Meeting 12 & 13

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mse263
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148207
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Meeting 12 & 13
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2012-04-19 17:19:02
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MCBII Exam
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Transport and Function
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  1. lipids can move across the membrane (3 ways)
    (1) transverse diffusion ('flip-flop'): switching from extracellular to intracellular facing surface; TAKES ENERGY (sometimes need to change what's facing outward from the cell, can act as signal)

    (2) rotation: moving about their stationary position

    (3) lateral diffusion: traversing through the same-facing side of the membrane

    -2 & 3 are easy to achieve (through brownian motion)/natural fluctuations
  2. Why Flip Flop Lipids Across the Membrane? Ex: Phosphatidyl Serine
    • •flippases: enzyme located in the membrane that uses ATP to move phospholipids between the two leaflets that make up a cell's membrane (transverse diffusion)
    • -many cells maintain asymmetric distributions of phospholipids between their cytoplasmic and exoplasmic membrane leaflets
    • •a loss of asymmetry, ex. the appearance of the (anionic) phospholipid phosphatidylserine (eat me! signal) on the exoplasmic face is an indicator for apoptosis
  3. phosphatidylserine (PS)
    • •all PS is normally displayed on the inside
    • •when the cell decided to die, it'll distribute it's PS on both sides now; macrophages see the signal and eat the marked cells
    • •PS: (serine & threonine are 2 alcohol amino acids, meaning they're VERY hydrophilic so they end up on outside or inside of membrane [have to touch polar environments])
  4. caspase
    flippase constantly expends energy keeping PS signals on the inside of the cell

    •caspase is an enzymes/protease that degrades the flippase; this means PS will inevitably flip to the outside, signaling apoptosis/cell death/the macrophages should eat it
  5. Ease of Transport Across Lipid Bilayers
    • • gasses & steroid hormones [b/c they're lipid soluble] diffuse (move easy) to transport across membranes
    • -*steroid hormones' hydroxyl groups make them hydrophobic but not to the point where they’d stick in bilayer
    • • small uncharged polar molecules: can move through membrane but not that easily; either need help or concentration gradient
    • -their small size facilitates transport, but that fact that they’re polar detracts from it
    • • charged polar molecules (ex. glucose, ATP, amino acids): difficult to transport
    • • ions: can’t pass through at all; heavily charged; incompatible with membrane; need pore/something for help (ex. H+, Na+, HCO3-, K+, Ca2+, Cl-, Mg2+)
  6. Movement Down Electrochemical Gradient: Takes No Energy
    1) simple diffusion: gas/steroid hormone

    2) channel-mediated diffusion: pore

    3) uniporters: membrane proteins that transport a single type of molecule down its concentration gradient (how glucose, nucleosides & amino acids move); use electrochemical gradient 4 energy
  7. Movement Against Electrochemical Gradient: Takes Energy
    1) ATPases: pumps that use the energy of ATP hydrolysis to move ions or small molecules across a membrane against the gradient or electric potential

    • 2) non-ATPases
    • -symporters: 2 molecules move through gradient at the same time in the same direction
    • -antiporters: 2 molecules move through gradient at the same time in opposite directions
  8. Osmosis
    -movement of WATER from lower to higher solute concentration

    -if the concentration of particles in the cell and in the medium is the same, the medium is iso-osmolar

    -solute (molecule) v. solvent (water)

    -there’s always a HUGE concentration of water outside a cell ~55.5 molar
  9. what matters for water movement:
    -concentrationof particles on one side of membrane v. other is what matters for water movement

    -particles can be: proteins, small charged ions, glucose, etc., what matters is the particles' concentration

    -water moves from areas of low solute concentration to areas of high; to prevent from happening, osmotic pressure must be put on it

    -have to to control control concentration of solute in order to control movement of water
  10. One can determined by the response of a cell by knowing the osmotic properties of the solution it's bathed in:
    -If cell shrinks, solution is hypertonic; (more solute outside than inside)

    -If cell swells, solution is hypotonic (more solute inside than outside)

    -If volume does not change, solution is isotonic (= amounts of solute inside & outside)
  11. passive transport
    • simple diffusion through a membrane;
    • -molecules move DOWN electrochemical gradient
    • -little specificity: only depends on solubility of membrane
    • -VERY few molecules enter a cell by passive diffusion through the membrane

    (charged molecules cannot go through lipid membrane: only non-polar can)

