BCOR 011 Lecture 10 Sept 21, 2005 Membrane Transport BCOR 011 Lecture 10 Sept 21, 2005 Membrane Transport

Membrane Transport 1.Permeability 2.Diffusion 3.Role of transport proteins - facilitated Channel proteins Carrier proteins 4. Active vs passive transport

1. Lipid bilayers are selectively permeable Decreasing permeability small,nonpolar small uncharged, polar larger uncharged, polar molecules ions Size – polarity - ions

The Permeability of the Lipid Bilayer Hydrophobic moleculesHydrophobic molecules –Are lipid soluble and can pass through the membrane rapidly Polar moleculesPolar molecules –Do not cross membrane rapidly IonsIons –Do not cross the membrane at all

Transport processes Solutes – dissolved ions and small organic molecules i.e., Na +,K +, H +, Ca ++, Cl, - sugars, amino acids, nucleotides Three transport processes: a. Simple diffusion – directly thru membrane b. Facilitated diffusion (passive transport) c. Active transport – requires energy Req Carrier prot

Simple Diffusion: Tendancy of a material to spread out Always moves toward equilibrium Net diffusion Equilibrium Net diffusion Equilibrium Figure 7.11 B

simple diffusion example: Oxygen crossing red cell membrane HIGH -> low O 2 CO 2 O 2 2 CO 2 O2O2 O 2 CO 2 Lungs Tissues Driving force: concentration gradient Trying to even out concentration HCO 3 - CO 2 HCO 3 -

H 2 O transport: diffusion from area with low [solute] to one with high [solute] Osmosis Diffusion of water Impermeable Solutes Figure 7.12 Lower concentration of solute (sugar) Higher concentration of sugar Same concentration of sugar Selectively permeable mem- brane: sugar mole- cules cannot pass through pores, but water molecules can More free water molecules (higher concentration) Water molecules cluster around sugar molecules Fewer free water molecules (lower concentration) Water moves from an area of higher free water concentration to an area of lower free water concentration  Osmosis

Animal cells – pump out ions Plants, bacteria – cell walls Hypotonic solution Isotonic solution Hypertonic solution Animal cell. An animal cell fares best in an isotonic environ- ment unless it has special adaptations to offset the osmotic uptake or loss of water. (a) H2OH2O H2OH2O H2OH2O H2OH2O Lysed NormalShriveled Plant cell. Plant cells are turgid (firm) and generally healthiest in a hypotonic environ- ment, where the uptake of water is eventually balanced by the elastic wall pushing back on the cell. (b) H2OH2OH2OH2O H2OH2O H2OH2O Turgid (normal)Flaccid Plasmolyzed Figure 7.13

…but most things are too large or too polar to cross at reasonable rates using simple diffusion Facilitated diffusion: protein–mediated movement down a gradient Transmembrane transport proteins

Figure 7.15 Carrier protein Solute A carrier protein alternates between two conformations, moving a solute across the membrane as the shape of the protein changes. The protein can transport the solute in either direction, with the net movement being down the concentration gradient of the solute. (b) Transmembrane transport proteins allow selective transport of hydrophilic molecules & ions 1. carrier protein Bind solute, conformational change, release Selective binding “turnstile”

Figure 7.15 EXTRACELLULAR FLUID Channel protein Solute CYTOPLASM A channel protein (purple) has a channel through which water molecules or a specific solute can pass. (a) Transmembrane transport proteins allow selective transport of hydrophilic molecules & ions aqueous channel hydrophilic pore very rapid selective –size/charge 2. channel protein “trap door”

Kinetics of simple vs facilitated Diffusion v (solute concentration gradient) -> Gets“saturated”Maximumrate DoesNotGet“saturated”

For CHARGED solutes (ions): net driving force is the electrochemical gradient has both a concentration + charge component; Ion gradients can create an electrical voltage gradient across the membrane (membrane potential) -60 mVolts

Channel Proteins: facilitate passive transport Ion channels: move ions down an electrochemical gradient; gated Voltage Ligand Mechanosensitive “keys”

Ligand-gated ion channel “ Wastebasket model” – step on pedal & lid opens

Ligand-gated example: ligand-gated ion channel “Key” - acetylcholine

Voltage-gated channels Note: channels are passive, facilitated transport systems

Example of voltage-gated ion channel

Protein ion channels: -are passive, facilitated transport systems -require a membrane protein -typically move ions very rapidly from an area of HIGH concentration to one of lower concentration

Carrier proteins: Transport solute across membrane by binding it on one side, undergoing a conformational change and then releasing it to the other side

Example: Glucose transporter GluT1 : carrier-mediated facilitated diffusion 1.Glucose binds 2. Conformational change 3. Glucose Released- Conformational shift inside cell Glucose out (HIGH)->glucose in (low) outside cell Glucose + ATP  glucose-6-phosphate + ADP hexokinase T1T1 T2T2 T1T1

Carrier proteins: three types Antiport – two solutes in opposite directions Uniport – one solute transported Symport – two solutes in the same direction [ (a) Uniport (b) Co-transport

Carrier Proteins can mediate either: 1. Passive transport driving force -> concentration/electrochemical gradient OR 2. Active transport against a gradient; unfavorable requires energy input Note: channel proteins mediate only passive transport

Active transportActive transport –Carrier protein moves solute AGAINST its concentration gradient –Requires energy, usually in the form of ATP hydorlysis –Or a favorable gradient established by use of ATP

ATP! 3 Na + out 2 K + in Active transport: Na + K + Pump (Na + K + ATPase) P P P P

The sodium -potassium pump pump Figure 7.16 P P i EXTRACELLULAR FLUID Na+ binding stimulates phosphorylation by ATP. 2 Na + Cytoplasmic Na + binds to the sodium-potassium pump. 1 K + is released and Na + sites are receptive again; the cycle repeats. 3 Phosphorylation causes the protein to change its conformation, expelling Na + to the outside. 4 Extracellular K + binds to the protein, triggering release of the Phosphate group. 6 Loss of the phosphate restores the protein’s original conformation. 5 CYTOPLASM [Na + ] low [K + ] high Na + P ATP Na + P ADP K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ [Na + ] high [K + ] low

The Na + /K + Pump: “bilge pump” Creates an electrochemical gradient (high external [Na + ]) potential energy – like “storing water behind a dam” uses ~1/3 of cell’s ATP!! Na +

Example of indirect active transport: Na + gradient drives other transport Na + glucose symport Glucose Gradient Coupled transport

An electrogenic pump –Is a transport protein that generates the voltage across a membrane Figure 7.18 EXTRACELLULAR FLUID + H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ Proton pump ATP CYTOPLASM – – – – – +

Cotransport: active transport driven by a concentration gradient Figure 7.19 Proton pump Sucrose-H + cotransporter Diffusion of H + Sucrose ATP H+H+ H+H+ H+H+ H+H+ H+H+ H+H+ H+H – – – – – –

Direct active Indirect active transporttransport Transport coupled to Exergonic rxn, i.e. ATP hydrolysis *Transport driven by cotransport of ions *note that the favorable ion gradient was established by direct active transport

….Each membrane has its own characteristic set of transporters

Summary: Simple diffusionFacilitated diffusion Active transport No protein channel carrier protein protein carrier protein HIGH to low conc low to HIGH conc favorable Unfavorable Add energy Figure 7.17 ATP Passive transport