Membrane Transport PDF

Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester:1 Module: Human Body Function (HBF) 102 20/11/2024 HBF - 102 1 Cell membrane signaling (channels) By: Dr. Ayman Saied Soliman Ass. Professor – Faculty of Medicine – Beni Suef University Department: Medical Physiology 20/11/2024 11/21/2024 HBF - 102 2 2 Objectives 1.Describe cell structure and function with special emphasis on cell membrane. 2.Define lipid and membrane proteins and its contribution to cell function. 3.List types of membrane proteins and describe characteristics of each marker, attachment, transport, receptor, enzyme 4.Define mechanisms involved in cell signaling. 20/11/2024 HBF - 102 3 3 Introduction - The cell is the structural unit of various tissues and organs in the human body. - It consists of a mass of protoplasm surrounded by the cell membrane. - The protoplasm includes: 1- The cytoplasm 2- The cell organelles 3- The nucleus 20/11/2024 HBF - 102 4 4 Introduction - The structure of the cell varies markedly according to the function it performs. - This is known as cell specialization. 20/11/2024 HBF - 102 5 5 Structure of the Cell Membrane 20/11/2024 HBF - 102 6 Structure of the Cell Membrane 20/11/2024 HBF - 102 7 Structure of the Cell Membrane  The cell membrane surrounds the cell completely.  It is a very thin, elastic & semipermeable membrane.  It is 7.5-10 nanometer thick (nanometer=10-9 meter)  It is composed mainly of proteins and lipids  The membranes are dynamic structures, and their constituents are being constantly renewed at different rates. 20/11/2024 HBF - 102 8 Structure of the Cell Membrane  Under the electron microscope, the basic structure of cell membrane is a lipid bilayer, only 2 molecules of phospholipids thick with globular masses of membrane proteins.  The lipid bilayer is for the flexibility and selective permeability of the cell membrane. 20/11/2024 HBF - 102 9 Structure of the Cell Membrane  The cholesterol molecules affect the permeability of the membrane and give toughness to it.  The membrane carbohydrates occur in the form of glycoproteins and glycolipids. as recognition sites & attach cells together. 20/11/2024 HBF - 102 10 Functions of cell membrane proteins: 1) Structural proteins: They keep the integrity of the membrane and give it strength. 2) Form passive channels: They form protein channels with various diameters, various shapes and electric charges along their surfaces. 20/11/2024 HBF - 102 11 Functions of cell membrane proteins: They are classified according to presence or absence of gates into: i. Non-gated channels ---- open all the time. ii. Gated channels ---- closed during rest by a part of the protein molecule. 20/11/2024 HBF - 102 12 Functions of cell membrane proteins: These gated channels are either: - a)Voltage gated: They open or close when the membrane potential is changed. b)Ligand gated: They open or close when a ligand binds a specific receptor on the cell membrane. 20/11/2024 HBF - 102 13 Functions of cell membrane proteins: 3. Carriers in facilitated diffusion:  For large molecules passively e.g. facilitated diffusion of glucose.  They bind the molecule and then change their configuration, moving the bound molecule from one side of the cell membrane to the other. 20/11/2024 HBF - 102 14 Functions of cell membrane proteins: 4. Carriers in active transport (= Pumps): This form of transport requires energy as it transports substances against their electrical and chemical gradients. 20/11/2024 HBF - 102 15 Functions of cell membrane proteins: 3 types of carriers in active transport 20/11/2024 HBF - 102 16 Functions of cell membrane proteins: They are of 3 types: a)Uniport: this is a carrier that transports one substance in one direction e.g., Ca++ b)Symport: this is a carrier that transports two substances simultaneously in the same direction, e.g., carriers of glucose and Na+ from the intestinal lumen to inside of the cell. 20/11/2024 HBF - 102 17 Functions of cell membrane proteins: c) Antiport: this is a carrier that transports one substance in one direction and another substance in the opposite direction e.g., Na+ - K+ pump  N.B.: Symport and Antiport are called Cotransport carriers. 20/11/2024 HBF - 102 18 Functions of cell membrane proteins: 5. Receptors:  These are proteins or glycoproteins present mainly on outer cell membrane.  They are inactive during rest, but when they combine with their specific ligand (neurotransmitter, drug or hormone) they become activate and start a series of cellular reactions to stimulate or inhibit a certain cellular function. 20/11/2024 HBF - 102 19 Functions of cell membrane proteins: The number and sensitivity of the receptors may change: a)Down regulation: When a ligand is present in excess, the number of the receptors for this ligand decreases and the sensitivity to the ligand also decreases. b)Up regulation: When a ligand is deficient, the number of receptors for this ligand increases. 