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Literature summary extracted from
- Medium- and short-chain dehydrogenase/reductase gene and protein families: Dual functions of alcohol dehydrogenase 3: implications with focus on formaldehyde dehydrogenase and S-nitrosoglutathione reductase activities (2008), Cell. Mol. Life Sci., 65, 3950-3960.
Activating Compound
| EC Number | Activating Compound | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.1 | S-nitrosoglutathione | ADH3-mediated alcohol oxidation is promoted in the presence of S-nitrosoglutathione | Mus musculus |  |
| 1.1.1.284 | NADH | increasing intracellular NADH levels are likely to trigger S-nitrosoglutathione reduction | Homo sapiens | |
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 1.1.1.284 | medicine | under asthmatic conditions, including lung epithelial cell damage, ADH3, GSH and NAD+ are likely to be present in the airway lining fluid, where inhalation of formaldehyde can then lead to rapid depletion of S-nitrosoglutathione, resulting in bronchoconstriction and enhanced airway hyperresponsivity | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.1 | dodecanoic acid | inhibits ADH3 irrespective of substrate | Mus musculus | |
| 1.1.1.284 | 4-Methylpyrazole | low sensitivity towards the potent inhibitor of alcohol dehydrogenase 1 enzymes | Homo sapiens | |
| 1.1.1.284 | dodecanoic acid | inhibits ADH3 irrespective of substrate | Homo sapiens | |
| 1.1.1.284 | additional information | it is unclear whether activation or inhibition by fatty acids is of physiological importance | Homo sapiens |
KM Value [mM]
| EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.1.1.284 | 0.011 | - |
S-nitrosoglutathione | - |
Homo sapiens | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.1.1.1 | cytoplasm | - |
Mus musculus | 5737 | - |
| 1.1.1.1 | nucleus | - |
Mus musculus | 5634 | - |
| 1.1.1.284 | cytoplasm | - |
Homo sapiens | 5737 | - |
| 1.1.1.284 | nucleus | - |
Homo sapiens | 5634 | - |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.1 | Zn2+ | 2 atoms are included in each 40 kDa subunit, while one of the zinc ions is considered to serve a structural function only, the other zinc ion functions as a Lewis acid and activates the substrate in the active site, which is located in a cleft between the catalytic and the coenzyme binding domain | Mus musculus | |
| 1.1.1.284 | Zn2+ | 2 atoms are included in each 40 kDa subunit, while one of the zinc ions is considered to serve a structural function only, the other zinc ion functions as a Lewis acid and activates the substrate in the active site, which is located in a cleft between the catalytic and the coenzyme binding domain | Homo sapiens | |
Molecular Weight [Da]
| EC Number | Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|---|
| 1.1.1.284 | 40000 | - |
2 * 40000 | Homo sapiens |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.1.1.1 | a primary alcohol + NAD+ | Mus musculus | ADH3 is involved in multiple cellular pathways, as diverse as formaldehyde detoxification, retinoid metabolism and NO homeostasis, ADH3 is considered to play only a minor role in hepatic alcohol metabolism because ethanol concentrations rarely exceed 50 mM | an aldehyde + NADH + H+ | - |
? | |
| 1.1.1.1 | all-trans-retinol + NAD+ | Mus musculus | - |
all-trans-retinal + NADH | - |
? | |
| 1.1.1.1 | octanol + NAD+ | Mus musculus | - |
octanal + NADH | - |
? | |
| 1.1.1.284 | 12-hydroxydodecanoic acid + glutathione + NAD+ | Homo sapiens | best substrate for ADH3 | S-(11-carboxy)undecanyl-glutathione + NADH + H+ | - |
? | |
| 1.1.1.284 | formaldehyde + NAD+ + glutathione | Homo sapiens | multifunctional enzyme, ADH3 constitutes a key enzyme in the detoxification of endogenous and exogenous formaldehyde, formaldehyde is released during intracellular metabolism of endogenous compounds or xenobiotics, expression of ADH3 might thus fulfill a protective role against DNA damage resulting from formaldehyde sources, ADH3 itself catalyzes oxidative reactions which produce NADH, most importantly the oxidation of formaldehyde | S-formylglutathione + NADH | - |
? | |
