3 Membrane Transport

  1. Plasma Membrane Permeability
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    • • PM has very selective permeability
    • • gasses are considered hydrophobic - can easily cross
    • • polar molecules diffuse through at such a slow rate that it’s not useful to the cell to achieve concentration gradient it needs
    • • ions have NO WAY of diffusing through the membrane
    • • main reason for membrane: to have separate compartments with different molecule concentrations inside & out
  2. Mechanisms of Small Molecule Transport
    1. Simple Diffusion

    • 2. Passive Transport (Channel or Carrier-mediated)
    • - E for this type of transport comes from moving a molecule down its gradient

    3. Active Transport (takes ENERGY)

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  3. Glucose Permease Channel
    • • moves glucose down it’s chemical gradient (from high to low concentration)
    • • glucose binds to a very specific binding site on permease (only right kind of sugar can bind)
    • • the energy of it binding creates a conformational change that opens a channel
    • • glucose passes through the channel & is released into the cytoplasm
    • • the release causes another conformation change & the permease reverts to its original conformation where it can accept more glucose molecules
  4. By how much does the Glucose Permease Channel speed up glucose transport?
    it speeds up diffusion by about 100 fold
  5. Coupled Transport
    • • usually mediated by carrier proteins
    • • is still Passive - doesn’t require energy because it’s using the energy created by 1 molecule going down its gradient to move the other molecule UP it’s gradient (chemical OR electrochemical)
  6. Symporters (Cotransporters)
    • move solutes together in the same direction, 1 up & 1 down their concentration gradient

    • eg. Na+/Glucose cotransporter: couples the downhill movement of Na+ into epithelial cells with the uphill movement of glucose into epithelial cells
  7. Antiporters
    • moves solutes in opposite directions, again 1 up & 1 down its concentration gradient

    • eg. Band 3 anion antiporter (anion exchanger, typically bicarbonate for chloride)

    • start moving the molecule going down it’s gradient 1st to generate the energy to move the other molecule in the opposite direction
  8. Na+ & K+ Baseline Gradients
    • Na+ → low inside, high outside
    • K+ → high inside, low outside
  9. Na+/K+ ATPase Pump
    • • moves 3 Na+ out of cell to bring in 2 K+ into the cell using ATP
    • • whenever a molecule is burning ATP to do transport it’s called a PUMP → means there’s ATP cleavage involved

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    • it’s like an antiporter in that both molecules are going in opposite directions however it isn’t one because they’re both moving AGAINST their gradients
  10. What happens when you eat something:
    • • have glucose in your intestinal lumen
    • - because of the size of the lumen in comparison to the size of an intestinal epithelial cell, no matter how many candy bars you eat, there will always be ↓ glucose in the intestine than in the epithelial cell (volume issue)

    • Na+/Glucose Symporter: moves glucose ↑ it’s gradient while moving Na+ ↓ its gradient

    • once in the cell, Glucose can be transported out into blood using Glucose Permease (carrier protein, passive transport)

    • to reestablish Na+ gradient, use Na+/K+ ATPase Pump: actively transports Na+ out into blood & brings 2 K+ into cell
  11. Name the Diseases of ABC ATPase Transporters
    • 1. Cystic Fibrosis: defective CF Transmembrane Regulator
    • - without a normal CFTR, Cl- transport across the cell membrane is messed up

    • 2. Drug Resistance: over-expression of P-glycoprotein/MDR complex (mutant tumors survive because they over-express this ATPase pump that expels chemo drugs from tumor cell)

    3. Tangier Disease

    (Hypoglycemia in infancy: Sulfonylurea Receptor)
  12. Tangier Disease
    • rare genetic disorder characterized by severe HDL deficiency in plasma caused by a mutated ATP-Binding Cassette 1 gene (an ATPase that’s important for the efflux of cholesterol from the cell)

    • without any cholesterol to pick up, HDL is cleared from the plasma & ends up in various tissues

    • hallmark: accumulation of cholesteryl ester (CE) in various tissues leading to severe cardiovascular disease, lymphadenopathy, hepatosplenomegaly & peripheral neuropathy

    • ~500 patients world-wide, most on Tangier Island
  13. What is the most common lipid disorder in patients with heart disease?
    abnormally LOW HDL

    • ↓ HDL → ↑ heart disease
  14. What are the 3 mechanisms of macromolecular (large molecule) transport into cells?
    • 1. Phagocytosis
    • 2. Receptor-mediated Endocytosis
    • 3. Pinocytosis
  15. Phagocytosis
    a receptor-mediated process that internalizes & degrades large objects like bacteria & cell debris (eg. at site of inflammation)

