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THE TRANSPORTER. ( TARGET FOR DRUG ACTION ). Heny Ekowati PHARMACY DEPARTMENT MEDICINE AND HEALTH SCIENCES FACULTY UNIVERSITY OF JENDERAL SOEDIRMAN 2013 . Membrane protein transporter types. Channels facilitate diffusion through an aqueous pore when a conformational
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THE TRANSPORTER ( TARGET FOR DRUG ACTION ) Heny Ekowati PHARMACY DEPARTMENT MEDICINE AND HEALTH SCIENCES FACULTY UNIVERSITY OF JENDERAL SOEDIRMAN 2013
Membrane protein transporter types Channels facilitate diffusion through an aqueous pore when a conformational change opens a gate Some carrier types facilitate diffusion, others use energy to pump molecules against Their gradient. They must bind the solute to initiate a conformational change
The membrane lipid barrier:Passive diffusion through the lipid bilayer • Concentration gradient up, diffusion up • Molecule lipid solubility up, diffusion up • Molecular size up, diffusion down • Molecule electrically charged, diffusion blocked
Specialized membrane proteins transport molecules across membranes • Simple diffusion • Species of molecule limited by membrane physics • Rate is slow and linearly related to concentration gradient • Membrane transport • Overall not limited by size, charge, or hydrophilia • Is highly selective for specific needed molecules • Rate is fast and not linear
Carrier types • Uniporter- transports only one molecule species • Symporter- coupled transport of 2 different molecular species in the same direction • Antiporter- coupled transport of 2 different molecular species in the opposite direction • Symporters & antiporters are usually pumps • Some types transport more than one molecule of a species/cycle
The glucose uniporter transports glucose across membranes • Ligand (glucose) binding flips the transporter to a different conformation (changes shape) • The new conformation releases glucose on the other side of the membrane • Release allows it to flip back to repeat the cycle
Band 3 facilitated diffusion anion antiporter in red blood cells • Multipass protein that binds to spectrin • Exchanges Cl- for HCO3- • Important for transporting CO2 to the lungs
Band 3 facilitated diffusion anion antiporter in red blood cells • When the bicarbonate diffusion gradient is reversed, the process reverses
Primary active transport example:The Na+- K+ antiporter pump • Pumps 3 Na+ ions out of cell & 2 K+ ions in • Maintains Na+ & K+ cell membrane gradients • Each cycle uses one ATP, 100 cycles/sec • Uses ¼ energy of most cells, ¾ for neurons
Secondary active transport example: The sodium-glucose symporter pump • Gradients from primary pumps power secondary active transport • Different types, can be antiporters or symporters • Pictured, the Na+ gradient powers conformational change • Glucose is pumped in against its gradient
THE NEPHRON Glomerulus Bowman’s capsule prox. conv. tubule Loop (ansa) of Henle:descend. limb, arcus, ascend. limb dist. conv. tubule collect. tubule