isocitrate dehydrogenase

Summary

Summary: An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and NADH. It occurs in cell mitochondria. The enzyme requires Mg2+, Mn2+; it is activated by ADP, citrate, and Ca2+, and inhibited by NADH, NADPH, and ATP. The reaction is the key rate-limiting step of the citric acid (tricarboxylic) cycle. (From Dorland, 27th ed) (The NADP+ enzyme is EC 1.1.1.42.) EC 1.1.1.41.

Top Publications

  1. pmc An integrated genomic analysis of human glioblastoma multiforme
    D Williams Parsons
    Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1807-12. 2008
  2. pmc IDH1 and IDH2 mutations in gliomas
    Hai Yan
    Department of Pathology, Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, NC 27710, USA
    N Engl J Med 360:765-73. 2009
  3. pmc Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma
    Houtan Noushmehr
    USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA
    Cancer Cell 17:510-22. 2010
  4. pmc Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
    Lenny Dang
    Agios Pharmaceuticals, Cambridge, Massachusetts 02139, USA
    Nature 462:739-44. 2009
  5. pmc Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation
    Maria E Figueroa
    Weill Cornell Medical College, New York, NY 10065, USA
    Cancer Cell 18:553-67. 2010
  6. pmc Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases
    Wei Xu
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Shanghai Medical School, Fudan University, Shanghai 20032, China
    Cancer Cell 19:17-30. 2011
  7. pmc IDH mutation impairs histone demethylation and results in a block to cell differentiation
    Chao Lu
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 483:474-8. 2012
  8. ncbi Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas
    Christian Hartmann
    Department of Neuropathology, Institute of Pathology, Ruprecht Karls Universitat Heidelberg, Im Neuenheimer Feld 220 221, Heidelberg, Germany
    Acta Neuropathol 118:469-74. 2009
  9. ncbi Analysis of the IDH1 codon 132 mutation in brain tumors
    Jörg Balss
    Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, 69120, Heidelberg, Germany
    Acta Neuropathol 116:597-602. 2008
  10. ncbi Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network
    Michael Weller
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    J Clin Oncol 27:5743-50. 2009

Research Grants

Detail Information

Publications286 found, 100 shown here

  1. pmc An integrated genomic analysis of human glioblastoma multiforme
    D Williams Parsons
    Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1807-12. 2008
    ..Most notably, we found recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) in 12% of GBM patients...
  2. pmc IDH1 and IDH2 mutations in gliomas
    Hai Yan
    Department of Pathology, Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, NC 27710, USA
    N Engl J Med 360:765-73. 2009
    ..of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that were known to have evolved ..
  3. pmc Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma
    Houtan Noushmehr
    USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA
    Cancer Cell 17:510-22. 2010
    ..Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome. These findings identify G-CIMP as a distinct subset of human gliomas on molecular and clinical grounds...
  4. pmc Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
    Lenny Dang
    Agios Pharmaceuticals, Cambridge, Massachusetts 02139, USA
    Nature 462:739-44. 2009
    Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers...
  5. pmc Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation
    Maria E Figueroa
    Weill Cornell Medical College, New York, NY 10065, USA
    Cancer Cell 18:553-67. 2010
    ..Finally, either expression of mutant IDH1/2 or Tet2 depletion impaired hematopoietic differentiation and increased stem/progenitor cell marker expression, suggesting a shared proleukemogenic effect...
  6. pmc Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases
    Wei Xu
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Shanghai Medical School, Fudan University, Shanghai 20032, China
    Cancer Cell 19:17-30. 2011
    ..Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations...
  7. pmc IDH mutation impairs histone demethylation and results in a block to cell differentiation
    Chao Lu
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 483:474-8. 2012
    Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from α-..
  8. ncbi Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas
    Christian Hartmann
    Department of Neuropathology, Institute of Pathology, Ruprecht Karls Universitat Heidelberg, Im Neuenheimer Feld 220 221, Heidelberg, Germany
    Acta Neuropathol 118:469-74. 2009
    Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III...
