Activating Compound | Comment | Organism | Structure |
---|---|---|---|
NADH | increasing intracellular NADH levels are likely to trigger S-nitrosoglutathione reduction | Homo sapiens |
Application | Comment | Organism |
---|---|---|
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 | Comment | Organism | Structure |
---|---|---|---|
4-Methylpyrazole | low sensitivity towards the potent inhibitor of alcohol dehydrogenase 1 enzymes | Homo sapiens | |
dodecanoic acid | inhibits ADH3 irrespective of substrate | Homo sapiens | |
additional information | it is unclear whether activation or inhibition by fatty acids is of physiological importance | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.011 | - |
S-nitrosoglutathione | - |
Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | - |
Homo sapiens | 5737 | - |
nucleus | - |
Homo sapiens | 5634 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
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] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
40000 | - |
2 * 40000 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
12-hydroxydodecanoic acid + glutathione + NAD+ | Homo sapiens | best substrate for ADH3 | S-(11-carboxy)undecanyl-glutathione + NADH + H+ | - |
? | |
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 | - |
? | |
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+ | - |
? | |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Arabidopsis thaliana | - |
- |
- |
Branchiostoma lanceolatum | - |
- |
- |
Ciona intestinalis | - |
- |
- |
Drosophila melanogaster | - |
- |
- |
Escherichia coli | - |
- |
- |
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Homo sapiens | - |
embryo | - |
Branchiostoma lanceolatum | - |
liver | - |
Homo sapiens | - |
lung | - |
Homo sapiens | - |
additional information | ADH3 is expressed ubiquitously and with relatively little inter-tissue variation in mammals, in contrast to other ADHs | Homo sapiens | - |
root | highest ADH 3 levels | Arabidopsis thaliana | - |
rosette leaf | highest ADH 3 levels | Arabidopsis thaliana | - |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
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 | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
12-hydroxydodecanoic acid + glutathione + NAD+ | best substrate for ADH3 | Homo sapiens | S-(11-carboxy)undecanyl-glutathione + NADH + H+ | - |
? | |
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 | - |
? | |
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+ | - |
? | |
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+ + ? | - |
? | |
S-nitrosoglutathione + NADH + H+ | - |
Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | 2 * 40000 | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
ADH3 | - |
Drosophila melanogaster |
ADH3 | - |
Mus musculus |
ADH3 | - |
Escherichia coli |
ADH3 | - |
Homo sapiens |
ADH3 | - |
Arabidopsis thaliana |
ADH3 | - |
Ciona intestinalis |
ADH3 | - |
Branchiostoma lanceolatum |
alcohol dehydrogenase 3 | - |
Drosophila melanogaster |
alcohol dehydrogenase 3 | - |
Mus musculus |
alcohol dehydrogenase 3 | - |
Escherichia coli |
alcohol dehydrogenase 3 | - |
Homo sapiens |
alcohol dehydrogenase 3 | - |
Arabidopsis thaliana |
alcohol dehydrogenase 3 | - |
Ciona intestinalis |
alcohol dehydrogenase 3 | - |
Branchiostoma lanceolatum |
formaldehyde dehydrogenase | - |
Homo sapiens |
Glutathione-dependent formaldehyde dehydrogenase | - |
Homo sapiens |
GSNO reductase | - |
Drosophila melanogaster |
GSNO reductase | - |
Mus musculus |
GSNO reductase | - |
Escherichia coli |
GSNO reductase | - |
Homo sapiens |
GSNO reductase | - |
Arabidopsis thaliana |
GSNO reductase | - |
Ciona intestinalis |
GSNO reductase | - |
Branchiostoma lanceolatum |
S-nitrosoglutathione reductase | - |
Drosophila melanogaster |
S-nitrosoglutathione reductase | - |
Mus musculus |
S-nitrosoglutathione reductase | - |
Escherichia coli |
S-nitrosoglutathione reductase | - |
Homo sapiens |
S-nitrosoglutathione reductase | - |
Arabidopsis thaliana |
S-nitrosoglutathione reductase | - |
Ciona intestinalis |
S-nitrosoglutathione reductase | - |
Branchiostoma lanceolatum |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
20 | - |
S-nitrosoglutathione | - |
Homo sapiens | |
72000 | - |
S-nitrosoglutathione | - |
Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Mus musculus | |
NAD+ | - |
Escherichia coli | |
NAD+ | - |
Arabidopsis thaliana | |
NADH | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | ADH3 plays a minor role in hepatic alcohol metabolism | Homo sapiens |
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 |
physiological function | importance of ADH3 in formaldehyde resistance | Escherichia coli |
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 |
physiological function | important ADH3 roles in embryonic development | Drosophila melanogaster |
physiological function | important ADH3 roles in embryonic development | Ciona intestinalis |
physiological function | important ADH3 roles in embryonic development | Branchiostoma lanceolatum |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
1818 | - |
S-nitrosoglutathione | - |
Homo sapiens |