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Set: Tuesday
11th
Biology of Cells
November 2014
Illustrate with examples how proteins mediate different types of transport
across biological membranes.
Generally smaller non-polar hydrophobic molecules with high lipid solubility are
able to diffuse through the phospholipid bilayer passively without aid from
transport proteins, as long as a concentration gradient is present. For other
molecules, including those that are hydrophilic, charged, large or polar, transport
through membranes must be mediated by proteins. The main categories of
protein mediated transmembrane transport are passive and active transport,
each of which have subtypes.
Facilitated diffusion is protein mediated passive transport. Protein mediated
transport can be passive when there is a electrical or concentration gradient
present, and the net movement of solutes from a higher to lower concentration is
driven by the chemical (or electrochemical in the case of charged particles)
potential gradient of the molecules. This movement across membranes occurs
spontaneously since the free energy change is negative, so the process is
exergonic. There are two main types of facilitated diffusion; that mediated by
carrier proteins and that mediated by channel proteins.
The general mechanism of action of carrier proteins to transport molecules
passively across membranes is the solute binds its carrier at specific binding
sites on the side of greater concentration, which induces a series of
conformational change in shape. Then the carrier releases the solute on the other
side of the membrane, and returns to its original state. An example of passive
transmembrane transport by carrier proteins is by the plasma membrane
protein GLUT 1, which is used to facilitate the uptake glucose into cells. GLUT 1
can also act as a vitamin C carrier protein; this illustrates that although
transmembrane transport proteins can be very specific, as in the following
example of a channel protein, the specificity of these transport proteins can vary.
Channel proteins, which largely mediate the transport of ions across membranes,
function by providing a hydrophilic pore through which molecules can move.
Their selectivity for particular molecules is determined by their surface charge,
the diameter of the selectivity filters, and which amino acid residues line the
interior of the channels, meaning only molecules of the right size and charge may
pass through. Solutes exit the pores through a ‘gate’, which may be opened and
closed in response to a particular stimulus, such as voltage, mechanical stress or
the binding of a ligand. For example, voltage gated K+ ion channels, which are
sensitive to the cell membrane potential. Their selectivity filter, present at the
most narrow part of the pore, has a specific amino acid sequence which interacts
with the K+ ions, allowing them to pass through the channel down their
electrochemical gradient, after causing them to disassociate with water
molecules. Smaller positive ions cannot pass through, as the amino acids are
unable to interact with them in a way to cause water to disassociate. They open
and close in response to changes in membrane potential, triggered by amino
acids that act as voltage sensors. Ion channels like these are used when rapid ion
transport is required, such as in muscle contraction, and transmission of action
potentials in nerve fibres.
Set: Tuesday
11th
Biology of Cells
November 2014
While passive transport moves molecules down their concentration or
electrochemical gradient, active transport occurs when proteins are required to
move solutes through membranes against a gradient (chemical or
electrochemical), a process with a positive free energy change, meaning energy
input is required to drive these endergonic processes. All active transport across
membranes is protein mediated. The two main types of active transport are
primary and secondary.
In primary active transport the input of energy used to move solutes across the
membranes comes directly from hydrolysis of energy donors, most commonly
ATP. In general, the transport protein catalyses the hydrolysis of ATP, GTP or PPi
and the transport of the solutes across the membrane; the processes are coupled.
Each energy donor has one or more unstable energy rich phosphoanhydride
bond, which when hydrolysed release energy used to move solutes against their
concentration gradient. An example of a protein that carries out this type of
transport is the Na+-K+ translocating ATPase, which is present in plasma
membranes. It pumps Na+ out of the cytoplasm, and K+ in. Per ATP molecule
hydrolysed, 3Na+ ions are pumped out and 2K+ are pumped in, both moving
against their electrochemical potential gradients. When Na+ binds to the protein,
and it is phosphorylated using a phosphate group from an ATP molecule, a
conformational change in shape is triggered, transferring Na+ across the
membrane. It returns to its original shape by the binding of K+ from the
extracellular fluid, and dephosphorylation, resulting in transfer of K+ into the
cytoplasm.
The electrochemical potential gradient set up by the Na+-K+ ATPase can be used
in secondary active transport, also known as solute coupled transport. This type
of protein mediated transmembrane transport uses an energy input from the
movement of ions down their electrochemical potential gradient, which may
have been set up by primary active transport, to transport other solutes against a
gradient. If the solute is transported in the same direction as the ions that are
moving down their electrochemical gradient the protein that mediates this is
described as a symporter, while in opposite directions it is described as an
antiporter. An example of a symporter is in Na+-couple glucose transport in the
enterocytes of the small intestine. The electrochemical potential gradient
established by Na+-K+ ATPases in primary active transport results in a higher
concentration of Na+ ions in the lumen of the small intestine than in the cells.
This results in Na+ entering the cell coupled with glucose, through a Na+-glucose
symporter protein. The glucose is moving against its concentration gradient.
This component of secondary active transport mediated by proteins is very
similar to facilitated diffusion, as there is spontaneous movement of molecules
down their chemical potential gradient. However this gradient is created by a
process that uses ATP, so overall is defined as a type of active transport.
The main types of protein-mediated transport across membranes include
facilitated diffusion mediated by carrier and channel proteins, and primary and
secondary active transport. However, there are other types of transmembrane
transport by proteins of importance, such as the F-type ATPases, used in ATP
Set: Tuesday
11th
Biology of Cells
November 2014
synthesis, that do not fit into these categories. Proteins are responsible for the
transport of a range of molecules, including ions and polar molecules, across
membranes. These types of transport are vital for cell and organism function, as
they are used in production of ATP, homeostasis, cell volume regulation and
communication, among other essential functions.
Bibliography
Julia Davie Lecture notes ‘Membranes - molecular superstructures’
Alberts, B. et al (2008) Molecular Biology of the Cell, 5th Edition (Garland)
Berg, J., Tymoczko, J. and Stryer, L. (2011) Biochemistry, 7th Edition (Freeman)
Sagun et al. (2005) ‘Vitamin C enters mitochondria via facilitative glucose
transporter 1 (Glut1) and confers mitochondrial protection against oxidative
injury’ FASEB J