Transport Across Cell Membrane PDF

TRANSPORT ACROSS CELL MEMBRANE Lecturer Dr. Ekin Bilge Learning Objectives To learn the ways of transport across cell membrane To understand the factors that affect the rate of diffusion To know the differences between transport mechanisms To learn osmosis and related...

TRANSPORT ACROSS CELL MEMBRANE Lecturer Dr. Ekin Bilge Learning Objectives To learn the ways of transport across cell membrane To understand the factors that affect the rate of diffusion To know the differences between transport mechanisms To learn osmosis and related concepts 2  The contents of a cell are separated from the surrounding extracellular fluid by a thin bilayer of lipids and protein, which forms the plasma membrane The movements of molecules and ions between the cytosol and the extracellular fluid, depend on the properties of these membranes 3  Cell membrane constitutes a barrier against movement of water molecules and water-soluble substances between the extracellular and intracellular fluid compartments Lipid-soluble substances can diffuse directly through the lipid substance 4  Membrane proteins can function as transport proteins: - Channel proteins - Carrier proteins Channel proteins have watery spaces all the way through the molecule and allow free movement of water, as well as selected ions or molecules Carrier proteins bind with molecules or ions and conformational changes in the protein molecules then move the substances through interstices of the protein to the other side of membrane Channel proteins and carrier proteins are usually selective for the types of molecules or ions that are allowed to cross membrane 5  Transport through the cell membrane, either directly through the lipid bilayer or through the proteins, occurs via one of two basic processes: - Diffusion - Active transport 6 DIFFUSION One of the fundamental physical features of molecules of any substance, whether solid, liquid, or gas, is that they are in a continuous state of movement or vibration The energy for this movement comes from heat; the warmer a substance is, the faster its molecules move Because a molecule may at any instant be moving in any direction, such movement is random, with no preferred direction of movement 7  The random thermal motion of molecules in a liquid or gas will eventually distribute them uniformly throughout a container In an initially unevenly concentrated solution, the solute diffuses from high to low concentration areas until it's uniformly spread This movement of molecules from one location to another solely as a result of their random thermal motion is known as diffusion 8  The amount of material crossing a surface in a unit of time is known as a flux After a short time, some of the molecules that have entered compartment 2 will randomly move back into compartment 1 The net flux of molecule between the two compartments at any instant is the difference between the two one-way fluxes The net flux determines the net gain of molecules in compartment 2 per unit time and the net loss from compartment 1 per unit time 9  Eventually, the concentrations of molecules in the two compartments become equal The two one-way fluxes are now equal in magnitude but opposite in direction; therefore, the net flux of the molecule is zero The system has now reached diffusion equilibrium 10  Diffusion through the cell membrane is divided into 2 subtypes: - Simple diffusion - Facilitated diffusion 11 A) Simple Diffusion Kinetic movement of molecules or ions occurs through a membrane opening or through intermolecular spaces without interaction with carrier proteins in the membrane Simple diffusion can occur through the cell membrane by two pathways: - Through the interstices of the lipid bilayer if the diffusing substance is lipid-soluble - Through watery channels that penetrate all the way through some of large transport proteins 12 1. Diffusion of Nonelectrolytes Net diffusion of the solute (flux=J) depends on the following variables: - Size of the concentration gradient - Partition coefficient - Diffusion coefficient - Thickness of the membrane - Surface area available for diffusion 13  Concentration gradient (CA-CB): - The larger the difference in solute concentration between Solution A and Solution B, the greater the driving force and the greater the net diffusion - If the concentrations in the two solutions are equal, there is no driving force and no net diffusion 14  Partition Coefficient (K): - It is the ratio of concentrations of a compound in a mixture of two immiscible solvents at equilibrium; this ratio is therefore a comparison of the solubilities of the solute in these two liquids - The greater the relative solubility in oil, the higher the partition coefficient and the more easily the solute can dissolve in the cell membrane’s lipid bilayer - Nonpolar solutes tend to be soluble in oil and have high values for partition coefficient, whereas polar solutes tend to be insoluble in oil and have low values for partition coefficient 15  Diffusion Coefficient (D): - It depends on such characteristics as size of the solute molecule and viscosity of the medium - It is defined by the Stokes-Einstein equation: D: Diffusion coefficient kB: Boltzmann constant T: Absolute temperature (°K) Ƞ: Viscosity of the medium r: Molecular