Transport across Cell Membrane I & II (PDF)

Transport across cell membrane I & II Medical Physiology Department  ‫ﺴﻢ ﷲ اﻟﺮﲪﻦ اﻟﺮﺣﲓ‬ ‫﴿ َواﺗ ُﻘﻮا ا َ ۖ َوﯾ ُ َﻌ ُ ُ َ ُ‬ ‫ا‬‫و‬ ‫ۗ‬ ‫ا‬ ‫ُ‬ ‫ﲂ‬ ‫ُ‬ ‫ﻤ‬‫ّ‬ ‫ِ‬ ‫ﻠ‬ ‫ﳾ ٍء َ ِﻠ ٌﲓ﴾‬ ‫ِ ُ ِّ‬ ‫ﲁ َْ‬ Learning objectives: Human Physi...

Transport across cell membrane I & II Medical Physiology Department  ‫ﺴﻢ ﷲ اﻟﺮﲪﻦ اﻟﺮﺣﲓ‬ ‫﴿ َواﺗ ُﻘﻮا ا َ ۖ َوﯾ ُ َﻌ ُ ُ َ ُ‬ ‫ا‬‫و‬ ‫ۗ‬ ‫ا‬ ‫ُ‬ ‫ﲂ‬ ‫ُ‬ ‫ﻤ‬‫ّ‬ ‫ِ‬ ‫ﻠ‬ ‫ﳾ ٍء َ ِﻠ ٌﲓ﴾‬ ‫ِ ُ ِّ‬ ‫ﲁ َْ‬ Learning objectives: Human Physiology. Body compartments. Homeostasis. The cell membrane and its functions. Different methods of transport across the cell membrane. Functions of cell membrane proteins Intercellular communication. Human Physiology Human Physiology  Physiology is the study of the normal function of livings.  Human physiology is concerned with the way the human body works.  It is the study of the functions of organs and systems and their integration.  The human body comprises 75-100 trillion (1012) cells arranged in various combinations. Human Physiology  Collection of cells with similar properties forms tissues (e.g. muscular tissue).  Different tissues combine to form organs (e.g. heart, brain, liver).  Organs of complementary functions constitute the different systems (e.g. cardiovascular system, nervous system). Body compartments  Body compartments  The body of an average adult male contains: - 60 water. - 18% protein & related substances. - 15% fats. - 7% minerals.  Normally the body is divided into intracellular (IC) and extracellular (EC) compartments.  Body compartments  The total body water (TBW) in both compartments constitutes 60% of the total body weight of an average adult male.  In infants, it is about 70-75%.  It is less than 60% in adult females (about 54%) and obese people (varies with obesity type) due to the high content of fat in their bodies. Body compartments (15%) (5%)  Body compartments ECF  The total blood volume is about 8 % of ICF Plasma ISF body weight, including the blood's Cations (mmol / L) plasma and cellular elements. Na+ 14 145 140 K+ 140 4.5 4.0  The ICF differs significantly from ECF. Ca++ 0.1 x 10-3 2.5 1.2 Mg++ 58 1.2 1.2  Lymph fluid bridges ISF and IVF. Anions (mmol / L)  The total concentrations of +ve and –ve Cl- 3 115 110 HCO3- 10 28 27 ions are equal everywhere EXCEPT along HPO4-2 75 4 4 Non-charged (mg/dl) the cell membrane surfaces. Glucose 0-20 70-140 70-140 Osmolarity (mOsm/L) 290 290 290 Body compartments  Body compartments  Determination of the volumes of water in the body: -by using Fick's principle. 1. Determination of total body water: by the use of D2O (heavy water) or antipyrine that distribute themselves in water in all compartments of the body. 2. Determination of ECF volume: - by use of inulin or Na thiocyanate, which do not enter the cells but are distributed in ECF only. 3. Determination of plasma volume: - by the use of Evan's blue dye or plasma proteins labelled with radioactive iodine. 4. Calculation of ICF volume: indirectly calculated by: TBW – ECF 5. Calculation of ISF volume: indirectly calculated by: ECF – plasma volume. Homeostasis  Homeostasis  Homeostasis is keeping the conditions in the internal environment constant.  Most of the systems in the body, either directly or indirectly, work to maintain homeostasis  Cells are surrounded by ISF which constitutes the internal environment for these cells.  Life is compatible within narrow limits of change in the chemical or physical properties of the internal environment. The cell membrane and its functions  The cell membrane and its functions  The CM, that surrounds the cell completely, is a very thin elastic and semipermeable membrane of about 7.5-10 nm thick (75 -100 Angstrom units = A° = 10 -10 meter).  It is composed mainly of proteins and lipids; the approximate composition is: Proteins 55% Phospholipids (PLs) Lipids 25 % Cholesterol 13% Other lipids 4% Carbohydrates 3 %  The shape of PLs molecule is that of a clothespin. The cell membrane and its functions - A head which contains the phosphate radical (water soluble, hydrophilic, polar) exposed to the aqueous environment that bathes the exterior of the cells and the aqueous cytoplasm. - Two tails that contain the fatty acids radicals which are relatively insoluble in water (hydrophobic, non-polar) meet in the water poor interior of the membrane. - Thus, the molecule is amphipathic: that is; it has one part hydrophilic and the other hydrophobic.  