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  1. 1. Script for - MECHANISMS OF TRANSPORT ACROSS THE CELL MEMBRANE Slide #2- Transport and the Cell MembraneTransport?Definition: Any process wherein movement of matter and/or energy from one part of asystem to another occurs.Importance of Transport?To carry on life-sustaining and specialized activities, each cell must exchange materialsacross the cell membrane with the homeostatically maintained internal fluid environmentthat surrounds it, i.e. the ECF.Transport Across the Cell Membrane Depends on?Transport across the cell membrane depends on the permeability of the membrane.A membrane can be either permeable, semi-permeable or impermeable.If a substance can cross the membrane, the membrane is said to be permeable to thatsubstance, if a substance is unable to pass, the membrane is impermeable to it.The plasma (cell) membrane is selectively permeable in that it permits some particles topass through while excluding others.Properties of the Substance to Pass Through the Cell MembraneWithout any Assistance? 1. Relative solubility of the particle in lipid, i.e. lipid-solubility- so that it can pass through the lipid bilayer, which forms the cell membrane. 2. The size of the particle, for water-soluble substances that should be of less than o.8nm in diameter to actually pass through a protein channel that is part of the cell membrane.Uncharged/non-polar/highly lipid soluble molecules readily dissolve in the lipid bilayerand permeate through the membrane. Examples are oxygen, carbon dioxide and fattyacids.Charged/polar/poorly lipid soluble substances cannot pass through the lipid bilayer andrequire a passage to pass. Protein channels serve as the substitute pathway.
  2. 2. Slide #3- Structure of the Cell MembraneCell Membrane?It is the external limiting, outer boundary of the cell. The semi-permeable cell membranehelps control what substances enter or exit the cell. It is a delicate structure, whichencloses the cell, separating the contents of the cell from the surrounding environment.Some cell organelle cells are membrane-bound and also have this cell membrane, e.g.mitochondria, nucleus, endoplasmic reticulum, etc.The cell membrane surrounds the cytoplasm of a cell and physically separates theintracellular components from the extracellular environment, thereby serving a functionsimilar to that of skin. The cell membrane is known as the fluid mosaic model becauseproteins are embedded in a sea of lipids giving a mosaic effect in fluid contributed bylipids.The functions of the cell membrane include, but are not limited to: • Controlling what goes in and out of the cell. • Excretion of metabolic products. • Anchoring of the cytoskeleton to provide shape and size to the cell. • Attaching to the extracellular matrix to help group cells together in the formation of tissues. • Transportation of particles by way of ion pumps, ion channels, and carrier proteins. • Containing receptors that allow chemical messages to pass between cells and systems. • Participation in enzyme activity important in such things as metabolism and immunity. • Exchange of gases and nutrients. • Repels negatively charged molecules inside the cell, keeping them in.Lipid Bilayer?Cholesterol prevents fatty acid chains from crystallizing, increasing membrane fluidity.Membrane carbohydrates serve as self-identity markers that enable cells to identify andinteract with each other. Membrane proteins have a variety of functions such as to serveas channels for water-soluble substances, to transfer specific substances across themembrane, to act as receptor sites, to serve as docking-marker receptors (t-SNAREs)which is involved in secretion, function as membrane bound enzymes, recognize selffrom non-self cells, involved in cell-to-cell interaction and as cell adhesion moleculesthat grasp extracellular matrix.
  3. 3. Slide #4- Membrane ProteinsClassifying Proteins? 1. Peripheral- on the periphery of the membrane either outside or inside usually on the cytosolic surface, part of the cytoskeletal proteins to maintain cell shape. 2. Integral (a.k.a. transmembrane)- spans the membrane involved in transport of substances in and out of the cell membrane a. Carriers b. Pumps c. Channels • Leaky • Gated (Voltage, Ligand, Mechanically)3. Lipid-anchored- Located covalently bound to single or multiple lipid molecules,which hydrophobically insert into the cell membrane and anchor the protein. The proteinitself is not in contact with the membrane.Conformational changes of gated-channels take place when certain stimuli are applied tothem.Carriers change their shape as they transport substances.Pumps use energy to getsubstances across the membrane against the concentration gradient. Pumps have an ATPbinding site as well.Classify Transport? (Same as in slide)Passive transport involves net movement of a substance along its concentration gradientnot requiring metabolic energy. Active Transport involves net movement of a substancealong its concentration gradient requiring ATP. Bulk transport is to transport large polarmolecules or multimolecular particles. Slide #5- Passive TransportDiffusion is the net movement of material from an area of high concentration of thatmaterial to an area with lower concentration. The difference of concentration between thetwo areas is often termed as the concentration gradient, and diffusion will continue untilthis gradient has been eliminated. Since diffusion moves materials from an area of higherconcentration to the lower, it is described as moving solutes "down the concentrationgradient" (compared with active transport, which often moves material from area of lowconcentration to area of higher concentration, and therefore referred to as moving thematerial "against the concentration gradient").