20/11/2024 HBF - 102 20 Functions of cell membrane proteins: 6. Enzymes: They are present mainly on the inner surface of cell membrane to catalyze certain reactions. 20/11/2024 HBF - 102 21 Functions of cell membrane proteins: 7. Identity proteins: They are mostly glycoproteins which give the cells the individual label of identity, so that they would not be attacked by the immune system. 20/11/2024 HBF - 102 22 Functions of cell membrane proteins: 8. Intercellular connections: 20/11/2024 HBF - 102 23 Functions of cell membrane proteins: I- Binding junctions: Bind cells together to make strong tissues. These include: i. Tight junctions:  ridges project from certain cells and adhere strongly to similar ridges from neighboring cells.  The intercellular space is obliterated. 20/11/2024 HBF - 102 24 Functions of cell membrane proteins: i. Tight junctions: 20/11/2024 HBF - 102 25 Functions of cell membrane proteins: I- Binding junctions: ii. Desmosomes:  There is thickening of the membranes on two opposite cells.  They are connected with fibrils bridging the intercellular space. 20/11/2024 HBF - 102 26 Functions of cell membrane proteins: ii. Desmosomes: 20/11/2024 HBF - 102 27 Functions of cell membrane proteins: II- Channel junctions (=Gap junctions): 20/11/2024 HBF - 102 28 Functions of cell membrane proteins: II- Channel junctions (=Gap junctions): 1) These are channels running across the intercellular space connecting one cell to another. 2) They allow the rapid passage of ions and other substances with molecular weight up to 1000 between cells without entering the intercellular space. 20/11/2024 HBF - 102 29 Functions of cell membrane proteins: II- Channel junctions (=Gap junctions): 3) This permits the rapid propagation of electrical activity from one cell membrane to another. 4) At these junctions, hexagonal arrangement of protein units to form what is called "connexon" surrounding a channel that will be in line with the channel in corresponding connexon in the adjacent cell. 20/11/2024 HBF - 102 30 Functions of cell membrane proteins: II- Channel junctions (=Gap junctions): 5) Intracellular Ca++, pH, hormones and drugs regulate the diameter of the channel. 20/11/2024 HBF - 102 31 Functions of cell membrane proteins: 9. Cell adhesion molecules:  They are formed of proteins responsible for adhesions of the cells to basal lamina and to each other.  They are important in embryonic development of nervous system, in inflammation, wound healing and in the metastasis of tumors. 20/11/2024 HBF - 102 32 Functions of cell membrane proteins: 10.Fixation of parts of the cytoskeleton of the cell:  The cytoskeleton is a system of fibers that maintains the structure of the cell and permits it to change shape and move.  It is made up of microtubules, intermediate filaments and microfilaments. 20/11/2024 HBF - 102 33 Intercellular communications 20/11/2024 HBF - 102 34 Intercellular communications A.Cells communicate with each other via chemical messengers through three main types of communication: 1)Intercellular Gap Junctions: a chemical substance passes directly from cell to cell. 2)Neural: neurotransmitters are released from one neuron across synaptic clefts which exist between contiguous nerve cells. 20/11/2024 HBF - 102 35 Intercellular communications 3)Endocrine communication: Certain cells secrete chemical hormone.  The hormone reaches the cells over long distance via the blood stream.  The hormone may reach the cells nearly through distance via its diffusion in ISF, this is: paracrine communication.  The hormone may act directly on the cell that produces it; this is autocrine communication. 20/11/2024 HBF - 102 36 Intercellular communications B. The chemical messengers will bind with specific receptors present in the cell membrane, in the cytoplasm or in the nucleus. 20/11/2024 HBF - 102 37 Intercellular communications C. The mechanisms by which chemical messengers exert their intracellular effects may be through: 1)Opening of certain channels. 2)Activation of adenyl cyclase enzyme which catalyzes the conversion of ATP to cyclic AMP. 3)Increase the concentration of free Ca++ in the cytoplasm. 20/11/2024 HBF - 102 38 Interactive Question Connexin is an important component of the: A.Sarcoplasmic reticulum. B.Microtubule. C.Gap junction. D.Synaptic vesicle. E.Sodium channel. 20/11/2024 HBF - 102 39 39 Summary 1) The cell is the structural unit of various tissues and organs in the human body. 2) The structure of the cell varies markedly according to the function it performs. 3) The cell membrane surrounds the cell completely. 4) The lipid bilayer is for the flexibility and selective permeability of the cell membrane. 5) 10 Functions of cell membrane proteins 6) Intercellular communications 20/11/2024 HBF - 102 40 40 References 1) GUYTON AND HALL: TEEXT BOOK OF MEDICAL PHYSIOLOGY: 14th. Edition; Philadelphia: Elsevier, Inc.,2020. 2) Staff Members of Physiology Department: Medical physiology books; Faculty of Medicine – Cairo University, 2016. 