Ligand metabolism and transport - PXR en CAR
4 important questions on Ligand metabolism and transport - PXR en CAR
What are ligands of PXR?
- Pregnane (steroid)
- Adrostane (steroid)
So, CAR and PXR can induce CYP enzymes. Name some characteristics of CYP34A. (6)
- Induced and thus expressed only in the presence of PXR ligand = bijvoorbeeld rifampicin
- It moves to the endoplasmatic reticulum.
- Important for oxidation (phase I)
- Important for lipophilic drugs
- Can bioactivate compounds to become more toxic.
- Grapefruit= competitive inhibitor of CYP3A4
Where is CYP3A4 expressed?
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A transporter is also induced by PXR. Which one and name some characteristics (6)
- Induced by PXR agonist - rifampicin
- 170 kDa transmembrane glycoprotein
- Widely expressed including liver
- Efflux pump
- ATP dependent (active), broad substrate specificity
- Many CYP3A4 substrates are also P-gly substrates – can be issues with drug drug interactions as both export and metabolism affected.
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