Alcohol dehydrogenase

Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the conversion between alcohols and aldehydes or ketones. In humans and many other animals, they serve to break down alcohols which could otherwise be toxic; in yeast and many bacteria they catalyze the opposite reaction as part of fermentation.

The EC number of alcohol dehydrogenases is ; their CAS number is 9031-72-5.

In humans

In humans, the enzyme is contained in the lining of the stomach and in the liver. It catalyzes the oxidation of ethanol to acetaldehyde:

CH₃CH₂OH + NAD⁺ → CH₃CHO + NADH + H⁺

This allows the consumption of alcoholic beverages, but its original purpose is probably the breakdown of alcohols naturally contained in foods or produced by bacteria in the digestive tract.

Alcohol dehydrogenase is also involved in the toxicity of other types of alcohol: for instance, it oxidizes methanol to produce formaldehyde, and ethylene glycol to ultimately yield glycolic and oxalic acids. Humans have at least six slightly different alcohol dehydrogenases. All of them are dimers (consist of two polypeptides), with each dimer containing two zinc ions Zn²⁺. 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.

In yeast and bacteria

In yeast and many bacteria, alcohol dehydrogenase plays an important part in fermentation: pyruvate resulting from glycolysis is converted to acetaldehyde and carbon dioxide, and the acetaldehyde is then reduced to ethanol by alcohol dehydrogenase. The purpose of this latter step is the regeneration of NAD+, so that the energy generating glycolysis can continue. Humans exploit this process to produce alcoholic beverages, by letting yeast ferment various fruits or grains.

The main alcohol dehydrogenase in yeast is larger than the human one, consisting of four rather than just two subunits. It also contains zinc at its catalytic site. It is clear that the human and yeast alcohol dehydrogenases are closely related.

A simple and effective purification scheme is as follows: 25 mM Pyrophosphate Buffer containing 5 mM Zinc Chloride, 5 mM EDTA, and 0.5 mg/ml BSA. Cellular disruption with a bead mill. Ammonium sulfate precipitation at 40%, discard pellet. Ammonium sulfate precipitation at 70%, resuspend pellet in 1 ml of buffer. Run on Sephadex G-100 column, ADH will elute in first few fraction.

Insects

In insects such as the fruit fly, the alcohol dehydrogenase is smaller than in humans, does not contain a metal, and appears to be unrelated.

Iron containing

A third class of alcohol dehydrogenases, unrelated to the above two, are iron containing ones. They occur in bacteria, and an (apparently inactive) form has also been found in yeast.

In fuel cells

The enzyme can be used to catalyze the breakdown of fuel for an ethanol fuel cell. Scientists at Saint Louis University used carbon-supported alcohol dehydrogenase with poly(methylene green) as an anode, with a nafion membrane, to achieve about 50 μA/cm² ^*.

External links

PDBsum has links to three-dimensional structures of various alcohol dehydrogenases contained in the Protein Data Bank
ExPASy contains links to the alcohol dehydrogenase sequences in Swiss-Prot, to a Medline literature search about the enzyme, and to entries in other databases.
BRENDA most comprehensive compilation of information and literature references about the enzyme; requires payment for commercial users