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Ethanol, C₂H₅OH, is a small, simple molecule — two carbons, one hydroxyl group — yet it has a larger effect on human society than almost any other compound. Once swallowed, it moves through the body in a way that is a neat case study in solubility, oxidation reactions, enzyme saturation and toxicology. This article follows a drink from glass to breath to liver, looking at the chemistry at each stage. (It’s about how the body handles ethanol, not a guide to drinking; many countries set legal ages and limits for good reasons.)
Why ethanol gets everywhere
Ethanol mixes with water in any proportion because its –OH group forms hydrogen bonds with water molecules (see hydrogen bonding). Its small ethyl group is also slightly non-polar, so it can pass through cell membranes easily. These two properties explain why it’s absorbed so quickly and why it spreads evenly through all body water, including the brain.
Absorption
A small amount of ethanol is absorbed through the stomach wall, but most — typically around 80 % — is absorbed in the small intestine, which has a huge surface area. How fast depends mainly on how quickly the stomach empties:
- On an empty stomach, ethanol reaches the small intestine quickly, and blood alcohol concentration peaks within about 30 to 60 minutes.
- With food, the stomach holds its contents longer, so absorption is slower and the peak is lower.
- Carbonated drinks tend to speed stomach emptying, and so absorption.
Some ethanol is broken down before it ever reaches the general circulation — by enzymes in the stomach lining and during its first pass through the liver.
Distribution: why body water matters
Because ethanol spreads through body water, the same dose produces a higher concentration in a person with less body water. That depends on body size and composition: fat tissue contains little water, and on average women have a higher percentage of body fat and less body water than men of the same weight. This is one reason the same drink can produce a noticeably different blood alcohol concentration in two different people.
Metabolism: two oxidations
About 90–98 % of absorbed ethanol is metabolised, mainly in the liver. The rest leaves unchanged in breath, urine and sweat. The main pathway is a two-step oxidation, a sequence you’ll recognise from organic chemistry, where primary alcohols are oxidised first to aldehydes and then to carboxylic acids (see oxidation and reduction).
Step 1: ethanol → ethanal (acetaldehyde)
The enzyme alcohol dehydrogenase (ADH) removes two hydrogen atoms from ethanol, passing them to the coenzyme NAD⁺ (see cofactors and coenzymes):
CH₃CH₂OH + NAD⁺ → CH₃CHO + NADH + H⁺
The product, ethanal (acetaldehyde), is considerably more toxic than ethanol. It’s reactive: its aldehyde group can bond to proteins and DNA. It’s classified as a carcinogen when associated with alcohol consumption.
Step 2: ethanal → ethanoic acid (acetate)
A second enzyme, aldehyde dehydrogenase (ALDH), oxidises ethanal to ethanoate (acetate), again reducing NAD⁺:
CH₃CHO + NAD⁺ + H₂O → CH₃COO⁻ + NADH + 2H⁺
In most people, ALDH works fast enough that ethanal doesn’t build up much. The acetate is released into the blood and used by tissues throughout the body: it’s converted to acetyl-CoA and oxidised in the Krebs cycle to carbon dioxide and water, releasing energy. That’s why alcoholic drinks carry calories — ethanol provides about 29 kJ per gram.
The backup pathway: MEOS
A second system, the microsomal ethanol-oxidising system (MEOS), uses a cytochrome P450 enzyme called CYP2E1. It handles a small share of ethanol normally, but becomes more active in people who drink heavily over long periods. This partly explains why regular heavy drinkers develop “tolerance” in metabolism. CYP2E1 also processes some medicines and generates reactive oxygen species, which adds to liver damage.
Zero-order kinetics: a constant rate
Most drugs are removed by first-order kinetics: a constant fraction per hour, giving a constant half-life (see pharmacology basics). Ethanol is different. At the concentrations produced by even a single drink, alcohol dehydrogenase is close to saturated — nearly every enzyme molecule is busy, so it’s working at its maximum rate, Vmax (see enzyme kinetics).