    • • bacteria or larger particles (eg. protozoans, asbestos fibers) bind to specific receptors on the cell surface
    • • the membrane then Evaginates (outpouches) to engulf the particle, forming a phagosome
    • • the phagosome is rapidly acidified by an H+/ATPase in the vesicle membrane
    • • the phagosome fuses with a primary lysosome to become a phagolysosome
    • • lysosomal enzymes are usually able to degrade contents of the lysosome

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  16. What molecule mediates the process of Phagocytosis?
    ACTIN (microfilament)

    binding activates receptors that trigger actin assembly

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  17. What diseases take advantage of Phagocytosis to infect cells? (dark side of phagocytosis) [7]
    • Legionnaire􏰂s Disease
    • Leishmaniasis
    • Listeriosis
    • Leprosy

    • Toxoplasmosis (Coccidiosis)
    • Tuberculosis


    4Ls 2Ts 1S

    (also inert particles like asbestos or silica fibers pose particular problems because cells can’t degrade by phagocytosis leads to → mesothelioma, black lung)
  18. Which particles go into cells via Phagocytosis & which go in via Receptor-mediated Endocytosis?
    • bacteria & larger particles → Phagocytosis

    • viruses, smaller particles (proteins, macromolecular complexes) → RME
  19. Clathrin
    an extrinsic or peripheral membrane protein that helps concentrate ligand-receptor complexes & aids in membrane fission

    this protein linked to membrane via other proteins called adaptins
  20. Receptor-mediated Endocytosis (RME)
    • • proteins or viral particles bind to specific receptors on the cell surface, often in membrane regions coated with clathrin
    • • the membrane invaginates & dynamin pinches off the small vesicle (endosome) from the membrane
    • • vesicles lose their clathrin coat & then quickly become acidified by an H+/ATPase in the membrane
    • • the decreased pH facilities its fusion with the CURL (Compartment for Uncoupling of Receptor & Ligand) endosome
    • - in the CURL endosome the ligand separates from its receptor & is sorted into separate parts of the vesicle
    • • the receptor-containing portion of the CURL buds off & is recycled to the PM to await more ligand
    • • ligand-containing part of the CURL fuses with a primary lysosome & is degraded by lysosomal enzymes
  21. LDL-Cholesterol Uptake v. Maternal IgG to Baby
    • • with LDL/cholesterol, vesicle acidification causes separation of the LDL receptor & cholesterol ligand → cholesterol is degraded by lysosome & LDL receptor is recycled back to the PM
    • - in most cases receptor & ligand are designed to stay together at neutral pHs

    • • with the transport of maternal antibody, IgG enters baby first in digestive system (intestinal lumen → low pH)
    • - Fc receptor binds to IgG ligand in intestinal lumen
    • - complex is designed to be stable at LOW pH
    • • Fc receptor+IgG is internalized into cell via classic RME
    • • acidic early endosome doesn’t disassociate the complex
    • • vesicle will transcytose to the extracellular side of the cell, where the pH of neutral blood causes IgG to separate from receptor
    • • Fc receptor is recycled via small transport vesicle back to the intestinal lumen side of the cell

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  22. Familial Hypercholesterolemia (FH)
    • caused by defective receptor-mediated endocytosis that results in the inability of cells to transport cholesterol & results in elevated blood cholesterol & eventually arteriosclerosis

    • rare autosomal dominant disease in which homozygotes have extremely elevated cholesterol levels & generally die of cardiovascular problems before the end of their 2nd decade
  23. Differences Between FH & TD
    • • Familial Hypercholesterolemia is caused by some defect in the LDL receptor mechanism & undermines RME
    • - revealed the mechanism of cholesterol transport INTO cells
    • - because cholesterol can’t get into cells, it builds up in the blood & eventually insudates (soaks into) artery walls, where it exacerbates atherosclerotic lesions
    • - death in 2nd or 3rd decade of life when homozygous

    • • Tangier’s is caused by a defect in an ABC ATPase that pumps cholesterol OUT of cells
    • - revealed the mechanism of cholesterol transport OUT of cells
    • - cholesterol builds up & damages endothelial cells that line the large arteries
    • - death in the 4th or 5th decade of life
    • - there are abnormally low HDL levels in blood because there is no cholesterol in blood
  24. What diseases take advantage of RME to infect cells? (dark side of RME) [2]
    • Influenza Virus
    • Rabies Virus

    • viruses get into the cell via normal RME but before they can be degraded by lysosome, they fuse their capsid membrane with an endosome & release viral particles into the cell

    • the low pH doesn’t kill them in the endosome
Card Set
3 Membrane Transport
Cell Biology Exam1