Membrane Transport Flashcards
Transmembrane Transport of Ions and Small Molecules
Overview of Transmembrane Transport Proteins
What’s the difference between Simple Diffusion and the other types of Transports?
- Channels (for facilitated transport)
- Transporters
a. Uniporters (for facilitated transport)
b. Symporters (for cotransport)
c. Antiporters (for cotransport) - ATP-powered pumps (for active transport)
Simple diffusion does not require specific proteins.
Facilitated Transport, Active Transport, and Cotransport require specific proteins.
Facilitated Transport of Glucose and Water
Give example.
Uniporters= transport of a single type of molecule across plasma membrane ALONG gradient.
- much faster than simple diffusion bc protein-mediated
- movement of hydrophilic substances
- GLUT1 is a complex protein (12 alpha helices), embedded in biological membrane
○ Has 2 domains: C-term domain, and N-term domain, that together convert btwn 2 conformational states to facilitate diffusion across membrane
○ Binds glucose in its central cavity, and rapidly moves it along its gradient across cellular membranes.
1. Outward Open (open conformation of GLUT1 towards exterior)
2. Ligand-bound Occluded (closed conformation, captured)
3. Inward Open (open conformation toward cytosol)
4. Ligand-free occluded (closed, nothing inside)
ATP-Powered Pumps (Name all the classes too)
- move molecules/ions across membranes using ATP as energy source
- can be classified in 4 families:
○ P-class – for maintaining gradient of different types of ions (K, Ca, NA)
○ V-class – transport of Hydrogen ions only
○ F-class– transport of Hydrogen ions only
○ ABC superfamily – transport of multiple types of molecules through membrane
P-Pump Example: Operational Model of the Ca2+ ATPase in the SR of skeletal muscle cells
And the Intracellular Ionic Environment
[Calcium SR lumen] > [Calcium Cytosol(outside of organelle)] so this ATPase will take Ca from cytosol/cytoplasm into SR lumen
- we know that in muscle contraction, the Ca must come from the SR to go bind to its proteins, but in relaxation state, they need to go back into SR… this is the mechanism:
- based on the changing of the conformation of the pump from E1(=Ca binding site at cytosolic face) to E2(=Ca binding site at exoplasmic/ER lumen face)
- 2 Ca binding sites
- these changes are induced by the phosphorylation and dephosphorylation of Aspartate!
- E1= open to take in 2 calciums + ATP binds —> Phosphorylation of the pump + ATP hydrolysis —> becomes E2 conformation – binding site at ER lumen
- so for every 2 Ca, 1 ATP
P-Pump Example: operational model of the plasma-membrane Na+/K+ ATPase
and Intracellular Ionic Environment
[Na inside cell] < [Na exterior]
[K cytosol(inside of cell)] > [K exterior]
- each ion moves against its gradient
- E1= unphosphorylated, open to cytosol to take in 3 Na + ATP binds —> Phosphorylation of aspartate + ATP hydrolysis —> becomes E2 conformation– 3 Na leave, 2Ks come in from exoplasmic face (EXTERIOR) —-> dephosphorylation + conformational change —> 2K+ released at cytosol (inside of cell)
ABC superfamily multi-drug resistance transporter
- they can transport many different types of molecules (hydrophilic AND hydrophobic, toxins, drugs, phospholipids, peptides, etc.) into and out of cell – they have different specificities
- high expression in liver, kidneys, intestines – all where natural toxic and waste products are removed from the body
- 2 transmembrane (T) domains, and two cytosolic ATP-binding (A) domains
- The actual binding of the molecules being transported depends on the cavity that forms btwn the transmembrane domains: the ligand-binding binding cavity is alternately exposed to the exoplasmic/cytosolic faces
- mediated by conformational changes due to ATP hydrolysis
Nongated Ion Channels and the Resting Membrane Potential
- The composition of ions inside vs outside the cell is different. With a membrane permeable to different ions, there will be redistribution of POSITIVE ions (selective ion movement)– which will give you a certain type of transmembrane electrical gradient
- the animal cell pm resting potential (-70mV) is generated by the ATP-powered Na/K pump and Nongated K Channels
- our resting potential is different in neurons and muscle cells undergoing depolarization in membrane potential
Mechanism of ion selectivity and transport in resting K+ channels
K+ channels: tetramers of four identical subunits
- there’s a selectivity filter in K+ channels that is established by backbone carbonyl oxygens of AAs
- Na+ and K+ are hydrated in solution but dehydrated in K+ channel pores
- channel selectivity:
- dehydrated K+ bind perfectly (geometrically) to carbonyl oxygens and move freely through the channel,
- while (even though they’re smaller) Na+ ions bind poorly to the channel oxygen atoms and prefer to remain in water which is the more energetically favourable state
Cotransport by Symporters and Antiporters
-example: the 2-Na+/1-glucose symporter
- cotransporters use the energy released by ion (H+ of Na+) movement down its ELECTROCHEMICAL gradient to power the transport of another molecule or ion up its CONCENTRATION gradient
- moving two molecules in the SAME direction
- the 2-Na+/1-glucose symporter allows animal cells to accumulate a very high concentration of glucose, using the electrochemical gradient of Na+
- [Glucose cytosol] > [Glucose exterior]
[Na cytosol] < [Na exterior]
What two forces constitute the electrochemical gradient across a membrane?
Electric potential + ion concentration gradient (established mostly by Na+/K+-ATPase pump)
What different transport proteins are used in the transcellular transport of glucose from the intestinal lumen into the blood
- Na+/K+ ATPase on basolateral plasma membrane to depolarize epithelial cells – with help of K+ channel to recycle K+ ions (Na+ out of cell)
- 2Na+/glucose symporter on apical plasma membrane (from intestinal lumen to cytosol of epithelial cell)
- GLUT2 Uniporter on basolateral membrane (from cytosol into blood)
