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[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# 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.

## In detail

- 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.

## Memory aid

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

**Also called**
CYP, Mixed-function oxidases

## Clinical notes

- 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.

## Related conditions

- [Acetaminophen toxicity](https://durgical.com/en/conditions/acetaminophen-toxicity/)
- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)
- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)

## Related

- [Cytochrome P450 3A4 (CYP3A4)](https://durgical.com/en/biochemistry/enzymes/cytochrome-p450-3a4/)
- [Cytochrome P450 2E1 (CYP2E1, MEOS)](https://durgical.com/en/biochemistry/enzymes/cytochrome-p450-2e1/)
- [Xenobiotic biotransformation: phases I, II and III](https://durgical.com/en/biochemistry/topics/xenobiotic-biotransformation-phases-i-ii-and-iii/)
- [Heme](https://durgical.com/en/biochemistry/molecules/heme/)
- [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/)
- [Vitamin K epoxide reductase (VKORC1)](https://durgical.com/en/biochemistry/enzymes/vitamin-k-epoxide-reductase/)
- [Steroid hormone synthesis (overview)](https://durgical.com/en/biochemistry/topics/steroid-hormone-synthesis/)
- [Vitamin D (calcitriol)](https://durgical.com/en/biochemistry/molecules/vitamin-d/)
- [Cholesterol 7α-hydroxylase (CYP7A1)](https://durgical.com/en/biochemistry/enzymes/cholesterol-7-hydroxylase/)

## Test yourself

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).

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

Sources: [Cytochrome P450 - arranged by substrate type](https://reactome.org/PathwayBrowser/#/R-HSA-211897) (Reactome, 2026); [Phase I - Functionalization of compounds](https://reactome.org/PathwayBrowser/#/R-HSA-211945) (Reactome, 2026); [What is pharmacogenomics?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics/) (MedlinePlus, US National Library of Medicine, 2026); [CYP2C19 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/cyp2c19/) (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).

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