Cell membrance .pdf

Cell membranes By Dr Rana M Hameed BSc.,MSc.-Baghdad/ Iraq, PhD.-London/UK (Biochemistry) Biochemistry Department College of Medicine / University of Kerbala E. mail : [email protected] [email protected]  Obje...

Cell membranes By Dr Rana M Hameed BSc.,MSc.-Baghdad/ Iraq, PhD.-London/UK (Biochemistry) Biochemistry Department College of Medicine / University of Kerbala E. mail : [email protected] [email protected]  Objectives Composition of cell membranes Lipid bilayer ee d H a m Integral membrane M protein a Transport across n a cell menbranes. r R D channels. Membrane Reference: General, Organic, and Biological Chemistry/ Chapter 19/section 19.10  CELL MEMBRANES A cell membrane is a lipid-based structure that separates a cell’s aqueous-based interior from the aqueous environment surrounding the cell. eed H a m M Besides its “separation” function, a cell membrane also controls the a r R an movement of substances into and out of the cell. D  Structure of membranes: Membranes are mainly formed of lipids, proteins and carbohydrates. Membrane lipids: The membrane lipids include mainly phospholipids with less glycolipids and cholesterol. Phospholipids: Glycerophospholipid: Sphingophosphollpids Glycolipids: These are lipids containing sugar. These are mainly in the form of: Cerebrosides: contain one sugar unit e.g. glucose or galactose: Gangliosides: contain 3 or more sugar units. Cholesterol: It is present mainly in plasma membrane, and lesser amount is present in mitochondrial and nuclear membranes.  phospholipids Phospholipids and sphingoglycolipids are the main and the eed most abundant lipid in the plasma membrane H a m Phospholipids are amphipathic molecules, containing hydrophobic and hydrophilic regions (“head and two tails”) a M r R an D - ↳ "" drop " a - hydrophobic  Lipid bilayer membranes: When these lipids are placed in water, the polar heads of phospholipids and sphingoglycolipids favor contact eed with water, whereas their nonpolar tails interact with one another rather than with water. H a m a M The result is a remarkable bit of molecular architecture called a lipid bilayer. r R an D A lipid bilayer is a two-layer-thick structure of phospholipids and glycolipids in which the nonpolar tails of the lipids are in the middle of the structure and the polar heads are on the outside surfaces of the structure.  Lipid bilayer membranes: Such a bilayer is six-billionths to nine-billionths of a nanometers thick. eed There are three distinct parts to the bilayer: the exterior polar “heads,” H a m the interior polar “heads,” a M an and the central nonpolar “tails,” r R D  Lipid bilayer membranes: WATER Hydrophilic head eed Hydrophobic tail H a m a M r R an WATER D  Lipid bilayer membranes: A lipid bilayer is held together by intermolecular interactions, not by covalent bonds. Most lipid molecules in the bilayer contain at least one unsaturated fatty acid. eed The presence of such acids, prevents tight packing of fatty acid chains. The open a m packing imparts a liquidlike character to the membrane—a necessity because numerous types of biochemicals must pass into and out of a cell. H a M r R an D Figure: illustrate the Space-filling model of a section of a lipid bilayer. The key to the structure is the “head and two tails” structure of the membrane lipids that constitute the bilayer.  Cholesterol Cholesterol molecules are also components of cell membranes. They regulate membrane fluidity, because of their compact shape. eed H a m a M Cholesterol structure r R an Cholesterol molecules fit between the fatty acid chains of the lipid bilayer ,restricting movement of the fatty acid chains. Within the D membrane, the cholesterol molecule orientation is “head” to the outside (the hydroxyl group) and “tail” to the inside (the steroid ring structure with its attached alkyl groups). Cholesterol molecules fit between fatty acid chains in a lipid bilayer. Stability of lipid bilayer: It is stabilized by the following forces: Hydrophobic interactions: major force. Van Der Waals attractive forces: between the hydrocarbon tails. Electrostatic and hydrogen bonding: between the polar head group and water molecules. Membrane lipids are responsible for: Fluidity: 1. Definition: Ability of cell membrane components for movement. ↑ ↑ Fluidity Temperature 2. It depends on both temperature and lipid contents: ↑ fluidity unsaturated I. A ↑ The more temperature, the more fluidity. cholesterol ↑ ↑ Fluidity - hydrophobic - The more unsaturated fatty acids, the more fluidity. Cho lestrot ↑ ↓ Fluidity hydrophilic - - The more cholesterol content, the more fluidity in the hydrophobic core and less fluidity in the hydrophilic core. Selective permeability: Ionic and polar substances cannot pass cell membrane freely. This is due to the hydrophobic nature of the hydrocarbon chain in lipid bilayer. These substances can go out and in of all cells by specific membrane proteins. Asymmetry: Definition: It means that the lipid components of each half of the bilayer is different from the other. Also carbohydrates and proteins are irregularly distributed. Causes of membrane asymmetry: Phospholipids containing choline are located mainly in the outer layer, while phospholipids containing amino group e.g. phosphatidyl serine are located mainly in the inner layer. Carbohydrate content are located mainly in the out- layer. Protein content are irregularly distributed in the membrane. Many proteins e.g. hormone receptors are located in outer layer.  