Information on EC 1.1.1.284 - S-(hydroxymethyl)glutathione dehydrogenase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
1.1.1.284
-
RECOMMENDED NAME
GeneOntology No.
S-(hydroxymethyl)glutathione dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-(hydroxymethyl)glutathione + NAD(P)+ = S-formylglutathione + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
reduction
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
formaldehyde oxidation II (glutathione-dependent)
-
-
Methane metabolism
-
-
Microbial metabolism in diverse environments
-
-
protein S-nitrosylation and denitrosylation
-
-
formaldehyde oxidation
-
-
SYSTEMATIC NAME
IUBMB Comments
S-(hydroxymethyl)glutathione:NAD+ oxidoreductase
The substrate, S-(hydroxymethyl)glutathione, forms spontaneously from glutathione and formaldehyde; its rate of formation is increased in some bacteria by the presence of EC 4.4.1.22, S-(hydroxymethyl)glutathione synthase. This enzyme forms part of the pathway that detoxifies formaldehyde, since the product is hydrolysed by EC 3.1.2.12, S-formylglutathione hydrolase. The human enzyme belongs to the family of zinc-dependent alcohol dehydrogenases. Also specifically reduces S-nitrosylglutathione.
CAS REGISTRY NUMBER
COMMENTARY hide
9028-84-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain 2201
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain XG
-
-
Manually annotated by BRENDA team
strain XG
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain Rd KW20, gene adhC
UniProt
Manually annotated by BRENDA team
resistant to infection by the pathogen Plasmopara halstedii
-
-
Manually annotated by BRENDA team
resistant to infection by the pathogen Plasmopara halstedii
-
-
Manually annotated by BRENDA team
strain ZV 580
-
-
Manually annotated by BRENDA team
strain ZV 580
-
-
Manually annotated by BRENDA team
Kloeckera sp.
-
-
-
Manually annotated by BRENDA team
NRRL-Y-11328
-
-
Manually annotated by BRENDA team
VSB-792
-
-
Manually annotated by BRENDA team
VSB-792
-
-
Manually annotated by BRENDA team
Methylophilus methanolovorus
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
strain NCYC 495, gene FLD1
-
-
Manually annotated by BRENDA team
strain Tf-11-6, gene FLD1
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
alcohol dehydrogenase III
-
-
Manually annotated by BRENDA team
alcohol dehydrogenase III
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
NRRL-Y-11328
-
-
Manually annotated by BRENDA team
NRRL-Y-11328
-
-
Manually annotated by BRENDA team
Protaminobacter candidus
-
-
-
Manually annotated by BRENDA team
strain F61
-
-
Manually annotated by BRENDA team
strain F61
-
-
Manually annotated by BRENDA team
strain FT-1
-
-
Manually annotated by BRENDA team
NCTC 8325
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
10-hydroxydodecanoic acid + glutathione + NAD+
?
show the reaction diagram
-
-
-
-
?
12-hydroxydodecanoic acid + glutathione + NAD+
S-(11-carboxy)undecanyl-glutathione + NADH + H+
show the reaction diagram
12-hydroxydodecanoic acid + glutathione + NAD+
S-(11-carboxy)undecanylglutathione + NADH
show the reaction diagram
-
-
-
-
?
12-hydroxydodecanoic acid + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
12-hydroxydodedecanoic acid + glutathione + NAD+
12-oxododecanoic acid + ?
show the reaction diagram
3-ethoxy-2-hydroxybutyraldehyde + glutathione + NAD+
S-(3-ethoxy-2-hydroxybutyryl)-glutathione + NADH + H+
show the reaction diagram
butanol + glutathione + NAD+
?
show the reaction diagram
-
-
-
-
?
cinnamyl alcohol + glutathione + NAD+
S-cinnamylglutathione + NADH
show the reaction diagram
-
-
-
-
?
decanol + glutathione + NAD+
?
show the reaction diagram
-
-
-
-
?
farnesol + glutathione + NAD+
S-farnesylglutathione + NADH
show the reaction diagram
-
-
-
-
?
formaldehyde + 6-mercaptohexanoate + NAD+
S-formyl-6-mercaptohexenoate + NADH
show the reaction diagram
-
30% of the activity with glutathione
-
-
?
