Lec-3 Membrane Transport Lecturer: Dr. Twana A. Mustafa

KEY WORDS Solvent: (relatively large amount of a substance which is the dissolving medium; in the body is water). Solute: (relatively small amount of a substance which is the dissolved substance and it dissolves in the solvent). Solution: is a homogenous mixture of a solute in a solvent. Concentration: of a solvent is the amount of solute dissolved in a specific amount of solution. Concentration gradient: difference in the concentration of a solute on two sides of a permeable membrane. Equilibrium: exact balance between 2 opposing forces. Dynamic: continuous motion or movement.

Membrane Transport Proteins Many molecules must move back and forth from inside and outside of the cell Most cannot pass through without the assistance of proteins in the membrane bilayer Private passageways for select substances Each cell has membrane has a specific set of proteins depending on the cell

Membrane Permeability Size the smaller the particle, the more permeable small molecules (O2, CO2, H2O) can large molecules (protein, DNA) cannot Lipid Solubility YES: non-polar molecules (O2, cholesterol), NO: charged atoms/molecules (Na+, Cl-, HCO3-), large polar molecules (glucose)

Ion Concentrations The maintenance of solutes on both sides of the membrane is critical to the cell Helps to keep the cell from rupturing Concentration of ions on either side varies widely Na+ and Cl- are higher outside the cell K+ is higher inside the cell Must balance the the number of positive and negative charges, both inside and outside cell

Impermeable Membranes Ions and hydrophilic molecules cannot easily pass thru the hydrophobic membrane Small and hydrophobic molecules can Must know the list to the left

2 Major Classes Carrier proteins – move the solute across the membrane by binding it on one side and transporting it to the other side Requires a conformation change Channel protein – small hydrophilic pores that allow for solutes to pass through Use diffusion to move across Also called ion channels when only ions moving

Proteins Channels, if open, will let solutes pass if they have the right size and charge Carriers require that the solute fit in the binding site Why carriers are specific like an enzyme and its substrate

Mechanisms of Transport Provided that there is a pathway, molecules move from a higher to lower concentration Doesn’t require energy Passive transport or facilitated diffusion Movement against a concentration gradient requires energy (low to high) Active transport Requires the harnessing of some energy source by the carrier protein Special types of carriers

Passive Membrane Transport Simple Diffusion movement of particles along a concentration gradient Osmosis diffusion of water across a semi-permeable membrane Facilitated Diffusion movement of particles along a concentration gradient through a carrier protein

Passive vs Active Transport

Carrier Proteins Required for almost all small organic molecules Exception – fat-soluble molecules and small uncharged molecules that can pass by simple diffusion Usually only carry one type of molecule Carriers can also be in other membranes of the cell such as the mitochondria

Facilitated Diffusion Cell Membrane Permeable Selectively Permeable 1. Relative solubility of the particle in Lipids Lipid-Soluble Permeate the Membrane: Passive Transport Diffusion Osmosis Lipid-Insoluble 2. Size of the particle Size: Less than 0.8nm in diameter Protein Channel (e.g. for NA+ , K+) Size: more than 0.8 nm in diameter Assisted Transport or Carrier-mediated Transport Active Transport Facilitated Diffusion Impermeable

Categories of Transport Across the Plasma Membrane Cell membrane is selectively permeable to some molecules and ions. Mechanisms to transport molecules and ions through the cell membrane: Passive transport: Non-carrier mediated transport. Simple Diffusion. Facilitated Diffusion: Via Carrier Channel Voltage, Chemical and Mechanical gating channel 2. Active Transport

Categories of Transport Across the Plasma Membrane May also be categorized by their energy requirements: Passive transport: Net movement down a concentration gradient does not need ATP Active transport: Net movement against a concentration gradient needs ATP

1. Simple Diffusion Diffusion is: 1. Passive. 2. Requires a concentration gradient. 3. Occurs until a dynamic equilibrium is reached. 4. Rapid over short distance, slow over long distance. 5. Increased at increased temperature. 6. Inversely related to molecular size, as molecular size increases the resistance. 7. Can occur in an open system or across a membrane.

