Modes of Transport: Diffusion and Facilitated Diffusion

A Detailed Examination Guide for Students

Overview: Classification of Membrane Transport

1. Does it require metabolic energy?
2. Does it involve a protein carrier?

• Costanzo Physiology 7th Ed, p. 12

PART 1: SIMPLE DIFFUSION

Definition

Two Subtypes of Simple Diffusion

A. Diffusion Through the Lipid Bilayer (Lipid-Soluble Substances)

"The lipid solubilities of oxygen, nitrogen, carbon dioxide, and alcohols are high, and all these substances can dissolve directly in the lipid bilayer and diffuse through the cell membrane... Especially large amounts of oxygen can be transported in this way; therefore, oxygen can be delivered to the interior of the cell almost as though the cell membrane did not exist."

• Guyton & Hall Medical Physiology, p. 65

B. Diffusion Through Protein Pores/Channels (Lipid-Insoluble Substances)

Fick's Law of Diffusion

• J = Net rate of diffusion (mmol/s)
• P = Permeability (cm/s) - includes partition coefficient, diffusion coefficient, membrane thickness
• A = Surface area (cm²)
• C_A - C_B = Concentration gradient

Diffusion of Electrolytes (Ions)

PART 2: FACILITATED DIFFUSION

Definition

"Like simple diffusion, facilitated diffusion occurs down an electrochemical potential gradient; thus it requires no input of metabolic energy. Unlike simple diffusion, however, facilitated diffusion uses a membrane carrier and exhibits all the characteristics of carrier-mediated transport: saturation, stereospecificity, and competition."

• Costanzo Physiology 7th Ed, p. 15

Two Subtypes of Facilitated Diffusion

A. Via Channel Proteins

• Voltage-gated - opened by changes in membrane potential (e.g., Na⁺ channels in action potentials)
• Ligand-gated - opened by binding of a specific chemical (e.g., ACh receptor)
• Always open (leak channels)

B. Via Carrier (Transporter) Proteins

The "Ping-Pong" Model (Harper's Biochemistry)

• "Ping" state: Carrier is exposed to high concentration side - solute binds to specific sites
• "Pong" state: Conformational change exposes carrier to low concentration side - solute is released
• The empty carrier then reverts to the "ping" state to restart the cycle

1. Concentration gradient across the membrane
2. Amount of carrier available (key rate-limiting step)
3. Affinity of the solute-carrier interaction
4. Speed of the conformational change for both loaded and unloaded carrier

Kinetics: The Critical Difference from Simple Diffusion

Three Hallmark Properties of Carrier-Mediated Transport (All apply to Facilitated Diffusion)

1. Saturation

• Carriers have a finite number of binding sites
• At low concentration: rate increases steeply
• At high concentration: all sites occupied - rate plateaus at Transport Maximum (Tm), analogous to Vmax in enzyme kinetics
• Clinical example: Glucose reabsorption in renal proximal tubule - when plasma glucose exceeds renal Tm (~180-200 mg/dL), glucose spills into urine (glucosuria in diabetes)

2. Stereospecificity

• Carrier binding sites are stereospecific - they recognize molecular shape
• Example: GLUT4 transports D-glucose but NOT L-glucose
• Simple diffusion, having no carrier, does NOT distinguish stereoisomers

3. Competition

• Chemically related solutes can compete for the same binding site
• They may be transported themselves (D-galactose competes with D-glucose and is also transported)
• Or they may block without being transported (phlorizin blocks glucose transport by occupying its site)

Key Clinical Examples of Facilitated Diffusion

"One of these, glucose transporter 4 (GLUT4), can increase the rate of facilitated diffusion of glucose as much as 10- to 20-fold in insulin-sensitive tissues such as skeletal muscle, adipose, and heart. Insulin stimulates translocation of GLUT4 from the cell cytosol to the plasma membrane, thus increasing cell membrane density of the transporter and increasing the maximum rate (Vmax) of glucose diffusion into these cells."

• Guyton & Hall Medical Physiology, p. 68

PART 3: COMPARISON TABLE - Simple vs. Facilitated Diffusion

PART 4: HIGH-YIELD EXAM POINTS

1. Both simple and facilitated diffusion are passive - NO ATP required
2. Both move substances down their electrochemical gradient (from high to low)
3. Facilitated diffusion is faster than simple diffusion at low concentrations but plateaus at high concentrations
4. The Tm (transport maximum) concept applies ONLY to carrier-mediated transport (facilitated and active)
5. Insulin increases GLUT4 insertion into the membrane - raising Vmax of glucose transport (not affecting Km)
6. Phlorizin is a classic competitive inhibitor of glucose transport (used experimentally)
7. Aquaporins are technically a form of facilitated diffusion (channel protein) - ADH regulates AQP2 insertion in collecting duct
8. Voltage-gated Na⁺ channels (facilitated diffusion) drive the action potential - tetrodotoxin (TTX) blocks these channels
9. Simple diffusion through lipid bilayer follows the partition coefficient - higher lipid solubility = faster diffusion
10. Fick's Law formula: J = PA(C_A - C_B)

PART 5: CLINICAL CONNECTIONS

• Diabetes mellitus: Impaired insulin signaling → less GLUT4 on muscle/fat cell membranes → impaired glucose uptake (Guyton & Hall)
• Volatile anesthetics (halothane, sevoflurane): Highly lipid-soluble - cross blood-brain barrier by simple diffusion through lipid bilayer
• Renal glucosuria (Familial): Defective GLUT2 or SGLT2 → glucose spills into urine despite normal blood glucose
• Bartter syndrome / Gitelman syndrome: Defective ion channels/transporters in kidney tubules

• Costanzo Physiology, 7th Ed, pp. 12-16
• Guyton and Hall Textbook of Medical Physiology, 14th Ed, pp. 64-68
• Harper's Illustrated Biochemistry, 32nd Ed, pp. 488-489