Topic 7

• Facilitated diffusion


  Transporter proteins and channel proteins
• How are ions transported across the membranes?

  1. Most ion channels are gated:

  2. Ligand-gated

  3. Voltage-gated
• Ion channels


  • They are highly selective
  • Channels with narrow pores
  • Channels with a narrow selectivity filter
• The relative permeability of a lipid bilayer to different classes of molecules

  
• Passive diffusion


  The driving force for this process is the concentration gradient of the chemical between each side of the membrane, allowing molecules to be transported from the side with higher concentration to the side with lower concentration. Passive diffusion requires no energy (no ATP).
• Only small, relatively hydrophobic molecules can diffuse across a phospholipid bilayer passively at significant rates
• Some biological molecules, are unable to dissolve in the hydrophobic interior of the phospholipid bilayer

  
• Electrochemical gradient


  When molecules carry an electric charge, they're influenced not only by their concentration gradient but also by the electrical gradient. These molecules move along their electrochemical gradients.
• Transport and channel proteins

  They control the traffic of most biological molecules into and out of the cell
• Passive transport


  Occurs spontaneously, either by simple diffusion through the lipid bilayer or by facilitated diffusion through channels and passive carriers
• Facilitated diffusion


  A form of passive transport that occurs when molecules move from high concentration to low concentration facilitated by proteins in the membrane. It does not require energy (or ATP).
• Transporter proteins


  Also called carriers (Occasionally, in limited sources, they are called permeases or porters)
• Channel proteins


  Also called pores
• How do transport proteins (carriers) transport molecules across membranes?

  Transporters bind to the specific molecules on one side of the membrane. They then undergo conformational changes that allow the molecule to pass through the membrane and be released on the other side.
• Conformational changes in transporters

  Binding of the substrate to the binding-site triggers a series of structural changes that result in the transporter structure opening in the opposite direction.
• Transporter structures are typically classified as inward-facing, outward-facing, or occluded
• How do channel proteins transport molecules across membranes?

  Channel proteins form open pores through the membrane, allowing the free diffusion of a molecule of the appropriate size and charge.

  
• In contrast to transporter proteins, channel proteins do not undergo conformational changes to transport the molecules
• Chemical interactions between protein channels and hydrophilic compounds

  Mainly noncovalent bonds: ionic, Van der Waals, hydrogen bonds sometimes

  
• Chemical interactions between protein pumps (transporters) and compounds


  Protein transporters have specific binding sites for the molecules they transport. These binding sites can interact with substrate molecules through noncovalent chemical interactions.
• Water channels (or aquaporins)

  They enable water to diffuse faster across plasma membranes
• Aquaporins are present in all organisms
• Structure of aquaporins


  • They usually have six transmembrane helical segments and two short helical segments that surround cytoplasmic and extracellular passages connected by a narrow pore.
• Aquaporins function as tetrameric structures in which each monomer has its own permeable pathway
• The first aquaporin was discovered

  1992
• The Nobel Prize in Chemistry was awarded jointly to Peter Agre for the discovery of aquaporins


  2003
• Glucose transporters


  They take glucose from the bloodstream into the cell

  
• How do glucose transporters work?

  The glucose transporter alternates between two conformations in which a glucose binding site is alternately exposed on the outside and the inside of the cell.

  
• The fructose transporter GLUT5 undergoes a conformational change to transport sugars inside the cell
• Passive transport


  Diffusion through the lipid bilayer, Facilitated diffusion (Channels, Transporters)
• Ions are transported across membranes through facilitated diffusion and active transport
• Ion channels


  • Extremely rapid transport
  • Most ion channels are gated
  • Ion channels are highly selective
• Gated ion channels


  They are not permanently open, but open briefly in response to a specific stimulus
• Ligand-gated ion channels


  They are integral membrane proteins with the ability to bind small soluble ligand molecules. Structurally, they are large, multi-subunit receptors (3 to 5 subunits) that form a membrane ion channel.

  
• Voltage-gated channels


  Channels that can respond to changes in membrane potential or voltage
• Ligand-gated channels


  Channels that can bind small soluble ligand molecules

  
• Ligand-gated ion channels


  • They are integral membrane proteins with the ability to bind small soluble ligand molecules
  • They are large, multi-subunit receptors (3 to 5 subunits) that form a membrane ion channel
  • When open, they allow the passage of Na+, K+, Ca++, or Cl−
  • Typically, each subunit contains 4 hydrophobic transmembrane domains linked by hydrophilic groups

  
• Pentameric ligand-gated ion channel (pLGIC)

  Composed of 5 subunits
• Ligand


  A molecule that binds to a receptor protein (channels)
• The ligand can be either an extracellular mediator or an intracellular mediator