MEMBRANE TRANSPORT .pdf

MEMBRANE TRANSPORT Friday, September 15, 2023 10:46 AM MEMBRANE TRANSPORT UNASSISTED MEMBRANE T...

MEMBRANE TRANSPORT Friday, September 15, 2023 10:46 AM MEMBRANE TRANSPORT UNASSISTED MEMBRANE TRANSPORT ASSISTED MEMBRANE TRANSPORT Reminder CARRIER-MEDIATED TRASNPORT - TWO FOMRS: ACTIVE OR PASSVE TRANSPORT → Notions of membrane permeability, membrane impermeability, and selective permeability - Water moves to where there is less concentration of water ( concentration gradient) → Two properties influence whether a substance can permeate the plasma membrane without any assistance: - Solute moves to where there is more solute → Active transport: → Relative solubility of the particle in lipid - more soluble to lipids = the easier it is to cross ○ Also requires a carrier protein ○ Uncharged or nonpolar molecules TONICITY ○ Expends energy § O2, CO2, fatty acids = highly lipid-soluble = easy permeate the plasma membrane ○ Transfer its passenger "uphill" against a concentration gradient ○ Charged or polar molecules → Def: the effect the solution has on cell volume ○ Saturation, competition, and specificity still applies to active transport → The tonicity of the solution is determined by the concentration of the solution in nonpenetrating solute ( the penetrating ones are rapidly ○ Concentration gradient follows the direction of glucose in low to high concentration § Ions, proteins and glucose = low lipid solubility and very soluble in water = it cant cross freely, equally distributed between ECF and ICF) → Self notes: requires assistance ○ Nonpenetrating solute can't cross the membrane on its own ○ For active transport, molecules move against its gradient □ Ions need a channel □ Proteins and such are too large for channels so they need assisted transport ○ The carrier changes shape to make the molecule bind to it and use ATP to do so but returns to its original shape for free → Demonstration of tonicity: ○ Affinity is the attraction b/w molecules → Size of the particle ○ Drop a cell into a test tube with a solute / solution § The stronger the affinity the stronger the bind / attraction, vice versa ○ Small and lipid soluble = fast crossover ○ The amount of solution can affect the size/volume of the cell § You want to make the affinity high where the concentration is low bc were going AGASINT the gradient Going through the membrane (lipid-soluble) or through a channel requires forces to induce the movement ○ Water in a cell will be forced to leave or enter the cell § At high concentration you lower the affinity to prevent the molecule to go out → → Forces that require the cell to expend energy = active forces § Changing affinity requires ATP → Tonicity reactions → Those that do no require the cell to spend energy = passive forces Example of equal equilibrium ○ Isotonic solutions hypotonic solutions hypertonic solution PRIMARY ACTIVE TRANSPORT: ○ Ex: Passage of oxygen ○ Has energy but doesn't need a force ○ Tend to swell the cell → Energy (ATP) is directly required to move a substance against its concentration gradient ○ Results in a constant cell ○ Tend to shrink the cell UNASSISTED MEMBRANE TRANSPORT ○ Water goes into cell → Carrier's binding sites have a greater affinity for the passenger ion on the low-concentration side where the ion is picked up and a volume ○ Water leaves the cell ○ Less water inside cell lower affinity on the high-concentration side where the ion is dropped off ○ Stays the same ○ More solute in the cell → Molecules that can penetrate the plasma membrane on their own = passively driven across the membrane by ○ More solute in the cell = water → Carrier site has a ATP enzyme called ATPase ○ No net movement but ○ Water is more concentrated in two force: there is still movement moves into cell the cell so they leave to where These carriers are often called pumps (act as enzymes with ATPase activity) ○ Diffusion down a concentration / chemical gradient - when 1 side is more concentrated (by amount) → jus no NET movement its less concentrated than the other → Two types that always transport ions: ○ More solute outside the cell = ○ Movement along an electrical gradient - charge gradient, high electrical gradient pulls onto the least 1. Single type of passenger (i.e., H+ pump or Ca2+ pump) less water - Concentration goes from low to high electrical side 1. Passive diffusion of particles 2. Na+ - K+ pumps involves the transfer of two different substances either simultaneously in the same direction of sequentially in ○ Molecules are in continuous random motion opposite directions ○ Tend to become evenly distributed over time (i.e. steady state or equilibrium) - More Na outside than inside This creates potential for electrical impulses § Equilibrium - even distribution of molecules B/c molecule movement happens - More K+ inside than outside § Dynamic equilibrium - molecules move equally from one side to another equally b/w areas ○ Known as diffusion NA+ -K+ ATPASE PUMPS (NA+ -K+ PUMP) § Concentration gradient (chemical) § Net diffusion → Passive diffusion and plasma membrane: PICTURE DESCRIPTION: ○ Net diffusion and movement of molecules down the concentration gradient (from high to low OSMOLARITY concentration) 1. Pump is open to inside of the cell ○ Passive