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Literature summary for 1.1.1.284 extracted from

  • Staab, C.A.; Hellgren, M.; Hoeoeg, J.O.
    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.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
NADH increasing intracellular NADH levels are likely to trigger S-nitrosoglutathione reduction Homo sapiens

Application

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

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 [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.011
-
S-nitrosoglutathione
-
Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Homo sapiens 5737
-
nucleus
-
Homo sapiens 5634
-

Metals/Ions

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 [Da] Molecular Weight Maximum [Da] Comment Organism
40000
-
2 * 40000 Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Arabidopsis thaliana
-
-
-
Branchiostoma lanceolatum
-
-
-
Ciona intestinalis
-
-
-
Drosophila melanogaster
-
-
-
Escherichia coli
-
-
-
Homo sapiens
-
-
-
Mus musculus
-
-
-

Source Tissue

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 [micromol/min/mg]

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 and Products (Substrate)

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

Subunits Comment Organism
dimer 2 * 40000 Homo sapiens

Synonyms

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 [1/s]

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

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Mus musculus
NAD+
-
Escherichia coli
NAD+
-
Arabidopsis thaliana
NADH
-
Homo sapiens

General Information

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 [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1818
-
S-nitrosoglutathione
-
Homo sapiens