Chapter 8 Transporters and Active Membrane Transport Principles of Membrane Transport Chapter 8 Transporters and Active Membrane Transport Principles of Membrane Transport 1

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Relative Permeability of a Synthetic Lipid Bilayer to Different Classes of Molecules Not only is it the smaller the molecule the greater the permeability but also the less strongly it associates with water (via hydration), the more rapidly the molecule will diffuse across the bilayer. 3

4 Active Transport is Mediated by Transporters Coupled to an Energy Source

5 These channel proteins form a water-filled pore across the lipid bilayer through which specific molecules can diffuse.

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8 Transporters and Active Membrane Transport Rate of transport-mediated diffusion is at a “max” when the transporter is saturated.

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10 Three ways to perform active transport

11 Coupling of Free Energy

12 A Na + Driven Glucose Transporter State A: Binding of Na + and glucose is cooperative; binding of either one promotes the binding of the other ligand. Since sodium ion conc. is much higher on the outside, glucose is much more likely to bind.

Transporters in the Plasma Membrane Regulate the pH of the Cytosol –Why must the pH of cytosol (7.2) be regulated? Cytosol vs. organelles (as low as 5) –How are they regulated? Na + -H + Exchanger Na + -driven Cl - -HCO 3 - Exchanger 13

Transporters in the Plasma Membrane Regulate the pH of the Cytosol –How are they regulated? Na + -independent Cl - -HCO 3 - Exchanger 14

15 From EC fluid the glucose can pass into the blood.

16 P type: they phosphorylate themselves. F type: they make ATP instead of use it. they pump small molecules across a membrane.

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18 Ca 2+ Pump (P type) of the Sarcoplasmic Reticulum Unphosphorylated form Phosphorylated form Transmembrane helices change form.

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20 The Sodium/Potassium Ion Pump or Na + -K + ATPase

21 The importance of phosphorylation The import of dephosphorylation

The Role of the Sodium-Potassium Pump The Na+ gradient that is produced is used to transport most nutrients into the cells (symport). Crucial to maintaining cytosolic pH Establishes the proper gradient of these ions in your nerve cells after a nerve impulse is conducted. Controls osmolarity inside a cell. –Cells have a high concentration of ions inside of them that will tend to pull water into the cell through aquaporins. –To counteract this accumulation of excess water, the sodium/potassium pump pumps out sodium ions to maintain some balance. 22

23 RBCs have an extra high permeability to water. Hypotonic solution: lyse Hypertonic solution: shrink Plant cells:

24 Two ATP- binding areas in the cytosol. Two hydrophobic domains span the membrane. Procaryotes: ABC transporters can be importing and exporting. Eukaryotes: most ABC transporters are exporters.

ABC transporters (ABC because they contain two ATP-binding cassettes (areas) ABC transporters of eukaryotic cells pump hydrophobic drugs out of the cytosol. –Overexpression of the MDR Protein Selective survival of those cells that overexpress MDR. Up to 40% of human cancers develop MDR Resistance to chloroquine, an antimalarial drug –Plasmodium falciparum, a malaria causing protist, has an amplified gene that encodes an ABC transporter that pumps out chloroquine. 25

Cystic Fibrosis Transmembrane Conductance Regulator Protein (CFTR) –Cause –1 out of every 27 Caucasians carries a gene encoding a mutant form of this protein; 1 in 2900, both copies are mutated, thus causing the disease. –In this case, chloride ion channels are opened (as opposed to transporting a molecule). 26

27 Ion Channel Gates

28 Aquaporins

29 Hydrophilic red area provide temporary bonds to water molecules and help to line them up in a single row.