Simple Diffusion Through Plasma Membrane Cell membrane is permeable to: Non-polar molecules (O2). Lipid soluble molecules (steroids). Small polar covalent bonds (CO2). H2O (small size, lack charge). Cell membrane impermeable to: Large polar molecules (glucose). Charged inorganic ions (Na+).

Rate of Diffusion Speed at which diffusion occurs. Dependent upon: The magnitude of concentration gradient. Driving force of diffusion. Permeability of the membrane. Neuronal plasma membrane 20 x more permeable to K+ than Na+. Temperature. Higher temperature, faster diffusion rate. Surface area of the membrane. Microvilli increase surface area.

Fick’s Law of Diffusion:  

Facilitated Diffusion Simple Diffusion Kinetic movement of molecules/ ions through membrane opening or intermolecular spaces Facilitated Diffusion A carrier protein chemically binds with the molecule/ ion and aids in its passage across the membrane

Simple Diffusion thru gated channels Protein channels are present all the way from the ECF to the ICF, thus substances can move by simple diffusion directly along these channels from one side of the membrane to the other. These channels are distinguished by 2 important features: Selective permeability of the channel Presence of gates

Gated channels in Simple Diffusion: Sodium Channels: 0.3 by 0.5 nm in diameter Negatively charged on the inside Because of the negative charges they pull the positively charged sodium ion inside, away from the water molecule. Potassium channel: 0.3 by 0.3 nm in diameter No negative charge on the inside Pull the hydrated K ion inside. As no negative charge on the inside of the channel, no attractive forces for the Na ion… also, Na ions hydrated form is far too big….

2 Facilitated Diffusion Definition: the diffusion of lipid insoluble or water soluble substance across the membrane down their concentration gradients by aid of membrane proteins (carrier or channel) Substances: K+, Na+, Ca2+, glucose, amino acid, urea etc.

2. Facilitated Diffusion 1- Facilitated diffusion via carrier 2- Facilitated diffusion through channel 2.1 Voltage-gated ion channel 2.2 Chemically-gated ion channel 2.3 Mechanically-gated ion channel 2.4 Water channel

2.1 Facilitated Diffusion via carrier Concept: Diffusion carried out by carrier protein Substance: glucose, amino acid

Passive Transport by Glucose Carrier Glucose carrier consists of a protein chain that crosses the membrane about 12 times and has at least 2 conformations – switch back and forth One conformation exposes the binding site to the outside of the cell and the other to the inside of the cell

How it Works Glucose is high outside the cell so the conformation is open to take in glucose and move it to the cytosol where the concentration is low When glucose levels are low in the blood, glucagon (hormone) triggers the breakdown of glycogen (e.g., from the liver), glucose levels are high in the cell and then the conformation moves the glucose out of the cell to the blood stream Glucose moves according to the concentration gradient across the membrane Can move only D-glucose, not mirror image L-glucose

Calcium Pumps Moves Ca2+ back into the sarcoplasmic reticulum (modified ER) in skeletal muscle

Facilitated Diffusion via Carrier Characteristics of carrier mediated diffusion: Down concentration Gradient Chemical Specificity: Carrier interact with specific molecule only. Competitive inhibition: Molecules with similar chemical structures compete for carrier site. Saturation: Vmax (transport maximum): Carrier sites have become saturated.

2.2 Facilitated diffusion through channels Definition Some transport proteins have watery spaces all the way through the molecule allow free movement of certain ions or molecules. They are called channel proteins. Diffusion carried out by protein channel is termed channel mediated diffusion.

3 Types of Channels Voltage-gated channels – controlled by membrane potential Ligand-gated channels – controlled by binding of a ligand to a membrane protein (either on the outside or the inside) Stress activated channel – controlled by mechanical force on the cell

Voltage-gated Channel The molecular conformation of the gate responds to the electrical potential across the cell membrane this type of channel is called voltage gate (or dependent) channel.

