Cytochromes Flashcards
Where are CYPs located
ER and mitochondria
3 functions of CYPs
Xenobiotic metabolism
Steroid, fatty acid, vitamin oxidation
Steroid biosynthesis
Structure of CYPs
Haem prosthetic group
Fe (III) bound to 4 nitrogen’s
Cysteine residue at C terminal
General CYP reaction
DH + NADPH + O2 —> DOH + NADP + H2O
3 components needed for CYP reaction
P450 enzyme
NADPH cytochrome P450 Reductase
Phosphatidylcholine
What is NADPH reductase for
Electron transfer
FAD is reduced by NADPH (released as NADP+)
FAD carries 2 electrons as FADH2
Passes electrons to FMN forming FMNH2
Passed electrons to CYP
Effect of P450s in xenobiotic metabolism
Inactivate drugs
Activate carcinogens
Produce toxic metabolites from harmless drugs (paracetamol —> NAPQI)
Activate prodrugs
Main 3 CYPs
3A4
2D6
2C9
CYP3A4 abundance in liver
28-30% and metabolised over half of all drugs
Why does CYP3A4 metabolise so many drugs
Large and flexible binding site
CYP3A4 substrate specificity
Binding involves hydrophobic interactions
Mainly metabolised steroids
CYP3A4 example substrates
Cocaine
Tamoxifen
Verapamil
What is CYP3A4 induced by
Glucocorticoids
Rifampicin
St John’s wort
CYP2D6 abundance in liver
Only 2-4% of CYPs in liver but still responsible for over 70 different drug oxidations
CYP2D6 substrate specificity
Basic nitrogen and ionised at physiological pH
Antipsychotics & antidepressants
Amitriptyline, propranolol, clozapine