  9. ncbi Analysis of the IDH1 codon 132 mutation in brain tumors
    Jörg Balss
    Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, 69120, Heidelberg, Germany
    Acta Neuropathol 116:597-602. 2008
    A recent study reported on mutations in the active site of the isocitrate dehydrogenase (IDH1) gene in 12% of glioblastomas. All mutations detected resulted in an amino acid exchange in position 132...
  10. ncbi Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network
    Michael Weller
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    J Clin Oncol 27:5743-50. 2009
    ..The prognostic value of genetic alterations characteristic of glioblastoma in patients treated according to present standards of care is unclear...
  11. pmc Recurring mutations found by sequencing an acute myeloid leukemia genome
    Elaine R Mardis
    Department of Genetics, Washington University, St Louis, MO 63110, USA
    N Engl J Med 361:1058-66. 2009
    ..The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known...
  12. pmc Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability
    David R Wise
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 108:19611-6. 2011
    ..Glutamine-derived α-ketoglutarate is reductively carboxylated by the NADPH-linked mitochondrial isocitrate dehydrogenase (IDH2) to form isocitrate, which can then be isomerized to citrate...
  13. pmc Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations
    Stefan Gross
    Agios Pharmaceuticals Incorporated, Cambridge, MA 02139, USA
    J Exp Med 207:339-44. 2010
    Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present in most gliomas and secondary glioblastomas, but are rare in other neoplasms. IDH1/2 mutations are heterozygous, and affect a single arginine residue...
  14. pmc Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome
    Zachary J Reitman
    The Preston Robert Tisch Brain Tumor Center at Duke, Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 108:3270-5. 2011
    ..NAAG also was significantly lower in human glioma tissues containing IDH mutations than in gliomas without such mutations. These metabolic changes provide clues to the pathogenesis of tumors associated with IDH gene mutations...
  15. pmc SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status
    Wei Yu
    Department of Biomolecular Chemistry and the Wisconsin Institute for Discovery, University of Wisconsin Madison, Madison, Wisconsin 53715, USA
    J Biol Chem 287:14078-86. 2012
    ..The mitochondrial matrix protein isocitrate dehydrogenase 2 (IDH2) is a major source of NADPH...
  16. ncbi Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas
    Marc Sanson
    L Institut National de la Santé et de la Recherche Médicale U711, Fédération de Neurologie Mazarin, Groupe Hospitalier Pitie Salpetriere, 75651, Paris Cedex 13, France
    J Clin Oncol 27:4150-4. 2009
    Unexpected mutations affecting the isocitrate dehydrogenase (IDH1) gene at codon 132 have been found in 12% of glioblastomas.
  17. pmc IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas
    Koichi Ichimura
    Molecular Histopathology, Level 3, Lab Block, Addenbrooke s Hospital, Box 231, Cambridge CB20QQ, UK
    Neuro Oncol 11:341-7. 2009
    We screened exon 4 of the gene isocitrate dehydrogenase 1 (NADP+), soluble (IDH1) for mutations in 596 primary intracranial tumors of all major types...
  18. ncbi IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours
    M Fernanda Amary
    Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK
    J Pathol 224:334-43. 2011
    Somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in gliomas and acute myeloid leukaemia (AML)...
  19. pmc 2-hydroxyglutarate production, but not dominant negative function, is conferred by glioma-derived NADP-dependent isocitrate dehydrogenase mutations
    Genglin Jin
    The Preston Robert Tisch Brain Tumor Center at Duke, Pediatric Brain Tumor Foundation Institute, and Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS ONE 6:e16812. 2011
    Gliomas frequently contain mutations in the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase (IDH1) or the mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2)...
  20. ncbi Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas
    Christian Hartmann
    Department of Neuropathology, Institute of Pathology, Ruprecht Karls University Heidelberg, Germany
    Acta Neuropathol 120:707-18. 2010
    ..We sequenced the isocitrate dehydrogenase 1 gene (IDH1) at codon 132 in 382 patients with anaplastic astrocytoma and glioblastoma from the NOA-04 ..
