Membrane Transport Mechanisms
Channels
Carriers
Form a pore that can be open or closed. When open, the pore allows ions or water to diffuse across the membrane at rates up to many millions of molecules per second.
Selective channels exist only for ions and water molecules.
They can be highly selective or non-selective
Bind specific substrates and allow them to move across the membrane only when they undergo conformational changes; they are slow compared to diffusion.
Binding sites must become available to bind a transported molecule on one membrane side and on the other side. (alternating access model)
Transport rates usually saturate as the concentration of transported solute is increased; simple diffusion of permeable solutes increases as the transported solute concentration is increased to high concentrations
Uniporters (facilitated diffusion)
Antiporters
Symporters
A specific solute is bound on one side of the membrane.
Translocated across the membrane and released on the other side.
The empty binding sites then rearrange to bind another substrate
All of the reactions are reversible and only the energy of the solute gradient across the membrane "drives" the reaction in one direction
Glucose enters most cells via uniports called GLUT transporters; humans have 10 different GLUT isoforms. They can work in either direction.
If glucose concentrations are high both inside and outside of the cells, the transporter exchanges one glucose inside for one glucose outside; glucose-glucose self-exchange
They function similarly to uniports, except that two substrates must bind for the transport steps to take place. The energy of one substrate gradient can be used to "drive" the transport of the other substrate.
Lumen of the intestine contains a high concentration of Na+, while the cytoplasm of enterocytes has a low concentration of Na+; glucose can be accumulated into enterocytes to a high concentration, even when the glucose concentration is very low
In the kidney, they are responsible for the reabsorption of sugar from the lumen of the nephron. Two Na+ are transported for each glucose. (10:1 Na+ and 100:1 glucose gradient)
Binding sites re-orient only when substrates are bound and not when binding sites are empty. The energy of one ion gradient can be used to drive a different ion in the other direction
In heart cells and many neurons, transport reaction exchanges 3 Na+ ions for one Ca ion. This exchange reaction is not electronically neutral
Pumps
P-type
Na+ and K+ ATPase pump is an example. Called a "P" type because the terminal Phosphate of ATP becomes covalently bound to the cytoplasmic side of the protein. Step 1: ATP is bound to the enzyme in the E1 state. Step 2: 3 Na+ ions bind on the cytoplasmic side. Step 3: Na+ occupation triggers hydrolysis which occludes the Na+ ions. Step 4: Na ions are de-occluded on the other side. Step 5: Na+ are released and two K+ ions bind with high affinity. Step 6: ATP immediately binds and K+ ions are released in the inside of the cell
V-type
Proton pumps that hydrolyze ATP to move protons across.V1 (peripheral domain) hydrolyze ATP and transfer the energy to a ring of transmembrane subunits that rotate within the V0 subunit. ATP is NOT covalently bounded
V-ATPase acidly the acrosome of sperm acrosomes. V-ATPases in osteoclast membranes pump protons onto the bone surface. V-ATPases pump protons into the urine, allowing for bicarbonate reabsorption into the blood. Also make lysosomes acidic
ATP-Binding Cassette Transporters
Usually two transmembrane domains per transporter. When cytoplasmic ATP binds each cassette and is hydrolyzed, a conformational change occurs in which the NBDs and transmembrane domains shift to reveal a cavity
The CFTR and the MDR protein ( a pump that becomes expresses in many tumors to resist drug therapy)