Membrane Transport Flashcards
What are the types of membrane transport?
There are 4 mechanisms of transporting molecules across the cell membrane: Simple Diffusion Facilitated Transport Active Transport Co-transport
What are the differences in permeability of substances across the lipid membrane?
Highly permeable - gases and hydrophobic molecules (benzene)
Partially permeable - small, polar molecules (H2O and ethanol)
Not permeable - large polar molecules and charged molecules (glucose, ions and amino acids)
If the substance isn’t permeable they may require a protein to aid the transport
Describe the permeability of pharmaceutical drugs across the lipid membrane?
Permeability of pharmaceutical drugs used to be predicted by partition coefficient, K or log P, between octanol/water
Therefore most drugs are hydrophobic to some degree
Alternatively, drugs can have similar structures as nutrients and ‘hitch a ride’ with a transporter
Example Bestatin - this is believed to be transported by PepT2
What are the three protein classes of transporters?
Channels - ion channels, aquaporins, pores
Channels are substrate specific and pores are only ‘size’ specific
Transporters:
Uniport - the movement of a single molecule at a time
Symport - simultaneously transports two different molecules in the same direction
Antiport - simultaneously transports two different molecules in opposite directions
ATP-powered pumps
Where does the protein classification of transporters ‘fall down’?
Cystic fibrosis transmembrane conductance regulator (CFTR) is a ion-channel that belongs to a protein family, ABC transporters (ATP-powered pumps)
Some transporters, for instance the Na+/Ca2+ antiporter in cardiac cells, transport ions
A uniporter that transport ions, e.g. the Chloride Channel (ClC), is that a transporter or a ion-channel
What is the driving force of transport (thermodynamics)?
Transmembrane diffusion (i.e. not driven by ATP or cotransport), diffusion is dependent on:
1. Concentration difference
ΔGc = RT ln [Ain]/[Aout]
2. Transmembrane potential (charged molecules)
ΔGm = FE
3. Osmotic pressure (water)
Do not confuse thermodynamics with rate
Describe facilitated diffusion?
Only transported down the concentration gradient but with no energy input, therefore requires a specific protein to facilitate its movement
Examples of molecules - glucose, amino acids, ions and water (aquaporin)
What type of transporters is passive-mediated transport carried out by?
Ionophores Porins Ion channels Aquaporins Transport proteins
What are ionophores?
Small hydrophobic organic molecules that dissolve inlipidbilayers and increase their permeability to specific inorganic ions
What are the two types of ionophores?
Carrier ionophore - increases the permeabilities of membranes by binding an ion, diffusing through the membrane, and releasing it on the other side
Their ionic complexes are soluble in nonpolar solvents
Channel-forming ionophore - form transmembrane channels or pores through which their selected ions can diffuse
What are porins/pores?
Beta-barrel structures with a central aqueous channel
The size of the channel and the residues lining it decide what types of substances pass through (e.g. cation or anion)
B-barrel pores appear in the outer membranes of Gram-negative bacteria, chloroplasts, and mitochondria
Passive diffusion channels (rapid, temperature-independent transport or solutes)
Some b-barrels are transmembrane (TM) proteins
Not all membrane b-barrels are pores
They act like a sieve with some/but little selectivity - they essentially create an opening in the membrane
Describe the structure of of b-barrel pores?
Known b-barrel structures vary from 8 to 22 b-strands per monomer or ‘barrel’
TM b-Barrels have hydrophobic external residues and mostly hydrophilic internal residues
Contains aromatic girdle on the protein i.e. Ring of aromatic amino acid side chains like tryptophan and tyrosine on the interface of either side of the lipid bilayer
Give an example of porins in E.coli?
OmpF and OmpC - they are the dominating outer-membrane porin
They have little selectivity for solutes
One loop folds into the barrel, providing a restriction in the middle
Acidic residues in this loop gives some cation specificity - it determines how big the pore is
At high ion osmolarity, OmpC is expressed which has a smaller pore
At low osmolarity, OmpF is expressed, which has a bigger pore
Give an example of a b-barrel pore with greater selectivity?
PhoE
It has limited specificity but transports phosphate
It has some positively charged residues (lys) in the loop allowing selectivity for negativity
PhoE and OmpF have almost identical structures with only a change in the ‘constricting’ loop
PhoE mutants of E. coli only show a nine-fold decrease in phosphate transport
What are ion channels?
Integral proteins form channels in membranes carrying salts/ions
They span the membrane and generate water filled pores that allow water molecules to stabilize the ions as they pass through the membrane
They contain: outer vestibule, selectivity filter and inner vestibule
They are gated - mechanosensitive, ligand, signal or voltage
