MEMBRANES: STRUCTURE AND FUNCTION TOPIC 4 1
BIOMEDICAL IMPORTANCE • Plasma membranes- form closed compartments around cellular protoplasm to separate one cell from another • Selective permeabilities- provided by channels and pumps for ions and substrates • Receptor property • Exchange materials with extracellular environment – excocytosis and endocytosis • Gap juctions • Cell-cell interactions • Transmembrane signaling • Form specialized compartments within cell – provide shape for mitoch, ER, golgi • Membrane localize enzymes-excitation response coupling- • Site for energy transduction • Changes in membrane structure? 2
Maintenance of a normal intra- &extracellular environment is fundamental to life Life originated in aqueous environments- enzyme reactions, cellular and subcellular processes evolved to work in this milieu. How this aqueous state is maintained? 3
Fluid distribution 2 large compartments that distribute water 1. Intracellular fluid – ICF • 2/3 of body water • Provides the environment for the cell to make, store and utilize energy to repair itself to replicate to perform special functions 4
Fluid distribution 2. Extracellular Fluid – ECF • 1/3 of body water • A delivery system for glucose, f.a, a.a, O2, ions and trace minerals etc • Remove CO2 and waste product from cellular environment 5
The ionic compositions of intracellular and extracellular fluids Mammalian cell maintained the ionic compositions through the membranes 6
Membranes structure Lipids, Proteins and Carbohydrates 7
MEMBRANES MODEL 8
LIPIDS COMPOSITION IN MEMBRANE • Major lipids – phospholipids, glycosphingolipids & cholesterol amphipatic 9
Membrane lipids form bilayer • Bilayers- a structure formed resemble the micelle structure – provide optimal condition for amphipatic molecules • Hydrophobic regions are protected from the aqueous environment and hydrophilic regions are immersed in water • Micelles can only extedn to 200nm – and bilayers can extend to 1mm • Formed by self-assembly – driven by the hydrophobic effect 10
Lipid bilayer How many biologic materials are lipid soluble and can therefore readily enter the cells? • O2, CO2, N2- readily diffuse • Other molecules (Figure) diffuse according their permeability in non polar solvents • Steroids more readily traverse the lipid bilayer compared with electrolytes 11
Lipid bilayer How molecules that are non lipid-soluble cross the membrane? • Membrane contain protein – form channels for the movement of ions and small molecules • Serve as transporter for larger molecules • Different membrane consist of different composition of protein • Include – enzymes, pumps and channels, structural components, antigen (for MHC), and receptor for various molecules • 2 types of proteins – integral and peripheral 12
Integral protein • Deeply embbedded in the membrane • Span the bilayer • Usually globular and amphipatic • Certain protein (transporter, receptor, G proteins) – span the bilayer many times • Asymmetrically distributed across the membrane bilayer • Require detergent or their solubilization • Eg: insulin receptor, glycophorin, rhodopsin 13
Peripheral protein • Do not interact directly with phospholipids in the bilayer- don’t need detergents for their release • Bound to charge group of lipid bilayer • Attach to the integral protein or penetrate the peripheral regions of lipid bilayer • Can be released by treatment with salt solutions • Eg- enzyme (phosphilipases, glycosyltransferases and many more! • Transportr of small hydrophobic molecules-glycolipid transfer protein, sterol carrier protein 14
Fluid Mosaic Model • Proposed by Singer and Nicholson • Resemble to icebergs (membrane protein) floating in a sea of predominantly phospholipid molecules • Integral protein and phospholipid were found rapidly and randomly redistributed in the plasma membrane-fluidity • Fluidity- depends on the lipid composition of the membrane 15
Fluid Mosaic Model • Unsaturated-have kink in the hydrocarbon chain- cause disorder in the packing of the chains-more open structure and fluid • Saturated f.a – no kink and have longer hydrocarbon chain – interact more strongly – more rigid structure • Cholesterol-enhance order and rigidity 16
Effect of temperature • Temperature increase- hydrophobic side chains undergo a transition from an ordered state (gel like) to a disordered state (fluid) • Transition temperature • The longer and saturated the hydrocarbon chains- the higher temperature needed to increase the fluditiy 17