  4. 4. Slide #6- Simple DiffusionIt means that kinetic movement of molecules or ions occurs through a membrane openingor through intermolecular spaces without any interaction with carrier proteins in themembrane. The amount of substances available, the velocity of kinetic motion, and thenumber and sizes of openings in the membrane through which the molecules or ions canmove determine the rate of diffusion.The protein channels involved in simple diffusion are distinguished by 2 importantcharacteristics: they are often selectively permeable to certain substances and many of thechannels can be opened or closed by gates.Selectively permeability depends the channel itself-diameter, shape and nature of itselectrical charges and chemical bonds along its inside surface. Example: The Na Channelhas a strongly negative charge on the inside, which can pull small-dehydrated Na ionsactually pulling them away from their hydrating water molecules. The K Channel on theother hand are smaller and not negatively charged but have different chemical bonds. Thehydrated for of K ions are real small therefore it can pass through the K channels easilyas a hydrated structure. These are leaky channels.Conformational changes of gated-channels take place when certain stimuli are applied tothem. Voltage-gated channels open and close on electrical stimulus (e.g. action potential)whereas the ligand-gated channels respond to chemical stimuli (e.g. neurotransmitters,hormones) and mechanically gated channels respond to mechanical stimuli (e.g. pressure,touch, pain). An example of simple diffusion is how oxygen, a non-polar lipid soluble compound,diffuses across the respiratory membrane. There is a high concentration of oxygen in the lungs and a low one in tissues since it has given up most of its oxygen to the respiring tissues, therefore oxygen diffuses across the membrane from the lungs into the blood.
  5. 5. Slide #7- Facilitated DiffusionIt is movement of molecules across the cell membrane via special transport proteins thatare embedded within the cellular membrane. Many large molecules, such as glucose, areinsoluble in lipids and too large to fit through the membrane pores. Therefore, it will bindwith its specific carrier proteins, and the complex will then be bonded to a receptor siteand moved through the cellular membrane. The carrier facilitates diffusion of thesubstance to the other side. It is like a revolving door- a person enters from one side andthe door revolves to the other side of the door, where the person leaves.Carrier-mediated transport systems are of two kinds- facilitated diffusion and activetransport. The three characteristics that determine the kind and amount of substance to betransported through the cell membrane are: 1. Specificity- each carrier protein is specialized to transport a specific substance or closely related compounds. Example, the cysteine carriers found in the kidney membranes that remove the essential amino acid from urine and transport it back to the blood 2. Saturation- There is a limit to the amount of a substance that can be transported across the membrane via a carrier in a given time; that is, a limited number of carrier binding sites are available within a particular plasma membrane for a specific substance. The limit is known as the transport maximum. Until it is reached, the numbers of carrier binding sites occupied by a substance and, accordingly, the substance’s rate of transport across the membrane are directly related to its concentration. The more of a substance available to be transported, the more will be transported. When transport maximum has been reached, the carrier is saturated (all binding sites are occupied) and the rate of transport across the membrane is maximal. Further increases in the substance’s concentration are not accompanied by corresponding increases in the rate of transport. Example, glucose carrier mechanism is capable of actively reabsorbing up to 375 mg of glucose per minute before it reaches its maximum transport capacity, the rest being excreted in urine. 3. Competition- several closely related compounds may compete for a ride across the membrane on the same carrier. If a given binding site can be occupied by more than one type of molecule, the rate of transport of each substance is less when both molecules are present when either is present by itself. In other words, when a carrier can transport 2 closely related substances, the presence of both diminishes the rate of transport of either. Example, the case of alanine and glycine amino acids. An example of facilitated diffusion is by which glucose enters cells. The cells metabolize glucose almost rapidly as it enters the cells from the blood. There is, therefore, a continuous gradient for net diffusion of glucose into the cells. However, glucose is polar and uses a glucose carrier.
