In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.

[2][3][4] Early on in evolution, an effective method for eliminating both endogenous and exogenous formaldehyde was important and this capacity has conserved the ancestral ADH-3 through time.

[3][4] The ability to produce ethanol from sugar (which is the basis of how alcoholic beverages are made) is believed to have initially evolved in yeast.

Though this feature is not adaptive from an energy point of view, by making alcohol in such high concentrations so that they would be toxic to other organisms, yeast cells could effectively eliminate their competition.

This was thought to explain the conservation of ethanol active ADH in species other than yeast, though ADH-3 is now known to also have a major role in nitric oxide signaling.

[5][6] In humans, sequencing of the ADH1B gene (responsible for production of an alcohol dehydrogenase polypeptide) shows several functional variants.

In one, there is a SNP (single nucleotide polymorphism) that leads to either a Histidine or an Arginine residue at position 47 in the mature polypeptide.

[7][12] The hypothesis posits that those individuals with the Histidine variant enzyme were sensitive enough to the effects of alcohol that differential reproductive success arose and the corresponding alleles were passed through the generations.

Classical Darwinian evolution would act to select against the detrimental form of the enzyme (Arg variant) because of the lowered reproductive success of individuals carrying the allele.

[citation needed] The first-ever isolated alcohol dehydrogenase (ADH) was purified in 1937 from Saccharomyces cerevisiae (brewer's yeast).

[14] Many aspects of the catalytic mechanism for the horse liver ADH enzyme were investigated by Hugo Theorell and coworkers.

[16][17][18] In early 1960, the alcohol dehydrogenase (ADH) gene was discovered in fruit flies of the genus Drosophila melanogaster.

[22] Further research has shown that the antioxidant alpha-ketoglutarate may be beneficial in reducing the oxidative stress produced by alcohol consumption.

[24] Two alleles that are commonly used for experimentation involving ethanol toxicity and response are ADHs (slow) and ADHF (fast).

[21] Regardless of genotype, Drosophila show a negative response to exposure to samples with an ethanol content above 5%, which render any tolerance inadequate, resulting in a lethal dosage and a mortality rate of around 70%.

[27] From a mechanistic perspective, if the enzyme adds hydride to the re face of NAD+, the resulting hydrogen is incorporated into the pro-R position.

The structural zinc site is composed of four closely spaced cysteine ligands (Cys97, Cys100, Cys103, and Cys111 in the amino acid sequence) positioned in an almost symmetric tetrahedron around the Zn ion.

[32] Another evolutionary purpose is reversible metabolism of retinol (vitamin A), an alcohol, to retinaldehyde, also known as retinal, which is then irreversibly converted into retinoic acid, which regulates expression of hundreds of genes.

One of those ions is crucial for the operation of the enzyme: It is located at the catalytic site and holds the hydroxyl group of the alcohol in place.

[citation needed] Alcohol dehydrogenase activity varies between men and women, between young and old, and among populations from different areas of the world.

Humans exploit this process to produce alcoholic beverages, by letting yeast ferment various fruits or grains.

[citation needed] Brewer's yeast also has another alcohol dehydrogenase, ADH2, which evolved out of a duplicate version of the chromosome containing the ADH1 gene.

[44] It is an ideal gene to use due to its convenient size (2–3 kb in length with a ≈1000 nucleotide coding sequence) and low copy number.

Scientists at Saint Louis University have used carbon-supported alcohol dehydrogenase with poly(methylene green) as an anode, with a nafion membrane, to achieve about 50 μA/cm2.

[54] In 1949, E. Racker defined one unit of alcohol dehydrogenase activity as the amount that causes a change in optical density of 0.001 per minute under the standard conditions of assay.

[56] There have been studies showing that variations in ADH that influence ethanol metabolism have an impact on the risk of alcohol dependence.

[citation needed] Fomepizole, a drug that competitively inhibits alcohol dehydrogenase, can be used in the setting of acute methanol[60] or ethylene glycol[61] toxicity.