OAT and OCT transport Flashcards
What is the specificity of OATs and OCTs, and what is the benefit of this?
They are both poly-specific transporters. This means that they can transport a range of specific substrates.
The benefit of this is that it is saves resources and space within the lipid bilayer, as there doesn’t need to be one receptor for each different molecule.
What kinds of cells, on what organs, and what kinds of substances do OATs and OTCs transport?
They are found predominantly on endothelial and epithelial tissue on organs such as the pancreas, kidney, liver and brain.
They transport material between fluid compartments, such as blood, urine and cerebrospinal fluid.
What charge of molecules do OATs and OCTs transport?
OAT = negative.
OCT = positive.
What are endogenous and exogenous anions, and give some examples that OATs transport.
Endogenous = found within the body, such as:
- Vitamins.
- Amino acid metabolites.
- Neurotransmitter metabolites.
- Cyclic nucleotides.
Exogenous = originate from outside the body, such as drugs, toxins and metabolites:
- Antibiotics and antivirals.
- NSAIDs.
- Herbal formulations.
Why do OATs remove the drug metabolites and toxins?
They remove them to prevent them from being toxic to the body. Some drugs do harm to both injured/ infected/ cancerous cells, but also to healthy cells of the body. They stop the accumulation of these harmful substances.
Other than removal of drugs, what other processes are OATs and OCTs involved in?
Absorption and distribution of exogenous and endogenous organic ions.
Outline how OATs remove organic anions.
The OA- is transported into the lumen by facilitated diffusion and are removed in the urine.
Explain how charges, affinities and competition affect the rate of removal for OATs
The greater the charge, the easier it is to be removed.
The greater the affinity, the easier it is for it to be removed.
This means that the half- life of the drug decreases.
However, other drugs, such as Probnecid for antibiotics, can act as a competitive inhibitor. This means that it also uses the OAT and so the transporter cannot be used to remove the drug as frequently. This increases the half-life of the drug.
Explain how OATs and OCTs can communicate using their ions.
They can communicate between organs and between organisms. The latter through means such as:
- Breast milk.
- Placental barrier.
- Pheromones.
State some exogenous and endogenous cations that OCTs transport.
Exogenous = antimicrobials, hypoglycaemic, and anti-psychotics and -depressants.
Endogenous = neurotransmitters, vitamins and carnitine.
What proportion of drugs are cations (+ve), and what does this mean for their transport?
Around 40%.
This means there is greater competition and potentially a longer half-life.
Outline the renal organic cation transport mechanism.
The OTC acts as a facilitated diffuser due to the membrane potential driving the OC+ inwards.
Explain how metformin is transported from the blood and into hepatocytes, and it’s effect on plasma glucose.
Metformin is used in treating type II diabetes, by lowering plasma glucose levels.
When it is drawn into the hepatocytes, it works by facilitating greater glucose absorption into cells (via the GLUT2 transporter), and inhibiting gluconeogenesis.
Some people express variant alleles of the OCT1 transporter and so there are different efficiencies of the intake of metformin. Those with a greater affinity often tend to display greater hyperglycaemia as it has been removed faster than those with lower affinity OCTs.
Explain how cisplatin can cause damage to healthy body cells.
Cisplatin is used in treating difficult cancers. It does this by accumulating in cancer cells, disrupting the DNA and preventing proliferation.
However, it can cause damage to healthy cells as OCT2 has a very high affinity for cisplatin, but the transporter that removes it from the cell (MATE carriers) has a low affinity.
This means that cisplatin builds up in healthy cells, which is toxic and causes damage.
It can build up in kidney cells, hair cells of the inner ear and in neurones, causing kidney failure, hearing loss and neuropathy, respectively.
