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2011/10/12 I. Ch 4. Movement of Molecules across Cell Membrane • • • • • Diffusion us o Mediated-Transport Systems Osmosis Endocytosis and Exocytosis Epithelial Transport II. Diffusion A. Magnitude and direction of diffusion B. Diffusion through cell membranes 1. Diffusion through the lipid bilayer g protein p channels 2. Diffusion of ions through Mediated transport A. Difference between mediated transport and diffusion B. Passive mediated transport (facilitated diffusion) C. Active transport a y active act ve transport t a spo t 1.. Primary 2. Secondary (gradient-driven) active transport Question: Is it diffusion, facilitated diffusion, or active transport? III. IV. V. Osmosis Endocytosis and exocytosis A. Kinds of endocytosis B. Fate of endocytotic vesicles C. Functions of exocytosis Epithelial transport Diffusion Definition: solute moves down its concentration gradient • simple diffusion: small (e.g., oxygen, carbon dioxide) lipid soluble (e.g., steroids) • facilitated diffusion: requires transporter (e.g., glucose) 1 2011/10/12 Active transport Active transport: solute moves against its concentration gradient • primary i active ti transport: t t ATP directly consumed (e.g., Na+ K+ATPase) Figure 4-1 START: Initially higher concentration of molecules randomly move toward lower concentration. Over time, solute molecules placed in a solvent will evenly distribute themselves. • secondary active transport: energy of ion gradient (usually Na+) used to move second solute (e (e.g., g nutrient absorption in gut) Terms Diffusional equilibrium ilib i is the result Figure 4-2 At time B, some glucose has crossed into side 2 as some cross into side 1. • Flux: amount of molecule movement/ unit time • net flux fl • diffusion equilibrium 2 2011/10/12 The magnitude of the net flux depends on Note: the partition between the two compartments is a membrane that allows this solute to move through it. Figure 4-3 • magnitude of the net flux: J=PA (Co-Ci), P=membrane ppermeabilityy coefficient (Co-Ci)=concentration difference across membrane A= surface area of membrane • temperature • mass of the molecule • medium di through h h which hi h the h molecules l l are moving i eg. Faster in air than in water Net flux accounts for solute movements in both directions. Figure 4.04 Diffusion rate vs distance • Diffusion time α (distance)2 • human: diffusion too slow, use circulation system with a pressure source (heart) • 20 μm diameter cell: reach equilibrium with extracelluar oxygen in 15 ms basketball size cell: 265 days 3 2011/10/12 Ion channels Diffusion through the lipid bilayer • polar molecules diffuse into cells very slowly , because of the hydrophobic interior of the lipid bilayer • Oxygen, carbon dioxide, fatty acids, and steroids are non-polar molecules, diffuse rapidly through the membranes • diffusion of ions through protein channels Na+, K+, Cl-, Ca 2+ Ion movement • Ions are charged • A seperation of electrical charge across plasma membranes is known as membrane potential • The direction of ion movement depend on both concentration difference and the electrical difference Electrochemical gradient • Ion diffusion needs channels, otherwise very slow • Small size of channels prevents larger, polar, organic g molecules from enteringg or leaving • selectivity A thin shell of positive (outside) and negative (inside) charge provides the electrical gradient that drives ion movement across the membranes of excitable cells. Figure 4-6 4 2011/10/12 Regulation of diffusion through ion channels Figure 4-7 • Channel gating: channel open and close pass through g a channel depends p on how • Number of ions p often the channel open and how long it stays open The opening and closing of ion channels results from conformational changes in integral proteins. Discovering the factors that cause these changes is key to understanding excitable cells. An example of ion channel 3 types of ion channels according to factors that induce conformational changes of ion channels • Ligand-gated channels • Voltage gated channels • Mechanically gated channels The regulated opening and closing of these channels is the basis of how neurons function. Figure 4-5 5 2011/10/12 Figure 7.38 Ach gated ion channel Hair cell Neurotoxins act on postsynaptic receptors 作用在突觸後受氣之神經毒素 Cone Snail Bungarus Multicinctus 雨傘節 Betel Nuts 檳榔 Hundreds of peptide --conotoxins, block Neuromuscular junction Addictive nervous ion channels --Ach receptor system stimulant– nicotinic Ach receptor Puffer 6 2011/10/12 Black Widow Spider Mediated transport systems • Diffusion through channels, not enough • Some molecules are too large for ion channel & too polar to diffuse through membrane (eg. a.a., glucose) need transporters (or carriers) Neuromuscular junction: increase and then eliminates ACh(neurotransmitter) release Process of transporting molecules through transporters Carrier-mediated transport: Facilitated Diffusion e.g. glucose • Solute bind to a specific site on a transporter • Change shape • Expose this binding site to the opposite side of the membrane • Dissociation of the solute from the transporter The solute acts as a ligand Figure 4-8 protein shape change releases the solute on the other side of the membrane. 