Permeability Of Lipid Bilayer Smaller and more hydrophobic molecules diffuse across membrane more...

Permeability Of Lipid Bilayer

• Smaller and more hydrophobic molecules diffuse across membrane more rapidly

Membrane Transport Proteins

• Many types; each transports specific molecule• Carrier proteins- bind molecule, conformational change• Channel proteins- aqueous pore allows passage

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

Types Of Carriers

• Uniport- single molecule• Symport- two molecules in same direction• Antiport- two molecules in opposite directions

Passive Transport By Carriers

Resembles enzyme-substrate reaction• Binding affinity reflected by Km

• Vmax achieved when binding saturated

• Binding can be inhibited

Mechanisms Of Active Transport

• Driven by ATP hydrolysis (primary active transport)• Driven by coupling to passive transport of a different

molecule (secondary active transport)

Na+-K+ Pump

• [Na+] higher on outside; [K+] higher on inside• ATP-driven Na+-K+antiporter

• 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

Transcellular Transport

• Transport through epithelial cells• Active transport by Na+-driven symporters on apical surface• Diffusion via carriers on basolateral surface

Regulating pH

• Na+-H+ exchanger: Na+ gradient drives H+ out of the cell

• ATP-driven H+ pumps: H+ into intracellular compartments such as lysosomes

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

Classes of ATP-Driven Pumps

P-Type Transport ATPases

• Includes Na+-K+ pump and Ca2+ ATPase• Autophosphorylation and subsequent dephosphorylation

transmit conformational changes

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

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

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

Ion Channels

• Passive transport• Selective• Gated

Gating Of Ion Channels

Resting Membrane Potential

• Between -20 mV and -200 mV• Small flow of ions has large effect

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

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