3) Barerett KE et al.: Ganong's Review of Medical Physiology: 26th. Edition; New York: The McGraw- Hill companies, 2019. 4) Linda S. Costanzo, : BRS Physiology Seventh Edition. 20/11/2024 HBF - 102 41 41 Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester:1 Module: Human Body Function (HBF) 102 PASSIVE TRANSPORT By: ASHRAF ALGENDY PROFESSOR Department: MEDICAL PHYSIOLOGY 11/23/2024 2 2 OBJECTIVES At the end of the lecture you will be able to:  Clarify the importance of biological transport.  List biological membranes that encircle different compartments of the body fluid.  List different types of transport.  List and describe different types of passive transport.  Describe different types of passive transport. 23/11/2024 HBF - 102 3 Introduction Importance of transport 1- It supplies the tissues with oxygen and nutrients 2- It removes waste products and carbon dioxide. 3- It is a way of communication between different tissues. Introduction Importance of transport 4- Immunity. 5- Secretory products have essential physiological function. Introduction Transport in our body occurs through two type of membrane: 1-Capillary 2-Cell membrane membrane between between ICF and plasma and tissue ISF fluid(ISF). 11/23/2024 Helwan Special Medical Program 8 11/23/2024 Helwan Special Medical Program 9 Transport passive active does not need energy Need energy Mostly uphill Down hill transport transport pass from high concentration Pass from low concentration to to low concentration high concentration Passive transport Passive transport -It does not need energy -The substances pass from high concentration to low concentration -Down hill transport. Passive transport Passive transport Simple diffusion Facilitated diffusion osmosis Filtration( bulk flow) Solvent drag Passive transport diffusion Diffusion -It is ability of substance to expand to fill available space or it is ability of substances to pass from high concentration to low concentration. -Down hill transport. -It does not need energy Passive transport diffusion Diffusion simple Facilitated Does not need energy Does not need carrier Need carrier Passive Transport simple diffusion Simple Diffusion The main force of simple diffusion is a random thermal motion that result from self kinetic energy Passive Transport simple diffusion Simple Diffusion Transport of lipid soluble substance through lipid bilayer Transport of small uncharged lipid insoluble substance through lipid bilayer Transport of ions through channels. Transport across cell membrane through channel Question: Which of the following substance can pass through cell membrane by simple diffusion: a. CO2. b. Glucose. c. Amino acids. d. Protein. e. Poly peptide hormones. Passive Transport facilitated diffusion Facilitated Diffusion Transport of glucose across cell membrane using glucose transporters Transport of amino acid across cell membrane using amino acid transporters Transport of urea across cell membrane using urea transporter Passive transport facilitated diffusion Criteria Of Facilitated Diffusion Saturation Stereo specificity competition Passive transport facilitated diffusion Criteria Of Facilitated Diffusion Saturation stereo specificity competition Passive Transport Criteria of Facilitated Diffusion Saturation : a carrier has a limited number of binding site for solute Saturation has TRANSPORT MAXIMUM Passive transport facilitated diffusion Criteria Of Facilitated Diffusion saturation Stereo specificity competition Passive Transport Criteria of Facilitated Diffusion Stereo specificity: each carrier is specific for certain substance or even to certain isomer of molecule Passive Transport Criteria of Facilitated Diffusion Glucose carrier transport glucose only and cannot transport amino acid. Glucose transporter in renal proximal convoluted tubule transport only D-isomer (natural) of glucose. In contrast it is not able to transport L-isomer of glucose(unnatural). Passive transport facilitated diffusion Criteria Of Facilitated Diffusion saturation stereo specificity competition Passive Transport Criteria of Facilitated Diffusion competition: the specific site of certain molecule on a carrier could be occupied by another chemically related substance. Later substance could inhibit the transport of original molecule Passive Transport Criteria of Facilitated Diffusion competition: the specific site of certain molecule(D-glucose) on a carrier could be occupied by another chemically related substance(D-galactose). D-galactose could inhibit the transport d-glucose Question: Which of the following substance can pass through cell membrane by facilitated diffusion: a. CO2. b. O2. c. Steroid hormone. d. Amino acid. e. Polypeptide hormones. Passive Transport Factors affecting rate of diffusion: J = P A (CA-CB) J = net rate of diffusion P= Permeability A= Surface area for diffusion CA = Concentration of substance in solution A CB = Concentration of substance in solution B Rate