7 2011/10/12 Transporters • Protein • Encoded by different genes & expressed in different cells • Vary in binding site affinity • Vary in maximal rates of transport • Modulation, e.g. hormone insulin insulin # of glucose transporters in muscle & adipocyte insulin # of glucose transporters can’t efficiently transport glucose glucose in extracellular Diabetes 3 factors determine the magnitude of solute flux in transporter systems • Degree of binding site saturation • Number of transporters • Rate of conformation change Similarity and difference between ion channels and transporters • Similarity: 1. involve membrane protein 2. chemical specificity • Difference: ion channels move thousands times more ions/ unit time than do transporters (transporter need to change shape for each molecule) Figure 4-9 In simple diffusion, flux rate is limited only by the concentration gradient. In carrier-mediated transport, the number of available carriers places an upper limit on the flux rate. 8 2 types of mediated transporter • Facilitated diffusion: downhill, high concentration to low,, no energy gy needed • Active transport: uphill, use energy, low to high Figure 4-10 membrane 2011/10/12 Do nhill Downhill Concentration gradient Uphill Concentration gradient Two types of active transporters • uphill, uphill referred to as pumps • Requires substances to bind to transporters • Saturation • Specificity • Need energy • Primary active transporters use ATP as energy transporter is an ATPase e.g. Na-K ATPase pump, Ca 2+ -ATPase, H+-ATPase, H+/K+ATPase • Secondary active transporters use se electrochemical gradient 9 2011/10/12 Primary active transporter, e.g. Na+-K+ ATPase Need ATP phosphorylation High Na affinity conformation change Important role of Na-K ATPase transporters (pumps): Move 3 Na out & 2 K in net 1 positive out Maintain negative membrane potential, low [Na]i, high[K]i Na affinity dephosphorylation High K affinity low K affinity Figure 4-11 Figure 4-12 Other major primary active-transporters Two types of active transporters • Ca 2+ -ATPase, keep low[Ca2+ ]i Pumpp direction: plasma membrane: Cytosol extracellular organelle membrane: cytosol organelle • Primary active transporters use ATP as energy transporter is an ATPase e.g. Na-K ATPase pump, Ca 2+ -ATPase, H+-ATPase, H+/K+ATPase • H+-ATPase, move H+ out of cell to maintain cellular pH • Secondary active transporters use se electrochemical gradient • H+/K+-ATPase, one H+ out of and one K+ into the cell in the plasma membrane of acid secreting cells in the stomach & kidney 10 2011/10/12 Secondary active transport Secondary active transport • Electrochemical gradient as energy source • Ion I move down d the th electrochemical l t h i l gradient di t andd cotransport another molecule, e.g. glucose or amino acid • 2 binding sites, ion( typically Na) and co-transported molecule Na binding solute binding site affinity Na: downhill Solute: uphill High affinity Conformational change Low affinity Figure 4-13 The most important difference between primary and secondary active transport • Energy source primary: ATP secondary: use stored energy of an electrochemical gradient to move both an ion and a second solute • Creation and maintenance of the electrochemical gradient depends on primary active transporters If no ATP primary active transport of Na Na concentration gradient secondary y active transport p 11 2011/10/12 Figure 4-14 Cotransport and countertransport during secondary active transport driven by sodium Cotransport or Symport: Na and solute move in same direction Na: downhill Solute: uphill Countertransport or antiport: Na & solute move in opposite direction Table 4-1 Diverse examples of carrier-mediated transport. Reality: Co≠ Ci Table 4-2 Figure 4-15 12 2011/10/12 Ch 4. Movement of Molecules across Cell Membrane • • • • • Diffusion us o Mediated-Transport Systems Osmosis Endocytosis and Exocytosis Epithelial Transport How to change the water concentration? Osmosis • Osmosis: The net diffusion of water across membranes • Water is a polar molecule molecule, diffuse very slowly across the membrane • Facilitaed Water diffussion through water channels: aquaporins • Types of water channel vary between cells permeability difference • Water channels permeability can be altered in response to various signals Addition of solute molecules to pure water lowers water concentration in the solution • Which one has higher water concentration? 