  21. ncbi Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells
    Su Min Lee
    Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu, South Korea
    Free Radic Biol Med 32:1185-96. 2002
    ..by glucose 6-phosphate dehydrogenase (G6PD), malic enzyme, and the cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc). Little information is available about the role of IDPc in antioxidant defense...
  22. ncbi IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication
    Peter Paschka
    University Hospital of Ulm, Ulm, Germany
    J Clin Oncol 28:3636-43. 2010
    To analyze the frequency and prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations in acute myeloid leukemia (AML).
  23. pmc IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis
    A Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Leukemia 24:1302-9. 2010
    ..collaborative project, 1473 patients with myeloproliferative neoplasms (MPN) were screened for isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations: 594 essential thrombocythemia (ET), 421 polycythemia vera (PV), 312 primary ..
  24. pmc A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation
    Christopher G Duncan
    The Preston Robert Tisch Brain Tumor Center, The Pediatric Brain Tumor Foundation Institute, The Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Genome Res 22:2339-55. 2012
    ..These data provide insight on epigenetic alterations induced by IDH1 mutations and support a causal role for IDH1(R132H/WT) mutants in driving epigenetic instability in human cancer cells...
  25. pmc DNA methylation, isocitrate dehydrogenase mutation, and survival in glioma
    Brock C Christensen
    Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA
    J Natl Cancer Inst 103:143-53. 2011
    ..that distinguish glioma histological subtypes, DNA methylation patterns of gliomas and their association with other tumor features such as mutation of isocitrate dehydrogenase (IDH) genes have only recently begun to be investigated.
  26. pmc Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping
    Darrell R Borger
    Division of Hematology Oncology, Massachusetts General Hospital, Boston 02114 2698, USA
    Oncologist 17:72-9. 2012
    ..with a gastrointestinal malignancy has led to the novel discovery of mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) in tumors from a subset of patients with cholangiocarcinoma...
  27. pmc Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers
    Stephen Yip
    Department of Pathology and Laboratory Medicine, BC Cancer Agency, BC, Canada
    J Pathol 226:7-16. 2012
    ..Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion...
  28. pmc Mutant metabolic enzymes are at the origin of gliomas
    Hai Yan
    The Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, North Carolina, USA
    Cancer Res 69:9157-9. 2009
    Mutations of the isocitrate dehydrogenase (IDH) metabolic enzymes IDH1 and IDH2 have been found to be frequent and early genetic alterations in astrocytomas and oligodendrogliomas...
  29. pmc Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome
    Twinkal C Pansuriya
    Department of Pathology, Leiden University Medical Center, The Netherlands
    Nat Genet 43:1256-61. 2011
    ..Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation...
  30. pmc Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha
    Shimin Zhao
    Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, 130 Dong an Road, Shanghai 200032, China
    Science 324:261-5. 2009
    Heterozygous mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) occur in certain human brain tumors, but their mechanistic role in tumor development is unknown...
  31. pmc The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate
    Patrick S Ward
    Abramson Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cancer Cell 17:225-34. 2010
    The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG)...
  32. pmc Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism
    Zachary J Reitman
    Department of Pathology, The Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, NC 27710, USA
    J Natl Cancer Inst 102:932-41. 2010
    ..Study of alterations in these metabolic enzymes may provide insights into the metabolism of cancer cells and uncover novel avenues for development of anticancer therapeutics...
  33. ncbi Monoclonal antibody specific for IDH1 R132H mutation
    David Capper
    Department of Neuropathology, Institute of Pathology, Ruprecht Karls University Heidelberg, Im Neuenheimer Feld 220 221, 69120 Heidelberg, Germany
    Acta Neuropathol 118:599-601. 2009
    ..This antibody is highly useful for tumor classification, in detecting single infiltrating tumor cells and for the characterization of the cellular role of mutant IDH1 protein...
