Membrane Transport Mechanisms:

(a) Simple Diffusion:

Mechanism:

• Molecules move directly through lipid bilayer
• Down concentration gradient (high → low)
• No protein required

Requirements:

• ✗ No energy (ATP) needed - passive
• ✗ No transport protein needed
• Molecules must be small and/or nonpolar

Rate factors:

• Concentration gradient
• Temperature
• Molecular size
• Lipid solubility

Examples:

• O₂, CO₂ (respiratory gases)
• N₂
• Small nonpolar molecules (ethanol, glycerol)
• Lipid-soluble substances (steroid hormones)

Equation (Fick's Law): $\text{Rate} \propto \frac{\Delta C \cdot A}{\Delta x}$

(b) Facilitated Diffusion:

Mechanism:

• Molecules move through channel proteins or carrier proteins
• Down concentration gradient (high → low)
• Protein-mediated

Requirements:

• ✗ No energy (ATP) needed - passive
• ✓ Requires specific transport protein
• Selective based on protein specificity

Types:

1. Channel proteins:

• Aquaporins (water)
• Ion channels (Na⁺, K⁺, Ca²⁺, Cl⁻)
• Can be gated (open/close in response to signal)

2. Carrier proteins:

• Bind substrate
• Change conformation
• Release on other side
• Example: GLUT1 (glucose transporter)

Characteristics:

• Shows saturation kinetics (max rate at high [S])
• Specific for certain molecules
• Faster than simple diffusion for large/polar molecules

Examples:

• Glucose into cells (GLUT transporters)
• Amino acids
• Ions through channels
• Water through aquaporins

(c) Active Transport:

Mechanism:

• Molecules pumped against concentration gradient (low → high)
• Requires energy input (ATP)
• Uses carrier proteins (pumps)

Requirements:

• ✓ Energy (ATP) required - active
• ✓ Requires specific pump protein
• Can create concentration gradients

Types:

1. Primary active transport:

• ATP directly powers transport
• Example: Na⁺/K⁺-ATPase pump
  • 3 Na⁺ out, 2 K⁺ in
  • Maintains electrochemical gradient
  • ~30% of cell's ATP used!

2. Secondary active transport (cotransport):

• Uses gradient created by primary transport
• Symport: both move same direction (Na⁺-glucose)
• Antiport: move opposite directions (Na⁺/Ca²⁺ exchanger)

Examples:

• Na⁺/K⁺ pump (all animal cells)
• Ca²⁺ pumps (muscle cells)
• H⁺ pumps (stomach acid, plant roots)
• Na⁺-glucose cotransporter (intestine)

Comparison Table:

$\boxed{\text{Passive (down gradient): simple/facilitated; Active (against gradient): requires ATP}}$

Energetics:

• Passive: $\Delta G < 0$ (spontaneous)
• Active: $\Delta G > 0$ (requires energy input from ATP hydrolysis)

Na⁺/K⁺-ATPase Pump:

(a) Step-by-step mechanism:

Cycle has 6 main steps:

Step 1: Binding (Cytoplasmic side)

• 3 Na⁺ ions bind to pump from inside cell
• Pump in "E₁" conformation (open to cytoplasm)
• High affinity for Na⁺ in this state

Step 2: Phosphorylation

• ATP binds to pump
• ATP hydrolyzed: ATP → ADP + Pi
• Phosphate (Pi) covalently attached to aspartate residue
• Pump now "energized"

$\text{E}_1\text{-ATP} \rightarrow \text{E}_1\text{-P} + \text{ADP}$

Step 3: Conformational change

• Phosphorylation causes shape change
• Pump switches to "E₂" conformation (open to extracellular)
• Na⁺ binding sites now face outside
• Affinity for Na⁺ decreases

Step 4: Na⁺ release

• 3 Na⁺ released to extracellular fluid
• Pump still phosphorylated

Step 5: K⁺ binding

• 2 K⁺ bind from outside
• E₂ conformation has high affinity for K⁺
• K⁺ binding triggers dephosphorylation

Step 6: Dephosphorylation and return

• Phosphate released from pump
• Pump returns to E₁ conformation
• K⁺ binding sites now face cytoplasm
• Affinity for K⁺ decreases
• 2 K⁺ released into cytoplasm
• Cycle repeats

Net Result: $\text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ATP} \rightarrow \text{3 Na}^+ \text{ (out)} + \text{2 K}^+ \text{ (in)} + \text{ADP} + \text{P}_i$

(b) Why is this electrogenic?

Electrogenic = generates electrical potential

Charge imbalance:

• 3 positive charges (Na⁺) pumped OUT
• 2 positive charges (K⁺) pumped IN
• Net: 1 positive charge removed per cycle

Result:

• Creates membrane potential
• Inside becomes more negative relative to outside
• Typical: -70 mV (inside negative)

Contribution to resting potential:

• Direct: ~-10 mV from pump itself
• Indirect: ~-60 mV from K⁺ leak channels (enabled by gradient)
• Total: ~-70 mV

$\Delta V = \frac{RT}{F}\ln\frac{[K^+]_{out}}{[K^+]_{in}}$

(c) Secondary active transport - glucose absorption:

Primary transport creates gradient:

Na⁺/K⁺ pump → low [Na⁺] inside, high [Na⁺] outside

Secondary transport exploits gradient:

SGLT1 (Sodium-Glucose Linked Transporter) in intestinal epithelium:

Mechanism:

1. SGLT1 binds 2 Na⁺ + 1 glucose from intestinal lumen
2. Na⁺ moving down gradient (high → low) provides energy
3. Energy used to move glucose against its gradient (low → high)
4. Both released into cytoplasm

This is SYMPORT (both move same direction)

Energy source:

• NOT directly ATP
• Uses Na⁺ gradient (created by Na⁺/K⁺ pump using ATP)
• Indirect use of ATP

Complete pathway for glucose absorption:

Intestinal Lumen → Epithelial Cell → Blood

Step 1: SGLT1 (apical membrane)
   Glucose + 2Na⁺  →  into cell
   (secondary active, symport)

Step 2: GLUT2 (basolateral membrane)
   Glucose  →  out to blood
   (facilitated diffusion, down gradient)

Step 3: Na⁺/K⁺ pump (basolateral membrane)
   Maintains low [Na⁺] inside
   (primary active transport)

Why this works:

• Na⁺ gradient provides "free" energy for glucose transport
• One ATP → multiple glucose molecules transported
• More efficient than direct ATP use for each glucose

Energetics:

Primary active: $\Delta G_{ATP} = -30.5$ kJ/mol Drives: [Na⁺] gradient = +10-12 kJ/mol Used for: glucose uptake against gradient = +5-8 kJ/mol

$\boxed{\text{Pump creates Na}^+ \text{ gradient → SGLT1 uses gradient → glucose absorbed}}$

Clinical relevance:

• Oral rehydration therapy (ORT) uses this!
• Na⁺ + glucose solution
• Glucose absorption drives Na⁺ and water absorption
• Treats dehydration from diarrhea