Transporters Flashcards
Membrane transport proteins
-Cellular survival requires that numerous compounds travel across cellular membranes
-majority of transmembrane traffic of small molecules across biological barriers is accomplished by membrane transport proteins known as transporters
Why’d do transport modulators treat
The modulation of transporter activity is a major clinical tool in the treatment of psychiatric disorders
ABC transporters
ATP-binding cassette transporters
-ABC-transporter pump drugs out of cells as a fence mechanism
Difference between transport and ion channels
Ion channels form a tunnel for passage of material while membrane transporters employ a binding site that is only available on one side of a cellular membrane at a time
How do transporters work
-The conformational change induced by binding of solute molecule to transporter leads to the transfer of the solute from one side of the membrane to the other
Types of basic transporters
Uniport
-can only transfer one molecule in one direction
Symport
-Can transfer multiple molecules only in one direction
Antiport
-Can move multiple molecules in opposite directions
Passive transport
Facilitated diffusion
-driving force is concentration/electrochemical gradient (high to low)
-No energy required
-It is much faster than normal diffusion
Example of passive transport
GluT1 ( glucose transporter)
E.Primary active transport
Sodium potassium ATPase pump
-antiport system
-two potassium ions are moved into the cell while three sodium ions are moved out to cause membrane potential to be -70mV
-25% of resting energy production is used for these pumps
-energy is used directly
Secondary active transport
They employ energy stored in the form of electrochemical gradient
-sodium-glucose cotransporters utilise the sodium gradient created by NA+/K+ ATPase pumps to drive transport of glucose into cells
-They utilize energy indirectly
Mechanism of primary active transport
-The Na-K pump binds ATP and three intracellular Na+ ions
-ATP is hydrolysed resulting in ADP and an inorganic phosphate. The free phosphate phosphorylates the sodium-potassium pump
-A conformational change in the pump exposes the Na ions to the outside. The phosphorylated pump now has low affinity for Na ions and so releases them
-The pump binds to 2 K+ ions that dephosphorylate the pump, reverting it to its previous conformational state which transports K+ into the cell
-The unphosphorylated form has higher affinity to Na+ ions and so releases the K+ ions
Transporter inhibition
-Occupy the substrate-binding site with a substrate mimic that is not transported and so clogs the pipe
-substrate mimic that is preferentially transported as compared to normal substrate
-Bind or allosteric site of the transporter to distort the active site
Example of transport inhibitors
-SSRIs such as Prozac, Celexa and Zoloft inhibit serotonin transporter (SERTs) mediated transport of serotonin by presynaptic cells of neural junctions
-This increases the serotonin concentration in the synaptic cleft available to act upon serotonin receptors of post synaptic cells and eventually down regulation of serotonin receptor expression occurs
Psychiatric disorder causes
ADHD, OCD , schizophrenia and depression occur when serotonin is taken up too quickly
SSRI
Selective serotonin reputable inhibitors
