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

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

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

7. Final state – Initial state =G= positive
(out)
(in) GA
(in) >
(out)
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 = RTln [A]in [A]out GA = ZAF Total Energy Text p398 GA RTln
Chemical potential
GA
= GA(in) - GA(out)
= RTln
[A]in
[A]out
and
Electrochemical potential
GA
= GA(in) - GA(out)
= ZAF
Membrane potential
Total Energy
Text
p398
GA =
RTln
[A]in
[A]out +
ZAF

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

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

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

13. GCl- RTln [A]out [A]in ZAF = 8.314 x (310 K) x ln– In
Out Cl – _ + Cl – Cl – Cl – Cl – Cl – Cl – Cl – Cl – Cl – Cl –
10 mM
150 mM
(– 60 mV)
GCl- =
RTln
[A]out
[A]in +
ZAF
= x (310 K) x ln
[0.150]
[0.010]
+ (1) 96,500 x – 0.06 volts
= 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. The trans-Golgi network
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. Golgi RER Secretory granule Trans Pre-lysosome Cis Golgi
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. Signal Hypothesis SRP Lumen of cisternae Carbohydrate
Docking
SRP
GDP
+NH3
GTP
+NH3
GTP
Signal Peptide
cleaved
SRP receptor
Lumen of cisternae
Carbohydrate
Rough Endoplasmic Reticulum