Membrane Transport - Quick Reference

Plasma Membrane Structure

Selectively permeable barrier; structure dictates selectivity
Core components:
- Phospholipid bilayer: amphipathic (hydrophilic heads, hydrophobic tails)
- Embedded proteins: integral (channels, pumps, carriers), peripheral (signaling, structure)
- Cholesterol: maintains fluidity; modulates permeability
- Carbohydrates: cell recognition (glycoproteins/glycolipids)

Small nonpolar (O₂, CO₂): ext{High permeability}; diffuse through hydrophobic core
Small polar (H₂O, urea): ext{Moderate permeability}; may pass via aquaporins
Large polar (glucose, amino acids): ext{Low permeability}; require transporters
Ions (Na⁺, K⁺, Cl⁻): ext{Very low permeability}; need channels or pumps
Note: Nonpolar = lipid soluble; Polar/charged = requires assistance

Integral (transmembrane) proteins: channels, pumps, carriers
Peripheral proteins: support and signaling
Functions in permeability:
- Ion channels: selective passage of Na⁺, K⁺, Cl⁻, Ca²⁺
- Carrier proteins (e.g., GLUT): facilitated diffusion
- Pumps (e.g., Na⁺/K⁺-ATPase): active transport against gradients

Interspersed in bilayer; increases stability
Decreases permeability to small water-soluble molecules
Regulates fluidity with temperature:
- High temp → ↓ fluidity (stiffer membrane)
- Low temp → ↑ fluidity (prevents freezing)

Facilitated Diffusion:
- Uses protein carriers or channels; no ATP; moves down gradient
- Examples: GLUT transporters (glucose), Aquaporins (water)
Simple Diffusion:
- No energy; down concentration gradient
- Examples: O₂, CO₂, steroid hormones
Channel-Mediated Transport:
- Form hydrophilic pores; rapid ion/water flow; highly selective
- Gate control: voltage-, ligand-, mechanically-gated
- Always passive; examples: Voltage-gated Na⁺ channels, Aquaporins, Cl⁻ channels
Carrier-Mediated Transport:
- Carriers bind solute, undergo conformational change, release on other side
- Slower than channels; highly specific; can saturate (transport maximum, Tm)
- Can be passive (facilitated) or active (ATP required)
- Examples: GLUT transporters (glucose), Na⁺/glucose (SGLT1)
Aquaporins:
- Integral membrane proteins forming pores for water only
- Facilitated diffusion; no ATP; down osmotic gradient

Nephrogenic Diabetes Insipidus: AQP2 mutation or lack of response to ADH → dilute urine
SIADH: Excess ADH → ↑ AQP2 → water retention → hyponatremia
Brain edema: AQP4 in astrocytes; target in trauma/stroke research

Kidneys: concentrate urine (AQP2 in collecting duct)
Lungs: airway hydration
Salivary glands: saliva secretion
Brain: CSF balance (AQP4 in astrocytes)
Eyes: aqueous humor regulation (AQP0, AQP1)
AQP localization:
- AQP1: proximal tubule, RBCs
- AQP2: collecting duct (ADH-regulated)
- AQP3 & AQP4: basolateral membranes (kidney, brain)

Direct use of ATP; moves against the gradient (low → high)
Na⁺/K⁺-ATPase: 3\,\, ext{Na}^+\text{ out} \;\text{and} \;2\,\, ext{K}^+\text{ in}
Ca²⁺-ATPases:
- PMCA: 1\,\, ext{Ca}^{2+}\text{ expelled per 1 ATP}
- SERCA: 2\,\, ext{Ca}^{2+}\text{ into SR/ER per 1 ATP}
H⁺/K⁺-ATPase: exchanges 2\,\, ext{H}^+ for 2\,\, ext{K}^+ at neutral pH (can vary with pH)

Uses energy stored in gradients (often Na⁺)
Na⁺ downhill → energy for uphill transport of solute
Symport (co-transport): uphill solute moves in same direction as Na⁺
- Example: Na⁺/glucose (SGLT1)
Antiport (counter-transport): uphill solute moves opposite Na⁺ direction
- Example: Na⁺/Ca²⁺ exchanger

Endocytosis (into cell):
- Phagocytosis: cell eating (e.g., macrophages)
- Pinocytosis: cell drinking
- Receptor-mediated endocytosis: selective uptake (e.g., LDL)
Exocytosis (out of cell): secretion (neurotransmitters, enzymes)
Transcytosis: transport across a cell (e.g., capillaries, intestines)

CFTR: Cystic fibrosis → thick mucus, lung infections
SGLT1/SGLT2: Glucose transporters; inhibitors (SGLT2 inhibitors) used in type 2 diabetes; cause glucosuria; risk of UTI/dehydration
GLUT family: GLUT1 (RBC/BBB), GLUT2 (liver/pancreas), GLUT4 (muscle/adipose); insulin regulates GLUT4 translocation
ENaC: Epithelial Na⁺ channel; location in collecting duct; Liddle syndrome (gain of function) → HTN, hypokalemia; Amiloride blocks ENaC
P-glycoprotein (MDR1): drug efflux in intestine/BBB; contributes to chemotherapy resistance
ATP7B: Wilson disease; defective copper excretion → copper accumulation; chelation therapy

Primary vs Secondary transport distinction based on ATP use
Channel vs Carrier transport: channels are fast but less selective; carriers slower but highly specific; carriers can be saturable
Aquaporins enable water movement; disruption affects water balance and osmolarity
Major ion gradients drive many secondary transport processes