Alcohol dehydrogenase

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Alcohol dehydrogenase
Alcohol dehydrogenase
ADH1A
Secondary to quaternary structure Homodimer
Cofactor Zn 2+
Isoforms 7th
Enzyme classification
EC, category 1.1.1.1 oxidoreductase
Substrate Alcohol + NAD +
Products Carbonyl compound + NADH + H +

Alcohol dehydrogenases ( ADH ) are enzymes which both the reaction of alcohols to the corresponding aldehydes or ketones , and also the reverse reaction of (aldehyde to alcohol) catalyze . Examples of this are the last step of alcoholic fermentation by yeast , in which acetaldehyde is converted to ethanol , as well as the reverse variant (ethanol to acetaldehyde), which takes place in the human body as part of alcohol breakdown. In any case, it is a matter of redox reactions . Alcohol dehydrogenases occur in all living things.

The catalyzed reactions

Alcoholic fermentation process

Only primary and secondary alcohols react ; tertiary alcohols do not react with NAD + .

Primary alcohol

A primary alcohol reacts with NAD + to form an aldehyde and NADH and vice versa (equilibrium reaction ):

Secondary alcohol

A secondary alcohol and NAD + result in ketone and NADH and vice versa (equilibrium reaction):

ADH isoenzymes in humans

At least five different alcohol dehydrogenases coexist in human metabolism. All are dimers of two polypeptide chains, with each subunit containing two zinc ions (Zn 2+ ) and between 374 and 386 amino acids in length. One of these ions is essential for the enzyme to function: It is located at the active site and stabilizes the hydroxyl group of the alcohol.

class Possible subunit properties
Gene name UniProt OMIM
I. ADH1A P07327 103700 Ethanol and methanol oxidation
ADH1B P00325 103720
ADH1C P00326 103730
II ADH4 P08319 103740 3,4-dihydroxyphenylglycol and 4-hydroxy-3-methoxyphenylglycol biosynthesis, as well as benzaldehyde hydrogenation (in the breakdown of adrenaline and noradrenaline )
retinol metabolism
III ADH5 P11766 103710 Glutathione- dependent formaldehyde dehydrogenation ( EC  1.1.1.284 )
IV ADH6 P28332 103735 Ethanol oxidation, benzyl alcohol
V ADH7 P40394 103700 Retinol oxidation, ethanol oxidation (only high concentrations)

Class-I ADH

Alcohol dehydrogenase 1 (ADH1) catalyzes the breakdown of toxic alcohols in the human body and in many animal species. The enzyme present in the stomach and liver mainly catalyzes the oxidation of ethanol to acetaldehyde with the participation of the cofactor NAD + :

Oxidation of ethanol by NAD + to acetaldehyde and NADH

In the human body, ADH1 acts primarily in the liver , but also in the stomach . In this way, for example , ethanol contained in alcoholic beverages is first oxidized to acetaldehyde and finally to acetic acid by the enzyme aldehyde dehydrogenase 2 (ALDH2) . This is then broken down into water and carbon dioxide in the citric acid cycle . The enzyme acetyl-CoA synthetase, which forms acetyl-CoA with consumption of ATP , is necessary for the introduction into the citric acid cycle .

The amount of the ADH1 enzyme in the body varies from person to person and determines how quickly the alcohol consumed is broken down in the body. How much alcohol a person can tolerate (in the sense of "drinkability") depends on many factors, e.g. B. the habit of dealing with a high alcohol content. In general, East Asians , Indigenous peoples of America, and Aboriginal Australians are more likely to have low levels of ADH in their bodies, and women are less likely than men.

Alcohol dehydrogenase 1 is responsible for the toxicity of other alcohols: for example, it oxidizes methanol to the much more toxic product methanal ( formaldehyde ) and ethylene glycol to glycolaldehyde and glyoxalic acid . The conventional treatment of this type of poisoning consists in the application of ethanol (competitive inhibition of ADH1 by ethanol), which is preferentially implemented in the liver. As long as the ethanol is broken down, the methanol is excreted through the kidneys. The methanal therefore does not poison the body. In addition, with fomepizole (4-methylpyrazole) there is the possibility of competitively inhibiting ADH1 . Another inhibitor is 2-fluoroethanol . In addition, all rheumatic drugs / painkillers of the NSAID type inhibit ADH more or less strongly.

Functions

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

Pyruvate from glycolysis is converted into acetaldehyde and carbon dioxide, which catalyzes a pyruvate decarboxylase ( EC  4.1.1.1 ). The aldehyde is then reduced to ethanol by the ADH with consumption of NADH. In this way, the NAD + required for glycolysis is regenerated. Yeast ADH is larger than human ADH and consists of four subunits. Its active center has zinc as a metal ion. Nevertheless, the enzymes from fungi and humans are closely related.

