Cytochrome P450 system !

A family of haem enzymes that oxidise drugs, toxins, hormones and vitamins; their induction and inhibition explain many drug interactions.

Updated 2026-11-01

Key facts

Typical reaction: R–H + O₂ + NADPH + H⁺ → R–OH + H₂O + NADP⁺ (monooxygenase: one oxygen to the substrate and one to water).
Electrons come from NADPH through NADPH-cytochrome P450 reductase (FAD and FMN).
Name: it absorbs at 450 nm when its reduced iron binds carbon monoxide.
Six enzymes do almost all the drug work: CYP3A4, 2D6, 2C9, 2C19, 1A2 and 2E1.
Mitochondrial and adrenal P450s make steroids, bile acids and active vitamin D.

The drug enters the active pocket and binds close to the haem iron (Fe³⁺).
The reductase passes one electron from NADPH; the iron becomes Fe²⁺ and takes up O₂.
A second electron and two protons split the O₂: one oxygen leaves as water and the other stays in a highly reactive iron–oxo complex.
That oxygen is inserted into the drug (hydroxylation, dealkylation, epoxidation…): it becomes more polar or gains a handle for phase II.
Induction: the drug activates nuclear receptors (PXR, CAR, AhR) and the cell makes more enzyme over days.
Inhibition: another drug occupies the site or inactivates the enzyme within hours; substrate levels rise.
Polymorphisms (CYP2D6, 2C19, 2C9) divide people into poor, normal and ultrarapid metabolisers.

Inhibitors: «AZOLE MAC RIT»: azoles, macrolides, ritonavir (and grapefruit).

Clopidogrel is a prodrug activated by CYP2C19; poor metabolisers get less antiplatelet effect.
Codeine: CYP2D6 converts it to morphine; ultrarapid metabolisers can be poisoned and poor ones get little pain relief.
Warfarin: CYP2C9 clears it; its variants and inhibitors (amiodarone, metronidazole) raise the bleeding risk.
Classic inducers: rifampicin, carbamazepine, phenytoin, phenobarbital, St John's wort, tobacco smoke (CYP1A2). Inhibitors: azoles, macrolides, ritonavir, cimetidine, grapefruit.

Think of the answer, then tap the question to see it.

Why is it called cytochrome P450?

Because its reduced iron bound to carbon monoxide absorbs light at 450 nm.

What does a CYP2C19 poor metaboliser do with clopidogrel?

Activates little of it, so there is less antiplatelet effect and more risk of thrombosis.

How do enzyme induction and inhibition differ in timing?

Induction takes days because new enzyme must be made; inhibition acts within hours.

Where do the electrons used by P450 come from?

From NADPH, through NADPH-cytochrome P450 reductase (FAD and FMN).

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Cytochrome P450 - arranged by substrate type (Reactome, 2026); Phase I - Functionalization of compounds (Reactome, 2026); What is pharmacogenomics?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); CYP2C19 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.