L3 Transport Mechanisms PDF

TRANSPORT MECHANISMS Dr. Rasha Eldeeb Associate Professor of Physiology September 4, 2024 1 www.gmu.ac.ae COLLEGE OF PHARMACY  TR...

TRANSPORT MECHANISMS Dr. Rasha Eldeeb Associate Professor of Physiology September 4, 2024 1 www.gmu.ac.ae COLLEGE OF PHARMACY  TRANSPORT MECHANISMS Learning Objectives: Enlist the different types of transport mechanisms existing across the cell membrane Explain the mechanism of each transport mechanism; passive transport and active transport Explain the differences in their function. Discuss their physiological importance  TRANSPORT MECHANISMS Solutes (e.g. ions, glucose, gases …… etc) can cross the cell membrane by: ▪ Diffusion: either simple or facilitated ▪ Active transport: either primary or secondary ▪ Endocytosis and exocytosis Solvents (e.g. H2O) can pass across the cell membrane by: ▪ Filtration ▪ Osmosis  Diffusion It is a passive process substance in a solution (or gas) that expands to occupy all the available volume. The kinetic motion of the molecules produces it, and it occurs in the direction of their concentration (= chemical) i.e. from areas of high concentration to regions of lower concentration. It depends on the: – molecular size – lipid solubility – charge of the substance. Generally, diffusion across cell membranes can be divided into 2 main types: ▪ Simple diffusion ▪ Facilitated diffusion  Simple Diffusion It occurs through the lipid bilayer. The following substances can diffuse through the lipid bilayer of cell membranes: ❖ Lipid-soluble substances (e.g. O2, N2 and alcohols) ❖ Water ❖ Small uncharged water-soluble molecules (which cross the lipid bilayer along with water molecules) e.g. CO2 (which is also lipid soluble). Factors Affecting Diffusion o Diffusion is directly related to: o Lipid solubility o Concentration gradient o Surface area o Temperature o Diffusion is inversely related to: o Thickness of the membrane o Molecular weight  Facilitated Diffusion This mechanism moves substances passively in the direction of their chemical (concentration) gradient, but it requires a type of transport protein in the cell membranes called carrier proteins (so it is also called carrier-mediated diffusion). The molecules of substances that diffuse by this mechanism (e.g. glucose and most amino acids) In many sites, facilitated diffusion is regulated by hormones e.g. insulin can increase the rate of glucose diffusion into the cells 10-20 folds. Types: ▪ If the carrier transports only one molecule, it is called uniport [e. g. glucose transporters (GLUT1, GLUT2,….) ▪ If the carrier transports two molecules (Cotransport) in the same direction it is called symport e.g. Na-dependent glucose transport ▪ If the carrier transports two molecules (Cotransport) in opposite directions, it is called antiport (Counter transport) e.g. Cl-/HCO3- exchange.  Characters of facilitated diffusion: ▪ It needs a carrier protein ▪ Specificity: each carrier is specific for one or a few substances. ▪ Competitive inhibition: similar molecules compete with each other for the same carrier. ▪ Saturation: as the concentration of the substance increases, the rate of facilitated diffusion increases up to a maximum due to saturation of all carriers. Simple diffusion has no maximum level as it does not need such a carrier. Remember  Primary Active Transport It is the transport of substances against their electrical or concentration gradients (i.e. from a lower to a higher concentration. It requires: – Specific carrier proteins – Energy (provided only by hydrolysis of ATP) Examples: – Na+ - K+ pump (Na+/K+ ATPase) – Ca2+ pump – H+ pump (proton pump).  Na+ - K+ pump In the cell membrane, there are carrier proteins that have: – Three receptor sites for Na+ from inside – Two receptor sites K+ from outside. – The inside part (near mitochondria) has ATPase activity. So, three Na+ ions will bind to the carrier from inside, while two K+ ions will bind from outside. This will activate the ATPase carrier leading to hydrolysis of ATP liberating the energy. This energy causes configuration change in the carriers pushing Na+ to outside and K+ to inside the cell [i.e. it has a coupling ratio of 3/2]. Function of Na+ - K+ pump: – Electrogenic pump; creates more positivity outside the cell (and more negativity inside). – Controls the cell volume.  