Biochemistry · Enzyme
Cytochrome P450 2E1 (CYP2E1, MEOS) !
A liver enzyme that oxidises ethanol in heavy drinkers and turns acetaminophen and other toxins into harmful products.
Updated 2026-11-01
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Key facts
- A haem monooxygenase in the hepatocyte endoplasmic reticulum (most abundant in centrilobular zone 3).
- Ethanol + NADPH + O₂ → acetaldehyde + NADP⁺ + 2 H₂O; it has a high Km, so it works when alcohol is plentiful.
- Chronic drinking induces it (mainly by stabilising the protein): more tolerance and more free radicals.
- It activates toxins: acetaminophen → NAPQI, carbon tetrachloride, benzene, nitrosamines; this is why chronic drinkers are more sensitive to them.
- Also called
- Microsomal ethanol-oxidising system (MEOS)
- EC number
- 1.14.14.1
- Genes
- CYP2E1
- Structure (PDB)
- 3E4E
Structure
- Membrane protein with the typical P450 fold; its active pocket is small, suited to little molecules such as ethanol, acetone or pyrazoles.
Regulation
- Induced by ethanol, acetone, isoniazid and prolonged fasting or uncontrolled diabetes (ketone bodies).
- Ethanol that is present competes with other substrates: acute drinking inhibits it and chronic drinking induces it.
Inhibitors and toxins
- Disulfiram (through its metabolite diethyldithiocarbamate)
- 4-Methylpyrazole (fomepizole, the one in the 3D structure)
- Clomethiazole
Clinical notes
- Chronic drinkers suffer acetaminophen liver injury with smaller amounts: more CYP2E1 makes more NAPQI, and they have less glutathione.
- Its «leaky» cycle releases superoxide and hydrogen peroxide: lipid peroxidation in alcoholic liver disease.
- It explains part of the metabolic tolerance to alcohol in habitual drinkers.
Pathways
Related conditions
Related
- Cytochrome P450 system
- Alcohol dehydrogenase (ADH)
- NAPQI (N-acetyl-p-benzoquinone imine)
- Acetaminophen metabolism and NAPQI
- Ethanol
- Heme
- NADPH
- Reactive oxygen species and antioxidants
- Fomepizole (4-methylpyrazole)
Test yourself
Think of the answer, then tap the question to see it.
Why is a chronic drinker more vulnerable to acetaminophen?
They have more CYP2E1, which makes more NAPQI, and less glutathione to neutralise it.
Which reduced coenzyme does CYP2E1 use to oxidise ethanol?
NADPH (with O₂), unlike alcohol dehydrogenase, which uses NAD⁺.
In which zone of the liver lobule is CYP2E1 abundant and what follows?
In zone 3 (centrilobular); that is where acetaminophen necrosis begins.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: CYP2E1: Cytochrome P450 2E1 (human), UniProt P05181 (UniProt, 2026); RCSB PDB - 3E4E: Human cytochrome P450 2E1 in complex with the inhibitor 4-methylpyrazole (RCSB Protein Data Bank, 2026); Cytochrome P450 - arranged by substrate type (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.