| 1.1.1.284 | S-(hydroxymethyl)glutathione + NAD(P)+ | Homo sapiens | multifunctional enzyme, large active site pocket of enzyme entails special substrate specificities: short-chain alcohols are poor substrates, while medium-chain alcohols and particularly the glutathione adducts S-hydroxymethylglutathioneand S-nitrosoglutathione are efficiently converted, universal presence and structural conservation imply that ADH3 performs essential housekeeping functions in living organisms | S-formylglutathione + NAD(P)H + H+ | - |
? | |
| 1.1.1.284 | S-nitrosoglutathione + NADH + H+ | Homo sapiens | ADH3 can affect the transnitrosation equilibrium between S-nitrosoglutathione and S-nitrosated proteins, arguing for an important role in NO homeostasis | S-amino-L-glutathione + NAD+ + ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.1.1.1 | Mus musculus | - |
- |
- |
| 1.1.1.284 | Arabidopsis thaliana | - |
- |
- |
| 1.1.1.284 | Branchiostoma lanceolatum | - |
- |
- |
| 1.1.1.284 | Ciona intestinalis | - |
- |
- |
| 1.1.1.284 | Drosophila melanogaster | - |
- |
- |
| 1.1.1.284 | Escherichia coli | - |
- |
- |
| 1.1.1.284 | Homo sapiens | - |
- |
- |
| 1.1.1.284 | Mus musculus | - |
- |
- |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.1.1.1 | liver | - |
Mus musculus | - |
| 1.1.1.1 | additional information | ADH3 is expressed ubiquitously and with relatively little inter-tissue variation in mammals, in contrast to other ADHs | Mus musculus | - |
| 1.1.1.284 | brain | - |
Homo sapiens | - |
| 1.1.1.284 | embryo | - |
Branchiostoma lanceolatum | - |
| 1.1.1.284 | liver | - |
Homo sapiens | - |
| 1.1.1.284 | lung | - |
Homo sapiens | - |
| 1.1.1.284 | additional information | ADH3 is expressed ubiquitously and with relatively little inter-tissue variation in mammals, in contrast to other ADHs | Homo sapiens | - |
| 1.1.1.284 | root | highest ADH 3 levels | Arabidopsis thaliana | - |
| 1.1.1.284 | rosette leaf | highest ADH 3 levels | Arabidopsis thaliana | - |
Specific Activity [micromol/min/mg]
| EC Number | Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|---|
| 1.1.1.284 | additional information | - |
enzyme shows very poor activity towards ethanol, and the human enzyme exhibits non-hyperbolic kinetics with ethanol concentrations up to 3.5 M, at high ethanol concentration ADH3 displays positive cooperativity with ethanol (0.5-3.5 M) compatible with a contribution to first-pass metabolism in vivo, despite negligible activity with ethanol at lower concentrations | Homo sapiens |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.1.1.1 | a primary alcohol + NAD+ | ADH3 is involved in multiple cellular pathways, as diverse as formaldehyde detoxification, retinoid metabolism and NO homeostasis, ADH3 is considered to play only a minor role in hepatic alcohol metabolism because ethanol concentrations rarely exceed 50 mM | Mus musculus | an aldehyde + NADH + H+ | - |
? | |
| 1.1.1.1 | all-trans-retinol + NAD+ | - |
Mus musculus | all-trans-retinal + NADH | - |
? | |
| 1.1.1.1 | octanol + NAD+ | - |
Mus musculus | octanal + NADH | - |
? | |
| 1.1.1.284 | 12-hydroxydodecanoic acid + glutathione + NAD+ | best substrate for ADH3 | Homo sapiens | S-(11-carboxy)undecanyl-glutathione + NADH + H+ | - |
? | |
| 1.1.1.284 | formaldehyde + NAD+ + glutathione | multifunctional enzyme, ADH3 constitutes a key enzyme in the detoxification of endogenous and exogenous formaldehyde, formaldehyde is released during intracellular metabolism of endogenous compounds or xenobiotics, expression of ADH3 might thus fulfill a protective role against DNA damage resulting from formaldehyde sources, ADH3 itself catalyzes oxidative reactions which produce NADH, most importantly the oxidation of formaldehyde | Homo sapiens | S-formylglutathione + NADH | - |
? | |
| 1.1.1.284 | S-(hydroxymethyl)glutathione + NAD(P)+ | multifunctional enzyme, large active site pocket of enzyme entails special substrate specificities: short-chain alcohols are poor substrates, while medium-chain alcohols and particularly the glutathione adducts S-hydroxymethylglutathioneand S-nitrosoglutathione are efficiently converted, universal presence and structural conservation imply that ADH3 performs essential housekeeping functions in living organisms | Homo sapiens | S-formylglutathione + NAD(P)H + H+ | - |
? | |
| 1.1.1.284 | S-nitrosoglutathione + NADH + H+ | ADH3 can affect the transnitrosation equilibrium between S-nitrosoglutathione and S-nitrosated proteins, arguing for an important role in NO homeostasis | Homo sapiens | S-amino-L-glutathione + NAD+ + ? | - |