Proteins Proteins are also components of lipid bilayers. The proteins are responsible for moving substances such as nutrients and electrolytes across the membrane, ed They also act as receptors that bind hormones and neurotransmitters. e H a m There are two general types of membrane proteins: ❖ Integral: integral membrane protein is a membrane protein that a M penetrates (go through) the cell membrane. R an Some membrane proteins penetrate only partially through the lipid bilayer r D while others go completely from one side to the other side of the lipid bilayer. ❖ Peripheral: A peripheral membrane protein is a nonpenetrating membrane protein located on the surface of the cell membrane.  Proteins Intermolecular forces rather than chemical bonds govern the eed interactions between membrane proteins and the lipid bilayer. H a m a M r R an D Figure shows diagrammatically the relationship between membrane proteins and the overall structure of a cell membrane. Functions of membrane proteins: They carry out most membrane processes as: Transport of substances and communication. Cell membrane receptors. Immunoglobulins are integral proteins of membranes of lymphocytes which can be released and circulating In the blood. Proteins of mitochondrial membrane are essential for energy production (ATP). Many enzymes are membrane bound. Erythrocyte membrane proteins have important functions.  Carbohydrate Small carbohydrate molecules are also components of cell membranes. eed They are found on the outer membrane surface covalently bonded to H a m protein molecules (a glycoprotein) or lipid molecules (a glycolipid). The carbohydrate portions of glycoproteins and glycolipids function as markers, substances a M R an They play key roles in the process by which different cells recognize each r other. D Membrane carbohydrates: They are present in the form of glycoproteins and glycolipids. They are located on the external surface of cell membrane. Functions of membrane carbohydrate: Receptors: in the form of glycoprotein. Glycophorin: is a glycoprotein present in red cell membrane Glycoprotein of ovum which Is essential for recognition by sperm receptors. This is important for fertilization.  Functions of cell membrane: A. Structural functions: 1. Cell membranes (also called plasma membranes) form enclosed compartments around cells. They separate the inside cells from external environment. 2. Membranes also may be formed around organelles e.g. nucleus and mitochondria. B. Metabolic functions: 1. Membranes contain specific molecular pumps and gates 2. They contain specific receptors, which bind with different substances e.g. hormone receptors. lipid receptors.....etc. 3. Some membranes generate signals , which may be chemical or electric. 4. Membranes are the site of energy production: ATP production by oxidative phosphorylation in the inner mitochondrial membrane.  Transport across membranes  Passive transport Passive transport is the transport process in which a ed substance moves across a cell membrane by diffusion from a e H a m region of higher concentration to a region of lower concentration without the expenditure of any cellular energy. a M r R an Only a few types of molecules, including O2, N2, H2O, urea, and ethanol, can cross membranes in this manner. D Passive transport is closely related to the process of osmosis  Facilitated transport Facilitated transport is the transport process in which a substance moves across a cell membrane, with the aid of membrane proteins, from a eed region of higher concentration to a region of lower concentration without the expenditure of cellular energy. H a m The specific protein molecules involved in the process are called carriers or transporters. a M an A carrier protein forms a complex with a specific molecule at one surface of the membrane. D r R Formation of the complex induces a conformational change in the protein that allows the molecule to move through a “gate” to the other side of the membrane. Once the molecule is released, the protein returns to its original conformation. Glucose, chloride ion, and bicarbonate ion cross membranes in this manner.  