Secondary Active Transport It is the cotransport of Na+ down its electrochemical gradient (created by the primary active transport) and another substance (e.g. glucose or amino acids) by a carrier protein (symport). Example: Sodium-dependent glucose transport (glucose absorption in the intestine and glucose reabsorption in the kidney).  Characteristics: ▪Transport of two or more solutes is coupled. ▪One of the solutes (usually Na+) is transported downhill and this provides energy for uphill transport of the other. ▪Metabolic energy is not provided directly, but indirectly from the Na+ gradient which is maintained across the cell membrane. So, inhibition of Na+-K+ ATPase will decrease Na+ transport decreasing Na+ gradient and inhibiting secondary active transport.  Endocytosis and Exocytosis Both pinocytosis and phagocytosis are called Endocytosis. Pinocytosis (Cell Drinking): This is a transport mechanism by which large particles. The particle at first contacts the cell membrane, then, the latter is depressed, and, on each side, it rises and folds over the particle (which will thus become a vacuole inside the cytoplasm, the wall of which is made of a part of the cell membrane). Phagocytosis (Cell Eating) It is a process by which bacteria and dead tissue are engulfed by cells, and ingested. Exocytosis (Cell Vomiting): This is the reverse of endocytosis. The membrane of the granule or vesicle fuses with the cell membrane, then the area of fusion breaks down and its contents are expelled outside the cell while the cell membrane remains intact. Remember  Filtration Filtration is the passive movement of water through a porous membrane due to a difference in hydrostatic pressure on the two sides of the membrane [e.g. formation of interstitial (tissue) fluid through the capillary membrane and glomerular filtrate in nephrons]. The amount of fluid filtered per time unit is directly proportional to the: ▪ Pressure gradient ▪ Surface area of the membrane ▪ Membrane permeability ▪ Dissolved molecules (solutes) with smaller diameters than the pores pass with the filtered fluid.  Osmosis Osmosis is the passive movement of water through a semipermeable membrane from an area containing pure water or a diluted solution of a solute (NaCl or glucose) to an area in which there is a higher concentration of solute (the membrane is impermeable to the solute and permeable to the solvent). The pressure required to apply the concentrated solution to prevent water movement from the diluted solution is called the osmotic pressure. The amount of osmotic pressure is directly proportional to the number of particles per unit volume of solution. So, ionizing solutes (e.g. NaCl) are more osmotically active (because each ion is active by itself) than non-ionizable solutes (e.g. glucose). The osmotic pressure is expressed in osmoles or milliosmoles which can be converted to mmHg, since one milliosmole = about 19.3 mmHg.  The osmolarity of a certain solution is the number of osmoles per liter of this solution, while its osmolality is the number of osmoles per kilogram of solvent. In the body, the osmotically-active substances are dissolved in water (= solvent), and are usually measured and are expressed in milliosmoles per liter of water (since water density is 1). All body fluids have the same osmolality =290 milliosmoles/liter. Solutions that have an osmolality equal to that of the plasma are called isotonic solutions, while those having a higher osmolality are hypertonic, and those having a lower osmolality are hypotonic. A 0.9% NaCl solution is isotonic with the plasma and is known as the isotonic (or physiological) saline solution. Remember https://www.menti.com/al6wv7q36ahv Learning Resources: 1. Marieb EN. Human Anatomy and Physiology, 9th Edition, Pearson International Edition; 2014. ISBN-13: 978-1-2920-2649-7 2. Guyton, Arthur C. Textbook of medical physiology / Arthur C. Guyton, John E. Hall.—11th ed. 3. Ganong's Review of Medical Physiology/Kim E. Barrett, Susan M. Barman, Scott Boitano and Heddwen L.Brooks,23rd ed. 4. Instructional Web site 5. Lecture PDF on Moodle 6. https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780702031144000026  DISCLAMER The contents of this presentation, can be used only for the purpose of a Lecture, Scientific meeting or Research presentation at Gulf Medical University, Ajman. www.gmu.ac.ae