Microsomal cytochrome P450 monooxygenase reactions insert one atom of molecular oxygen into a xenobiotic substrate. What are the two obligatory cosubstrates consumed in every such reaction?
- A NADH and FAD
- B ATP and molecular oxygen
- C NADPH and molecular oxygen ✓
- D NADPH and glutathione
Explanation
The P450 monooxygenase system is a mixed-function oxidase: one atom of O2 enters the substrate (as OH) and the other is reduced to water, with NADPH supplying the two electrons via NADPH-cytochrome P450 reductase. Hence both NADPH and molecular oxygen are obligatory cosubstrates. Glutathione participates only in subsequent Phase II conjugation, not in the P450 reaction itself, which is the fact that eliminates option D.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
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