Active transport Active transport is the transport process in which a substance moves across a cell membrane, with the aid of membrane proteins, against a concentration gradient with the expenditure of cellular energy. eed H a m Proteins involved in active transport are called “pumps,” because they require energy much as a water pump requires energy in order to function. M The needed energy is supplied by molecules such as ATP. The need for energy a an expenditure is related to the molecules moving against a concentration gradient— D R from lower to higher concentration. r It is essential to life processes to have some solutes “permanently” at different concentrations on the two sides of a membrane, a situation contrary to the natural tendency (osmosis) to establish equal concentrations on both sides of a membrane. Hence the need for active transport. Sodium, potassium, and hydronium ions cross membranes through active transport.  Passive transport Passive transport Simple diffusion Isotonic Solution Diffusion Facilitated Diffusiondiffusion Osmosis Hypotonic Osmosiseed Solution Filtration Filtration Simple diffusion H a m Hypertonic Solution Isotonic Solution Facilitated diffusion n a M Hypotonic Solution r R a Hypertonic Solution D  Simple Diffusion Diffusion is a passive process of transport. A single substance tends to move from an area of high concentration to an eed area of low concentration until the concentration is equal across space. Materials move within the cell’s cytosol by diffusion, and certain H a m materials move through the plasma membrane by diffusion. M Diffusion expends no energy. Rather the different concentrations of a r R an materials in different areas are a form of potential energy, and diffusion is D the dissipation of that potential energy as materials move down their concentration gradients, from high to low.  Factors effect Simple Diffusion The rate of diffusion will be increased when there is : eed Concentration: the difference in between two areas (the gradient) causes diffusion. a m The greater the difference in concentration, the faster the diffusion. H Molecular size: smaller substances diffuse more quickly. Large molecules (such as a M starches and proteins) simply cannot diffuse through. R an Shape of Ion/Molecule: a substance’s shape may prevent it from diffusing rapidly, r D where others may have a shape that aids their diffusion. Viscosity of the Medium: the lower the viscosity, the more slowly molecules can move through it.  Facilitated diffusion In facilitated transport, also called facilitated diffusion, material moves across the plasma membrane with the assistance of transmembrane proteins down a concentration gradient (from high to low concentration) without the expenditure of cellular energy. However, the substances that undergo facilitated transport would otherwise not diffuse easily or quickly across the plasma membrane. eed The solution to moving polar substances and other substances across the plasma membrane rests in the proteins that span its surface. H a m The material being transported is first attached to protein or glycoprotein receptors on the M exterior surface of the plasma membrane. This allows the material that is needed by the cell to a an be removed from the extracellular fluid. D R The substances are then passed to specific integral proteins that facilitate their passage r because they form channels or pores that allow certain substances to pass through the membrane. The integral proteins involved in facilitated transport are collectively referred to as transport proteins, and they function as either channel for the material or carriers  Several factors affect the rate of diffusion The extent of the concentration gradient: The greater the difference in concentration, equilibrium, the slower the rate of diffusion becomes.eed the more rapid the diffusion. The closer the distribution of the material gets to H a m Mass of the molecules diffusing: More massive molecules move more slowly because M it is more difficult for them to move between the molecules of the substance they are a R an moving through; therefore, they diffuse more slowly. Temperature: Higher temperatures increase the energy and therefore the movement of r D the molecules, increasing the rate of diffusion. Solvent density: As the density of the solvent increases, the rate of diffusion decreases. The molecules slow down because they have a more difficult time getting through the denser medium.  Filtration Filtration is the movement of water and solute molecules across the cell system. eed membrane due to hydrostatic pressure generated by the cardiovascular H a m Depending on the size of the membrane pores, only solutes of a certain size may pass through it. a M r R an For example, the membrane pores of the Bowman’s capsule in the kidneys D are very small, and only albumins, the smallest of the proteins, have any chance of being filtered through. On the other hand, the membrane pores of liver cells are extremely large allowing a variety of solutes to pass through and be metabolized.  