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Enzyme Nomenclature
Information on EC 1.1.99.24 - hydroxyacid-oxoacid transhydrogenase
Word Map on EC 1.1.99.24
- 1.1.99.24
- semialdehyde
- gamma-hydroxybutyrate
- 2-ketoglutarate
- d-2-hydroxyglutarate
-
acidurias
- d-2-hga
- fibroblasts
-
oxoacids
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
1.1.99.24
-
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RECOMMENDED NAME
GeneOntology No.
hydroxyacid-oxoacid transhydrogenase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(S)-3-hydroxybutanoate + 2-oxoglutarate = acetoacetate + (R)-2-hydroxyglutarate
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
transhydrogenation
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SYSTEMATIC NAME
IUBMB Comments
(S)-3-hydroxybutanoate:2-oxoglutarate oxidoreductase
4-Hydroxybutanoate and (R)-2-hydroxyglutarate can also act as donors; 4-oxobutanoate can also act as acceptor.
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CAS REGISTRY NUMBER
COMMENTARY
117698-31-4
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-hydroxybutanoic acid + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
-
-
?
additional information
?
-
-
D-2-hydroxyglutaric aciduria is not associated to the enzyme activity
-
-
-
3-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
-
-
-
r
3-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
radiolabeled substrate 3-hydroxybutyrate, stereospecific reaction
radiolabeled product D-2-hydroxyglutarate
-
r
4-hydroxybutyrate + 2-oxoglutarate
D-2-hydroxyglutarate + succinate semialdehyde
-
-
-
-
?
4-hydroxybutyrate + 2-oxoglutarate
D-2-hydroxyglutarate + succinate semialdehyde
-
-
-
-
?
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + 2-hydroxyglutarate
-
-
-
r
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + 2-hydroxyglutarate
-
hydrogen attached to hydroxyl-bearing C of 4-hydroxybutyrate is transferred to ketone-bearing C of 2-oxoglutarate, oxoacid not NAD+ or NADP+ acts as hydrogen acceptor
-
r
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + 2-hydroxyglutarate
-
hydrogen attached to hydroxyl-bearing C of 4-hydroxybutyrate is transferred to ketone-bearing C of 2-oxoglutarate, oxoacid not NAD+ or NADP+ acts as hydrogen acceptor
-
r
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
-
-
-
?
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
recombinant enzyme in HEK-293 cells
-
-
?
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
-
-
-
r
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
stereospecific reaction, no activity with L-2-hydroxyglutarate
-
-
r
D-2-hydroxyglutarate + succinic semialdehyde
2-oxoglutarate + 4-hydroxybutyrate
-
-
-
?
D-2-hydroxyglutarate + succinic semialdehyde
2-oxoglutarate + 4-hydroxybutyrate
-
-
-
?
D-2-hydroxyglutarate + succinic semialdehyde
2-oxoglutarate + 4-hydroxybutyrate
-
-
-
?
L-3-hydroxybutyrate + 2-oxoglutarate
acetoacetate + 2-oxoglutarate
-
-
-
?
L-3-hydroxybutyrate + 2-oxoglutarate
acetoacetate + 2-oxoglutarate
-
oxidized at 33% the rate of 4-hydroxybutyrate
-
?
L-3-hydroxybutyrate + 2-oxoglutarate
acetoacetate + 2-oxoglutarate
-
oxidized at 33% the rate of 4-hydroxybutyrate
-
?
L-3-hydroxybutyrate + succinic semialdehyde
acetoacetate + 4-hydroxybutyrate
-
-
-
?
L-3-hydroxybutyrate + succinic semialdehyde
acetoacetate + 4-hydroxybutyrate
-
oxo-acids that can act as hydrogen acceptors are 2-oxoadipate, 24% as effective as 2-oxoglutarate and oxaloacetate, 19% as effective as 2-oxoglutarate, D-3-hydroxybutyrate, DL-2-hydroxybutyrate, D/L-malate, D/L-lactate, acetoacetate, 3-oxobutyrate, 3-oxoadipate do not act as hydrogen acceptors, poor acceptors are pyruvate and 2-oxobutyrate
-
?
L-3-hydroxybutyrate + succinic semialdehyde
acetoacetate + 4-hydroxybutyrate
-
62.5% of activity with D-2-hydroxyglutarate
-
?
L-3-hydroxybutyrate + succinic semialdehyde
acetoacetate + 4-hydroxybutyrate
-
oxo-acids that can act as hydrogen acceptors are 2-oxoadipate, 24% as effective as 2-oxoglutarate and oxaloacetate, 19% as effective as 2-oxoglutarate, D-3-hydroxybutyrate, DL-2-hydroxybutyrate, D/L-malate, D/L-lactate, acetoacetate, 3-oxobutyrate, 3-oxoadipate do not act as hydrogen acceptors, poor acceptors are pyruvate and 2-oxobutyrate
-
?
L-3-hydroxybutyrate + succinic semialdehyde
acetoacetate + 4-hydroxybutyrate
-
62.5% of activity with D-2-hydroxyglutarate
-
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
-
-
-
r
additional information
?
-
-
D-2-hydroxyglutaric aciduria is not associated to the enzyme activity
-
-
-
4-hydroxybutyrate + 2-oxoglutarate
D-2-hydroxyglutarate + succinate semialdehyde
-
-
-
-
?
4-hydroxybutyrate + 2-oxoglutarate
D-2-hydroxyglutarate + succinate semialdehyde
-
-
-
-
?
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
recombinant enzyme in HEK-293 cells
-
-
?
4-hydroxybutyrate + 2-oxoglutarate
succinic semialdehyde + D-2-hydroxyglutarate
-
-
-
-
r
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD(P)+
2-oxoglutarate serves as an intermediate acceptor to generate NAD(P)H
additional information
-
enzymatic activity is unaffected by NAD+ or NADP+ up to 1 mM
-
additional information
-
enzymatic activity is unaffected by NAD+ or NADP+ up to 1 mM; no requirement for NAD+ or NADP+
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
bi or trivalent, no stimulation with 0.01-0.05 mM Fe2+, Fe3+, Co2+, Ni2+, Mn2+, Zn2+, Mg2+ or Ca2+; not affected by 0.5 mM Fe2+, Fe3+, Co2+, Ni2+, Mn2+, and Zn2+, or 1 mM Mg2+ and Ca2+
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no effect by EDTA and EGTA; no inhibition with EDTA, EGTA
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
no activity with L-isomer of 2-hydroxybutyrate, Km for succinate semialdehyde is below 0.01 mM, 30°C, pH 7.1
-
0.077
2-oxoglutarate
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+/-0.009 mM, in overexpressed HEK cells, in presence of 0.1 mM 4-hydroxybutyrate
0.067
4-hydroxybutyrate
-
+/-0.012 mM, in overepressed HEK cells, in presence of 0.5 mM 2-oxoglutarate
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
0.0166 micromol/min*g brain tissue; 0.172 micromol/min*g kidney tissue
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.1
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
highest activity in liver and kidney and an intermediate activity in heart; low enzyme activity
additional information
-
no activity in brain and skeletal muscle; tissue distribution, overview
-
; highest activity in liver and kidney and an intermediate activity in heart
-
; highest activity in liver and kidney and an intermediate activity in heart
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
1300fold, partial from liver; native enzyme from liver 1300fold by precipitation using PEG 6000, anion exchange and hydrophobic interaction chromatography, and gel filtration
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, expression in HEK-293 cells as soluble protein
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LINKS TO OTHER DATABASES (specific for EC-Number 1.1.99.24)
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