BCOR 011 Sept 21, 2005 Lecture 10 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 •small,nonpolar •small uncharged, polar •larger uncharged, polar molecules •ions The Permeability of the Lipid Bilayer • Hydrophobic molecules Decreasing permeability – Are lipid soluble and can pass through the membrane rapidly • Polar molecules – Do not cross membrane rapidly • Ions – Do not cross the membrane at all Size – polarity - ions Transport processes Simple Diffusion: Solutes – dissolved ions and small organic molecules i.e., Na+,K+, H+, Ca++, Cl,- sugars, amino acids, nucleotides •Tendancy of a material to spread out •Always moves toward equilibrium Three transport processes: a. Simple diffusion – directly thru membrane Req b. Facilitated diffusion (passive transport) Carrierc. Active transport – requires energy prot Net diffusion Net diffusion Net diffusion Figure 7.11 B Net diffusion simple diffusion example: Oxygen crossing red cell membrane HIGH -> low Lungs Tissues O2 CO2 O2 CO2 O22 CO2 CO2 O2 HCO3- Equilibrium Equilibrium Net diffusion Equilibrium H2O transport: diffusion from area with low [solute] to one with high [solute] Lower concentration of solute (sugar) Higher concentration of sugar Same concentration of sugar HCO3- Osmosis Diffusion of water HCO3- Selectively permeable membrane: sugar molecules cannot pass through pores, but water molecules can Water molecules cluster around sugar molecules More free water molecules (higher concentration) Driving force: concentration gradient Trying to even out concentration Net diffusion Fewer free water molecules (lower concentration) Osmosis • Figure 7.12 Water moves from an area of higher free water concentration to an area of lower free water concentration Impermeable Solutes Animal cells – pump out ions Plants, bacteria – cell walls Hypotonic solution (a) Animal cell. An animal cell fares best in an isotonic environment unless it has special adaptations to offset the osmotic uptake or loss of water. H2O Figure 7.13 Isotonic solution H2O H2O Shriveled H2O H2O H2O H2O H2O Normal Lysed (b) Plant cell. Plant cells are turgid (firm) and generally healthiest in a hypotonic environment, where the uptake of water is eventually balanced by the elastic wall pushing back on the cell. Hypertonic solution …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 Turgid (normal) Flaccid Plasmolyzed Transmembrane transport proteins allow selective transport of hydrophilic molecules & ions 1. carrier protein Transmembrane transport proteins allow selective transport of hydrophilic molecules & ions aqueous channel hydrophilic pore Bind solute, conformational change, release Selective binding 2. channel protein very rapid EXTRACELLULAR selective –size/charge FLUID “trap door” “turnstile” Carrier protein Channel protein Solute Solute CYTOPLASM (b) 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. Figure 7.15 (a) A channel protein (purple) has a channel through which water molecules or a specific solute can pass. Figure 7.15 Kinetics of simple vs facilitated Diffusion Gets “saturated” Maximum rate 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) + + + + + + + Does Not Get “saturated” v -60 mVolts + + + + + ++ + + + + +++ +++ --- --- --- +++ +++ --- + + (solute concentration gradient) -> Channel Proteins: facilitate passive transport Ion channels: move ions down an electrochemical gradient; gated “keys” Voltage Ligand Mechanosensitive Ligand-gated ion channel “Wastebasket model” – step on pedal & lid opens Ligand-gated example: ligand-gated ion channel Voltage-gated channels “Key” - acetylcholine + + + + + + - - - - - - + - + - - + - + 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 Example: Glucose transporter GluT1 : carrier-mediated facilitated diffusion Carrier proteins: Transport solute across membrane by binding it on one side, undergoing a conformational change and then releasing it to the other side Glucoseout (HIGH)->glucose (low) outside cell 2. Conformational change 3. Glucose T2 ReleasedConformational shift 2. 1. Glucose binds T1 in 1. inside cell 3. T1 Glucose + ATP Æ glucose-6-phosphate + ADP hexokinase Carrier proteins: three types Carrier Proteins can mediate either: 1. Passive transport driving force -> concentration/electrochemical gradient OR (a) Uniport (b) Co-transport Uniport – one solute transported [ Symport – two solutes in the same direction Antiport – two solutes in opposite directions 2. Active transport against a gradient; unfavorable requires energy input Note: channel proteins mediate only passive transport • Active transport – Carrier protein moves solute AGAINST its concentration gradient Active transport: Na+K+ Pump (Na+K+ATPase) – Requires energy, usually in the form of ATP hydorlysis – Or a favorable gradient established by use of ATP P P P 3 Na+ out 2 K+ in P ATP! 1 Cytoplasmic Na+ binds to the sodium-potassium pump. 2 Na+ binding stimulates phosphorylation by ATP. [Na+] high [K+] low Na+ Na+ Na+ Na+ The Na+/K+ Pump: Na+ The sodium -potassium pump [Na+] low [K+] high Na+ CYTOPLASM “bilge pump” ATP P ADP Creates an electrochemical gradient (high external [Na+ ]) EXTRACELLULAR FLUID Na+ Na+ Na+ 3 K+ is released and Na+ sites are receptive again; the cycle repeats. 4 K+ P K+ Phosphorylation causes the protein to change its conformation, expelling Na+ to the outside. Na+ Na+ Na+ Na+ Na+ + potential energy Na+Na – like “storing water behind a dam” Na+ Na+ K+ P K+ Figure 7.16 5 Loss of the phosphate restores the protein’s original conformation. K+ uses ~1/3 of cell’s ATP!! Pi K+ 6 Extracellular K+ binds to the protein, triggering release of the Phosphate group. Example of indirect active transport: Na+ gradient drives other transport Na+ glucose symport • An electrogenic pump – Is a transport protein that generates the voltage across a membrane – – ATP EXTRACELLULAR FLUID + + H+ H+ Proton pump H+ – Glucose Gradient + H+ + Coupled transport – CYTOPLASM Figure 7.18 – • Cotransport: active transport driven by a concentration gradient – + H+ ATP H+ + – + + – Indirect active transport Transport coupled to Exergonic rxn, i.e. ATP hydrolysis *Transport driven by cotransport of ions + H+ – + Sucrose-H+ cotransporter H+ Diffusion of H+ H+ – – + + Sucrose H+ Direct active transport H+ Proton pump H+ Figure 7.19 H+ *note that the favorable ion gradient was established by direct active transport ….Each membrane has its own characteristic set of transporters Summary: Passive transport Simple diffusion Facilitated diffusion No protein HIGH to low conc favorable Active transport channel carrier protein protein carrier protein low to HIGH conc HIGH to low conc favorable Unfavorable Add energy ATP Figure 7.17
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