steady traffic of small molecules and ions
moves across the plasma membrane in both
directions.
– For example, sugars, amino acids, and other
nutrients enter a muscle cell and metabolic waste
products leave.
– The cell absorbs oxygen and expels carbon dioxide.
– It also regulates concentrations of inorganic ions, like
Na+, K+, Ca2+, and Cl-, by shuttling them across the
membrane.
• However, substances do not move across the
barrier indiscriminately; membranes are
selectively permeable.
Transport Across Membranes: Overcoming
the Permeability Barrier
 • Cells and Transport Processes
• Simple Diffusion: Unassisted Movement Down
the Gradient
• Facilitated Diffusion: Protein-Mediated
Movement Down the Gradient
• Active Transport: Protein-Mediated Movement
Up the Gradient
• Examples of Active Transport
Cells and Transport Processes
• Solutes cross membranes by simple diffusion,
facilitated diffusion, and active transport
• The movement of a solute across a membrane is
determined by its concentration gradient or its
electrochemical potential
• The erythrocyte plasma membrane provides
examples of transport mechanisms
Solutes cross membranes by simple diffusion,
facilitated diffusion, and active transport
• Simple Diffusion
– O2, CO2, ethanol
• Facilitated Diffusion (Transport protein required)
– A gradient of concentration, charge, or both
(glucose)
• Active Transport (Transport protein required)
– Na+, K+, Ca2+, Cl-, H+
The movement of a solute across a membrane is
determined by its concentration gradient or its
electrochemical potential
• Concentration gradient
• Electrochemical potential (the movement of ion)
– Combined effect：concentration gradient and the
charge gradient
– Ion
• Membrane potential (Vm) caused by active transport
– Most cells have a negatively membrane potential.
– Ion gradient can create an electrical voltage, or
membrane potential
• Across the membrane that makes one side of the
membrane negative and the other side positive.
• Permeability of a molecule through a
membrane depends on the interaction of that
molecule with the hydrophobic core of the
membrane.
– Hydrophobic molecules, like hydrocarbons, CO2,
and O2, can dissolve in the lipid bilayer and cross
easily.
– Ions and polar molecules: hard to cross membrane.
• This includes small molecules, like water, and larger
critical molecules, like glucose and other sugars.
• Ions, whether atoms or molecules, and their surrounding
shell of water also have difficulties penetrating the
hydrophobic region.
– Proteins can assist and regulate the transport of ions
and polar molecules.
• Specific ions and polar molecules can cross the
lipid bilayer by passing through transport
proteins that span the membrane.
– Some transport proteins have a hydrophilic channel
that certain molecules or ions can use as a tunnel
through the membrane.
– Others bind to these molecules and carry their
passengers across the membrane physically.
• Each transport protein is specific as to the
substances that it will translocate (move).
– For example, the glucose transport protein in the
liver will carry glucose from the blood to the
cytoplasm, but not fructose, its structural isomer.
Transport Across Membranes: Overcoming
the Permeability Barrier
• Cells and Transport Processes
 • Simple Diffusion: Unassisted Movement Down
the Gradient
• Facilitated Diffusion: Protein-Mediated
Movement Down the Gradient
• Active Transport: Protein-Mediated Movement
Up the Gradient
• Examples of Active Transport
Simple Diffusion: Unassisted Movement
Down the Gradient
• Diffusion always moves solutes toward
equilibrium
• Osmosis is the diffusion of water across a
differentially permeable membrane
• Simple diffusion is limited to small, nonpolar
molecule
• The rate of simple diffusion is directly
proportional to the concentration gradient
Passive transport is diffusion across
a membrane
• Diffusion is the tendency of molecules of any
substance to spread out in the available space
– Diffusion is driven by the intrinsic kinetic energy
(thermal motion or heat) of molecules.
• Movements of individual molecules are random.
• However, movement of a population of
molecules may be directional.
• The diffusion of a substance across a biological
membrane is passive transport because it
requires no energy from the cell to make it
happen.
– The concentration gradient represents
potential energy and drives diffusion.
• However, because membranes are selectively
permeable, the interactions of the molecules with
the membrane play a role in the diffusion rate.
• Diffusion of molecules with limited permeability
through the lipid bilayer may be assisted by
transport proteins.