mechanism → Def: the measure of solute concentration per unit volume of solvent ○ Affinity is high for sodium and low for potassium so only sodium § No energy required → Its not the same as tonicity! Osmolarity takes into account ALL of the solute concentrations (penetrating and nonpenetrating solutes) ○ Ex: oxygen transport across lung membrane ions can bind ○ Na has 3 pockets → Osmolarity reactions: ○ K has 2 pockets Type of reaction Description Image 2. ATP is used to change conformation Iso-osmotic ○ no net movement of water, no ○ ATPase converts ATP into ADP and a single phosphate → Bc the substance is permeable it can change in cell volume ○ That phosphate binds to the carrier cross over ○ If the osmolarity of the solution is 3. Pump is facing the ECF → Can travel in both directions but equal to the osmolarity of the cell ○ Pocket changes to low affinity to sodium and high affinity for K moving to the least concentrated side 4. K ions bind to its pocket → Force is present occurs more slowly 5. The phosphate that was binded is now released once the K ions are → The wall bounces the solute molecule off → When it reaches steady equilibrium bounded and the pump opens to the IFC bc its in its original molecules from both sides cross evenly conformation 6. The K ions leave The affinity for Na increase again Returning to step 1 Hypo-osmotic ○ Water diffuses into cells; cell swells ADDITIONAL NOTES: ○ If the osmolarity of the solution is lower than the osmolarity of the FICK'S LAW OF DIFFUSION → A single nerve cell membrane contains ≈ 1 million Na+ -K+ pumps cell capable of transporting ≈ 200 million ions per second → The collective influence of factors on the rate of net diffusion of a substance across a membrane → Establishes NA+ & K+ concentration gradients across plasma membrane → Factors: → Also indirectly serves as the energy source for secondary active ○ The magnitude (or steepness) of the concentration gradient transport § The higher the gradient (concentration) the faster the rate of diffusion ○ The surface area of the membrane across which diffusion is taking place Hyper-osmotic ○ Water diffuses out of the cell; cell § Size: the larger the membrane the more molecules can cross shrink ○ The lipid solubility weight of the substance ○ If the osmolarity of the solution is § Solubility: the more non-polar the faster it crosses higher than the osmolarity of the ○ Weight: size of the molecules matters cell SECONDARY ACTIVE TRANSPORT § Big = slower , small = faster ○ The distance through which diffusion must take place → Energy is required in the entire process but is NOT DIRECTLY required to run the pu;llmp (NO ATP is used directly by pump) § Thickness of membrane: thicker = slow , thinner = fast → Uses "secondhand" energy stored in the form of Na ion (e.g. Na+) concentration gradient to move the cotransporter molecule uphill □ Thin membranes can be found in red blood cells for the diffusion of oxygen → Called transporters not pumps 2. Passive diffusion of ions → The transporters that are going to allow the other molecules to go against its → Ions are electrically charged: in addition to concentration gradients (chemical), their movement is affected by CALCULATING OSMOLARITY AND TONICITY gradient will not use ATP directly → ATP was used earlier to build the sodium potential from a different pump their electrical charge → Ions with like charges repel each other, whereas those with opposite charges attract each other (positively → Ion forming compounds; osmolarity > solutions molarity! → Most transporters use sodium to co-transport a molecule ○ Compounds can form ions but dissolve in a general solution / water → Moving something against its gradient requires a pump = primary transport charged = cations, negatively charged = anions ) → A difference in charge b/w two adjacent areas thus produces an electrical gradient → Osmolarity ( osmol / L ) involves total amount of solutes present → Moving something (ex: sodium) down its gradient generates energy that can → The combinatorial effect of the concentration and electrical gradients on the ion forms the electrochemical → Molarity ( mol /L ) involves concentration of the compound as a whole be used to transport another molecule: either in the same or opposite gradient - a mix of both kinds of pulls / forces direction w Note that these gradients, for a given ion, can be working in the same direction, or in opposing directions → Concept to understand: ○ You have one compound that dissociates into 2 different ions that are both nonpenetrating solutes → Two types: Osmosis ○ Each solute creates its own osmotic pressure b/c each ion will create a movement of water 1. Symport / cotransport = the solute and Na+ move through the membrane 3. ○ Osmolarity doubles the amount in the same direction → Osmosis - the net diffusion of water ○ If a solute does not form then the osmolarity of it remains the same 2. Antiport / counter - transport = the solute and Na+ move through the → Water can readily permeate the plasma membrane membrane in opposite directions ○ Can slip between the phospholipid molecules → Example (1): ○ Or through specific water channels called Aquaporins (up to one billion molecules / sec) ○ If NaCl concentration is 200 mmol/L (nM) at the start -> upon