Cell Membrane Structure & Drug Absorption – Quick Review Notes

Cell Membrane: Key Structural Points

  • Bilayer of amphiphilic phospholipids: non-polar tails inside (lipophilic core), polar heads outside (hydrophilic boundaries)
  • Embedded / surface proteins create aqueous pores (4!-10 A˚4!\text{-}10\,\text{Å}) and act as carriers or pumps
  • Hydrophobic core ⇒ high resistance to polar / large molecules

Major Drug-Transport Pathways

  • Transcellular (intracellular): across cells; main route
  • Paracellular (intercellular): through tight junctions; minor
  • Vesicular (endocytosis): pinocytosis & phagocytosis; energy-dependent

Transcellular Transport – Sub-mechanisms

• Step 1 membrane permeation → Step 2 cytosol movement → Step 3 basolateral exit

1. Passive Processes (energy-independent)

  • Passive diffusion (non-ionic)
  • Pore (convective) transport
  • Ion-pair transport
  • Facilitated diffusion (carrier-mediated)

2. Active Processes (ATP-dependent)

  • Primary active transport (uniport; e.g. P-gp, ion pumps)
  • Secondary active transport (coupled)
    • Symport (co-transport) • Antiport (counter-transport)

Passive Diffusion Essentials

  • Driven by concentration gradient (downhill)
  • Described by Fick’s first law:
    dQdt=DAK<em>m/wh(C</em>GIT−C)\frac{dQ}{dt}=\frac{DAK<em>{m/w}}{h}(C</em>{GIT}-C)
    With sink conditions ⇒ dQdt=P CGIT\frac{dQ}{dt}=P\,C_{GIT} (first-order)
  • Faster with ↑area, ↓thickness, ↑Km/wK_{m/w}, lower molecular weight (≈100–400 Da100\text{–}400\,\text{Da})
  • Unionised species diffuse 3–4× faster than ionised

Pore (Convective) Transport

  • Driven by hydrostatic / osmotic pressure (solvent drag)
  • For small, water-soluble molecules (<∼100 Da\sim100\,\text{Da}; linear up to ∼400\sim400 Da)
  • Important in renal filtration, CSF, hepatic entry

Ion-Pair Transport

  • Permanent ions form neutral complexes with endogenous oppositely charged ions ⇒ transient lipophilicity
  • Example: propranolol + oleic acid

Carrier-Mediated Transport: Shared Features

  • Specific, saturable (Michaelis–Menten kinetics)
  • Competitive inhibition possible (e.g. dietary amino acids vs levodopa)
  • Defined absorption windows ⇒ limits controlled-release design

Facilitated Diffusion

  • Down gradient; no ATP; faster than passive diffusion
  • Examples: glucose into RBCs, GI uptake of B12B_{12} (IF-dependent)

Active Transport

  • Against gradient (uphill); needs energy
  • Primary (direct ATP)
    • Ion pumps (Na⁺/K⁺, H⁺ pumps) • ABC transporters (e.g. P-gp → multidrug resistance)
  • Secondary (uses existing gradient)
    • Symport: Na⁺–glucose, H⁺-coupled PEPT1 (β-lactams)
    • Antiport: Na⁺/H⁺ exchanger

Paracellular Transport

  • Via tight-junction gaps; size slightly > aqueous pores
  • Handles peptides like insulin, cardiac glycosides
  • Persorption: transient gaps from cell shedding

Vesicular (Endocytic) Transport

  • Pinocytosis (fluids/solutes) & phagocytosis (particles)
  • Enables uptake of macromolecules (vitamins A, D, E, K; proteins; Sabin polio vaccine)
  • Entry into lymph ⇒ bypasses first-pass metabolism

Combined Mechanisms & Clinical Notes

  • Many drugs use multiple routes (e.g. cardiac glycosides: passive + active; B12B_{12}: passive, facilitated, endocytosis)
  • Passive diffusion dominates (>90 % of drugs)
  • Saturable carriers ⇒ nonlinear bioavailability at high doses (vitamins B<em>1,B</em>2,B12B<em>1, B</em>2, B_{12})