  34. ncbi MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells
    Hirotomo Tanaka
    Department of Neurosurgery, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    J Neurooncol 111:273-83. 2013
    ..examined the expression levels of miR-183 in various types of gliomas and the association of miR-183 with isocitrate dehydrogenase 2 (IDH2), which has complementary sequences to miR-183 in its 3'-untranslated region (3'UTR)...
  35. pmc Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas
    P Wang
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
    Oncogene 32:3091-100. 2013
    Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer...
  36. pmc Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin
    Albert Lai
    David Geffen School of Medicine at theUniversity of California at Los Angeles, Los Angeles, CA, USA
    J Clin Oncol 29:4482-90. 2011
    Mutation in isocitrate dehydrogenase 1 (IDH1) at R132 (IDH1(R132MUT)) is frequent in low-grade diffuse gliomas and, within glioblastoma (GBM), has been proposed as a marker for GBMs that arise by transformation from lower-grade gliomas, ..
  37. ncbi Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2
    M Fernanda Amary
    Histopathology Unit, Royal National Orthopaedic Hospital National Health Service Trust, Stanmore, UK
    Nat Genet 43:1262-5. 2011
    ..We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein...
  38. pmc Isocitrate dehydrogenase (IDH) mutations promote a reversible ZEB1/microRNA (miR)-200-dependent epithelial-mesenchymal transition (EMT)
    Alexandra R Grassian
    Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA
    J Biol Chem 287:42180-94. 2012
    Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG)...
  39. ncbi Regulation of an enzyme by phosphorylation at the active site
    J H Hurley
    Department of Biochemistry and Biophysics, University of California, San Francisco 94143 0448
    Science 249:1012-6. 1990
    The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification...
  40. ncbi Crystal structure of porcine mitochondrial NADP+-dependent isocitrate dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme mechanism
    Christopher Ceccarelli
    Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA
    J Biol Chem 277:43454-62. 2002
    The crystal structure of porcine heart mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH) complexed with Mn2+ and isocitrate was solved to a resolution of 1.85 A...
  41. ncbi Regulation of mitochondrial NADP+-dependent isocitrate dehydrogenase activity by glutathionylation
    In Sup Kil
    Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702 701, Korea
    J Biol Chem 280:10846-54. 2005
    ..redox balance and oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm)...
  42. ncbi Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity
    Xiang Xu
    Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    J Biol Chem 279:33946-57. 2004
    ..This mechanism might be applicable to other eukaryotic NADP-IDHs. The results also provide insights into the recognition and specificity of substrate and cofactor by eukaryotic NADP-IDHs...
  43. ncbi Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia
    Felicitas Thol
    Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl Neuberg Strasse 1, Hannover, Germany
    Blood 116:614-6. 2010
    Mutations in the nicotinamide adenine dinucleotide phosphate(+)-dependent isocitrate dehydrogenase gene 2 (IDH2) have recently been found in patients with acute myeloid leukemia (AML) as well as in patients with leukemic transformation of ..
  44. ncbi Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma?
    Nanne K Kloosterhof
    Department of Neurology and Neuro Oncology, Daniel den Hoed Cancer Center, Netherlands
    Lancet Oncol 12:83-91. 2011
    The discovery of somatic mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) in glioblastomas was remarkable because the enzyme was not previously identified with any known oncogenic pathway...
  45. ncbi IDH mutations in glioma and acute myeloid leukemia
    Lenny Dang
    Agios Pharmaceuticals, 38 Sidney Street, Suite 200, Cambridge, MA 02139, USA
    Trends Mol Med 16:387-97. 2010
    ..multiforme (GBM) genomes has identified the recurrent mutation of IDH1, a gene encoding NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) that catalyzes the oxidative decarboxylation of isocitrate yielding alpha-ketoglutarate (alpha-..