formaldehyde + 8-mercaptooctanoate + NAD+
S-formyl-8-mercaptooctanoate + NADH
show the reaction diagram
-
35% of the activity with glutathione
-
-
?
formaldehyde + captopril + NAD+
S-formylcaptopril + NADH
show the reaction diagram
-
8% of the activity with glutathione
-
-
?
formaldehyde + glutathione + 3-acetylpyridine-adenine dinucleotide
S-formylglutathione + ?
show the reaction diagram
-
-
-
-
?
formaldehyde + glutathione + NAD+
S-formylglutathione + NADH + H+
show the reaction diagram
formaldehyde + glutathione + NADP+
S-formylglutathione + NADPH + H+
show the reaction diagram
formaldehyde + glutathione + nicotinamide-hypoxanthine dinucleotide
S-formylglutathione + ?
show the reaction diagram
-
-
-
-
?
formaldehyde + glutathione + thio-NAD+
S-formylglutathione + thio-NADH
show the reaction diagram
-
-
-
-
?
formaldehyde + glutathione monomethyl ester + NAD+
S-formylglutathione monomethyl ester + NADH
show the reaction diagram
-
70% of the activity with glutathione
-
-
?
formaldehyde + NAD+ + glutathione
S-formylglutathione + NADH
show the reaction diagram
-
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
-
-
?
formaldehyde + S-hydroxymethyl glutathione + NAD+
?
show the reaction diagram
geraniol + glutathione + NAD+
S-geranylglutathione + NADH
show the reaction diagram
-
-
-
-
?
glyoxal + glutathione + NAD+
S-oxoacetylglutathione + NADH
show the reaction diagram
hydroxypyruvaldehyde + glutathione + NAD+
S-hydroxypyruvylglutathione + NADH
show the reaction diagram
methylglyoxal + glutathione + NAD+
S-pyruvylglutathione + NADH
show the reaction diagram
n-octanol + NAD+
n-octanal + NADH
show the reaction diagram
-
-
-
-
?
octanol + glutathione + NAD+
?
show the reaction diagram
pentanol + glutathione + NAD+
?
show the reaction diagram
-
-
-
-
?
S-(hydroxymethyl)glutathione + NAD(P)+
S-formylglutathione + NAD(P)H + H+
show the reaction diagram
-
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-(hydroxymethyl)glutathione + NAD+
S-formylglutathione + NADH + H+
show the reaction diagram
S-formylglutathione + NADH
formaldehyde + glutathione + NAD+
show the reaction diagram
S-formylglutathione + NADPH
formaldehyde + glutathione + NADP+
show the reaction diagram
S-hydroxymethylglutathione + NAD+
S-formylglutathione + NADH + H+
show the reaction diagram
S-nitrosoglutathione + NAD(P)H + H+
?
show the reaction diagram
S-nitrosoglutathione + NAD+
S-amino-L-glutathione + NADH + H+
show the reaction diagram
-
-
-
-
r
S-nitrosoglutathione + NADH
? + NAD+
show the reaction diagram
S-nitrosoglutathione + NADH
GSH + NAD+ + NO
show the reaction diagram
S-nitrosoglutathione + NADH + H+
?
show the reaction diagram
S-nitrosoglutathione + NADH + H+
S-amino-L-glutathione + NAD+ + ?
show the reaction diagram
-
ADH3 can affect the transnitrosation equilibrium between S-nitrosoglutathione and S-nitrosated proteins, arguing for an important role in NO homeostasis
-
-
?
S-pyruvylglutathione + NADH
methylglyoxal + glutathione + NAD+
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
12-hydroxydodecanoic acid + glutathione + NAD+
S-(11-carboxy)undecanyl-glutathione + NADH + H+
show the reaction diagram
-
best substrate for ADH3
-
-
?
formaldehyde + glutathione + NAD+
S-formylglutathione + NADH + H+
show the reaction diagram
formaldehyde + NAD+ + glutathione
S-formylglutathione + NADH
show the reaction diagram
-
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-(hydroxymethyl)glutathione + NAD(P)+
S-formylglutathione + NAD(P)H + H+
show the reaction diagram
-
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-(hydroxymethyl)glutathione + NAD+
S-formylglutathione + NADH + H+
show the reaction diagram
S-nitrosoglutathione + NADH
? + NAD+
show the reaction diagram
S-nitrosoglutathione + NADH
GSH + NAD+ + NO
show the reaction diagram
-
the enzyme provides a defense mechanism against nitrosative stress, enzymatic pathway that modulates the bioactivity and toxicity of NO
-
-
?