Membrane fluidity The fluidity of membrane affect its functions • Fluidity ↑ - permeability to water and other small hydrophilic molecule ↑ -lateral mobility of integral protein ↑ • active site in hydrophilic region maybe affected • if protein involve in transportation, location changes cause disruption in transportation Eg. Insulin receptor ↑ in unsaturated f.a cause ↑ in fluidity - alter the receptor so it binds more insulin (pls check) 18
Membrane Selectivity 19
TYPE OF TRANSPORT MECHANISM 20
Active and Passive transport • Passive – do not involve energy- substance move from ↑ conc to ↓ conc – in the same direction as conc gradient • Active – substance moves from ↓ conc to ↑ conc – against conc gradient – require energy • Passive – simple diffusion and facilitated 21
Passive transport Factors affect diffusion of a substance: 1. Conc gradient across the memb 2. The electrical potential across the memb – solutes move toward the solution that has the opposite charge – inside of cell has a neg charge 3. The permeability coefficient of the substance for the memb 4. The hydrostatic pressure gradient across the memb - ↑pressure will ↑the rate and force of the collision between the molecules and memb 5. Temperature - ↑ temp will↑ the freq of collisions between external particles and the memb 22
Passive transport- simple diffusion • Small, uncharged molecules, such as O2, N2, and C02 • Rate of movement depend on the conc difference across the membrane 23
Active transport • Identified by the presence of carrier protein • The need for an energy source to move solutes against a gradient • Primary active transport-linked to hydrolysis of energy – pumping water uphill -E.g sodium- potassium pump • Secondary active transport – e.g- galactosidase permease in cell 24
Transport system • Uniport system-move one type of molecule bidirectitonally • Co transport system-transfer of one solute depends upon the stoiciometric simultaneous or sequential transfer of another solute • Symport – moves these solutes in the same direction – eg: proton- sugar transporter in bacteria and Na+ - sugar transporter and Na+- amino acid transporters in mammalian cells • Antiport-moves 2 molecules in opposite directions. Eg.Na+ in and Ca2+ out 25
Passive transport- facilitated diffusion • Uniport system • Using carrier protein • Glucose pass thru the membrane using glucose permease as the carrier protein • No energy is expended • E.g. Ping-Pong mechanism 26
Passive transport- facilitated diffusion • Hormones regulate facilitated diffusion by changing the number of transporters available • Insulin increases glucose transport from intracellular reservoir • Glucocorticoid hormones-enhance transport of aa into liver • Growth hormon-increase amino acid transport in all cells 27
Transport System 1. Ion channels 2. Ionophores 3. Water channels (Aquaporins) 4. Gap Junction 28
ION CHANNELS • Ion channels- transmembrane, pore like structure composed of proteins • Specific channels for Na+, K+. Ca2+ and Cl- have been identified • Open transiently and thus gated – can be controlled by opening and closing 29
ION CHANNELS • Ligand-gated channels- specific molecule binds to a receptor and opens the channel- neurotransmitter • Voltage-gated channels-open or close in response to changes in membrane potential- activated by changes in electrical potential difference – neuron and muscle tissue • Example of active transport using ion channels – Sodium Potassium Ion Pump and Galactose Permease Visit Youtube for animation 30
Sodium Potassium Ion Pump • Under normal condition, ([K+] inside > [K+] outside ) and ([Na+] inside < [Na+] outside ) • Energy required to move these ions against their gradients comes from hydrolysis of ATP • The protein function as enzyme that hydrolyze ATP and as transporter- ATPase • The pumping process transport 3 Na+ ions out of the cell for every 2 K+ ions transported in the cell • Self-study: Details mechanism involve in Na+K+ pump 31
Galactose Permease • In bacteria • [lactose]inside the bacterial cell>outside – moving lactose into the cell req energy • Galactose permease does not directly hydrolyze ATP-but harnesses the energy by using the higher concentration of H+ outside cell to drive the conc of lactose inside cell • Self-study: Details mechanism involve in Na+K+ pump 32
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