  46. ncbi IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with intermediate risk karyotype and unfavorable prognosis in adults younger than 60 years and unmutated NPM1 status
    Susanne Schnittger
    Munich Leukemia Laboratory, Munich, Germany
    Blood 116:5486-96. 2010
    Mutations in the IDH1 gene at position R132 coding for the enzyme cytosolic isocitrate dehydrogenase are known in glioma and have recently been detected also in acute myeloid leukemia (AML)...
  47. ncbi The next generation of glioma biomarkers: MGMT methylation, BRAF fusions and IDH1 mutations
    Andreas von Deimling
    Department of Neuropathology, Institute of Pathology, Ruprecht Karls University Heidelberg, and Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany
    Brain Pathol 21:74-87. 2011
    ..In contrast, BRAF fusion and IDH1 mutation analyses promise to be very helpful for classifying and grading gliomas, while their potential predictive value has yet to be established...
  48. ncbi IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas
    C Houillier
    Service de Neurologie 2 Mazarin, Groupe Hospitalier Pitié Salpêtrière AP HP, Paris, France
    Neurology 75:1560-6. 2010
    ..Recent studies have shown that IDH1 and IDH2 mutations occur frequently in gliomas, including low-grade gliomas. However, their impact on the prognosis and chemosensitivity of low-grade gliomas remains unclear...
  49. pmc IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
    Guido Marcucci
    Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 28:2348-55. 2010
    ....
  50. pmc Inborn and acquired metabolic defects in cancer
    Christian Frezza
    Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, UK
    J Mol Med (Berl) 89:213-20. 2011
    ....
  51. pmc An in vivo patient-derived model of endogenous IDH1-mutant glioma
    H Artee Luchman
    Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
    Neuro Oncol 14:184-91. 2012
    Somatic mutations in the catalytic domain of isocitrate dehydrogenase (IDH) 1/2 and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG) appear to be among the earliest events in gliomagenesis and may contribute to malignant ..
  52. ncbi Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value
    Saman Abbas
    Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
    Blood 116:2122-6. 2010
    Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) were recently demonstrated in acute myeloid leukemia (AML), but their prevalence and prognostic impact remain to be explored in large extensively characterized AML ..
  53. ncbi Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma
    Benjamin R Kipp
    Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Hum Pathol 43:1552-8. 2012
    Somatic mutations in isocitrate dehydrogenase 1 and 2 genes are common in gliomas and help stratify patients with brain cancer into histologic and molecular subtypes. However, these mutations are considered rare in other solid tumors...
  54. pmc Cloning, sequence analysis, expression, and inactivation of the Corynebacterium glutamicum icd gene encoding isocitrate dehydrogenase and biochemical characterization of the enzyme
    B J Eikmanns
    Institut für Biotechnologie des Forschungszentrums Jülich, Germany
    J Bacteriol 177:774-82. 1995
    NADP(+)-dependent isocitrate dehydrogenase (ICD) is an important enzyme of the intermediary metabolism, as it controls the carbon flux within the citric acid cycle and supplies the cell with 2-oxoglutarate and NADPH for biosynthetic ..
  55. pmc Disruption of wild-type IDH1 suppresses D-2-hydroxyglutarate production in IDH1-mutated gliomas
    Genglin Jin
    The Preston Robert Tisch Brain Tumor Center, The Pediatric Brain Tumor Foundation Institute, and the Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Cancer Res 73:496-501. 2013
    Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG)...
  56. pmc COLD-PCR enrichment of rare cancer mutations prior to targeted amplicon resequencing
    Coren A Milbury
    Division of DNA Repair and Genome Stability, Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Clin Chem 58:580-9. 2012
    ..We applied COLD-PCR (coamplification at lower denaturation temperature PCR), a PCR methodology that selectively enriches variants, to improve the detection of unknown mutations before NGS-based amplicon resequencing...
