Toxicology 2
Biotransformation: Bioactivation vs Detoxification
Cytochrome P450
- Group of hemoproteins
- Xenobiotic binds to cytochrome at a substrate binding site
- Alters conformation to allow transfer of electrons to the heme from
NADPH via a nearby flavoprotein (NADPH cytochrome P450 reductase)
- Reduction of heme iron from its normal ferric state to the ferrous state allows a molecule of oxygen to bind
- The xenobiotic-cytochrome-oxygen receives another electron resulting in splitting of the molecular oxygen
- One atom oxidises the chemical, the other picks up protons to form water