Electrochemical Gradient This gradient determines the direction of the solute during passive transport

Ligand-Gated Channel Example: Na+-K+ gated channel Closed when a neurotransmitter is not bound to the extracellular receptor Open when a neurotransmitter is attached to the receptor - Na+ enters the cell and K+ exits the cell

Ligand-Operated ACh Channels Ion channel runs through receptor. Receptor has 5 polypeptide subunits that enclose ion channel. 2 subunits contain ACh binding sites. Channel opens when both sites bind to ACh. Permits diffusion of Na+ into and K+ out of postsynaptic cell. Inward flow of Na+ dominates . Produces EPSPs.

2.3 Mechanically-gated channel Some protein channel gates may be opened by the mechanical deformation of the cell membrane. mechanically-gated channel. It plays a very important role in the genesis of excitation of the hair cells

Auditory Hair Cells Stress activated Sound waves cause the stereocilia to tilt and this causes the channels to open and transport signal to the brain Hair cells to auditory nerve to brain

OSMOSIS Here, we see pure water separated from a solution containing a solute (e.g. Sodium chloride) by a semi-permeable membrane. The membrane is impermeable to the solute but permeable to water. The water diffuses from the left to the right side and the level rises. It dilutes the solution in the right side of the beaker.

OSMOSIS Definition: The diffusion of water down its concentration gradient (that is, an area of higher water concentration to an area of lower water concentration) thru a semi-permeable membrane is called Osmosis. Concept: Because solutions are always referred to in terms of concentration of solute, water moves by osmosis to the area of higher solute concentration. Despite the impression that the solutes are “pulling,” or attracting, water, osmosis is nothing more than diffusion of water down its own concentration gradient across the membrane.

Here in Fig. A, we see a dilute soln Here in Fig. A, we see a dilute soln. (with less solute) separated from a concentrated soln. (with more solute) by a semi-permeable membrane. The membrane is permeable to water, but not so much to the solute. What will happen? The solvent which is the water will move from the dilute solution to the concentrated solution. Thus, the net movement occurs from left to right.

Osmotic pressure and Hydrostatic pressure…. Hydrostatic pressure is the pressure exerted by a stationary or standing fluid on an object (which in this case is the membrane). The hydrostatic pressure exerted by the larger water column after osmosis is greater than the hydrostatic pressure exerted by the shorter column. The net movement of water by osmosis continues till the osmotic pressure exactly equals the hydrostatic pressure. In simpler words, Osmotic pressure is a “PULLING” pressure that pulls water into the solution whereas Hydrostatic pressure is the “PUSHING” pressure that pushes the water out of the solution.

Osmotic pressure: is the pressure that is required to stop osmosis Osmotic pressure: is the pressure that is required to stop osmosis. It is the pressure necessary to prevent osmosis into a given solution when the solution is separated from the pure solvent by a semipermeable membrane. The greater the solute conc. of a solution, the greater its osmotic pressure. (HYDROSTATIC PRESSURE = OSMOTIC PRESSURE) An osmole is one mole of dissolved particles in a solution. E.g. glucose when dissolved in solution does not dissociate, so 1 mole of glucose is also 1 osmole of glucose. On the other hand, NaCl dissociates into 2 ions (Na and Cl) so is taken as 2 moles. Osmolarity is the number of osmoles of solute per liter of solution. Simply put, osmolarity is a measure of total solute conc. given in terms of number of particles of the solute in 1 liter of solution. The osmolarity of body fluids is usually expressed in milliosmoles per liter (mOsm/L). (The normal osmolarity of body fluid is 300 mOsm.) It is usually employed in clinical settings. Osmolality is the number of milliosmoles of solute per kg of solvent. It is usually calculated in laboratories using an osmometer.

NO NET MOVEMENT OF H2O (equal amounts entering & leaving) The Plasma Membrane 4/26/2017 Isotonic Solution Hypotonic Solution Hypertonic Solution NO NET MOVEMENT OF H2O (equal amounts entering & leaving) CYTOLYSIS PLASMOLYSIS copyright cmassengale G. Podgorski, Biol. 1010

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