In insects such as the fruit fly, there is an alcohol dehydrogenase, unrelated to humans, to which 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 has been found in yeast.

literature

Web links

Individual evidence

  1. ^ G. Mårdh, AL Dingley, DS Auld, BL Vallee: Human class II (pi) alcohol dehydrogenase has a redox-specific function in norepinephrine metabolism . In: Proceedings of the National Academy of Sciences of the United States of America . tape 83 , no. December 23 , 1986, pp. 8908-8912 , doi : 10.1073 / pnas.83.23.8908 , PMID 3466164 , PMC 387042 (free full text).
  2. Sílvia Martras, Rosana Alvarez, Oriol Gallego, Marta Domínguez, Angel R. de Lera, Jaume Farrés, Xavier Parés: Kinetics of human alcohol dehydrogenase with ring-oxidized retinoids: effect of Tween 80 . In: Archives of Biochemistry and Biophysics . tape 430 , no. 2 , October 15, 2004, p. 210-217 , doi : 10.1016 / j.abb.2004.07.002 , PMID 15369820 .
  3. K. Engeland, JO Höög, B. Holmquist, M. Estonius, H. Jörnvall, BL Vallee: Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding site required for formaldehyde dehydrogenase activity and fatty acid activation . In: Proceedings of the National Academy of Sciences of the United States of America . tape 90 , no. 6 , March 15, 1993, p. 2491-2494 , doi : 10.1073 / pnas.90.6.2491 , PMID 8460164 , PMC 46113 (free full text).
  4. CS Chen, A. Yoshida: Enzymatic properties of the protein encoded by newly cloned human alcohol dehydrogenase ADH6 gene . In: Biochemical and Biophysical Research Communications . tape 181 , no. 2 , December 16, 1991, p. 743-747 , doi : 10.1016 / 0006-291x (91) 91253-9 , PMID 1755855 .
  5. Alexander Parlesak, Michael Hans-Ulrich Billinger, Christiane Bode, Johann Christian Bode: Gastric alcohol dehydrogenase activity in man: influence of gender, age, alcohol consumption and smoking in a caucasian population . In: Alcohol and Alcoholism (Oxford, Oxfordshire) . tape 37 , no. 4 , 2002, ISSN  0735-0414 , p. 388-393 , doi : 10.1093 / alcalc / 37.4.388 , PMID 12107043 .
  6. K. Dohmen, E. Baraona, H. Ishibashi, G. Pozzato, M. Moretti, C. Matsunaga, K. Fujimoto, CS Lieber: Ethnic differences in gastric sigma-alcohol dehydrogenase activity and ethanol first-pass metabolism . In: Alcoholism, Clinical and Experimental Research . tape 20 , no. 9 , December 1996, ISSN  0145-6008 , p. 1569–1576 , doi : 10.1111 / j.1530-0277.1996.tb01701.x , PMID 8986205 .
  7. Marisa Battistella: Fomepizole as an antidote for ethylene glycol poisoning . In: The Annals of Pharmacotherapy . tape 36 , no. 6 , June 2002, p. 1085-1089 , doi : 10.1345 / aph.1A397 , PMID 12022913 .
  8. Vladimir Leskovac, Svetlana Trivić, Draginja Pericin: The three zinc-containing alcohol dehydrogenases from baker's yeast, Saccharomyces cerevisiae . In: FEMS yeast research . tape 2 , no. 4 , 2002, ISSN  1567-1356 , p. 481-494 , doi : 10.1111 / j.1567-1364.2002.tb00116.x , PMID 12702265 .
  9. PW Heinstra, GE Thörig, W. Scharloo, W. Drenth, RJ Nolte: Kinetics and thermodynamics of ethanol oxidation catalyzed by genetic variants of the alcohol dehydrogenase from Drosophila melanogaster and D. simulans . In: Biochimica et Biophysica Acta . tape 967 , no. 2 , 1988, p. 224-233 , doi : 10.1016 / 0304-4165 (88) 90013-x , PMID 3142528 .
  10. Motoaki Yabe, Kazuyuki Shitara, Jun Kawashima, Hirofumi Shinoyama, Akikazu Ando, ​​Takaaki Fujii: Purification and Properties of an Alcohol Dehydrogenase Isozyme from a Methanol-using Yeast, Candida sp. N-16 . In: Bioscience, Biotechnology, and Biochemistry . tape 56 , no. 2 , 1992, p. 338-339 , doi : 10.1271 / bbb.56.338 .