of diffusion is directly proportional permeability Surface area Concentration gradient Passive Transport Factors affecting rate of diffusion: P=KD/X P= Permeability. K= Partition coefficient. D = Diffusion coefficient. X = thickness of the membrane. Factors affecting permeability - (1)Partition (3)Thickness coefficient. of the (2) Diffusion membrane coefficent - Partition coefficient (K) Is the ratio between solubility of substance in oil and its solubility in water K= solubility in oil/ solubility in water Lipid soluble substance has high partition coefficient, high permeability and high rate of diffusion Diffusion coefficient (D) It is best expressed by Stockes –Einstein equation Diffusion coefficient (D) Is inversely correlated with molecular size pf substance and viscosity of the medium. Large solutes in highly viscous medium has low diffusion coefficient and less permeability. Diffusion coefficient (D) It could be expressed by Fick's low Question: Which of the following substance that has the highest partition coefficient: a. polypeptide hormone. b. O2. c. CO2. d. Amino acid. e. Na. Passive transport filtration it is passage of water from high concentration of water to low concentration of water through capillary membrane. Passive transport filtration It is passage of water from area with high hydrostatic pressure to area with low hydrostatic pressure through capillary membrane. Question: Which of the following force that is responsible for filtration: a. Kinetic energy. b. Osmotic pressure. c. Colloidal pressure. d. Hydrostatic pressure. e. Oncotic pressure. Passive transport SOLVENT DRAG It is the diffusion of a solute following the diffusion of its solvent through the membrane, i.e. the solvent drags the solute after it. Passive transport SOLVENT DRAG This occurs in the renal tubules where there is absorption of large amounts of water through tight junction. Water drags some urea to be reabsorbed with it. Question: Define solvent drag and give one example? Summary  Transport is a vital biological process.  There are tow types of transport : active and passive  Passive transport are five types.  Facilitated diffusion is aided transport and has transport maximum.  There are many factors that affect rate of diffusion. 60 60 References  Linda S. Costanzo: physiology, six edition, ELSEVER.  Linda S. Costanzo: BRS physiology, seventh edition, Lippincott Williams & Wilkins.  Lecture notes. 11/23/2024 HBF - 102 61 61 Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester: 1 Module: Human Body Function (HBF) 102 Lecture 4 Transport Across the Cell Membrane By: Dr.Maessa M. Elnhas Prof. of physiology Tanta University Dr.Mohamed abo El Hassan Prof. of physiology Elazar University Department: Department of Clinical physiology 11/24/2024 22 Objectives By the end of this lecture students of first year must know Describe the structure of cell membrane Describe the significance of transport across biologic membranes Classify mechanisms involved in the transport of substances across cell membranes Describe the characteristics of different transport mechanisms Classify the transporters involved in carrier mediated transports Summarize the differences between diffusion through lipid bilayer, diffusion through protein channels and carrier mediated facilitated diffusion. Describe facilitated diffusion & carrier protein. Determine osmosis ,normo , hyper & hypoosmolality Compare and contrast the structure and functions of voltage gated channels and ligand gated channels Compare the kinetics of facilitated diffusion with active transport 11\24\2024 HBF - 102 3 The cell membrane The cell membrane is also called the plasma membrane or biologic membrane, it is a thin structure that surrounds the cells. Functions of the cell membrane 1.It protects the protoplasmic mass & binds its components together. 2.It regulates ionic & non-ionic fluxes in or out of the cell. 3.It contains receptors for chemical messengers which would activate or inhibit various cellular functions. 11\24\2024 HBF - 102 4 The cell membrane  The structure of the plasma membrane, described as a fluid mosaic, consists of phospholipids, cholesterol, proteins, and carbohydrates.  The membrane is considered fluid because the phospholipids and the other molecules in the membrane are not linked together by chemical bonds and can move about laterally, and they even occasionally move from one side of the bilayer to the other.  Cholesterol molecules are found within the lipid bilayer, where they interfere with hydrophobic interactions between phospholipid tails, which could cause crystallization of the bilayer and decrease the fluidity. 11\24\2024 HBF - 102 5 The cell membrane Membrane lipids Each phospholipid molecule has a head & tail. The head is formed of phosphate radical & is placed on the outer & inner surfaces of the membrane. It dissolves in & mixes with water, thus it is called hydrophilic (love water). The tail is formed of fatty acid radicles & is present in the center or the middle of the membrane. It is insoluble in water but soluble in fat solvents. It is called hydrophobic (hate water). The hydrophilic portions of the molecules are projected to the outer & inner surfaces of the membrane so that they are in contact with the exterior watery extracellular fluid that bathes the cells & the aqueous cytoplasmic interiorly. The hydrophobic tails are present in between i.e. in center of the membrane. 11\24\2024 HBF - 102 6  Membrane proteins - There are several types of proteins embedded in the membrane as separate globular units. - Some protein globules are located on the inner or outer surfaces of the lipid bimolecular layer & are called "peripheral proteins" & some extend through the membrane & are called ''transe-membrane proteins or integral proteins". - Also, proteins have hydrophilic parts, located on the outer & inner surfaces & a hydrophobic part present in 'the 'interior of the membrane, - Some proteins of cell membrane: may contain lipids (lipoproteins) or carbohydrates (glycoproteins). Proteins are Crucial to Membrane Function Functions of proteins in the cell membrane  Structural proteins: they keep the integrity of the membrane & give it strength.  Make passive channels: for passage -of ions & water.  Active pumps: for active transport of ions across the membrane.  Receptors: for binding with specific chemical messengers (hormones or neurotransmitters). Receptors are mainly glycoproteins found on the outer surface of the membrane.  Enzymes: which catalyze certain reactions on the inner or outer surfaces ofthe membrane.  Identity protections: which give the cells the individual's label of identity, so that they would not attacked by the immune system. - Protein channles classified into I-Non-gated channels - Open all the time allowing passage of ions all the time. So, they are called "Leak channels." II) Gated channels - They have gates that open or close. - They are either: 1-Voltage-gated'. Open or close by alterations in membrane potential. 2-Ligand-gated: Open or close by binding to a ligand e.g. acetyl choline (A.Ch.). Osmosis. Diffusion of water(or any solvent) across a membrane Moves from HIGH water concentration to LOW water concentration Water is attracted to solutes (like salt) so it will also travel to areas of low solute concentration to high solute concentration. Cells in Solutions Isotonic A solution whose solute concentration is the same as the solute concentration inside the cell. Hypotonic A solution whose solute concentration is lower than the solute concentration inside a cell Hypertonic A solution whose solute concentration is higher than the solute concentration inside a cell. Cell in Isotonic Solution What is the direction of water movement? The cell is at EQUILIBRIUM Water will flow in both directions outside and inside the cell. The solute and water concentrations are the same inside and outside the cell. Cell in Hypertonic Solution What is the direction of water movement? The water is GOING OUT of the cell. The solute concentration is greater outside the cell, therefore water will flow outside the cell. Cell in Hypotonic Solution What is the direction of water movement? The water is going INSIDE the cell. Water is attracted to the solute inside the cell. The solute concentration is greater inside the cell than outside, therefore water will flow into the cell. Cells in Solutions Osmosis in Red Blood Cells Isotonic Hypotonic Hypertonic Transport across cell membrane I-Transport of small molecules: (Micro molecules) a. Passive transport (diffusion) 1.Simple diffusion. 2.Facilitated diffusion. b.Active transport. II. Transport of large molecules: (macromolecules( -Endocytosis. -Exocytosis. Simple Diffusion Requires NO energy Molecules move from area of HIGH to LOW concentration Diffusion Diffusion is a PASSIVE process which means no energy is used to make the molecules move, they have a natural KINETIC ENERGY Passive diffusion - Passive diffusion needs no energy. - There are 2 pathways for passing through cell membrane by passive (simple) diffusion [A] Diffusion through lipid bilayer - Lipid soluble substances e.g. O2, N2 & alcohols. - Water (because of small molecular size & its high kinetic energy). Many of the body’s cell membranes contain protein “pores” called aquaporins that selectively permit rapid passage of water through the membrane. The aquaporins are highly specialized, and there are at least 13 different types in various cells of mammals. - Charged particles e.g. Na+ & K+ & glucose can not pass. [B] Diffusion through protein channels - Important for diffusion of ions & some water-soluble substances. - Highly selective i.e. there are specific channels for transport of Na+, K+, Ca++. Diffusion Through a Membrane Solute moves DOWN the concentration gradient. (HIGH to LOW) Diffusion of Water Across A Membrane High water concentration Low water concentration Low solute concentration High solute concentration Three Forms of Transport Across the Membrane Passive Transport Active Transport Passive Transport: Simple Diffusion Simple Diffusion Doesn’t require energy Moves high to low concentration Example: Oxygen or water diffusing into a cell and carbon dioxide diffusing out. Factors Affecting Rates of Simple Diffusion I-The Magnitude of the Driving Force II-Membrane Surface Area III-Membrane Permeability Among the factors influencing the permeability of cell membranes are the following: 1. The lipid solubility of the diffusing substance. 