S-nitrosoglutathione + NADH + H+
S-amino-L-glutathione + NAD+ + ?
show the reaction diagram
-
ADH3 can affect the transnitrosation equilibrium between S-nitrosoglutathione and S-nitrosated proteins, arguing for an important role in NO homeostasis
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-acetylpyridine adenine dinucleotide
-
can substitute for beta-NAD+
NADP+
NADPH
nicotinamide hypoxanthine dinucleotide
-
can substitute for beta-NAD+
thio-NAD+
-
can substitute for beta-NAD+
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
-
1 mM, 30% inhibition
12-oxododecanoic acid
2,2'-dipyridyl
-
1 mM, 20% inhibition
2-mercaptoethanol
inhibits both the reductase and dehydrogenase reactions by 30% at 1 mM
3-(1-tert-butyl-4-amino-1H-indazol-3-yl)phenol
-
CBR1 inhibitor, does not inhibit NADH-dependent S-nitrosoglutathione reduction
3-[1-(4-acetylphenyl)-5-phenyl-1H-pyrrol-2-yl]propanoic acid
4-([2-[(2-cyanobenzyl)sulfanyl]-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]methyl)benzoic acid
4-Methylpyrazole
-
low sensitivity towards the potent inhibitor of alcohol dehydrogenase 1 enzymes
5-chloro-3-[2-[(4-ethoxyphenyl)(ethyl)amino]-2-oxoethyl]-1H-indole-2-carboxylic acid
ADP-ribose
AgNO3
-
NADH protects more effectively than NAD+
Alpha-NAD+
ascorbic acid
inhibits both the reductase and dehydrogenase reactions by 30% at 1 mM
citrate
-
1 mM, 24% inhibition
decanedioic acid
-
sebacic acid
Decanoic acid
dithiothreitol
inhibits both the reductase and dehydrogenase reactions by 30% at 1 mM
dodecanedioic acid
-
most efficient inhibitor
dodecanoic acid
folic acid
-
-
formaldehyde
glutathione
GSSG
-
-
imidazole
-
1 mM, 32% inhibition
iodoacetamide
-
1 mM, 20% inhibition
iodoacetate
methylglyoxal
-
-
N6022
noncompetitive
NADPH
-
inhibits reaction with formaldehyde, glutathione and NAD+
NEM
-
1 mM, 35% inhibition
NO2-
-
1 mM, 14% inhibition
Nonanoic acid
-
pelargonic acid
Octanoic acid
p-hydroxymercuribenzoate
-
-
pyrazole
S-acetamidoglutathione
-
-
S-formylglutathione
S-hydroxymethylglutathione
-
-
S-Methylglutathione
Tridecanoic acid
-
tridecylic acid
Undecanoic acid
-
undecylic acid, most efficient inhibitor
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
formaldehyde
-
in the presence of NAD+ and initial absence of NADH, ADH3-mediated S-nitrosoglutathione reduction is triggered by the presence of formaldehyde
NADH
-
increasing intracellular NADH levels are likely to trigger S-nitrosoglutathione reduction
pyrazole
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.041 - 4.7
12-Hydroxydodecanoic acid
0.0509
3-acetylpyridine-adenine dinucleotide
-
-
0.0048
beta-NAD+
-
-
3.5 - 22
cinnamyl alcohol
0.003 - 0.0077
farnesol
0.0071 - 1.14
formaldehyde
0.8
geraniol
-
pH 10, 25C
0.006 - 0.48
glutathione
0.125
glutathione monomethyl ester
-
-
1.2 - 2.8
methylglyoxal
0.0033 - 0.31
NAD+
0.0002 - 0.25
NADH
0.57 - 9.5
NADP+
0.045
NADPH
-
pH 5.7
0.0352
nicotinamide-hypoxanthine dinucleotide
-
-
4
pyruvylglutathione
-
pH 5.7, with NADH as cofactor
0.16
reduced glutathione
-
-
0.058 - 1.2
S-(hydroxymethyl)glutathione
0.12 - 0.6
S-formylglutathione
0.0004 - 0.094
S-hydroxymethyl glutathione
0.00012 - 2.65
S-hydroxymethylglutathione