Osmosis Osmosis: It is the spontaneous net movement of a solvent like water, across a semipermeable membrane from a less concentrated solution into a more concentrated ed one, until the concentrations become equal on either side of the membrane. e There are three different types of solutions:H a m An isotonic solution is one that n a M has the same concentration of solutes both a cell. D r R inside and outside the A hypertonic solution is one that has a higher solute concentration outside the cell than inside. A hypotonic solution is the one that has a higher solute concentration inside the cell than outside.  Cells in Solutions eed H a m a M r R an D Significance of Osmosis NO NET MOVEMENT OF H2O (equal amounts entering CYTOLYSIS PLASMOLYSIS ed & leaving) e Osmosis influences the transport of nutrients and the release of metabolic waste products. a m It stabilizes the internal environment of a living organism by maintaining the balance between water and intercellular fluid levels. H a M This process controls the cell to cell diffusion of water. r R an Semipermeable membrane? D The semipermeable membrane is a biological membrane, which functions by permitting the movements of certain molecules or ions to pass through it. https://www.khanacademy.org/science/ap-biology/cell-structure-and-function/mechanisms-of-transport-tonicity-and- osmoregulation/v/diffusion-and-osmosis Factors affecting transport Cell membrane eed Chemical gradient H a m n a M Electrical gradient r R a D Rate of transport  Factors affecting transport: Cell membrane The cell needs to absorb and excrete various compounds throughout its life. These compounds need to pass through the membrane which is made from a phospholipid bilayer eed a m The phospholipid bilayer is formed by phospholipid molecules bipolar H molecule: the fatty acid side is hydrophobic, the phosphoric side is a M hydrophilic r R an D  Factors affecting transport: Cell membrane The membrane is impermeable to: d The membrane is permeable to: ❖ H2O ee ❖ Small, charged molecules m ❖ Gases (O2, CO2, N2) H a ❖Lipids a M ❖“large molecules” such as amino an acids, glucose and larger ❖Small, neutral molecules (such as urea) D r R ❖ These compounds must go through channels present in the membrane in order to enter or exit the cell  Factors affecting transport: Chemical gradient Compound moves from an area of high concentration to low concentration (or eed concentration gradient) H a m a M R an All compounds permeable to the phospholipid bilayer will r move this way D  Factors affecting transport: Electrical force Positive ions are attracted to negative ions and vice versa eed H a m a M R of the same charge (+ r an Ions are repelled by ions D against + and – against -)  Factors affecting the rate of transport The rate of transport will depend on: eed ❖The concentration gradient H a m ❖ The compound permeability to the membrane a M r R an ❖ The type and number of charges present on the compound D  Significance of Passive Transport It commonly occurs in the blood-brain barrier as specific molecules, such as sodium thiopental, can diffuse across the membrane. and fetus. eed Passive diffusion occurs across the placenta as all solute particles are exchanged between mother across membranes. H a m The passive forms of transport, diffusion and osmosis, move materials of small molecular weight a M Digested food molecules (amino acids, glucose) move down a concentration gradient from the intestine to the blood. Waste products such as carbon dioxide or urea travel by diffusion from body cells into the bloodstream. r R an Oxygen moves from high concentration (in the air sac) to a lower concentration (in the blood). D Carbon dioxide moves from high concentration (in the blood) to a lower concentration (in the air sac). The biological importance of osmosis is that it facilitates the distribution of essential nutrients in the body and the excretion of metabolic waste products. Cells have semipermeable membranes, and osmosis makes it possible for liquid solvents to pass through these cell membranes. In animals (including humans), renal filtration removes waste from the blood.  Active Transport Protein d Pumps mee H a a M r Ran Vesicles D Endocytosis Pinocytosis Phagocytosis Receptor-mediated Exocytosis  Active transport 1) Pumps Ion pumps are the only molecules capable of performing primary active transport. Most ion pumps of interest to us are transport ATPases, that is, they eed are bifunctional molecules that both hydrolyze ATP H a m a M and perform the translocation of the substrate R an against the prevailing electrochemical gradient. The r D Na+,K+-ATPase, Na+ K+ pump, or Na+ pump, was the first enzyme demonstrated to be an active ion transporter ❖ATP (energy) is needed  pump ❖Moves materials from LOW to HIGH concentration ❖AGAINST concentration gradient  Example-1 ATPase pumps eed H a m a M r R an The most common: Na/K pumps reestablish membrane potential. Present in all cells. D Two K+ ions are exchanged with 3 Na + ions  EXAMPLES OF ACTIVE TRANSPORT Example 2: The thyroid gland accumulates iodine as it is needed to eed manufacture the hormone thyroxin. H a m a M R an The iodine concentration can be as much as 25 times more concentrated r D in the thyroid than in blood. Example 3: In order to make ATP in the mitochondria, a proton pump (hydrogen ion) is required. eed H a m a M r R an D  Electron transfer and proton pumping. As electrons are passed down the chain, they move from a higher to a lower energy level, releasing energy. Some of the energy is used to pump H ions, moving them out of the matrix and into the intermembrane space. This pumping establishes an electrochemical gradient.  