Osmosis is the diffusion of water across a
differentially permeable membrane
• Osmosis is the passive transport of water
– Differences in the relative concentration of dissolved
materials in two solutions can lead to the movement of
ions from one to the other.
• The solution with the higher concentration of solutes is
hypertonic.
• The solution with the lower concentration of solutes is
hypotonic.
• These are comparative terms.
– Tap water is hypertonic compared to distilled water
but hypotonic when compared to sea water.
• Solutions with equal solute concentrations are
isotonic.
• Imagine that two sugar solutions differing in
concentration are separated by a membrane that
will allow water through, but not sugar.
• The hypertonic solution has a lower water
concentration than the hypotonic solution.
– More of the water molecules in the
hypertonic solution are bound up in hydration
shells around the sugar molecules, leaving
fewer unbound water molecules.
Cell survival depends on balancing
water uptake and loss
• An animal cell immersed in an isotonic
environment no net movement of water across its
plasma membrane.
– Water flows across the membrane, but at the
same rate in both directions.
– The volume of the cell is stable.
• For a cell living in an isotonic environment (for
example, many marine invertebrates) osmosis is
not a problem.
– Similarly, the cells of most land animals are bathed
in an extracellular fluid that is isotonic to the cells.
• Organisms without rigid walls have osmotic
problems in either a hypertonic or hypotonic
environment and must have adaptations for
osmoregulation to maintain their internal
environment.
Simple Diffusion is Limited to Small,
Nonpolar Molecules
• Solute size
– Lipid bilayers are more permeable to small
molecules than to larger molecules
– Water, O2, CO2
• Solute polarity
– Permeable to nonpolar molecules and less
permeable to polar molecules
• Solute charge
– Highly impermeable to ions that is very important to
cells
• Cell must maintain an ion gradient across its
membrane in order to function
Transport Across Membranes:
Overcoming the Permeability Barrier
• Cells and Transport Processes
• Simple Diffusion: Unassisted Movement Down
the Gradient
 • Facilitated Diffusion: Protein-Mediated
Movement Down the Gradient
• Active Transport: Protein-Mediated Movement
Up the Gradient
• Examples of Active Transport
Specific proteins facilitate passive transport
of water and selected solutes:
• Many polar molecules and ions that are normally
impeded (阻擋) by the lipid bilayer of the
membrane diffuse passively with the help of
transport proteins that span the membrane.
• The passive movement of molecules down its
concentration gradient via a transport protein is
called facilitated diffusion.
Facilitated Diffusion: Protein-Mediated
Movement Down the Gradient
• Carrier proteins and channel proteins facilitate diffusion
by different mechanism.
• Carrier proteins alternate between two conformation
states
• Carrier proteins are analogous to enzymes in their
specificity and kinetics
• Carrier proteins transport either one or two solutes
• The erythrocyte glucose transporter and anion exchange
protein are examples of carrier proteins
• Channel protein facilitate diffusion by forming
hydrophilic transmembrane channel.
Carrier proteins and channel proteins
facilitate diffusion by different mechanism
• Two classes of proteins involved facilitate diffusion
– Carrier Proteins (transporters or permeases )
• bind to the solute molecules
• with change in the conformation of the protein
• move the polar or charged molecules in or out of the cell
through the hydrophobic membrane
– Channel Proteins
•
•
•
•
form hydrophilic channel through the membrane
without any change in the conformation of the protein
molecular weight-up to 600 Da
ion channel
– The transport rate: channel protein > carrier protein
• Transport proteins have much in common with
enzymes.
– They may have specific binding sites for the
solute.
– Transport proteins can become saturated when
they are translocating passengers as fast as
they can.
– Transport proteins can be inhibited by
molecules that resemble the normal
“substrate.”
