Induction

Question 1

What induces CYP1A1

Answer 1

Polycyclic aromatic hydrocarbons

Question 2

What induces CYP2C9

Answer 2

Barbiturates, rifampicin

Question 3

What induced CYP3A4

Answer 3

Barbiturates, rifampicin, glucocorticoids, St John’s wort

Question 4

What induces CYP2E1

Answer 4

Alcohol

Question 5

Mechanism of CYP1A1 induction

Answer 5

AhR ligand binds AhR-heat shock protein complex
Migrates to nucleus
Heterodimerizes with ARNT
Binds XRE on CYP causing increase in txn

Question 6

Mechanism of induction of CYP2C9

Answer 6

CAR and coactivator SRC1
Induces CAR to bind SRC1 more tightly, accelerates rate of txn

Question 7

Mechanism of CYP3A4 induction

Answer 7

PXR receptor
Binds RXR
Binds upstream of CYP gene sequence
Increase txn
Responds to steroids
- used CAR too but PXR is dominant

Question 8

Rifampicin inductiom consequence

Answer 8

Decreased protection from contraceptive pill

Question 9

How to investigate PXR in vivo

Answer 9

In mice PXR for CYP3A11
K/out PXR
K/in human PXR
k/out and k/in (remove noice PXR & insert human form)