? | |
| 1.1.1.284 | S-nitrosoglutathione + NADH + H+ | - |
Homo sapiens | ? | - |
? | |
Subunits
| EC Number | Subunits | Comment | Organism |
|---|---|---|---|
| 1.1.1.284 | dimer | 2 * 40000 | Homo sapiens |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.1.1.1 | ADH | - |
Mus musculus |
| 1.1.1.1 | ADH3 | - |
Mus musculus |
| 1.1.1.1 | alcohol dehydrogenase 3 | - |
Mus musculus |
| 1.1.1.1 | alcohol dependent dehydrogenase | - |
Mus musculus |
| 1.1.1.284 | ADH3 | - |
Drosophila melanogaster |
| 1.1.1.284 | ADH3 | - |
Mus musculus |
| 1.1.1.284 | ADH3 | - |
Escherichia coli |
| 1.1.1.284 | ADH3 | - |
Homo sapiens |
| 1.1.1.284 | ADH3 | - |
Arabidopsis thaliana |
| 1.1.1.284 | ADH3 | - |
Ciona intestinalis |
| 1.1.1.284 | ADH3 | - |
Branchiostoma lanceolatum |
| 1.1.1.284 | alcohol dehydrogenase 3 | - |
Drosophila melanogaster |
| 1.1.1.284 | alcohol dehydrogenase 3 | - |
Mus musculus |
| 1.1.1.284 | alcohol dehydrogenase 3 | - |
Escherichia coli |
| 1.1.1.284 | alcohol dehydrogenase 3 | - |
Homo sapiens |
| 1.1.1.284 | alcohol dehydrogenase 3 | - |
Arabidopsis thaliana |
| 1.1.1.284 | alcohol dehydrogenase 3 | - |
Ciona intestinalis |
| 1.1.1.284 | alcohol dehydrogenase 3 | - |
Branchiostoma lanceolatum |
| 1.1.1.284 | formaldehyde dehydrogenase | - |
Homo sapiens |
| 1.1.1.284 | Glutathione-dependent formaldehyde dehydrogenase | - |
Homo sapiens |
| 1.1.1.284 | GSNO reductase | - |
Drosophila melanogaster |
| 1.1.1.284 | GSNO reductase | - |
Mus musculus |
| 1.1.1.284 | GSNO reductase | - |
Escherichia coli |
| 1.1.1.284 | GSNO reductase | - |
Homo sapiens |
| 1.1.1.284 | GSNO reductase | - |
Arabidopsis thaliana |
| 1.1.1.284 | GSNO reductase | - |
Ciona intestinalis |
| 1.1.1.284 | GSNO reductase | - |
Branchiostoma lanceolatum |
| 1.1.1.284 | S-nitrosoglutathione reductase | - |
Drosophila melanogaster |
| 1.1.1.284 | S-nitrosoglutathione reductase | - |
Mus musculus |
| 1.1.1.284 | S-nitrosoglutathione reductase | - |
Escherichia coli |
| 1.1.1.284 | S-nitrosoglutathione reductase | - |
Homo sapiens |
| 1.1.1.284 | S-nitrosoglutathione reductase | - |
Arabidopsis thaliana |
| 1.1.1.284 | S-nitrosoglutathione reductase | - |
Ciona intestinalis |
| 1.1.1.284 | S-nitrosoglutathione reductase | - |
Branchiostoma lanceolatum |
Turnover Number [1/s]
| EC Number | Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.1.1.284 | 20 | - |
S-nitrosoglutathione | - |
Homo sapiens | |
| 1.1.1.284 | 72000 | - |
S-nitrosoglutathione | - |
Homo sapiens | |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 1.1.1.1 | 7.5 | - |
assay at | Mus musculus |
| 1.1.1.284 | 7.5 | - |
assay at | Homo sapiens |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.1 | NAD+ | - |
Mus musculus | |
| 1.1.1.1 | NADH | - |
Mus musculus | |
| 1.1.1.284 | NAD+ | - |
Mus musculus | |
| 1.1.1.284 | NAD+ | - |
Escherichia coli | |
| 1.1.1.284 | NAD+ | - |
Arabidopsis thaliana | |
| 1.1.1.284 | NADH | - |
Homo sapiens | |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.1.1.284 | physiological function | ADH3 plays a minor role in hepatic alcohol metabolism | Homo sapiens |
| 1.1.1.284 | physiological function | formaldehyde toxicity in Adh3 null mutant mice is significantly increased relative to that in wild-type mice. Adh3-deficient mice demonstrate significantly decreased levels of all-trans-retinoic acid in serum, providing evidence for the involvement of ADH3 in retinoic acid formation in vivo | Mus musculus |
| 1.1.1.284 | physiological function | importance of ADH3 in formaldehyde resistance | Escherichia coli |
| 1.1.1.284 | physiological function | importance of ADH3 in formaldehyde resistance. Mutants with modified ADH3 expression seem incapable of detecting intracellular changes in the GSH pool | Arabidopsis thaliana |
| 1.1.1.284 | physiological function | important ADH3 roles in embryonic development | Drosophila melanogaster |
| 1.1.1.284 | physiological function | important ADH3 roles in embryonic development | Ciona intestinalis |
| 1.1.1.284 | physiological function | important ADH3 roles in embryonic development | Branchiostoma lanceolatum |
kcat/KM [mM/s]
| EC Number | kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.1.1.284 | 1818 | - |
S-nitrosoglutathione | - |
Homo sapiens | |
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