The cell membrane and its functions 1. The lipid bilayer is important for the flexibility and selective permeability. 2. The cholesterol molecules affect membrane permeability and give it toughness. 3. The cell membrane proteins are present floating in the lipid bilayer. Two types of proteins:  The integral proteins.  The peripheral proteins. 4. The membrane carbohydrates occur almost in combinations with proteins and lipids in the form of glycoproteins and glycolipids. They are important in: 1. Acting as recognition sites. 2. Self-differentiation. 3. Immune responses. 4. Helping attaching the cells together. Different methods of transport across the cell membrane  Different methods of transport across the cell membrane  The differences between the components of ICF and ECF are extremely important to the life of the cell. The mechanisms that control the transport through the cell membranes are so important to maintain these differences. Substances can pass through a cell membrane in three separate ways: 1-Diffusion 2-Active transport 3-Vesicular A. Simple A. Primary A. Pinocytosis B. Facilitated B. Secondary B. Phagocytosis C. Osmosis  Different methods of transport across the cell membrane 1. Diffusion. A. 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. The rate of diffusion is affected by many factors that are summarized in the formula.  Different methods of transport across the cell membrane  Simple diffusion can occur across the CM through the lipid bilayer or protein channels: 1. Through the lipid bilayer. a) The lipid soluble substances: such as oxygen and nitrogen can dissolve directly in lipid bilayer through CM. The rate of diffusion is directly proportional to their lipid solubility. O2 can be delivered to the cell interior almost as though CM did not exist. molecules if they are small enough and uncharged.  Different methods of transport across the cell membrane 1. through the lipid bilayer. b) Water molecules: - They pass directly through the lipid bilayer and also through protein channels (aquaporin) as well. - Water is highly insoluble in the membrane lipids; but as water molecules are small enough and their kinetic energy is great enough that they can simply penetrate like bullets through the lipid portion of the membrane before the hydrophobic character of the lipids can stop them. c) Lipid insoluble molecules can pass through the lipid bilayer in the same way as water molecules if they are small enough and uncharged.  Different methods of transport across the cell membrane 2. Through protein channels:  Different methods of transport across the cell membrane  The gated channels are: 1. Voltage-gated: i.e., open or close by alterations in the trans-membrane potential. 2. Mechanically (stretch or pressure) gated: theses mechanosensitive channels play an important role in cell movement. 3. Ligand-gated: i.e., open or close when a ligand binds to a specific receptor in the cell membrane. This receptor may be extracellular or intracellular. Phosphorylation-gated: where protein phosphorylation or de-phosphorylation regulate opening and closing.  Different methods of transport across the cell membrane B. Facilitated Diffusion (carrier-mediated).  They bind large molecules (e.g., glucose) from one side of the cell membrane to the other.  The carrier protein has a channel large enough to transport a specific molecule part- way but not all the way through the membrane.  Different methods of transport across the cell membrane B. Facilitated Diffusion (carrier-mediated).  The molecule to be transported enters the channel and then becomes bound to a specific receptor on the protein carrier.  In a fraction of a second, a conformational change occurs in the carrier protein so that the channel now opens to the opposite side of the membrane and the attached molecule will be released on the opposite side  Different methods of transport across the cell membrane  In facilitated Diffusion, different carriers differ from each other in: * The specificity of the carrier protein. * The competition between similar substances (glucose and galactose) for the same carrier.  