BRENDA - Enzyme Database

Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations

Gross, S.; Cairns, R.A.; Minden, M.D.; Driggers, E.M.; Bittinger, M.A.; Jang, H.G.; Sasaki, M.; Jin, S.; Schenkein, D.P.; Su, S.M.; Dang, L.; Fantin, V.R.; Mak, T.W.; J. Exp. Med. 207, 339-344 (2010)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
1.1.1.42
IDH1, genotyping in acute myelogenous leukemia patients, overview; IDH2, genotyping in acute myelogenous leukemia patients, overview
Homo sapiens
Engineering
EC Number
Amino acid exchange
Commentary
Organism
1.1.1.42
R132C
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells. The mutation reduces the affinity for isocitrate, and increases the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
Homo sapiens
1.1.1.42
R132G
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
Homo sapiens
1.1.1.42
R132H
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
Homo sapiens
1.1.1.42
R172K
IDH2 R172 mutation causes production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
Homo sapiens
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
1.1.1.42
cytosol
IDH1
Homo sapiens
5829
-
1.1.1.42
mitochondrion
IDH2
Homo sapiens
5739
-
1.1.1.42
peroxisome
IDH1
Homo sapiens
5777
-
Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
1.1.1.42
Mg2+
activates; activates
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.1.42
isocitrate + NADP+
Homo sapiens
-
2-oxoglutarate + NADPH + H+ + CO2
-
-
r
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.1.1.42
Homo sapiens
O75874
IDH1
-
1.1.1.42
Homo sapiens
P48735
IDH2
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.1.42
glioblastoma cell
multiforme tumors; multiforme tumors
Homo sapiens
-
1.1.1.42
glioma cell
;
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.42
isocitrate + NADP+
-
712614
Homo sapiens
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
r
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.1.1.42
7.5
-
assay at; assay at
Homo sapiens
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
1.1.1.42
NADP+
;
Homo sapiens
1.1.1.42
NADPH
;
Homo sapiens
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
1.1.1.42
IDH1, genotyping in acute myelogenous leukemia patients, overview
Homo sapiens
1.1.1.42
IDH2, genotyping in acute myelogenous leukemia patients, overview
Homo sapiens
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
1.1.1.42
NADP+
-
Homo sapiens
1.1.1.42
NADPH
-
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
1.1.1.42
R132C
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells. The mutation reduces the affinity for isocitrate, and increases the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
Homo sapiens
1.1.1.42
R132G
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
Homo sapiens
1.1.1.42
R132H
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
Homo sapiens
1.1.1.42
R172K
IDH2 R172 mutation causes production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
Homo sapiens
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
1.1.1.42
cytosol
IDH1
Homo sapiens
5829
-
1.1.1.42
mitochondrion
IDH2
Homo sapiens
5739
-
1.1.1.42
peroxisome
IDH1
Homo sapiens
5777
-
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
1.1.1.42
Mg2+
activates
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.1.42
isocitrate + NADP+
Homo sapiens
-
2-oxoglutarate + NADPH + H+ + CO2
-
-
r
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.1.42
glioblastoma cell
multiforme tumors
Homo sapiens
-
1.1.1.42
glioma cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.42
isocitrate + NADP+
-
712614
Homo sapiens
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
r
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.1.1.42
7.5
-
assay at
Homo sapiens
General Information
EC Number
General Information
Commentary
Organism
1.1.1.42
metabolism
IDH1 is critical in cellular metabolism
Homo sapiens
1.1.1.42
physiological function
mutation at R172 in the active site of IDH2 leads to a change in the molecular mechanism of enzyme catalysis, resulting in production and accumulation of elevated 2-hydroxyglutarate in acute myelogenous leukemia. The mutation reduces the affinity for isocitrate, and increases the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate; mutations at R132 in the active site of IDH1 lead to a change in the molecular mechanism of enzyme catalysis, resulting in production and accumulation of elevated 2-hydroxyglutarate in acute myelogenous leukemia. The mutations reduce the affinity for isocitrate, and increase the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
Homo sapiens
General Information (protein specific)
EC Number
General Information
Commentary
Organism
1.1.1.42
metabolism
IDH1 is critical in cellular metabolism
Homo sapiens
1.1.1.42
physiological function
mutation at R172 in the active site of IDH2 leads to a change in the molecular mechanism of enzyme catalysis, resulting in production and accumulation of elevated 2-hydroxyglutarate in acute myelogenous leukemia. The mutation reduces the affinity for isocitrate, and increases the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
Homo sapiens
1.1.1.42
physiological function
mutations at R132 in the active site of IDH1 lead to a change in the molecular mechanism of enzyme catalysis, resulting in production and accumulation of elevated 2-hydroxyglutarate in acute myelogenous leukemia. The mutations reduce the affinity for isocitrate, and increase the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
Homo sapiens