0.0048 - 0.28
S-nitrosoglutathione
0.057
S-nitrosylglutathione
pH 8.0, 30C, recombinant enzyme
0.0301
thio-NAD+
-
-
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.217 - 5.6
12-Hydroxydodecanoic acid
5.4 - 20.33
cinnamyl alcohol
0.1 - 2.1
farnesol
0.267
formaldehyde
Komagataella pastoris
-
-
20
geraniol
Arabidopsis thaliana
-
pH 10, 25C
0.233
glutathione
Komagataella pastoris
-
-
0.217 - 16.7
NAD+
34.5 - 230
NADH
22.5
S-(hydroxymethyl)glutathione
Arabidopsis thaliana
-
pH 8, 25C
1.04 - 156
S-hydroxymethyl glutathione
1.4 - 51.7
S-hydroxymethylglutathione
0.02 - 72000
S-nitrosoglutathione
additional information
additional information
Zea mays
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
249.2 - 1818
S-nitrosoglutathione
980
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.437
decanedioic acid
-
inhibition of S-nitrosoglutathione reduction
0.231
Decanoic acid
-
inhibition of S-nitrosoglutathione reduction
0.173
dodecanedioic acid
-
inhibition of S-nitrosoglutathione reduction
0.148 - 0.76
dodecanoic acid
21
glutathione
-
inhibition of S-nitrosoglutathione reduction
50
GSSG
-
with 10 and 20 mM, inhibition of S-nitrosoglutathione reduction
0.00043
N6022
pH 8.0, 30C, recombinant enzyme
0.621
Nonanoic acid
-
inhibition of S-nitrosoglutathione reduction
0.909
Octanoic acid
-
inhibition of S-nitrosoglutathione reduction
6.1
S-acetamidoglutathione
-
inhibition of S-nitrosoglutathione reduction
15
S-Methylglutathione
-
inhibition of S-nitrosoglutathione reduction
0.224
Tridecanoic acid
-
inhibition of S-nitrosoglutathione reduction
0.19
Undecanoic acid
-
inhibition of S-nitrosoglutathione reduction
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.1
Decanoic acid
Solanum lycopersicum
D2Y3F4
pH 8.0, 30C, recombinant enzyme
0.526
dodecanoic acid
Solanum lycopersicum
D2Y3F4
pH 8.0, 30C, recombinant enzyme
3.9
glutathione
Solanum lycopersicum
D2Y3F4
pH 8.0, 30C, recombinant enzyme
0.0003
N6022
Solanum lycopersicum
D2Y3F4
pH 8.0, 30C, recombinant enzyme
6.1
Octanoic acid
Solanum lycopersicum
D2Y3F4
pH 8.0, 30C, recombinant enzyme
5.8
S-Methylglutathione
Solanum lycopersicum
D2Y3F4
pH 8.0, 30C, recombinant enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00089
0.0012
0.006
-
antisense cell culture, nutritional stress conditions, pH 7.2, 25C
0.02
-
antisense cell culture, optimal growth conditions, pH 7.2, 25C
0.029
-
wild-type cell culture, nutritional stress conditions, pH 7.2, 25C
0.043
-
wild-type cell culture, optimal growth conditions, pH 7.2, 25C
0.117
-
overexpressing cell culture, nutritional stress conditions, pH 7.2, 25C
0.225
-
-
0.566
-
overexpressing cell culture, optimal growth conditions, pH 7.2, 25C
2.78
-
-
3.17
-
-
4
-
native strain Tf 11-6
4.68
-
-
12
-
purified recombinant enzyme
17
-
purified recombinant enzyme, 25C
27
-
purified recombinant enzyme, 37C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.7
-
reaction with S-formylglutathione and NADH
7.2
-
assay at
7.5 - 9
-
-
7.5 - 8.5
-
recombinant enzyme
7.5 - 8.4
-
-
7.6 - 8.8
-
-
7.9 - 8.2
-
-
8 - 9
-
reaction with formaldehyde + NAD+ + glutathione
8 - 9.5
-
-
8.4
-
enzyme immobilized on the surface of Si/SiO2/Si3N4 structure
9.6
-
assay at