Membrane Transport Flashcards
How biomolecules get from one compartment to another
- Going around the membrane
- Membrane fusion and budding
- Through the membrane: Simple Diffusion, Passive Transport, Active Transport
Passive Transport Diffusion
- Uses chemical gradient for “energy”
- Non-mediated: transport occurs through simple diffusion
- mediated: Facilitated diffusion leads to much higher transport rates than simple diffusion, transport uses a specific transport protein
Energetics of Passive membrane transport
- Free energy of a solute depends on concentration
- In membrane transport, solute moves from high concentration to low concentration
- At equilibrium, both concentrations are equal and the rate of transport is equal in both directions
Non-mediated Transport: Simple Diffusion
- Small hydrophobic compound can diffuse across the membrane
- O2, N2, H2O, CO2
Rate of Transport
- Rate of transport across the membrane
- Ja = flux of solute / rate of transport
- [A]out - [A]in = concentration gradient
- Pa = permeability coefficient of A in the membrane = Da/x
Facilitated Diffusion
- How bigger molecules get into cells
- Delta G < 0, but proteins assist
- Solutes only move in thermodynamically favoured direction (goes from high to low), also a distinguishing feature
- Proteins may facilitate transport, increasing the rates of transport
- Two important distinguishing features
- Transport displays saturation kinetics
Facilitate Diffusion: Glucose Transporter
- Selective to glucose and faster than simple diffusion
- Molecule crosses the membrane via a transport protein
Simple and facilitated diffusion kinetics
- Molecules move from high to low concentration in both
- Simple diffusion is slow and not saturated
- Facilitated diffusion is faster and can be saturated
- Glucose permease in red blood cell rapidly and specifically transports glucose
Glucose Transport Proteins: GLUT 1
- Transport of glucose across the blood brain barrier
- Reticulocytes
Glucose Transport Proteins: GLUT 2
Glucose sensor in pancreatic beta cells
Glucose Transport Proteins: GLUT 3:
Glucose transport in neurons also expressed in tissues with high demand for glucose
Glucose Transport Proteins: GLUT 4
Skeletal muscle, adipose tissue, the only insulin sensitive isoform
Pore Forming Proteins
- Open channels that allow polar molecules to cross the cell membrane, and along concentration gradient
- Sugars, Water, Ions
- Maltoporin is a bacterial protein that allows maltodextrins into the cells
Greasy Slide
The pore is lined with aromatic residues that interact with the non-polar face of the glucose molecules in the maltose
Aquaporins
Allow water in and out to regulate osmotic pressure
- Homotetramer, each monomer contains a pore
- Pores contain an NPA motif which helps orent the water in the channel so that protons cannot be transferred through the pore
- Charged residues at the ends of the tube also prevent charged OH- and H3O+ from entering the pore
- Orientation of the two short helices with the partial positive charge on the N terminus of this two helices contributes to the electrostatic barrier in the middle of the pore
Ion Channels
- All cells contain ion channels, combined with active transport protein they are important in neurotransmission and signal transduction
- Transmembrane proteins that make the membrane permeable to ions
- The structure of the channels selects the ions transported
- Much faster transport than the ionophores
- Extremely selective
- Can be gated
Potassium Channels
- A large family of integral membrane proteins
- Tetrameric proteins that are helical bundles
Voltage gated K+ channel
- Helix S4 contains 4 arg residues that move when the membrane is depolarized, opening the channel
- The T1 domain and beta subunits provided a 2nd closing mechanism that prevents the channel from activating immediately
Ionophores
- Special Case of facilitated diffusion
- Organic molecules that increase the permeability of membranes to specific ions
- Carriers vs channel formers
Valinomycin
- Example of a carrier ionophore
- Contains ester and amide bonds
- Contains L and D amino acids
- Antibiotic isolated from streptomyces
- Specifically complexes to K+ and transports it across the membrane
Gramicidin A
- Example of a channel forming ionophore
- Two molecules in a head-to-head conformation form a transmembrane pore for H+, Na+, and K+, but blocked by Ca2+
- Unusual structure due to alternating L- and D-residues
- 6.5 residues/turn
- right handed helix
- Successive N-H groups in peptide point up and down
- All side chains point outward
Active Transport Systems
- Energy input required
- Some transport occurs such that solutes flow against thermodynamic potential
- Energy input drives transport
- Energy source and transport machinery are coupled directly or indirectly
- Energy source may be ATP, light, or a concentration gradient
Active Transport: Primary Transport
- Transfer is directly coupled to hydrolysis of ATP or absorption of light
- Example is Na+/K+ ATPase, ATP is hydrolyzed to transport both ions against their concentration gradients
Active Transport: Secondary Transport
- transport of a molecule against the concentration gradient is coupled to transport of a second substance down the concentration gradient
- Example is Lac Permease
Na+/K+ ATPase
- In all animal cells
- Maintains ion gradient across cell membrane
- Increased Na+ outside cell regulates osmotic pressure within the cell
- Responsible for propagation of nerve impulses
- Cell membranes also contain gated K+ and Na+ channels
- Inhibited by vanadate and other phosphate analogs
ABC Transport Proteins
- Transport by different types of substrates including amino acids, sugars
- Remove toxins from the blood in kidneys and liver
- Responsible for resistance to chemo therapy
Secondary Active Transport
- Consider the possibilities of more than one molecule
- Transported at a time, one against its concentration gradient, one along its concentration gradient
- Energy for transport comes from an ion gradient
Lactose Permease in Bacteria
- Delta G is greater than 0 for lactose transport
- Energy for transport comes from the H+ gradient