radius 16  Thickness of the Membrane (∆X): - The thicker the cell membrane, the greater the distance the solute must diffuse and the lower the rate of diffusion Surface Area (A): - The greater the surface area of membrane available, the higher the rate of diffusion 17  To simplify the description of diffusion, several of the previously cited characteristics can be combined into a single term called permeability (P) Permeability includes the partition coefficient, the diffusion coefficient, and the membrane thickness: 18  By combining several variables into permeability, the rate of net diffusion is simplified to the following expression: J: Net rate of diffusion (mmol/s) P: Permeability (cm/s) A: Surface area for diffusion (cm2) CA: Concentration in Solution A (mmol/L) CB: Concentration in Solution B (mmol/L) 19 2. Diffusion of Electrolytes Some of membrane proteins form ion channels that allow ions to diffuse across the membrane The diameters of ion channels are very small, only slightly larger than those of the ions that pass through them The small size of the channels prevents larger molecules from entering or leaving Ion channels show selectivity for the type of ion or ions that can diffuse through them 20  When describing the diffusion of ions, since they are charged, there is one factor to consider: the presence of electrical forces acting on the ions A separation of electrical charge exists across plasma membranes of all cells; this is known as a membrane potential, the magnitude of which is measured in units of millivolts The membrane potential provides an electrical force that influences the movement of ions across the membrane 21  Like charges repel each other, opposite charges attract each other If the inside of a cell has a net negative charge with respect to the outside, as is generally true, there will be an electrical force attracting positive ions into the cell and repelling negative ions Consequently, the direction and magnitude of ion fluxes across membranes depend on both the concentration difference and the electrical difference (the membrane potential) These two driving forces are collectively known as the electrochemical gradient across a membrane 22  Ion channels can exist in an open or closed state, and changes in a membrane’s permeability to ions can occur rapidly as these channels open or close 3 basic types of ion channels: - Ligand-gated channels - Voltage-gated channels - Mechanically gated channels 23 24 B) Facilitated Diffusion As in simple diffusion, in facilitated diffusion the net flux of a molecule across a membrane always proceeds from higher to lower concentration, or “downhill” across a membrane The key difference between these processes is that facilitated diffusion uses a transporter to move solute Net facilitated diffusion continues until concentrations of the solute on the two sides of the membrane become equal Neither simple diffusion nor facilitated diffusion is directly coupled to energy (ATP) derived from metabolism 25  The rate of simple diffusion through an open channel increases proportionately with the concentration of the diffusing substance In facilitated diffusion the rate of diffusion approaches a maximum, called Vmax, as the concentration of the diffusing substance increases 26  An example of facilitated diffusion is the GLUT transporters that transport glucose Some of these GLUT proteins transport other monosaccharides that have structures similar to that of glucose, including galactose and fructose One of these, glucose transporter 4 (GLUT-4), is activated by insulin, which can increase the rate of facilitated diffusion of glucose as much as 10-20 fold in insulin-sensitive tissues 27 ACTIVE TRANSPORT Active transport uses energy to move a substance uphill across a membrane —that is, against the substance’s concentration gradient Because these transporters move the substance uphill, they are often referred to as pumps 28 A) Primary Active Transport The hydrolysis of ATP by a transporter provides the energy for primary active transport The transporter itself is an enzyme called ATPase that catalyzes the breakdown of ATP and, in the process, phosphorylates itself 29  One of the best-studied examples of primary active transport is the movement of Na+ and 2 K+ ions across plasma membranes by the Na +/K+- ATPase pump This transporter, which is present in all cells, moves 3 Na+ ions from intracellular to extracellular fluid, and 2 K+ ions in the opposite direction In both cases, the movements of the ions are against their respective concentration gradients The pumping activity of the Na+/K+-ATPase establishes and maintains the characteristic distribution of high intracellular K+ and low intracellular Na+ 30 31  In addition to the Na+/K+-ATPase transporter, the major primary active- transport proteins found in most cells are Ca2+-ATPase; H+-ATPase; and H+/K+- ATPase Together, the activities of these and other active-transport systems account for a significant share of the total energy usage of the human body 32 A) Secondary Active Transport In secondary active transport, the movement of an ion down its electrochemical gradient is coupled to the transport of another molecule, such as a nutrient like glucose or an amino acid One of the solutes, usually Na+, moves down its electrochemical