The erythrocyte glucose transporter and
anion exchange protein are examples of
carrier proteins
• The glucose transporter: A uniport carrier
• The erythrocyte anion exchange protein: An
antiport carrier
Channel Protein Facilitate Diffusion by Forming
Hydrophilic Transmembrane Channel
• Most ion channel are gated
• Necessary for maintaining the proper
salt balance in the cells
– Lung cells：cystic fibrosis transmembrane
conductance regulator (CFTR)
• Maintain the proper Cl- concentration in lung
Channel Protein Facilitate Diffusion by Forming
Hydrophilic Transmembrane Channel
• Ion channels: Transmembrane proteins that allow rapid
passage of specific ions
– K+, Na+, Ca2+, Cl– Most ion channel are gated- 三種因子控制gate的開與閉
• Voltage-gated channels- membrane potential
• Ligand-gated channels- binding of specific substances
• Mechanosensitive channels- mechanical forces
• Porins: Transmembrane proteins that allow rapid
passage of various solutes
– in outer membrane of mitochondria, chloroplasts and bacteria
• Aquaporins Transmembrane channel that allow rapid
passage of water
– erythrocytes, kidney (reabsorb water), central vacuolar
Transport Across Membranes: Overcoming
the Permeability Barrier
• Cells and Transport Processes
• Simple Diffusion: Unassisted Movement Down
the Gradient
• Facilitated Diffusion: Protein-Mediated
Movement Down the Gradient
 • Active Transport: Protein-Mediated Movement
Up the Gradient
• Examples of Active Transport
Active Transport: Protein-Mediated
Movement Up the Gradient
• The Coupling of active transport to an energy
source may be direct or indirect
• Direct active transport depends on four types of
transport ATPases
• Indirect active transport is driven by ion
gradients
Active transport is the pumping of
solutes against their gradients
• This active transport requires the cell to expend its
own metabolic energy.
• Three major functions:
– uptake the essential nutrients from the
environment
– remove the substance (such as secretory products
and waste) away from cell or organelle
– maintain constant, nonequilibrium intracellular
concentration of inorganic ion, K+, Na+, Ca2+ and
H+
• Active transport always moves solutes away
from thermodynamic equilibrium
– Require an input energy - ATP
• Active transport is performed by specific
proteins embedded in the membranes.
• ATP supplies the energy for most active
transport.
– Often, ATP powers active transport by shifting a
phosphate group from ATP (forming ADP) to the
transport protein.
– This may induce a conformational change in the
transport protein that translocates the solute across
the membrane.
• The sodium-potassium pump actively maintains
the gradient of sodium (Na+) and potassium ions
(K+) across the membrane.
• An important distinction between active transport
and simple or facilitated diffusion: The direction
of transport
– Simple and facilitated diffusion:
nondirectionality
– Active transport: directionality- unidirectional
(vectorial )process
In cotransport, a membrane protein
couples the transport of two solutes
• A single ATP-powered pump that transports one
solute can indirectly drive the active transport of
several other solutes through cotransport via a
different protein.
• As the solute that has been actively transported
diffuses back passively through a transport
protein, its movement can be coupled with the
active transport of another substance against its
concentration gradient.
Four Types of Transport ATPase
• Most p-type ATPase are located in the plasma
membrane
– Maintaining an ion gradient across the membrane
• V-type ATPase
– Pump protons into organells, vacuoles, vesicles,
lysosome, endosome, and Glgi
• F-type ATPase found in bacteria, mitochondria an
chloroplasts
– Proton transport：use H+ gradient to drive ATP
synthesis.
• ABC-type ATPase
– Antitumor drugs：plasma membrane
• Multidrug resistance transport protein
ABC-Type ATPase
• Four domains
– Two are highly hydrophobic and are embedded in
the membrane
• ABC transporters are of considerable medical
interest because some of them pump antibiotics
or other drug out of the cells, thereby making
the cell resistant to the drug.
– Multidrug resistance (MDR) transport protein
Transport Across Membranes: Overcoming
the Permeability Barrier
• Cells and Transport Processes
• Simple Diffusion: Unassisted Movement Down
the Gradient
• Facilitated Diffusion: Protein-Mediated
Movement Down the Gradient
• Active Transport: Protein-Mediated Movement
Up the Gradient
 • Examples of Active Transport
• The Energetics of Transport
• On to Nerve Cells
Examples of Active Transport
• Direct active transport: The Na+/K+ pump
maintains electrochemical ion gradients
• Indirect active transport: Sodium symport drives
the uptake of glucose
• The bacteriorhodopsin proton pump uses light
energy to transport protons
Exocytosis and endocytosis
transport large molecules
• Small molecules and water enter or leave the cell
through the lipid bilayer or by transport proteins.
• Large molecules, such as polysaccharides and
proteins, cross the membrane via vesicles.