  6. 6. Slide #8- Factors influencing the Rate of Net Diffusion of a Substance across a Membrane (Fick’s Law of Diffusion)(Same as in slide)Movement of ions is also affected by their electrical charge. Like charges repel eachother whereas opposite charges attract. Cations move towards negatively charged areasand Anions move towards positively charged areas. Slide #9- OsmosisMost cell membranes are permeable to water, and since the diffusion of water plays suchan important role in the biological functioning of any living being, a special term hasbeen coined for it -- osmosis.The osmotic pressure exerted by particles in a solution, whether they are molecules orions, is determined by the number of particles per unit volume of fluid, not by the mass ofthe particles. The reason for this is that each particle in a solution, regardless of its mass,exerts, on average the same amount of pressure against the membrane. Large particleshaving greater mass move at slower velocities and vice versa.The tonicity of a solution refers to the effect on cell volume of the concentration of non-penetrating solutes in the solution surrounding the cell. 1. If the medium is hypotonic — a dilute solution, with a higher water concentration than the cell — the cell will gain water through osmosis. 2. If the medium is isotonic — a solution with exactly the same water concentration as the cell — there will be no net movement of water across the cell membrane. 3. If the medium is hypertonic- a concentrated solution, with a lower water concentration than the cell- the cell will lose water by osmosis.
  7. 7. Slide #10- Active Transport and Primary Active TransportActive transport requires a carrier to expend energy to transfer its passenger uphillagainst a concentration gradient. Some ions most be kept at higher concentrations in theICF than in the ECF or vice versa. This is possible only by active transport. For example,sodium ions should be of higher concentration in the ECF and potassium ions should behigher in concentration in the ICF.The hydrogen-ion pump present in gastric glands of the stomach and the late distaltubules and cortical collecting ducts of the kidneys exhibits primary active transport.Hydrogen ions are pumped into the stomach lumen to increase the acidic environmentbest for the activity of enzymes of the stomach.The Sodium- Potassium Pump transports sodium from the inside and to the outsidesimultaneously with potassium going in the opposite direction. By phosphorylating thecarrier on the intracellular side, the affinity for sodium to the carrier increases.Phosphorlylation is accomplished by the breakdown of ATP into ADP and inorganicphosphate, the inorganic phosphate binding to a specific site on the carrier molecule.Phosphorlyation also induces change in the shape of the carrier, leading to the depositionof sodium to the other side. The following dephosphorylation, affinity of the carrier topotassium increases on the extracellular side, changing the shape of the carrier, restoringit back to its original shape, depositing potassium on the other side, i.e. into the ECF.This pump establishes a concentration gradient which is necessary in generation ofelectrical impulses, helps regulate cell volume and also indirectly serves as the energysource in secondary active transport. Slide #11- Secondary Active TransportExample of Cotransport in glucose absorption in intestines- a cotransport carrier at theluminal border simultaneously transfers glucose against a concentration gradient andsodium down the gradient from the lumen to the cell. No energy is directly used by thecotransport carrier to move glucose uphill. Instead, operation of the carrier is driven bythe sodium concentration gradient (low sodium in ICF compared to lumen) established bythe energy-using sodium-potassium pump. The sodium-potassium pump activelytransports sodium out of the cell at the basolateral border, keeping the ICF sodiumconcentration lower than the luminal concentration.Example of Counter transport- sodium ions again attempts to diffuse to the interior of thecell because of their large concentration gradient. However, this time, the substance to betransported is on the inside of the cell and must be transported to the outside. Once bothsodium and the other substance to be transported have bonded to the carrier, aconformational change takes place and the substance is transported to the outside whilesodium enters the inside. Examples are of the sodium-calcium (in all cells mostly) andthe sodium-hydrogen (in proximal tubules of kidneys) counter-transport.
  8. 8. Slide #12- Bulk TransportSteps of endocytosis- 1. Cell membrane surrounds subject to be ingested by putting out pseudopodia. 2. Pseudopodia fuse over the surface. 3. Pinching of the membrane-enclosed vesicle so that engulfed material is trapped within the cell. There is membrane gain since vesicle membrane joins and adds to the cell membrane.Steps of exocytosis- 1. A membrane-enclosed vesicle formed within the cell fuses with the cell membrane. 2. The vesicle opens up outside the cell membrane. 3. Release of the substance.Filtration is movement of water and solute molecules across the cell membrane due tohydrostatic pressure generated by the cardiovascular system. Depending on the size of themembrane pores, only solutes of a certain size may pass through it. For example, themembrane pores of the Bowmans capsule in the kidneys are very small, and onlyalbumins, the smallest of the proteins, have any chance of being filtered through. On theother hand, the membrane pores of liver cells are extremely large, to allow a variety ofsolutes to pass through and be metabolized.Osmotic colloid pressure- in blood plasma, the dissolved compounds have an osmoticpressure. A small portion of the total osmotic pressure is due to the presence of largeprotein molecules and that is osmotic colloid pressure.Hydrostatic Pressure- is the pressure exerted by fluid on the walls that contain it.