gradient (downhill), and the other solute moves against its electrochemical gradient (uphill) This transport uses the stored energy of an electrochemical gradient to move both an ion and a second solute across a plasma membrane 33  The movement of the actively transported solute can be in the same direction, in which case it is known as cotransport (symport) Or the movement of the actively transported solute can be opposite the direction, which is called countertransport (antiport) 34  The distribution of substances between the intracellular and extracellular fluid is often unequal due to the primary and secondary active transporters, ion channels, and membrane potential 35 36 OSMOSIS Water is a polar molecule and yet it diffuses across the plasma membranes of most cells very rapidly This process is mediated by a family of membrane proteins known as aquaporins that form channels through which water can diffuse The type and number of these water channels differ in different membranes The net diffusion of water across a membrane is called osmosis 37  The total solute concentration of a solution is known as its osmolarity Although osmolarity refers to concentration of solute particles, it also determines water concentration in the solution because the higher the osmolarity, the lower the water concentration Osmotic pressure is the force needed to stop water from flowing into a solution separated by a semipermeable membrane from pure water due to the solute concentration difference 38  Both the intracellular and extracellular fluids contain water, and cells are surrounded by a membrane that is very permeable to water but impermeable to many substances The osmolarity of the extracellular fluid is normally in the range of 285-300 mOsm Because water can diffuse across plasma membranes (via aquaporins), water in the intracellular and extracellular fluids will come to diffusion equilibrium At equilibrium, therefore, the osmolarities of the intracellular and extracellular fluids are the same: approximately 300 mOsm 39  The concentration of nonpenetrating solutes in a solution, not the total osmolarity, determines its tonicity: isotonic, hypotonic, or hypertonic Penetrating solutes do not contribute to the tonicity of a solution 40  Another set of terms: isoosmotic , hypoosmotic , and hyperosmotic The term denotes the osmolarity of a solution relative to that of normal extracellular fluid without regard to whether the solute is penetrating or nonpenetrating 41 ENDOCYTOSIS AND EXOCYTOSIS There is another pathway by which substances can enter or leave cells, one that does not require the molecules to pass through the structural matrix of the plasma membrane In endocytosis, the cell's membrane folds inwards, creating pockets that pinch off, forming small vesicles containing extracellular fluid within the cell Exocytosis occurs when membrane-bound vesicles in the cytoplasm fuse with the plasma membrane and release their contents to the outside of the cell 42 A) Endocytosis Three general types of endocytosis may occur in a cell: - Pinocytosis (“cell drinking”) - Phagocytosis (“cell eating”) - Receptor-mediated endocytosis 43 B) Exocytosis Exocytosis performs two functions for cells: - It provides a way to replace portions of the plasma membrane that endocytosis has removed and, in the process, a way to add new membrane components as well - It provides a route by which membrane-impermeable molecules (such as protein hormones) that the cell synthesizes can be secreted into the extracellular fluid 44 References Vander's Human Physiology The Mechanisms of Body Function 13th edition Guyton and Hall Textbook of Medical Physiology 14th Edition Costanzo Physiology 6th Edition https://en.wikipedia.org/wiki/Partition_coefficient 45 References Pictures: https://teacher-sites-storage.inthinking.net/tib-galleries/6-154/img20151003113821212.jpg https://www.pharmacy180.com/media/article/article-Cell-Membrane---Stru-0h0.jpg https://img.brainkart.com/imagebk22/51FBsff.jpg https://www.sciencefacts.net/wp-content/uploads/2021/02/Transport-Proteins.jpg https://nmr.chem.ucsb.edu/education/DOSY_DebyeEinstein.jpg https://pub.mdpi-res.com/molecules/molecules-25-05340/article_deploy/html/images/molecules-25-05340-ag-550.jpg?1606703973 https://o.quizlet.com/VVeupR5ri.Xwo9mKp5K2Og.png https://d2jx2rerrg6sh3.cloudfront.net/image-handler/picture/2018/10/shutterstock_480412786.jpg https://i.pinimg.com/originals/eb/ed/37/ebed37b60f9cbb783ee15d285c96319a.jpg https://microbenotes.com/wp-content/uploads/2023/03/Primary-Active-Transport.jpg https://ars.els-cdn.com/content/image/3-s2.0-B9780128008836000161-f16-03-9780128008836.jpg https://cdn.kastatic.org/ka-perseus-images/64873bcc105edab3802571e18cfe0eba036b121f.png https://www.labiotech.eu/wp-content/uploads/2019/03/aquaporin-water-purification-membrane.jpg https://pcwww.liv.ac.uk/~petesmif/petesmif/help%20for%20non%20biologists/dissociation.gif https://media.cheggcdn.com/media/583/58386795-6400-483e-9f1e-1859dae1523f/phppvTqua https://upload.wikimedia.org/wikipedia/commons/thumb/1/1a/Endocytosis_types.svg/1200px-Endocytosis_types.svg.png https://www.thoughtco.com/thmb/MrkQqfDN0VNmlLT3VsaxNnLUFgU=/1500x0/filters:no_upscale():max_bytes(150000):strip_icc()/ exocytosis_process-5ae370b4a9d4f900373c9b48.jpg 46 THAT’S ALL e-mail: