Mammalian alcohol dehydrogenase - functional and structural implications.
Mammalian alcohol dehydrogenase (ADH) constitutes a complex system with different forms and extensive multiplicity (ADH1-ADH6) that catalyze the oxidation and reduction of a wide variety of alcohols and aldehydes. The ADH1 enzymes, the classical liver forms, are involved in several metabolic pathways beside the oxidation of ethanol, e.g. norepinephrine, dopamine, serotonin and bile acid metabolism. This class is also able to further oxidize aldehydes into the corresponding carboxylic acids, i.e. dismutation. ADH2, can be divided into two subgroups, one group consisting of the human enzyme together with a rabbit form and another consisting of the rodent forms. The rodent enzymes almost lack ethanol-oxidizing capacity in contrast to the human form, indicating that rodents are poor model systems for human ethanol metabolism. ADH3 (identical to glutathione-dependent formaldehyde dehydrogenase) is clearly the ancestral ADH form and S-hydroxymethylglutathione is the main physiological substrate, but the enzyme can still oxidize ethanol at high concentrations. ADH4 is solely extrahepatically expressed and is probably involved in first pass metabolism of ethanol beside its role in retinol metabolism. The higher classes, ADH5 and ADH6, have been poorly investigated and their substrate repertoire is unknown. The entire ADH system can be seen as a general detoxifying system for alcohols and aldehydes without generating toxic radicals in contrast to the cytochrome P450 system.
Höög
J O
JO
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden. jan-olov.hoog@mbb.ki.se
Hedberg
J J
JJ
Strömberg
P
P
Svensson
S
S
D000426:Alcohol Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D003001:Cloning, Molecular; D000431:Ethanol / Q000378:metabolism; D005557:Formaldehyde / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008322:Mammals; D010084:Oxidation-Reduction; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
D007527:Isoenzymes; D011994:Recombinant Proteins; D014801:Vitamin A; D005557:Formaldehyde; C029469:S-hydroxymethylglutathione; D012701:Serotonin; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D005978:Glutathione