2.The size and shape of diffusing molecules. 3.Temperature. 4.Membrane thickness. 11\24\2024 HBF - 102 30  Facilitated diffusion  Require no energy.  Require a carrier  The carrier is similar to enzyme & solute is similar to substrate i.e. similar to enzyme-substrate complex except there is no covalent interaction.  Features of the carrier:  There is specific binding i.e. specificity.  There is binding constant i.e. Km & affinity.  Can be inhibited by compounds that have structural similarity to solute i.e. competitive inhibitor.  Can be saturated. Depends on the concentration gradient across the membrane. Depends on the rapidity of conformational change. -The transport can occur bidirectionally. Passive Transport: Facilitated Diffusion Facilitated Diffusion Does not require energy Uses transport proteins to move high to low concentration Examples: Glucose or amino acids moving from blood into a cell. Among the many substances that cross cell membranes by facilitated diffusion are glucose and most of the amino acids. In the case of glucose, at least 14 members of a family of membrane proteins (called GLUT) that transport glucose molecules have been discovered in various tissues. Facilitated Diffusion Molecules will randomly move through the pores in Channel Proteins. Facilitated Diffusion Some carrier proteins do not extend through the membrane. They bond and drag molecules through the lipid bilayer and release them on the opposite side. Types of carrier proteins Uniport system Which move on type of molecules bidirectionally e.g. D-glucose. Co-transport system In which transfer of one solute depend upon the simultaneous transport of another solute. It is of two types I) Symport system In which the two solutes moves in the same direction. e.g. Na+-sugar transporters (glucose, mannose, galactose, xylose). II) Antiport system Which move two molecules in opposite directions. e.g. Na+ in & Ca++ out in nerve cell. Types of Transport Proteins Channel proteins are embedded in the cell membrane & have a pore for materials to cross Carrier proteins can change shape to move material from one side of the membrane to the other  Mechanism of facilitated diffusion (ping-pong) - The carrier protein exists in 2 conformations 1- Pong confirmation - Which is exposed to the higher concentration of the solute. - Solute molecules bind to this conformation. 2- Ping conformation - Conformational change of the carrier exposing the solute to lower concentration i.e. transport of the solute.  Factors affecting the rate of facilitated diffusion 1.Concentration gradient across the membrane. 2.Amount of carrier protein available (key control.( 3.Rapidity of solute carrier interaction i.e. the affinity of the carrier to the solute. 4.Rapidity of conformational change for both the loaded & unloaded carriers. 5.Hormone - Insulin hormone => Increase glucose transport in fat & muscle by increasing the number of Na+-glucose symports. - Growth hormone => Increase amino acids transport in all cells by increasing the number of Na+-amino acid symports. 24 November Module: 41 HBF-1022024 SUMMARY Transport across cell membrane I-Transport of small molecules: (Micro molecules) a. Passive transport (diffusion) 1.Simple diffusion. 2.Facilitated diffusion. b.Active transport. II. Transport of large molecules: (macromolecules( -Endocytosis. -Exocytosis. 24 November Module: 42 HBF-1022024 INTERACTIVE QUESIONS The cell contains several types of membranes that function as barriers between compartments. (Are you know them?) Define osmosis & diffusion? Write types of transport? References Linda S. Costanzo 11/24/2024 HBF - 102 43 43 Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester:1 Module: Human Body Function (HBF) 102 25/11/2024 HBF - 102 1 Active transport across the cell membrane By: Dr. Ayman Saied Soliman Ass. Professor – Faculty of Medicine – Beni Suef University Department: Medical Physiology 25/11/2024 11/26/2024 HBF - 102 2 2 Objectives 1.Describe primary and secondary active transport. 2.Describe exocytosis and endocytosis. 3.Differentiate between passive and active transport and identify shared characteristics. 25/11/2024 HBF - 102 3 3 Introduction ☼The mechanisms that control the transport through the cell membranes are so important to maintain the differences between the ICF & ECF. ☼Substances can pass through a cell membrane in 3 separate ways: I. Diffusion. II. Active transport. III. Vesicular transport. 