  57. pmc NADP-dependent isocitrate dehydrogenase from Arabidopsis roots contributes in the mechanism of defence against the nitro-oxidative stress induced by salinity
    Marina Leterrier
    Departamento de Bioquimica, Biologia Celular y Molecular de Plantas, Estacion Experimental del Zaidin, CSIC, Apartado 419, 18080 Granada, Spain
    ScientificWorldJournal 2012:694740. 2012
    ..Plants contain several NADPH-generating dehydrogenases including isocitrate dehydrogenase (NADP-ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and ..
  58. ncbi IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group
    Martin J van den Bent
    Dept Neuro Oncology and Pathology, Daniel den Hoed Cancer Center and Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
    Clin Cancer Res 16:1597-604. 2010
    ....
  59. ncbi TET2 promoter methylation in low-grade diffuse gliomas lacking IDH1/2 mutations
    Young Ho Kim
    International Agency for Research on Cancer, Lyon, France
    J Clin Pathol 64:850-2. 2011
    ..Most low-grade diffuse gliomas carry IDH1/2 mutations (>85%), but molecular mechanisms of pathogenesis in those lacking IDH1/2 mutations remain to be elucidated...
  60. pmc Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy
    Whitney B Pope
    Department of Radiological Sciences, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA 90095, USA
    J Neurooncol 107:197-205. 2012
    Mutations of the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are commonly found in primary brain cancers...
  61. pmc The potential for isocitrate dehydrogenase mutations to produce 2-hydroxyglutarate depends on allele specificity and subcellular compartmentalization
    Patrick S Ward
    Cancer Biology and Genetics Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Biol Chem 288:3804-15. 2013
    Monoallelic point mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) and its mitochondrial homolog IDH2 can lead to elevated levels of 2-hydroxyglutarate (2HG) in multiple cancers...
  62. ncbi Cloning, expression and characterization of NADP-dependent isocitrate dehydrogenase from Staphylococcus aureus
    U Venkateswara Prasad
    Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, India
    Appl Biochem Biotechnol 169:862-9. 2013
    ..cycle dictates oxidative and reductive conditions in Staphylococcus aureus and is mainly regulated by isocitrate dehydrogenase (IDH) which plays pivotal role in the growth and pathogenesis of the bacteria...
  63. ncbi IDH1 R132H decreases proliferation of glioma cell lines in vitro and in vivo
    Linda B C Bralten
    Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
    Ann Neurol 69:455-63. 2011
    A high percentage of grade II and III gliomas have mutations in the gene encoding isocitrate dehydrogenase (IDH1)...
  64. ncbi Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities
    Rob A Cairns
    Campbell Family Cancer Research Institute at Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
    Cancer Discov 3:730-41. 2013
    ..Knock-in mouse models of IDH1 mutations have shed light on these mechanisms and will provide valuable animal models for further investigation. ..
  65. ncbi Mitochondrial isocitrate dehydrogenase protects human neuroblastoma SH-SY5Y cells against oxidative stress
    Sun J Kim
    Sogang University, College of Science, Department of Life Science, Seoul, Korea
    J Neurosci Res 85:139-52. 2007
    The neuroprotective effect of mitochondrial isocitrate dehydrogenase (IDPm), an enzyme involved in the reduction of NADP(+) to NADPH and the supply of glutathione (GSH) in mitochondria, was examined using SH-SY5Y cells overexpressing IDPm ..
  66. ncbi Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology
    David Capper
    Department of Neuropathology, Institute of Pathology, Ruprecht Karls Universitat Heidelberg, Germany
    Acta Neuropathol 121:241-52. 2011
    b>Isocitrate dehydrogenase 1 (IDH1) mutations are frequent in astrocytomas, oligoastrocytomas and oligodendrogliomas...
  67. pmc The prognostic IDH1( R132 ) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma
    Fonnet E Bleeker
    Neurosurgical Center Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Acta Neuropathol 119:487-94. 2010
    Somatic mutations in the isocitrate dehydrogenase 1 gene (IDH1) occur at high frequency in gliomas and seem to be a prognostic factor for survival in glioblastoma patients...
