Membrane Channels and Pumps

1
Membrane Channels and Pumps

• Pumps
• Active transport, using free energy (ATP or
  light)
• Channels
• Passive transport. A switch

2
Concentration Gradient and Equilibrium
membrane
A
A
c1
c2
?G DG0 RTln(c2/c1) ?G RTln(c2/c1) where
R 1.987 x 10-3 kcal/mol/deg, T 298 k
3
Concentration Gradient and Equilibrium
membrane
A
A
c1
c2
?G RTln(c2/c1)
When c2 gt c1, ?G gt 0 Transport process is not
spontaneous. When c2 lt c1, ?G lt 0 Transport
process is spontaneous.
4
Membrane Electrochemical Potential
membrane
A
A
c1
c2

-
?G RTln(c2/c1) ZF ?V Z, electrical charge
of the transported species F, the Faraday
constant, (23.1 kcal/V/mol) ?V, the membrane
potential
5
Concentrations of Salts on both Sides of Cell
Membrane in a Typical Cell

-
Na 14 mM K 157 mM Ca2 0.1 µM
Na 143 mM K 4 mM Ca2 1.5 mM
Membrane potential is -50 mV
6
Ca2-ATPase

• Use ATP to transport Ca2 out of cytosol
• Two Ca2 per one ATP
• Belong to the P-ATPase family
• An intermediate of phospho-aspartate
  (Phosphorylation)

7
Ca2 ATPase
N-domain, ATP binding A domain, an actuator for
the N-domain P domain, acceptor of P group
8
Mechanism of P-type ATPase
9
Na-K ATPase

• Use ATP to transport Na out of cytosol and K
  into cytosol
• Three Na and two K per one ATP
• Structurally similar to Ca2-ATPase

10
Na-K-ATPase

• How much free energy is needed for transporting 3
  moles of Na out of cells and 2 moles of K into
  cells?
• ?G RTln(c2/c1) ZF ?V

11
Other P-ATPases

• Transport protons
• Transport metals
• Transport phospholipids

12
P-ATPase and H-ATPase

• P-ATPase
• Has an intermediate E-P
• H-ATPase
• Use ATP to pump H across membrane
• Or use H to synthesize ATP

13
Inhibitors of P-ATPase

• Digitoxigenin specifically inhibits the
  dephosphorylation of the E2-P step of the Na-K
  ATPase

14
Transporters with ATP-Binding Cassette (ABC)

• Multi-drug resistance protein (170 kd)
• Cystic fibrosis transmembrane regulator
• In bacteria, ABC transporters contain multiple
  subunits

15
ABC Transporters
16
Mechanism of ABC Transporter
17
Secondary Transporters

• Use the gradient as the energy source for
  transporting other substances

A B
A B
18
Antiporters and Symporters
Opposite direction of movement e.g. Ca2/Na
exchanger
Same direction of movement e.g. Lactose permease
19
Ca2/Na Exchanger

• Ca2 has to be tightly regulated in cells
• Ca2 ATPase has high affinity for Ca2, but slow
  kinetics (30 per second)
• Ca2/Na exchanger has low affinity for Ca2, but
  faster kinetics (2000 per second)

Input of Na to ouput Ca2.
20
Lactose Permease (A Symporter)
21
Na-Glucose Symporter