Pharmacology and Toxicology
Week 3
Dr. Mark Dallas
Transporters
- Passive Diffusion; no protein, molecule can pass through the membrane
- Facilitated Diffusion; need protein, down a conc gradient
- Primary Active Transport; protein, direct ATP synthesis, against concentration
gradient
- Secondary Active Transport; protein required, substrate against conc gradient, energy
provided indirectly via ATP synthesis. Gradient of ion is used to couple transport
[Na+] Can be symport / antiport.
Transporter Families;
1. Ion Transporters and Pumps;
a. P-Class;
o Phosphorylation ATPases, transport all types of ions [each pump is specific to
1-2 ions, but can transport more than 1 ion at a time] Na+/K+ Pump.
b. V-Class;
o Only transport H+ protons, maintain low pH in vacuoles and lysosomes.
c. F-Class;
o Only transport H+ protons, transport down electrochemical gradient to power
ATP synthesis [ATPsynthase pumps in mitochondria]
d. ABC Class;
o ATP Binding Cassette, transport different molecules [polysaccharides/protein]
contain 2 TMD and 2 cytosolic domains which bind to ATP
o CFTR; cystic fibrosis transmembrane conductance regulator, found in
membrane of epithelial cells and mutates to cause cystic fibrosis. Transports
Cl-, inhibited causes a build up of Na+ = defective mucus clearance.
2. Metabolic Transporters ;
- DMT, 31 families, membrane bound transporters.
- Chloroquine resistance transporter [PfCRT] found in eukaryotes and bacterium
- Exports toxic compounds, bacterial multi-drug resistant proteins = antibiotic
resistance
- Chloroquine anti malaria drug, targets PfCRT in mosquitos [can build up tolerance &
mutation = resistance.]
3. Neurotransmitter Transporters;
a. Vesicular;
i. Vesicular inhibitory amino acid transporters
ii. Vesicular excitatory amino acid transporters
iii. Vesicular amine transporters
o Mainly exploited in scientific research for neural identification.
o VGluTS; Glutamate transmission. Immunoreactivity for VGluTS, consecutive
sections through striatum/thalamus. Label proteins to identify location.
Week 3
Dr. Mark Dallas
Transporters
- Passive Diffusion; no protein, molecule can pass through the membrane
- Facilitated Diffusion; need protein, down a conc gradient
- Primary Active Transport; protein, direct ATP synthesis, against concentration
gradient
- Secondary Active Transport; protein required, substrate against conc gradient, energy
provided indirectly via ATP synthesis. Gradient of ion is used to couple transport
[Na+] Can be symport / antiport.
Transporter Families;
1. Ion Transporters and Pumps;
a. P-Class;
o Phosphorylation ATPases, transport all types of ions [each pump is specific to
1-2 ions, but can transport more than 1 ion at a time] Na+/K+ Pump.
b. V-Class;
o Only transport H+ protons, maintain low pH in vacuoles and lysosomes.
c. F-Class;
o Only transport H+ protons, transport down electrochemical gradient to power
ATP synthesis [ATPsynthase pumps in mitochondria]
d. ABC Class;
o ATP Binding Cassette, transport different molecules [polysaccharides/protein]
contain 2 TMD and 2 cytosolic domains which bind to ATP
o CFTR; cystic fibrosis transmembrane conductance regulator, found in
membrane of epithelial cells and mutates to cause cystic fibrosis. Transports
Cl-, inhibited causes a build up of Na+ = defective mucus clearance.
2. Metabolic Transporters ;
- DMT, 31 families, membrane bound transporters.
- Chloroquine resistance transporter [PfCRT] found in eukaryotes and bacterium
- Exports toxic compounds, bacterial multi-drug resistant proteins = antibiotic
resistance
- Chloroquine anti malaria drug, targets PfCRT in mosquitos [can build up tolerance &
mutation = resistance.]
3. Neurotransmitter Transporters;
a. Vesicular;
i. Vesicular inhibitory amino acid transporters
ii. Vesicular excitatory amino acid transporters
iii. Vesicular amine transporters
o Mainly exploited in scientific research for neural identification.
o VGluTS; Glutamate transmission. Immunoreactivity for VGluTS, consecutive
sections through striatum/thalamus. Label proteins to identify location.
