Alcohol dehydrogenase

Alcohol dehydrogenases (ADH ) are enzymes, which catalyze both the reaction of alcohols to the corresponding aldehydes or ketones, and also the reverse reaction of ( aldehyde to alcohol). Examples of these are the final step of the alcoholic fermentation by yeast, is converted to ethanol in acetaldehyde, and the inverted version ( ethanol to acetaldehyde ), which takes place in the human body as part of the alcohol removal. It is in any case to redox reactions. Alcohol dehydrogenases are present in all living things.

The catalyzed reactions:

ADH isozymes in human

In human metabolism coexist at least five different alcohol dehydrogenases. All of which are dimers composed of two polypeptide chains, each subunit contains two zinc ions ( Zn 2 ) and is 374 to 386 amino acids long. One of these ions is essential for the function of the enzyme: It is located in the active site and stabilizes the hydroxy group of the alcohol.

Class I ADH

The alcohol 1 is used in humans and many animals the reduction of toxic alcohols. Present in the stomach and liver enzyme catalyzes the oxidation of mainly ethanol to acetaldehyde with the participation of the cofactor NAD :

In the human body is ADH1 mainly in the liver, but also in the stomach. Ethanol from alcoholic beverages will be back in acetaldehyde ( ethanal also called ) is converted, then. Carried acetaldehyde into acetic acid and then through the citric acid cycle in water and carbon dioxide For the introduction into the citric acid cycle, the enzyme acetyl- CoA synthetase is necessary, which forms ATP-consuming acetyl -CoA.

The amount of the ADH1 enzyme in the body varies from person to person and determines how fast the alcohol is drunk degraded in the body. How much alcohol a person can tolerate (in the sense of "Drinking strength " ) is dependent on many factors, such as the habit of dealing with a high alcohol content. In general, East Asians, indigenous peoples of the Americas and Aboriginal Australians rather small amounts of ADH in the body, and women less than men.

Alcohol dehydrogenase 1 is responsible for the toxicity of other alcohols: for example, it is oxidized to considerably more toxic methanol product methanal (formaldehyde ), and ethylene glycol to glycolic and oxalic acid. Conventional treatment of this type of poisoning consists in the administration of ethanol ( by competitive inhibition of the ADH1 ethanol), which is preferably reacted in the liver. While ethanol degradation occurs, the methanol is eliminated by the kidneys. Thus, no poisoning of the body occurs through the methanal. In addition, with Fomepizole exists (4- methylpyrazole ) the possibility to inhibit ADH1 competitively. Another inhibitor is 2- fluoroethanol. In addition, all anti-rheumatic drugs / painkillers on the type of NSAID more or less inhibit ADH strong.

Functions

In yeasts and many bacteria, alcohol dehydrogenase plays an important role in the fermentation (see figure):

Pyruvate from glycolysis is converted to acetaldehyde and carbon dioxide, which catalyzes a pyruvate decarboxylase ( EC 4.1.1.1 ). Subsequently, the aldehyde is reduced by the ADH under consumption of NADH to ethanol. In this way is regenerated for glycolysis NAD needed. Yeast ADH is greater than the human, and is composed of four subunits. Your active center has zinc as a metal ion. However, the enzymes from fungi and humans are closely related.

In insects such as the fruit fly a human unrelated alcohol occurs where no metal ion is bound.

A third class of alcohol dehydrogenases contains iron as the central ion. These exist in bacteria, and an (apparently inactive ) form was found in yeast.

Alcohol dehydrogenase

ADH isozymes in human

Class I ADH

Functions

Further Reading