Membrane Proteins III

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Stephen Fish, Ph.D. Marshall University J. C. E.
School of Medicine Fish_at_Marshall.edu
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Note to instructors I use these PowerPoint
slides in cell biology lectures that I give to
first year medical students. Copy the slides, or
just the illustrations into your own teaching
media. We all know that teaching science often
requires compromises and simplification for
specific student populations, or the requirements
of a specific course. Please feel free to offer
suggestions for improvements, corrections, or
additional illustrations. I would be pleased to
hear from anyone who finds my work useful, and am
always willing to make it better. Also, the
images have been compressed to screen resolution
to keep PowerPoint file size down, and I can
provide them at any resolution. Stephen E.
Fish, Ph.D.
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Membrane Transport Carriers Channels
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The membrane lipid barrierPassive diffusion
through the lipid bilayer

• Concentration gradient up, diffusion up
• Molecule lipid solubility up, diffusion up
• Molecular size up, diffusion down
• Molecule electrically charged, diffusion blocked

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Specialized membrane proteins transport molecules
across membranes

• Simple diffusion
• Species of molecule limited by membrane physics
• Rate is slow and linearly related to
  concentration gradient
• Membrane transport
• Overall not limited by size, charge, or
  hydrophilia
• Is highly selective for specific needed molecules
• Rate is fast and not linear

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Membrane protein transporter types
Some carrier types facilitate diffusion, others
use energy to pump molecules against Their
gradient. They must bind the solute to initiate a
conformational change
Channels facilitate diffusion through an aqueous
pore when a conformational change opens a gate
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Carrier types

• Uniporter- transports only one molecule species
• Symporter- coupled transport of 2 different
  molecular species in the same direction
• Antiporter- coupled transport of 2 different
  molecular species in the opposite direction
• Symporters antiporters are usually pumps
• Some types transport more than one molecule of a
  species/cycle

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The glucose uniporter transports glucose across
membranes

• Ligand (glucose) binding flips the transporter to
  a different conformation (changes shape)
• The new conformation releases glucose on the
  other side of the membrane
• Release allows it to flip back to repeat the cycle

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How carrier proteins change conformation
The ligand binding site is exposed on the upper
membrane surface
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The folding pattern flips to a different position
The ligand binding site is now exposed on the
lower membrane surface
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Without the ligand bound, conformation returns to
the first state
The carrier is now ready to transport
another molecule
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Band 3 facilitated diffusion anion antiporter in
red blood cells

• Multipass protein that binds to spectrin
• Exchanges Cl- for HCO3-
• Important for transporting CO2 to the lungs

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Band 3 facilitated diffusion anion antiporter in
red blood cells

• When the bicarbonate diffusion gradient is
  reversed, the process reverses

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Band 3 function in RBCs
Why HCO3- for CO2? Why antiport Cl-?
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Primary active transport exampleThe Na- K
antiporter pump

• Pumps 3 Na ions out of cell 2 K ions in
• Maintains Na K cell membrane gradients
• Each cycle uses one ATP, 100 cycles/sec
• Uses ¼ energy of most cells, ¾ for neurons

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The Na - K pump cycle
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The Na- K ATPase pump is responsible for
maintaining cellular osmotic balance
Charged intracellular molecules attract ions
increase internal tonicity
The pumps net effect is to remove ions
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If the pump is blocked by ouabain
More water enters
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Secondary active transport example The
sodium-glucose symporter pump

• Gradients from primary pumps power secondary
  active transport
• Different types, can be antiporters or symporters
• Pictured, the Na gradient powers conformational
  change
• Glucose is pumped in against its gradient

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Retrieval of GI tract glucose by enterocytes
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Channels are selective for ion species

• Some are very specific, others less
• Specificity based on
• Size
• Charge
• Special problem for K channels
• Na is smaller same charge
• Requires a special filter

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IK channel blocks Na
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IIK channel blocks Na
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Most channel transporters are gated

• Opening closing of the gate mechanism
• Ligand gated
• Voltage gated
• Mechanically gated
• Other types later in the course
• A few are not gated leak channels

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Leak channels

• Open all the time
• Best known type are K channels
• K going down concentration gradient out of the
  cell
• Increases inside negativity of the cell
• Gradient created by the Na-K pump

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Ligand gated channels

• Binding of ligand changes conformation of the
  channel
• Gate opens to allow an ion ( or -) to enter or
  exit the cell

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The K leak channel charges up the membrane

• The K- Na pump charges up concentration
  gradients
• Excess ions out accounts for only a small
  portion of the -60mv membrane potential
• The leak channel lets more ions out
• The electrical potential rises until it equals
  balances the K concentration gradient no more
  leak

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Hormones can trigger secretion

• Example- Pancreatic cells secrete digestive
  enzymes into the small intestine
• The cell is charged up by the leak channel
• Ligand opens gate on Ca channel
• Membrane potential Ca gradient sum
• Ca entering triggers fusion of vesicles with
  membrane

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Voltage gated channels

• Are sensitive to voltage across the cell membrane
• When the voltage changes to a trigger level, it
  opens
• The gate will close again when the voltage
  returns to the trigger level
• What is the problem with this picture?

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Many channels are inactivated by a separate
mechanism than the gate

• The voltage gated Na channel serves as a good
  example
• Opening the channel depolarizes the cell if it
  stayed open the gate would never close
• The inactivating mechanism provides for a short
  positive pulse of current into the cell

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Mechanically gated channels hair cells in the ear
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Sherman says
Actually, I like to eat them proteins