permeability of lipid bilayer smaller and more hydrophobic molecules diffuse across membrane more...
TRANSCRIPT
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Permeability Of Lipid Bilayer
• Smaller and more hydrophobic molecules diffuse across membrane more rapidly
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Membrane Transport Proteins
• Many types; each transports specific molecule• Carrier proteins- bind molecule, conformational change• Channel proteins- aqueous pore allows passage
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Passive Versus Active Transport
• Driven by concentration or electrochemical gradient
• Mediated by carriers and channels
Passive
Active• Transport against gradient• Requires energy input• Mediated only by carriers
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Types Of Carriers
• Uniport- single molecule• Symport- two molecules in same direction• Antiport- two molecules in opposite directions
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Passive Transport By Carriers
Resembles enzyme-substrate reaction• Binding affinity reflected by Km
• Vmax achieved when binding saturated
• Binding can be inhibited
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Mechanisms Of Active Transport
• Driven by ATP hydrolysis (primary active transport)• Driven by coupling to passive transport of a different
molecule (secondary active transport)
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Na+-K+ Pump
• [Na+] higher on outside; [K+] higher on inside• ATP-driven Na+-K+antiporter
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• Na+ influx coupled to active transport across plasma membrane• Import of sugars and amino acids by Na+-driven symports
Using Na+ Gradient To Drive Active Transport
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Transcellular Transport
• Transport through epithelial cells• Active transport by Na+-driven symporters on apical surface• Diffusion via carriers on basolateral surface
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Regulating pH
• Na+-H+ exchanger: Na+ gradient drives H+ out of the cell
• ATP-driven H+ pumps: H+ into intracellular compartments such as lysosomes
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Maintaining Low Cytosolic Ca2+ Levels
• Ca2+ ATPase (calcium pump): Ca2+ out of cell or into intra-cellular compartments
• Na+-Ca2+ exchanger: Na+ gradient drives Ca2+ out of the cell
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Classes of ATP-Driven Pumps
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P-Type Transport ATPases
• Includes Na+-K+ pump and Ca2+ ATPase• Autophosphorylation and subsequent dephosphorylation
transmit conformational changes
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ABC Transporters
• ATP binding domains: dimerization from ATP binding, dissociation from ATP hydrolysis
• ATP binding/hydrolysis transmits conformational changes
• MDR overexpression causes resistance to cancer chemotherapy drugs
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Osmosis
• Diffusion of H20 across membrane; facilitated by aquaporins• H20 moves from side of low to high solute concentration
• Water enters cells in hypotonic and leaves in hypertonic solutions
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Control Of Cell Osmolarity
• Charged macromolecules and metabolites attract inorganic ions
• Osmotic gradient pulls in H20
• Opposing osmotic gradient generated by Na+ (pumped out) and Cl-
in extracellular fluid
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Ion Channels
• Passive transport• Selective• Gated
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Gating Of Ion Channels
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Resting Membrane Potential
• Between -20 mV and -200 mV• Small flow of ions has large effect
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Generating Resting Membrane Potential
• Depends mostly on K+ gradient and K+ leak channels
• K+ flows out of cell down its electrochemical gradient
• Equilibrium condition defines resting membrane potential
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Cystic Fibrosis
• Cystic fibrosis transmembrane conductance regulator (CFTR) is chloride channel
• Critical function in epithelial cells lining airway• CFTR F508 mutant not transported to plasma
membrane; retained in ER and degraded