Carrier-Mediated Transport

- Membrane impermeable to many hydrophilic ions and molecules with radii greater
than 4A or carbon chains longer than 5 carbons
o Means all essential nutrients and multi-valent ions can’t cross via passive
transport

Membrane-Bound Carriers
- Intrinsic proteins with a-helical polypeptide chains that multispan the lipid portion of
the membrane with cylindrical geometry
- Transport involves step-wise binding within the channel

Kinetics and Characteristics of Carrier-mediated Reactions

- Kinetics similar to enzyme kinetics with maximum velocity
- Has chemical specificity
- Exhibits competitive and non-competitive inhibition
- E.g. Ouabain as noncompetitive inhibitor of Na+/K+ pump

Specific Types of Carrier-Mediated Transport

- Facilitated Diffusion
o Transport of down a gradient
o Major fxn is maintenance of a rate of transport of essential large hydrophilic
molecules across extra and intracellular membranes
 E.g. Sugars, AAs, Nucleotides, and Organic acids and bases
o Energy source is gradient NOT METABOLIC ENERGY
 This energy is used for conformational changes in carrier
o Classic examples are GLUT 2 and 4 transporters
- Primary Active Transport
o Transport against gradient using metabolic energy
 Work is always done
o Closely associated with cellular metabolism
 Can be blocked by metabolic inhibitors
o Classic example is Na/K Pump
 Composed of a & B subunits
• a has ATP activity, 10 transmembrane segments
• B is essential for assembly and targeting
 Only pump for Na and most important for K
 Mechanism
• Initially in high energy E1 state with ATP bound and open to
intracellular space
• 3 Na+ bind to a-subunit
• ATP hydrolyzed to phosphorylate a-subunit closing both sides
• Channel spontaneously opens on outside (E2), releasing Na+
• 2 K+ bind
 • Phosphate leaves, closing open end
• Binding of another ATP opens it to inside, releasing K+
 Inhibitors, cardiac glycosides, bind on outside of empty E2-P blocking
entry of K+
• Non-competitive inhibitors
o Another example is H+ pump
 In gastric parietal, kidney tubule, and intestinal cells
 Functions to actively extrude 2 H+ into lumen in exchange for 2 K+
per hydrolysis of 1 ATP
o Another example is Ca pumps
 One located in ER and SR sequesters 2 Ca2+ and 2 H+ from cell
cytoplasm into SR per ATP
 Another in plasma membrane of all cells extrudes 1 Ca2+ in exchange
for 1 H+ per ATP
- Secondary Active Transport
o Transport against gradient using energy of second molecule’s energy gradient
o Can be symport or antiport
 But one molecule has to be against its own gradient and one has to be
with its own gradient
o Na/Glucose Transporter
 Located in apical membrane of cells in proximal kidney tubule and
small intestine
 Functions to reabsorb glucose from filtrate and intestine
o Na-Ca Exchanger
 Moves 3 Na+ with gradient into cell and 1 Ca2+ against its gradient
out of the cell