25/11/2024 HBF - 102 4 4 Transport Through the Cell Membrane 25/11/2024 HBF - 102 5 Active transport Definition: It is the transport of substance across the cell membrane against an electrochemical gradient. 25/11/2024 HBF - 102 6 Active transport Active transport depends on: 1- Specific carrier proteins. 2- Energy is needed for the substance to be transported.  The energy is derived from ATP.  The carrier protein has ATPase activity. 25/11/2024 HBF - 102 7 Active transport Types of Carrier proteins are: 1) Uniport:  This is a carrier that transports one substance in one direction.  e.g. Ca++ pump. 25/11/2024 HBF - 102 8 Active transport 2) Symport: ☆This is a carrier that transports two substances simultaneously in the same direction. ☆e.g. carriers of glucose and Na+ from the intestinal lumen to inside of the cells. 25/11/2024 HBF - 102 9 Active transport 3) Antiport: This is a carrier that transports one substance in one direction and another substance in the opposite direction. e.g., Na+ - K+ pump. Symport and antiport are also called cotransport carriers. 25/11/2024 HBF - 102 10 Active transport 25/11/2024 HBF - 102 11 TYPES OF Active transport According to the source of energy: A.Primary active transport:  Energy is provided from ATP hydrolysis  Examples include:  Na+ / K+ pump (In all cell membranes)  Ca++ pump (in excitable membranes)  H+ / K+ pump (in stomach for HCL secretion) 25/11/2024 HBF - 102 12 A- Primary active transport:  The best example is the Na+ / K+ pump.  It transports Na+ ions out of the cells to the (ECF) and at the same time pumps K+ ions from the outside to the inside of the cells (ICF). 25/11/2024 HBF - 102 13 Structure of the Na+ / K+ pump 25/11/2024 HBF - 102 14 Structure of the Na+ / K+ pump ◎It is composed of  and  subunits. ◎The  subunit is responsible for Na+ & K+ transport. It possesses: i. An ATP binding site. ii.Two K+ binding sites on the outer side. iii.Three Na+ binding sites on the inner side. 25/11/2024 HBF - 102 15 Structure of the Na+ / K+ pump ◎The  subunit is a protein with ATPase activity that breaks ATP into (ADP + P + energy.) 25/11/2024 HBF - 102 16 Mechanics of Na+ / K+ pump 25/11/2024 HBF - 102 17 Mechanics of Na+ / K+ pump 25/11/2024 HBF - 102 18 Mechanics of Na+ / K+ pump 1) 3 Na+ ions bind to their binding sites on  subunit 2) ATP binds to its site and is converted to ADP and phosphate 3) Phosphate is transferred to its phosphorylation site 25/11/2024 HBF - 102 19 Mechanics of Na+ / K+ pump 4)This causes conformational change in the protein (change in configuration) excluding Na+ into the exterior (ECF) 5)Then 2 K+ ions bind extracellularly in its site, dephosphorylating the  subunit that returns to its previous conformation releasing 2 25/11/2024 K+ ions into the cytoplasm. HBF - 102 20 Characters of Na+ / K+ pump ☆The Na+-K+ pump as an example for active transport. ☆The activity of the pump is energy dependent. ☆The energy is derived from ATP. ☆3 Na+ are pumped out of the cell and 2 K+ into the cell. 25/11/2024 HBF - 102 21 Characters of Na+ / K+ pump 25/11/2024 HBF - 102 22 IMPORTANCE of Na+ / K+ pump About 35% of the energy consumption of all living cells are used for this pump to perform the following functions: I- Sharing in the establishment of the membrane potential at rest (RMP): 25/11/2024 HBF - 102 23 IMPORTANCE of Na+ / K+ pump The pump transports 3 Na+ ions out for every 2 K+ ions due to this unequal transport the inside of the cell membrane is relatively more negative minimal share. It maintains a high extracellular Na+ and a high intracellular K+. 25/11/2024 HBF - 102 24 IMPORTANCE of Na+ / K+ pump II- Regulation of cell volume: It helps in the regulation of cell volume by controlling the concentrations of solutes inside the cell and thus minimizing osmotic effects that would induce swelling or shrinking of the cell 25/11/2024 HBF - 102 25 IMPORTANCE of Na+ / K+ pump III- helps indirectly in the secondary active transport: The Na+ gradient established by this pump energizes the secondary active transport processes for (calcium & hydrogen) and (glucose & amino acids) 25/11/2024 HBF - 102 26 2- Ca2+-ATPase (or Ca2+ pump)  It is an important primary active pump to keep intracellular Ca2+ extremely low.  In the sarcoplasmic reticulum (SR) or cell membranes transports Ca2+ against an electrochemical gradient.  Sarcoplasmic and endoplasmic reticulum Ca2+- ATPase is called 25/11/2024 HBF - 102 27 2- Ca2+-ATPase (or Ca2+ pump) Ca2+ uptake and skeletal muscle 25/11/2024 HBF - 102 28 3- H+, K+-ATPase (proton pump)  In gastric parietal cells transports H+ into the lumen (of the stomach) against its electrochemical gradient. 