The rate of facilitated diffusion increases proportionately with the concentration gradient up to a certain maximum rate (carrier saturation).  Its rate can never exceed the rate the carrier protein molecule can undergo change back and forth between its two states.  It is more sensitive to temperature than simple diffusion.  Different methods of transport across the cell membrane C. Osmosis.  It is defined as the tendency of solvent particles to diffuse down its concentration gradient, or to an area of higher solute concentration.  Different methods of transport across the cell membrane  Osmosis (solvent migration) can be prevented by applying pressure to the more concentrated solution, the osmotic pressure of the solution.  The Osmotic pressure is measured in mmHg and is determined by the numbers of particles (molecules or ions) per unit volume of fluid, and not the mass of the particles.  Osmosis is α number of particles/volume of solvent.  Different methods of transport across the cell membrane  Mole of any substance contains Avogadro's number (AN) of atoms = 6.02214076 X 1023  Osmole = number of osmotically active particles (molecules) that one mole liberates in solution.  One mole of glucose = 180 gm, contains or = one Osmole.  On the other hand, if the solute dissociates into two ions e.g., NaCI, one mole of NaCI = 58.5 gm = two osmoles.  Osmolality = number of osmoles dissolved in one kilogram of water.  Osmolarity = number of osmoles in one liter of water.  Different methods of transport across the cell membrane  Plasma osmolarity as regard the sum of all ions (cations and anions) would be over 300 mOsm/L.  Body fluids are not ideal solutions. Though dissociation of strong electrolytes is complete, the number of particles free to exert an osmotic power is reduced owing to the interaction between ions.  Osmolarity of plasma is 290 mOsm/L = 5597 mmHg osmotic pressure. ECF ICF Plasma ISF Osmolarity (mOsm/L) 290 290 290  Different methods of transport across the cell membrane  Tonicity is the osmolality of a solution relative to the osmolality of plasma.  An isotonic solution has the same osmolality as the plasma i.e. 290 mOsm /L. e.g. 0.9 % NaCI or 5% glucose solution.  A hypertonic solution has higher osmolality than plasma.  A hypotonic solution has lower osmolality than the plasma.  All isosmotic solutions would remain so if it were not for the fact that some solutes diffuse into the cells or being metabolized:  0.9% NaCl remains isotonic, while 5% glucose is initially isotonic and after being metabolized, the net effect is hypotonic solution infusion. Different methods of transport across the cell membrane  Different methods of transport across the cell membrane 2. Active transport.  It is the transport of substance across the cell membrane against an electrochemical gradient.  Active transport depends on specific carrier proteins.  Energy is needed for the substance to be transported.  The energy is derived from ATP and the carrier protein has ATPase activity.  The energy required is proportional to log ∆C.  Different methods of transport across the cell membrane  Types of active transport: - I. Uniport: Transports one substance in one direction. e.g., Ca+2 pumps. II. Co-transport: This is a carrier that transports two substances simultaneously, which is further subdivided into: a) Symport: Transports two substances in the same direction, e.g., carriers of glucose and Na+ from the intestinal lumen to inside of the cells. b) Antiport: Transports one substance in one direction and another substance in the opposite direction. e.g., Na+/K+ pump.  Active transport may be classified into: A. Primary. B. Secondary.  Different methods of transport across the cell membrane A. Primary (Na+/K+ ATPase pump).  Accounts for 24% of energy utilized by cells, 70% in neurons and 90% in kidneys.  Different methods of transport across the cell membrane  Has a coupling ratio of 3:2.  Inhibited by oubain & related digitalis glycosides.  Heterodimer, separation eliminates activity:  The α subunit o Have 5 intracellular binding sites for 3 Na+, phosphorylation and ATP. o Have 3 extracellular binding sites for 2 K+ and ouabain.  