[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Ethanol metabolism [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Ethanol metabolism The liver oxidises ethanol to acetaldehyde and then to acetate; along the way it makes a lot of NADH, which upsets the rest of metabolism. Updated 2026-11-01 ## Interactive map **Balance:** NADH +2 ATP -2 ## Key facts - Ethanol → acetaldehyde (alcohol dehydrogenase, cytosol) → acetate (ALDH2, mitochondria); each step reduces one NAD⁺ to NADH. - With heavy or chronic drinking the MEOS joins in: CYP2E1 in the endoplasmic reticulum oxidises ethanol with NADPH and O₂, and it is inducible (tolerance). - Alcohol dehydrogenase is saturated by little alcohol: elimination follows zero-order kinetics (an almost fixed amount per hour). - The high NADH/NAD⁺ ratio pushes pyruvate to lactate, slows gluconeogenesis and favours fat synthesis: lactic acidosis, hypoglycaemia and fatty liver. - Acetaldehyde is the toxic one: if ALDH2 fails (ALDH2*2 variant or disulfiram) it builds up and causes flushing, nausea and tachycardia. **Also called** Alcohol oxidation ## Regulation - There is no hormonal control: the rate is set by the amount of alcohol dehydrogenase and by how fast mitochondria reoxidise NADH. - Chronic drinking induces CYP2E1 (several-fold more activity): faster elimination, more free radicals and more activation of toxins such as acetaminophen. - Genetic variants change the speed: ADH1B*2 makes acetaldehyde faster and ALDH2*2 removes it poorly; both protect against dependence. ## The steps, one by one - **Step 1 · [Alcohol dehydrogenase (ADH, class I)](https://durgical.com/en/biochemistry/enzymes/alcohol-dehydrogenase/)** [Ethanol](https://durgical.com/en/biochemistry/molecules/ethanol/) + [NAD⁺](https://durgical.com/en/biochemistry/molecules/nad/) ⇌ [Acetaldehyde](https://durgical.com/en/biochemistry/molecules/acetaldehyde/) + NADH In the hepatocyte cytosol it removes two hydrogens from ethanol and turns it into acetaldehyde. MEOS branch: with heavy or chronic drinking, CYP2E1 in the endoplasmic reticulum does the same oxidation using NADPH and O₂, and releases free radicals. **If it fails:** The same enzyme oxidises methanol to formaldehyde and ethylene glycol to glycolaldehyde: the first step towards their toxic acids. [Methanol poisoning →](https://durgical.com/en/conditions/methanol-poisoning/) - **Step 2 · [Mitochondrial aldehyde dehydrogenase (ALDH2)](https://durgical.com/en/biochemistry/enzymes/aldehyde-dehydrogenase-2/)** irreversible [Acetaldehyde](https://durgical.com/en/biochemistry/molecules/acetaldehyde/) + [NAD⁺](https://durgical.com/en/biochemistry/molecules/nad/) + H₂O → Acetate + NADH In the mitochondrion it oxidises toxic acetaldehyde to acetate, which leaves the liver into the blood. **If it fails:** If ALDH2 does not work, acetaldehyde builds up: facial flushing, nausea, headache, tachycardia and hypotension (disulfiram-like reaction). [Disulfiram–ethanol reaction →](https://durgical.com/en/conditions/disulfiram-ethanol-reaction/) - **Step 3 · Acetyl-CoA synthetase (mitochondrial ACSS1, cytosolic ACSS2)** irreversible Acetate + [ATP](https://durgical.com/en/biochemistry/molecules/atp/) + coenzyme A → [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/) + amp + pyrophosphate Mostly in heart, muscle and brain, it activates the acetate arriving in the blood by joining it to coenzyme A; it costs the equivalent of two ATP. **If it fails:** No classic human disease from its deficiency is known; in a liver flooded with NADH, acetyl-CoA is diverted to fat and ketone bodies. - **Step 4 · [Citrate synthase (entry to the Krebs cycle)](https://durgical.com/en/biochemistry/enzymes/citrate-synthase/)** irreversible [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/) + oxaloacetate + H₂O → [Citrate](https://durgical.com/en/biochemistry/molecules/citrate/) + coenzyme A In the tissues that receive it, the acetyl-CoA from alcohol joins oxaloacetate and is burned in the Krebs cycle: this is how ethanol supplies energy (empty calories). **If it fails:** In the drinker's liver oxaloacetate is turned into malate by excess NADH: it is missing for this step and for gluconeogenesis. [Lactic acidosis →](https://durgical.com/en/conditions/lactic-acidosis/) ## Clinical notes - Hypoglycaemia in a fasting drinker or a child who swallows alcohol: excess NADH turns pyruvate into lactate and oxaloacetate into malate, and gluconeogenesis stops. - Fatty liver: NADH slows β-oxidation and supplies glycerol-3-phosphate to build triglycerides. - Alcoholic ketoacidosis: with fasting and vomiting β-hydroxybutyrate dominates (because of NADH), which nitroprusside dipsticks barely detect. - Lactate competes with urate in the renal tubule: alcohol can trigger gout attacks. - Methanol and ethylene glycol use the same enzymes to become toxic acids; blocking alcohol dehydrogenase with fomepizole (or ethanol) is the basis of the antidote. ## Related conditions - [Alcoholic liver disease (biochemistry)](https://durgical.com/en/conditions/alcoholic-liver-disease/) - [Disulfiram–ethanol reaction](https://durgical.com/en/conditions/disulfiram-ethanol-reaction/) - [Methanol poisoning](https://durgical.com/en/conditions/methanol-poisoning/) - [Ethylene glycol poisoning](https://durgical.com/en/conditions/ethylene-glycol-poisoning/) - [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/) - [Wernicke encephalopathy (thiamine deficiency)](https://durgical.com/en/conditions/wernicke-encephalopathy/) - [Gout](https://durgical.com/en/conditions/gout/) - [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/) ## Related - [Alcohol dehydrogenase (ADH)](https://durgical.com/en/biochemistry/enzymes/alcohol-dehydrogenase/) - [Aldehyde dehydrogenase 2 (ALDH2)](https://durgical.com/en/biochemistry/enzymes/aldehyde-dehydrogenase-2/) - [Cytochrome P450 2E1 (CYP2E1, MEOS)](https://durgical.com/en/biochemistry/enzymes/cytochrome-p450-2e1/) - [Ethanol](https://durgical.com/en/biochemistry/molecules/ethanol/) - [Acetaldehyde](https://durgical.com/en/biochemistry/molecules/acetaldehyde/) - [Fomepizole (4-methylpyrazole)](https://durgical.com/en/biochemistry/molecules/fomepizole/) - [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/) - [Citrate synthase](https://durgical.com/en/biochemistry/enzymes/citrate-synthase/) - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) - [Gluconeogenesis](https://durgical.com/en/biochemistry/pathways/gluconeogenesis/) - [Ketogenesis (ketone body synthesis)](https://durgical.com/en/biochemistry/pathways/ketogenesis/) - [Fatty acid synthesis (lipogenesis)](https://durgical.com/en/biochemistry/pathways/fatty-acid-synthesis/) - [Mitochondrial NADH shuttles](https://durgical.com/en/biochemistry/topics/mitochondrial-nadh-shuttles/) - [Thiamine (vitamin B1)](https://durgical.com/en/biochemistry/molecules/thiamine/) ## Test yourself Think of the answer, then tap the question to see it. ## Why can alcohol on an empty stomach cause hypoglycaemia? Because excess NADH turns pyruvate into lactate and oxaloacetate into malate; without those substrates gluconeogenesis stops. ## Which enzyme forms the MEOS and why does it explain tolerance? CYP2E1; chronic drinking induces it, so ethanol is cleared faster. ## Which molecule causes flushing and nausea when ALDH2 fails? Acetaldehyde, which builds up because it is not oxidised to acetate. ## What kind of kinetics does ethanol elimination follow at usual concentrations? Zero order: alcohol dehydrogenase is saturated and removes an almost fixed amount per hour. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/ethanol-metabolism/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Ethanol oxidation](https://reactome.org/PathwayBrowser/#/R-HSA-71384) (Reactome, 2026); [ADH1B: All-trans-retinol dehydrogenase [NAD(+)] ADH1B (human), UniProt P00325](https://www.uniprot.org/uniprotkb/P00325/entry) (UniProt, 2026); [ALDH2: Aldehyde dehydrogenase, mitochondrial (human), UniProt P05091](https://www.uniprot.org/uniprotkb/P05091/entry) (UniProt, 2026); [Alcoholic liver disease: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000281.htm) (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). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **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. --- Source: https://durgical.com/en/biochemistry/pathways/ethanol-metabolism/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/ethanol-metabolism/