Alcohol dehydrogenase
From Wikipedia, the free encyclopedia
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| Identifiers | |
| Symbol(s) | [1] |
| Entrez | [2] |
| RefSeq | [3] |
| UniProt | [4] |
| Other data | |
| EC number | 1.1.1.1 |
| Locus | Chr. [5] |
Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion 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 CAS number for this type of the enzyme is [9031-72-5].
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[edit] 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 evolutionary 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.
However, alcohol dehydrogenase does not exist in humans to aid in the metabolism of ingested alcohols. It is a necessary enzyme for sugar metabolism in the liver catalyzing the transformation of glyceraldehyde to glycerol. Thus, chronic alcoholism leads to the disruption of a metabolic pathway by flooding it with alien substrates. Therefore, cirrhosis develops.
[edit] 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 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.
Together with the zinc-containing alcohol dehydrogenases of animals and humans, these enzymes from yeasts and many bacteria form the family of "long-chain"-alcohol dehydrogenases.
[edit] Short-chain alcohol dehydrogenases
These enzymes make up a second family of alcohol dehydrogenases unrelated to the previously mentioned enzymes. They do not contain zinc, their subunits are shorter than and unrelated to those of the "long-chain"-alcohol dehydrogenases. Some of these enzymes also contain metals (e. g. Ca or Mg), but only for structural purpose, never in the catalytic centre. Short-chain alcohol dehydrogenases are usually involved in oxidising secondary alcohols and are widespread in all organisms, e. g. for the oxidation of the (S)-3-hydroxyacyl-CoA moieties during fatty acid beta-oxidation. Very similar enzymes are involved in fatty acid biosynthesis, reducing 3-oxoacyl-acyl carrier protein (ACP) building blocks. In some cases, short chain enzymes may also replace family I enzymes for oxidation of primary alcohols. One such case may be in insects such as the fruit fly, whose alcohol dehydrogenase is smaller than that of humans, does not contain a metal, and appears to be unrelated.
[edit] Iron containing alcohol dehydrogenases
A third family 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 comparison to enzymes the above families, these enzymes are oxygen-sensitive.
[edit] Other alcohol dehydrogenase types
A further class of alcohol dehydrogenases belongs to quinoenzymes and requires quinoid cofactors (e. g. pyrroloquinoline quinone, PQQ) as enzyme-bound electron acceptors. A typical example for this type of enzyme is methanol dehydrogenase of methylotrophic bacteria.
[edit] Applications
in fuel cells: Alcohol dehydrogenases 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 [6].
in biotransformation: Alcohol dehydrogenases are often used for the synthesis of enantiomerically pure stereoisomers of chiral alcohols. In contrast to the chemical process, the enzymes yield directly the desired enatiomer of the alcohol by reduction of the corresponding ketone.
[edit] See also
[edit] 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