the dissociation in water -> molarity remains 200 nM but osmolarity → "concentration" usually refers to the density of a solute (dissolved substance) in a given volume of water. increases to 400 mosmol / L. we have to consider the total number of solutes in solution (.e., the separated ions: 200 mosmol / L of Na+ Adding a solute to pure water decreases the water concentration. In general, one molecule of a solute and 200 mosmol / L of Cl- displaces one molecule of water → Example (2): ○ 1 cell is 300 mOsm. It goes into a solution with KCl that is 150 mmol and Urea that is 50 mmol → Osmosis - movement of water when a selectively permeable membrane separates two unequal solute ○ The osmolarity would be 350 = 350 hypertonic concentrations (and unequal water concentration) § 150 from K → This net diffusion of water is OSMOSIS § 150 from Cl § 50 from Urea Picture description: ○ The tonicity would be 300 = 300 isotonic Picture description: § Urea is not included bc it’s a penetrating solute → Solubility is NOT absolute → Water molecules will move passively → Water molecule movement is governed from high water concentration (low ASSISTED MEMBRANE TRANSPORT by concentration of water solute concentration) towards low water concentration (high solute → Large poorly lipid-soluble molecules can not cross the plasma membrane on their own (some of these molecules are essential nutrients; e.g. concentration) glucose) → The reason why some molecules can’t cross the membrane is bc its water soluble ( does not dissolve in water) → Two different mechanisms: ○ Carrier-mediated transport (for small water-soluble molecules) § Found on the membrane ○ Vesicular transport (larger molecules and multi-molecular particles) § Ex: bacteria, large vesicles that contain large proteins, iron and insulin CARRIER-MEDIATED TRANSPORT OSMOSIS WITH UNEQUAL CONCENTRATIONS OF A PENETRATING OR NON-PENETRATING SOLUTE → Carrier proteins span the plasma membrane - assist molecule to cross , no energy is needed if it goes down its gradient → They can reverse shape so binding sites are alternately exposed to the ECF and ICF (flip-flops) and can open from ither side → Three important characteristics: 1. Specificity = amino acids cannot bind to glucose carriers, carriers are specific to its own substance Picture description: 2. Saturation = limited number of carrier binding sites, not all molecules can leave / enter at the same time 3. Competition = closely related compounds compete for access, multiple compounds are suitable for the same carrier = first come first ○ In this situation only water can pass through the serve membrane → Carrier-mediated transporters have a pocket that the substrate / particle can bind to ○ Solute stays on its side ○ Bc there is less concentration of water on side 2, → Protein recap: water from side 1 will move towards its ○ Proteins are made up of amino acids concentration gradient ○ Have a primary. Secondary, and tertiary structure of folding ○ When the water passes through, the volume of ○ Have a core and sidechain ( R group) side 2 increases ○ Sidechains can be hydrophilic or hydrophobic ○ Volume changes until the concentration of water § The hydrophobic part will be crossing the membrane interacting with the lipid portion is equal on both sides § The hydrophilic part has a charge that face the water on the ECF side of the cell ○ Water will continue to cross with no net diffusion CARRIER-MEDIATED TRANSPORT - TWO FORMS: ACTIVE OR PASSIVE TRANSPORT → Active: required to spend energy in the form of ATP → Passive: do not require to spend energy → Facilitated diffusion: uses a carrier molecule to facilitate (assist) the transfer of a substance across the membrane from high to low concentrating (downhill) ○ Passive process = does not require energy OSMOSIS WITH A MEMBRANE SEPERATING PURE WATER FROM A SOLUTION OF NON-PENETRATING SOLUTE ○ Occurs naturally down a concentration gradient ○ Rate is limited by saturation of the carrier binding sites → Osmotic pressure - of a solution ( "a pulling" pressure) of a measure of the tendency for water to move into ○ e/g/: glucose is transported into the cells from the blood stream through GLUTs that solution b/c of the concentration of non-penetrating solutes and water → Passive diffusion does not require energy but needs a force which is the concentration gradient → Hydrostatic (fluid) pressure - is the pressure exerted by a standing, or stationary, fluid on an object-in this → Example: glucose case, the membrane ○ Pushing down on the movement of water § When the pressure is equal to the osmotic pressure that's when you reach equilibrium Picture description: 1. Glucose concentration is more concentrated in the ECF and the carrier protein is facing outside 2. The solute binds to the binding site and after that there is a conformational change of the carrier protein where it changes shape for the pocket to flip to the inside of the cell 3. Bc of the low concentration inside the cell, the molecule will be released automatically 4. Carrier protein flips back to the outside and the cycle continues → Can never reach equilibrium of water b/c side 2 is tainted, not pure TRANSPORT MAXIMUM → Comparison of carrier-mediated transport and simple diffusion down a concentration gradient