Drug Targets: Transporters Flashcards
What are transporters?
Membrane proteins that form a pore within the plasma membrane to allow passage of various types of molecules
Molecule transported is referred to as a?
Substrate
Facilitative/passive transporters describe
No energy needed
Movement of solutes follow the concentration gradient
Describe active transporters
Requires energy
Movement of solutes against the concentration gradient
Two types of active transporters
Primary active and secondary active transporters
describe driving energy source for primary vs secondary active transporters
Primary: energy source = ATP hydrolysis
Secondary: energy source = movement of another solute going down its concentration gradient
Transporter can be classified how?
Based on their structure/function
In type of transport
Direction of transport
Function of direction of the transport classification includes
Influx
Efflux
Bidirectional
Function of type of transport is classification includes?
Facilitative/passive transporters
Active transporters
Based on their structure/function classification includes?
SLC transporters
ABC transporters
ATPase transporters
…and others
SLC transporters are
Solute carriers
SLC transporters are mostly what transporters?
Facilitative/ secondary active transporters
How does ABC transporters work?
Use energy of ATP to transport various substances ( primary active transporters)
How do ATPase transporters work?
Use ATP hydrolysis to drive the transport of protons across a membrane
Role of transporters
Transport amino acids ( for protein synthesis), glucose, vitamins etc
Transport of metals- essential cofactors for enzymes
Transport of neurotransmitters
Drag targeting transporters
Example of transport of neurotransmitters
SERT- takes back serotonin (5-HT) into presynaptic neuron
SERT- target of many anti-depressive drugs
Example of drug targeting transporters
Diuretics, neuropsychiatric drugs, glucose transporter inhibitors etc
Na-K-Cl co-transporter located?
Found in kidney
Loop diuretics (furosemide) are used for? And whys?
Used for heart failure, hypertension, pulmonary oedema
Why? Inhibition of transport- less Na+/K+ reabsorbed- kidney pass more water- diuresis ( increased urine flow)
Explain Na-K-Cl cotransporter
Role in Na+ and K+ reabsorption (from the tubule lumen to the blood stream)
Classify Na/K/Cl cotransporter based on direction of transport, type of transport, structure /function
Direction- influx
Type of transport-secondary active
Structure / function- SLC transporter
Example of role of transporters in drug PK (ADME)
Transport drugs from intestinal lumen to bloodstream-can enhance drug absorption
Transporters can protect the intestine against ingested toxins - pump drugs out of intestines- decreased absorption
Physiological role of p-glycoprotein (p-gp) / multidrug resistance protein 1 (MDR1)
Enhances elimination of toxic substances and harmful agents
Classify P-gp/ MDR1 based on direction of transport, type of transport, structure /function
Direction of transport - efflux
Type of transport-primary active
Structure / function- ABC transporter
The human breast cancer resistance protein (BCRP) is a transporter that uses ATP hydrolysis to transport broad range of substrates out of the cell. How can we classify BCRP based on type of transport?
Primary active transporter