β subunit: anchor the protein complex in cell membrane.  Different methods of transport across the cell membrane  Binding of 3 Na+ is followed by ATP binding  converted to ADP with P being transferred to phosphorylation site  configurationally changes  extruding Na+ extracellularly.  This is followed by K+ binding  dephosphorylation  returning to its original configuration  releasing K+ to the cytoplasm.  Regulated by: 1. Substrate availability. 2. Thyroid hormones (genomic). 3. Aldosterone (2ry). 4. Insulin (increases activity by variety of mechanisms). 5. 2nd messenger molecules (cAMP and DAG). 6. Dopamine (phosphorylation-mediated inhibition).  Different methods of transport across the cell membrane B. Secondary.  The carriage of glucose secondary to the active transport of Na+.  It gains its energy from the energy stored in the form of ionic concentration differences created originally by 1ry active transport.  Different methods of transport across the cell membrane  Na+ is carried first actively outside the cell.  This lowers intracellular [Na+]  maintaining its chemical gradient.  Na+ and glucose bind to the carrier (SGLUT-II or I).  The carrier changes in shape and so becomes suitable for glucose carriage inside the cell.  Glucose is then extruded out down its concentration gradient through glucose transporters I & II (facilitated diffusion).  Different methods of transport across the cell membrane 3. Vesicular transport.  It is the movement of macromolecules that are enclosed inside cell membrane bound vesicles.  It is of two types: endocytosis and exocytosis.  Different methods of transport across the cell membrane A- Endocytosis: It is the movement from outside the cell to inside. a) Pinocytosis = cell drinking: It is the only mean by which some very large water-soluble macromolecules such as protein molecules can enter the cells as small invagination vesicles containing extracellular fluid. The portion of the membrane then breaks away from the surface of the cell forming a pinocytic vesicle. 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  Different methods of transport across the cell membrane B- 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 becomes redundant (if exocytosis is more). Functions of cell membrane proteins  Functions of cell membrane proteins 1. Structural proteins: They keep the integrity of the membrane and give it strength. 2. Form passive channels: 3. Carriers in facilitated diffusion: 4. Carriers in active transport (=Pumps): 5. Receptors: 6. Enzymes: 7. Identity proteins: They are mostly glycoproteins which give the cells the individual's label of identity, so that they would not be attacked by the immune system.  Functions of cell membrane proteins 8. Intercellular connections:  Fasten the cells to one another & to the surrounding tissues. 1. Tight junctions (zonula occludence). 2. Desmosomes. 3. Zonula adherence. Permit transfer of ions & other molecules from one cell to another: 1. Gap junctions. 9. Cell adhesion molecules (CAMs): Attach cell to basal lamina. 10.Cytoskeleton of the cell: System of fibers that maintains the structure of the cell and permits it to change shape and move. Intercellular communication Intercellular communication Gap Junctions Synaptic Paracrine & Autocrine Endocrine Directly from Across synaptic By circulating body By diffusion in ISF cell to cell cleft fluids Local Local Local Systemic Intercellular communication 1- Intercellular Gap Junctions: Conclusion Water distributes itself between ICF (40%), ISF (15%) and IVF (plasma, 5%). Homeostasis is defined as keeping the composition of the internal environment constant. Cell membrane is an amphipathic structure which contains proteins (55%), phospholipids (25%), cholesterol (13%), other lipids (4%) and carbohydrates (3%). Conclusion Transport through the cell membrane may be by diffusion, active transport or vesicular transport. Intercellular communication may occur through gap junctions, neuronal or endocrine. References Guyton and Hall, 13th edition. Unit V(25); 305-14. Ganong’s review of medical physiology 25th ed. Section I(2); 45-53. Questions Questions Thank You