25/11/2024 HBF - 102 29 3- H+, K+-ATPase (proton pump) HCl formation in stomach parietal cells 25/11/2024 HBF - 102 30 Secondary active transport:  The energy is provided from the concentration gradient of another ion.  in secondary (indirect) active transport molecules such as glucose or amino acids move against their concentration gradient from low to high concentration using the energy of sodium gradient produced by the primary active transport 25/11/2024 of Na+ with HBF - 102 no further need of 31 Types of carriers used in Secondary active transport: Symport carriers Antiport carriers (counter (cotransport) transport or exchange) Both solutes and sodium move Solutes and sodium move through the membrane in the through the membrane in same direction (together, Co) opposite directions (anti, counter) Example: Example:  Na+ glucose transporters.  Na+ - Ca++ exchanger (Heart)  Na+ dependent amino acid  Na+- H+ exchanger (Kidney) transporter  Site: 25/11/2024 it and the intestine 32 HBF - 102 Secondary active transport: The postulated mechanism of the sodium co -transport of glucose. 25/11/2024 HBF - 102 33 Na+–glucose cotransport (symport) in intestinal or proximal tubule epithelial cell. Na+–glucose cotransport (symport) in intestinal or proximal tubule epithelial cell. 25/11/2024 HBF - 102 34 Secondary active transport: The mechanism of the Sodium counter-transport of Calcium and Hydrogen. 25/11/2024 HBF - 102 35 Na+–Ca2+ counter transport (antiport). 25/11/2024 HBF - 102 36 Vesicular transport:  It is the movement of macromolecules that are enclosed inside cell membrane bound vesicles.  It is of two types: I. Endocytosis II. Exocytosis. 25/11/2024 HBF - 102 37 Vesicular transport: I. Endocytosis:  It is the movement from outside the cell to the inside. 25/11/2024 HBF - 102 38 I- Endocytosis: Types based upon fate of substance: a) Pinocytosis = cell drinking: b) Phagocytosis: cell eating: 25/11/2024 HBF - 102 39 I- Endocytosis: a) Pinocytosis = cell drinking: ☼It is the only mean by which some very large, water soluble, macromolecules & Protein molecules can enter the cells as small invaginating vesicles containing extracellular fluid. ☼The portion of the membrane then breaks away from the surface of the cell, forming a pinocytic vesicle. 25/11/2024 HBF - 102 40 I- Endocytosis: b) Phagocytosis: cell eating: ◎It occurs in the same way as pinocytosis except that it involves large particulate matter e.g. bacteria and dead tissue. ◎Only certain cells have the capability of phagocytosis e.g. some white blood cells. 25/11/2024 HBF - 102 41 II- Exocytosis: It is the movement from inside the cell to the outside. Exo- and Endocytosis: There is a balance between exo - and endocytosis so that the surface area of the cell membrane neither decreases (if endocytosis is more) nor it becomes redundant (if exocytosis is more). 25/11/2024 HBF - 102 42 Vesicular transport: Exocytosis and Endocytosis 25/11/2024 HBF - 102 43 Differentiate between passive and active transport: Simple diffusion: It means that the molecules or ions will diffuse through the membrane: ☆ according to the concentration gradient, ☆ passively ☆ without binding with carrier proteins in the membrane. 25/11/2024 HBF - 102 44 Differentiate between passive and active transport: B. Facilitated Diffusion  Large molecules such as: glucose and amino acids.  It is also called: carrier mediated diffusion as the substance needs a carrier that facilitates the diffusion.  This mechanism occurs passively and with concentration gradient.  The carrier protein has a channel large enough to transport a specific molecule part- way but not all the way through the membrane.  The molecule to be transported enters the channel and then becomes bound to a specific receptor on the protein carrier. 25/11/2024 HBF - 102 45 Differentiate between passive and active transport: Osmosis is a simple diffusion of solvent (water) molecules from high concentration of water to low concentration of water across a semi-permeable membrane that is permeable to water but not to the solute. 25/11/2024 HBF - 102 46 Interactive Question How do digitalis treat heart failure? Digitalis inhibits the Na+- K+ pump leading to:  The intracellular Na+ concentration increases  The Na+ gradient decreases  Thus, Ca++ extrusion reversed  Thus, Ca++ increases intracellularly  Increasing the force of heart contraction (positive inotropic effect) 25/11/2024 HBF - 102 47 47 Interactive Question 25/11/2024 HBF - 102 48 48 Summary ☼The mechanisms that control the transport through the cell membranes are so important to maintain the differences between the ICF & ECF. ☼Substances can pass through a cell membrane in 3 separate ways: I. Diffusion. II. Active transport. III. Vesicular transport. 25/11/2024 HBF - 102 49 49 References 1) GUYTON AND HALL: TEEXT BOOK OF MEDICAL PHYSIOLOGY: 14th. Edition; Philadelphia: Elsevier, Inc.,2020. 2) Staff Members of Physiology Department: Medical physiology books; Faculty of Medicine – Cairo University, 2016. 3) Barerett KE et al.: Ganong's Review of Medical Physiology: 26th. Edition; New York: The McGraw- Hill companies, 2019. 4) Linda S. Costanzo, : BRS Physiology Seventh Edition. 25/11/2024 HBF - 102 50 50

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