Active transport 2) Vesicles (Endocytosis) Endocytosis: (“Endo” means “in”). exocytosis and endocytosis: transport larger molecules such as proteins and eed polysaccharides, and even very large particles.. This requires energy. H a m a M r R an Endocytosis : a process in which the plasma membrane invaginates or fold inward, to form a vesicle that brings substances into the cell.. D  There are Three types of endocytosis Pinocytosis: or cellular drinking, occurs when the plasma membrane folds ed inward to form a channel allowing dissolved substances to enter the cell. When e H a m the channel is closed, the liquid is encircled within a pinocytic vesicle. Phagocytosis or cellular eating, occurs when the dissolved materials enter the a M an cell. The plasma membrane engulfs the solid material, forming a phagocytic vesicle. D r R Receptor-mediated: chemical (LDL carrying cholesterol) binds to receptor protein before being brought into the cell; specific There are Three types of endocytosis eed H a m a M r R an D Pinocytosis eed H a m a M r R an D  Receptor-Mediated Endocytosis Some integral proteins have receptors on their surface to recognize & take in hormones, cholesterol, etc. eed H a m a M r R an D  Phagocytosis Used to engulf large particles such as food, bacteria, etc. into vesicles Called “Cell Eating eed H a m a M r R an D  Active transport 2) Vesicles (Exocytosis) Exocytosis: (“Exo” means “out”.) Exocytosis is the reverse of endocytosis. e This is where a cell releases the contents of a vesicle e d outside of the cell, also requires energy. H a m other product for secretion. ana M These contents may be wastes, proteins, hormones, or some rin R D Exocytosis : a process which material inside a cell is packaged into vesicles and excreted into the extracellular medium. Example: vesicles from the Golgi fuse with the plasma membrane and the proteins are released outside of the cell.  Types of Membrane Transport Proteins Uniporters Solute Carriers Solute Carriers Symporters e Antiportersed H a m Ion Channelsna M Ligand-gated channels: R a Ion Channels Voltage-gated channels: Dr Mechanically-gated channels: ATP ATPdependent dependent ATPase Ion Transporters Transporters Transporters ATP – binding cassette (ABC) transporters  Solute Carriers-Secondary active transport > 40 types , > 300 transporters. ed Three groups- 1. Uniporters- single molecule across the e H a m membrane (GLUT ) 2. Symporters- Two or more molecules a M an Ex- Na-k-cl Symporter (Kidney) D r R Na - Glucose Co-transporter. 3. Antiporters- Two or more molecules in opposite directions Ex :Na- H antiporter ( PH regulation) 3Na- Ca , Cl- HCO3 Uniport pore One type of molecule transported Change of configuration P P P Phosphorylation Dephosophorylation ATP + H2O → ADP + Pi  Symporters Or Coupled pores Two molecules transported together Symport: Both molecules move in the same direction Change of configuration P P P Dephosophorylation Phosphorylation ATP + H2O→ ADP + Pi  Antiport pores Molecules move in opposite directions (one in the other out) P P P e.g. Na+ (out) and K+ (in). Usually using for pH regulation. Change of Phosphorylation configuration P P P Dephosophorylation  Ion channels (concepts) (1) Ligand-gated channels: eed Usually opened by intracellular or extracellular ligands e.g. IP3 (Inositol triphosphate receptor) -sensitive Ca2+ channel opens in the presence of IP3 H a m (2) Voltage-gated channels: a M R an Altering voltage beyond a threshold will cause the channel to open. r D channels: (3) Mechanically-gated e.g. “stretch-activated channels” open when cell shape is altered. Since channel is attached to the cytoskeleton, stretching causes a physical change in the protein Ion channels  ATP Dependent transporters 1. ATPase Ion Transporters e e d P- Type- gate phosphorylted during transport. Na- K ATP ase. V- Type- Vacuolar H- ATPase – urine H a m acidification on Vacuoles like endosomes and lysosomes. a M 2. ATP – binding cassette (ABC) transporters n – 7 subgroups transport diverse group R a of ions ex- Cl, Cholesterol, r bile acids, drugs, and organic anions. EX:- Cystic D fibrosis transmembrane regulator. Multidrug Resistance Protein organic Anions. Thank you Question Time ? eed H a m a M r R an D https://www.khanacademy.org/test-prep/mcat/cells/transport-across-a-cell-membrane/v/how-do-things-move- across-a-cell-membrane