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Literature summary for 1.1.1.42 extracted from

  • 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.
    Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations (2010), J. Exp. Med., 207, 339-344.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
IDH1, genotyping in acute myelogenous leukemia patients, overview Homo sapiens
IDH2, genotyping in acute myelogenous leukemia patients, overview Homo sapiens

Protein Variants

Protein Variants Comment Organism
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
R132G IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells Homo sapiens
R132H IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells Homo sapiens
R172K IDH2 R172 mutation causes production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol IDH1 Homo sapiens 5829
-
mitochondrion IDH2 Homo sapiens 5739
-
peroxisome IDH1 Homo sapiens 5777
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ activates Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
isocitrate + NADP+ Homo sapiens
-
2-oxoglutarate + NADPH + H+ + CO2
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens O75874 IDH1
-
Homo sapiens P48735 IDH2
-

Source Tissue

Source Tissue Comment Organism Textmining
glioblastoma cell multiforme tumors Homo sapiens
-
glioma cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
isocitrate + NADP+
-
Homo sapiens 2-oxoglutarate + NADPH + H+ + CO2
-
r

Synonyms

Synonyms Comment Organism
IDH1
-
Homo sapiens
IDH2
-
Homo sapiens
isocitrate dehydrogenase 1
-
Homo sapiens
isocitrate dehydrogenase 2
-
Homo sapiens

pH Optimum

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

Cofactor

Cofactor Comment Organism Structure
NADP+
-
Homo sapiens
NADPH
-
Homo sapiens

General Information

General Information Comment Organism
metabolism IDH1 is critical in cellular metabolism Homo sapiens
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
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