5 liter of gglucose solution or 5 liter of pure water Solvent + Solute = Solution • Adding solute to a solution will dilute water concentration Figure 4-16 13 2011/10/12 water concentration is decreased by the addition of solute • It depends on the number of solute particles in solution • example: 1mol of glucose, 1mol of amino acid, 1mol of urea or any other molecule that exists as a single particle in solution 2mol solute • example: 1 mol of NaCl Na+ + Cl+ • 1 mol of MgCl2 Mg2 + 2Cl3 mol solute Figure 4-17 Begin: The partition between the compartments is permeable to water and to the solute. After equilibrium has occurred: solute and water concentrations on both sides of the partition are equilized. Osmolarity • Definition: The total solute concentration of a solution is known as its osmolarity • 1 osmol is equal to 1 mol of solute particle • 1 Osm = 1 osmol per liter • example: 1M glucose 1 Osm 1M NaCl 2 Osm • refer to the concentration of the solute particles, also determine the water concentration, higher the osmolarity, lower the water concentration Figure 4-18 Begin: The partition between the compartments is permeable to water only. After equilibrium has occurred: Water and solute concentrations are equalized. equalized Volume in compartment 1 is reduced by 1/3 Conatant solute amount 2 Osm x 1L = 3 Osm x ?L ? = 0.67 14 2011/10/12 Osmotic pressure • when a solution containing solute is separated from pure water by a semipermeable membrane (only permeable to water) water), the pressure that must be applied to solution to prevent the net flow of water into it is termed the osmotic pressure • the lower the water concentration, the higher the osmotic pressure Figure 4-19 Extracellular osmolarity and cell volume A. Solutes are not permeable • hypertonic solution extracellular solution osmolarity > 300 mOsm • isotonic solution extracellular = 300mOsm • hypotonic solution extracellular < 300 mOsm Table 4.03 15 2011/10/12 Ch 4. Movement of Molecules across Cell Membrane • • • • • Diffusion us o Mediated-Transport Systems Osmosis Endocytosis and Exocytosis Epithelial Transport Figure 4-20 Endocytosis and Exocytosis • endocytosis: plasma membrane fold into the cell, forming small pockets that pinch off to produce intracellular, membrane-bound vesicles that enclosed a small volume of extracellular fluid • exocytosis: membrane bound vesicles in the cytoplasm fuse with the plasma membrane and release their contents co e s too thee outside ou s de of o thee cell ce Three types of endocytosis • fluid endocytosis (pinocytosis, cell drinking) non-specific, water, ion, nutrients, small molecules g y (cell ( eating), g), eg. g Immune system, y , • pphagocytosis bacteria, large molecules, cell debris internalized phagosomes migrate to and fuse with lysosomes destroyed • receptor mediated endocytosis specific, molecules bind to membrane bound receptors, leads to a concentrated specific ligand in the endocytotic vesicles e.g. cholesterol bind lipoprotein then bind lipoprotein _receptorendocytosis cholesterol delivered into the cell_ 16 2011/10/12 Figure 4-21 3 types of endocytosis Alternative functions of endocytosis: 1 Transcellular 1. transport 2. Endosomal processing 3. Recycling the membrane 4. Destroying engulfed materials Exocytosis • 2 functions: 1. replace portions of plasma membrane 2. a pathway for membrane impermeable molecule to be secreted into extracellular fluid • exocytosis is triggered by stimuli increase cytosolic Ca concentration exocytosis Ch 4. Movement of Molecules across Cell Membrane • • • • • Diffusion us o Mediated-Transport Systems Osmosis Endocytosis and Exocytosis Epithelial Transport 17 2011/10/12 Epithelial cells • luminal membrane: one surface of an epithelial cell faces a hollow or fluid filled chamber and the plasma membrane on this side is referred to • basaolateral membrane: the opposite side of luminal membrane Transcellular transport Luminal membrane 2 Pathways for Epithelial Transport • diffusion(paracellular pathway) --between between adjacent cells --require tight junction --small area available for diffusion • transcellular pathway --move into the cell, through cytosol, exit across the whole cell --luminal and basolateral membranes contain different transporters & ion channels Transepithelial transport of most organic solute basolateral membrane (transporter) diffusion Figure 4-22 Primary active transport Na downhill Figure 4-23 18 2011/10/12 Figure 4-24 Net water movements across an epithelium are dependent on net solute movement I. II. e.g. Na is the solute Na into cellLow osmolarity in the lumen water flow from lumen to cell Diffusion A. Magnitude and direction of diffusion B. Diffusion through cell membranes 1. Diffusion through the lipid bilayer g protein p channels 2. Diffusion of ions through Mediated transport A. Difference between mediated transport and diffusion B. Passive mediated transport (facilitated diffusion) C. Active transport a y active act ve transport t a spo t 1.. Primary 2. Secondary (gradient-driven) active transport Question: Is it diffusion, facilitated diffusion, or active transport? III. Osmosis IV. Endocytosis and exocytosis A. Kinds of endocytosis B. Fate of endocytotic vesicles C. Functions of exocytosis V. Epithelial transport 19