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Membrane Transport A Thermodynamic Perspective

Membrane Transport A Thermodynamic Perspective. 4 ways to penetrate the Cell Membrane. Simple Diffusion Passive transport (facilitated diffusion) Active transport (energy-dependent) Receptor-mediated endocytosis. Simple Diffusion. Initial. Final. High . Low.

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Membrane Transport A Thermodynamic Perspective

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  1. Membrane TransportA Thermodynamic Perspective

  2. 4 ways to penetrate the Cell Membrane • Simple Diffusion • Passive transport (facilitated diffusion) • Active transport (energy-dependent) • Receptor-mediated endocytosis

  3. Simple Diffusion Initial Final High Low

  4. = the chemical potential of A = chemical potential of standard state GA – GAo = RTln[A] (free energy varies with conc. A) = GA(in) - GA(out) (final - initial) [A]in = GA(in) - GA(out) = RTln GA GA GA GA GA GA GA [A]out If [A]out is > [A] in, is negative exergonic o' If [A]out is < [A] in, If [A]out = [A]in, is zero is positive endergonic (also called the partial molar free energy) Thus:

  5. Thermodynamics (ENERGY) of Transport A(out) A(in) GA GA (in) < (out) Diffusion Rule: Free energy is released when a solute moves from an area of high concentration to low concentration Spontaneous (in) (out) Low High Final state – Initial state =G = negative

  6. GA GA (in) = (out) (in) (out) Balanced Free energy change is zero when the concentration of A on both sides is the same Rule: Final state – Initial state =G = 0

  7. (in) > (out) GA GA (out) (in) Final state – Initial state =G= positive Rule: When chemical potential of A(in) is greater than A(out), energy must be provided to drive A across the membrane, i.e., make free energy change negative Energy = ATP or a proton gradient

  8. Rule: The movement of ions presents a separate challenge because not only must the mass difference (chemical potential) be taken into account, but also the charge differential (electrochemical potential) electrochemical potential refers to the state of (+) (-) charges on both sides of the membrane The electrochemical potential is referred to as the membrane potential when dealing with cells

  9. = GA(in) - GA(out) = ZAF [A]in = GA(in) - GA(out) = RTln GA GA GA [A]out [A]in ZAF RTln + = [A]out Chemical potential and Electrochemical potential Membrane potential Total Energy Text p398

  10. + + + + + + + + + + + + + + _ _ _ + + + Na Na Na Na Na Na Na Na Na Na Na Na Na Na 15:1 10 mM 150 mM (- 60 mV) [A]in ZAF RTln + = GNa+ [A]out [0.010] = 8.314 x (310 K) x ln + (1) 96,500 x -0.06 volts [0.150] = – 12.8 kJ/mole

  11. Out In + + + + + + + + + + + + + + + _ _ _ + + + Na Na Na Na Na Na Na Na Na Na Na Na Na Na Na 150 mM [A]out ZAF RTln + = GNa+ [A]in [0.150] = 8.314 x (310 K) x ln + (1) 96,500 x +0.06 volts [0.010] 10 mM (+ 60 mV) = + 12.8 kJ/mole

  12. Out In – – – – – – – – – – – – Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl _ _ _ + + + [A]in ZAF RTln + = GCl- [A]out [0.010] = 8.314 x (310 K) x ln + (1) 96,500 x +0.06 volts [0.150] 10 mM 150 mM (+ 60 mV) = – 6.85 kJ/mole + 5.79 kJ/mol = – 1.06 kJ/mol

  13. Out In – – – – – – – – – – – – Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl _ _ _ + + + [A]out ZAF RTln + = GCl- [A]in [0.150] = 8.314 x (310 K) x ln + (1) 96,500 x – 0.06 volts [0.010] 10 mM 150 mM (– 60 mV) = + 6.85 kJ/mole + (– 5.79 kJ/mol) = 1.19 kJ/mol

  14. Facilitated Diffusion (Mediated Transport)

  15. Modes of Transport

  16. ATP-Driven (Active) Transport [Ca2+-ATPase]

  17. Vesicle Trafficking • The secretory pathway • The trans-Golgi network • The signal hypothesis • Protein targeting

  18. Rule: Proteins destined for secretion from a cell or for relocation to a membrane or a specific organelle are synthesized on the rough endoplasmic reticulum (RER) Definition: The RER consists of ribosomes bound to membranes enclosing an internal hollow space or cisternae Selection: Proteins possess a signal sequence that is recognized by a receptor on the membrane Action: Proteins pass into the space and transit to the Golgi while entrapped in vesicles

  19. Protein inserted in plasma membrane Trans Secretory granule Golgi Pre-lysosome Cis Golgi RER

  20. Signal Hypothesis Proteins destined for secretion or transit to membranes and organelles, have a signal peptide that allows them to enter the RER cisternae The signal peptide is recognized by a receptor called the “signal recognition particle” (SRP) on the RER membrane Signal sequences on the N-terminal represent a string of leucine-rich hydrophobic amino acids that allow the peptide to dock with the receptor The signal peptide is removed after the peptide has penetrated the membrane

  21. Docking SRP GDP GTP GTP Signal Peptide cleaved SRP receptor +NH3 +NH3 Signal Hypothesis Lumen of cisternae Carbohydrate Rough Endoplasmic Reticulum

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