When an enzyme is saturated, adding more substrate can’t speed it up. The result is zero-order elimination: the body removes a roughly constant amount of ethanol per hour, regardless of how much is present. In a typical adult, blood alcohol falls by around 0.015 g per 100 cm³ per hour (with considerable variation between people).
This has an important consequence: drinking more doesn’t make the body clear it faster; it just takes longer. Coffee, cold showers and fresh air don’t change the rate, because they don’t increase the amount of enzyme.
Worked example. A person’s blood alcohol concentration is 0.09 g per 100 cm³. If it falls at 0.015 g per 100 cm³ per hour, how long until it reaches zero?
0.09 ÷ 0.015 = 6 hours.
Compare a first-order process, where the concentration would halve in equal intervals and never quite reach zero. On a graph, zero-order elimination is a straight line going down; first-order is a curve.
The NADH problem
Both oxidation steps convert NAD⁺ to NADH. When the liver processes a lot of ethanol, the NADH/NAD⁺ ratio rises sharply. This affects other metabolism that needs NAD⁺:
- Gluconeogenesis (making new glucose) slows down, which can cause low blood sugar, especially if someone hasn’t eaten.
- Pyruvate is converted into lactate, so blood lactate rises.
- Fat breakdown is suppressed and fat synthesis increases, contributing to fatty liver in heavy drinkers.
The flushing reaction
In many people of East Asian ancestry, a common variant of the ALDH2 gene produces an enzyme that works very poorly. After drinking, ethanal builds up, causing facial flushing, a rapid heartbeat and nausea. People with this variant are at higher risk of oesophageal cancer if they drink regularly, because of the ethanal build-up.
The drug disulfiram, used in treating alcohol dependence, blocks ALDH deliberately. Drinking while taking it causes an unpleasant ethanal reaction, intended to discourage drinking.
What causes a hangover?
The causes are still being researched, but several factors contribute:
- Dehydration: ethanol suppresses the hormone vasopressin (ADH — a different “ADH” from the enzyme), so the kidneys produce more urine.
- Ethanal and inflammatory signalling.
- Low blood sugar from the NADH effect.
- Disrupted sleep (see the chemistry of sleep).
- Congeners — other compounds produced during fermentation and ageing, including small amounts of methanol. Darker drinks such as whisky and red wine generally contain more of them.
Methanol: why a similar molecule is far more dangerous
Methanol, CH₃OH, is processed by the same enzymes, but the products are methanal (formaldehyde) and then methanoic acid (formic acid). Formic acid builds up, causing severe acidosis and damage to the optic nerve, which can lead to blindness or death. Methanol poisoning is treated with drugs that block alcohol dehydrogenase (fomepizole) or, where these aren’t available, with ethanol itself: ethanol competes for the same enzyme, acting as a competitive substrate, so the methanol is excreted unchanged before it’s converted into toxic products (see enzyme inhibition).
Breathalysers
About 1 % or less of ethanol leaves the body in the breath, in a fairly constant ratio to blood alcohol (often taken as about 2,100 : 1 for blood to breath). Early roadside devices used the colour change of orange potassium dichromate to green chromium(III) as ethanol was oxidised. Modern devices use fuel cells, in which ethanol is oxidised at a platinum electrode and the current produced is proportional to the amount of ethanol, or infrared spectroscopy, which detects the C–H and O–H bond vibrations of ethanol.
Key takeaways
- Ethanol is small and both water- and fat-compatible, so it’s absorbed quickly and spreads through body water.
- The liver oxidises it: ethanol → ethanal (ADH) → ethanoate (ALDH), reducing NAD⁺ to NADH.
- ADH is saturated, so elimination is zero-order — a constant amount per hour.
- Build-up of ethanal causes flushing and toxicity; extra NADH disrupts glucose and fat metabolism.
- Methanol follows the same route but gives toxic formic acid.
For another molecule the liver handles every day, read what caffeine does in the body.
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