    (4 types: diffusion, facilitated diffusion, filtration & osmosis)
  12. the Rate of Diffusion of a molecule is:
    • directly proportional to:
    • 1) lipid solubility
    • 2) temperature: (higher=more soluble membrane)
    • 3) concentration gradient across membrane

    • Inversely proportional to:
    • 1) solubility in water
    • 2) size of the molecule
    • 3) viscosity of membrane
    • 4) membrane thickness
  13. examples of facilitated diffusion (type of passive transport)
    aquaporins: proteins in cell membrane that only allow water to pass through

    gap junctions: non-specific proteins that facilitate communication between two cells (is essentially a junction between two cells)

    -transporters: (ex. ion channels) they're passive because flow results from electrochemical gradient, there's no energy consumption
  14. gap junctions are made up of:
    Connexins (in vertebrates) & innexins (in invertebrates); gap junction proteins, they're transmembrane...

    -they're not very specific, let things go through as long as they're small enough
  15. Glucose transporter (GluT)
    • -type of uniporter
    • -GluT protein transports glucose across the cell membrane DOWN its concentration gradient
    • -when bound glucose changes its outward facing conformation to an inwardly open facing one

    -system is reversible; which side the open end faces depends on where glucose concentration is highest
  16. This is a Graph of Glucose Transport:
    • •glucose can diffuse through membrane, just not very well on its own

    •adding the enyzme aids in transport

    • •Vmax: rate of transport when all GluT's are working; can't transport faster b/c every molecules of GluT is being used
    • -is a measure of how many transporter enzymes there are on the membrane

    • •Km: how well GluT likes to bind glucose; affinity factor (point on x-axis that corresponds to half of vmax)
    • -a higher value of Km means that type of GluT has a lower affinity for glucose (liver GluT has a higher affinity for glucose than RBCs: glucose is stored there as glycogen)
  17. Channel-mediated Diffusion of Ions
    • -transport is very rapid (107 – 108 ions/s) and highly selective
    • -two general types: non-gated (always open) & gated
  18. Type of Gated Ion Channels (3)
    1) ligand-gated: channels that open/close when bound to ligands

    2) voltage-gated: activated by changes in electrical potential difference near the channel (ex. nervous system)

    3) mechano/stretch-gated; channels whose pores open in response to mechanical deformation of a neuron's plasma membrane (ex. cochlea/cilia membrane deformation)
  19. look at the fatness of the arrows:
  20. CUT OFF (size) FOR GAP JUNCTIONS :
    600 Kda
  21. types of active transport
    1) coupled transport (ex. Na/glucose transporter); uses energy of Na+ to bring glucose into cell: energy is in form of electrochemical gradient

    2) ATP-driven pump (ex. Na/K-pump)

    3) light-driven pump
  22. Types of ATP-mediated transport
    1) Class P: transports ions

    2) ABC Transporters: transport small molecules

    3) Class V & F: transport of H+ (protons); against or along gradient
  23. P-type ATPases (pump)
    • -use ATP to pump out ions against their concentration gradients
    • -called P-type cause they catalyze phosphorylation of an aspartate residue within the pump

    • -used to pump Na+/K+, & Ca2+
    • -found in:
  24. for every 3 Na+ that get transported out of the cell: __ K+
    get moved into the cell
    for every 3 Na+ ions that get transported out of the cell, TWO K+ ions are moved into the cell

    -using a Na+/K+ pump!?

    -binds sodium inside the cell; loaded into pocket; ATP is used, changing conformation, releasing sodium to the OUTSIDE fo the cell; K binds & is pumped inside the cell when Na is released
  25. ABC Transporter
    • -contain 2 (T) transmembrane domains & 2 cytosolic ATP-binding (A) domains: these couple ATP hydrolysis to solute movement
    • -part of the ATPase superfamily

    • -found in:

    • -also serve to expell toxic things (cancer drugs) inside the cell
    • -P170: gene for ABC transporter is amplified in cancer cells
  26. V-class Pumps
    couple ATP-hydrolysis to transport of protons against a concentration gradient
  27. F-class Pumps
    utilize energy in a proton concentration or electrochemical gradient to synthesize ATP
  28. epithilial cells are polarized
    basal membrane (inside membrane) is different from apical membrane (often points to the outside); different proteins on different membranes
  29. I don't know what to do about this lecture

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