  68. pmc Diagnostic testing for IDH1 and IDH2 variants in acute myeloid leukemia an algorithmic approach using high-resolution melting curve analysis
    Keyur P Patel
    Department of Hematopathology, University of Texas M D Anderson Cancer Center, Houston, TX 77054, USA
    J Mol Diagn 13:678-86. 2011
    b>Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations and polymorphism are reported in 5% to 15% of acute myeloid leukemia (AML) cases, with G105 and R132 of IDH1 and R140 and R172 of IDH2 known to be clinically significant...
  69. ncbi IDH1 and IDH2 mutations are frequent in Chinese patients with acute myeloid leukemia but rare in other types of hematological disorders
    Yang Zou
    Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China
    Biochem Biophys Res Commun 402:378-83. 2010
    Frequent mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) have been identified in gliomas and acute myeloid leukemia (AML)...
  70. ncbi Regulation of ionizing radiation-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase
    Jin Hyup Lee
    School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702 701, Korea
    J Biol Chem 282:13385-94. 2007
    ..defense against oxidative damage are some of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm)...
  71. ncbi Cytosolic NADP(+)-dependent isocitrate dehydrogenase protects macrophages from LPS-induced nitric oxide and reactive oxygen species
    Oky Maeng
    Department of Biology, Chungnam National University, Daejeon, Republic of Korea
    Biochem Biophys Res Commun 317:558-64. 2004
    ..Using suppression subtractive hybridization (SSH) we found that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is strongly upregulated by nitric oxide in macrophages...
  72. pmc Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia
    Courtney D DiNardo
    University of Pennsylvania, Philadelphia, PA 19146, USA
    Blood 121:4917-24. 2013
    Cancer-associated isocitrate dehydrogenase (IDH) mutations produce the metabolite 2-hydroxyglutarate (2HG), but the clinical utility of 2HG has not been established...
  73. pmc Histone 3 lysine 9 trimethylation is differentially associated with isocitrate dehydrogenase mutations in oligodendrogliomas and high-grade astrocytomas
    Sriram Venneti
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Neuropathol Exp Neurol 72:298-306. 2013
    ..Cells transfected with mutant isocitrate dehydrogenase (IDH) show increased methylation of histone lysine residues, including H3K9me3, because of inhibition of ..
  74. ncbi Isocitrate dehydrogenase 1 mutant R132H sensitizes glioma cells to BCNU-induced oxidative stress and cell death
    Isabelle Vanessa Mohrenz
    Experimental Neurosurgery, Neuroscience Center, Goethe University Hospital, Theodor Stern Kai 7, 60590, Frankfurt, Germany
    Apoptosis 18:1416-25. 2013
    b>Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to α-ketoglutarate (α-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger...
  75. ncbi Comparison of isocitrate dehydrogenase from three hyperthermophiles reveals differences in thermostability, cofactor specificity, oligomeric state, and phylogenetic affiliation
    I H Steen
    Department of Microbiology, University of Bergen, P. O. Box 7800, Jahnebakken 5, N-5020 Bergen, Norway
    J Biol Chem 276:43924-31. 2001
    With the aim of gaining insight into the molecular and phylogenetic relationships of isocitrate dehydrogenase (IDH) from hyperthermophiles, we carried out a comparative study of putative IDHs identified in the genomes of the eubacterium ..
  76. ncbi Biochemical characterization of isocitrate dehydrogenase from Methylococcus capsulatus reveals a unique NAD+-dependent homotetrameric enzyme
    Runar Stokke
    Department of Biology, University of Bergen, P O Box 7800, 5020 Bergen, Norway
    Arch Microbiol 187:361-70. 2007
    The gene encoding isocitrate dehydrogenase (IDH) of Methylococcus capsulatus (McIDH) was cloned and overexpressed in Escherichia coli...
  77. pmc Glioblastoma with an oligodendroglioma component: distinct clinical behavior, genetic alterations, and outcome
    Yongzhi Wang
    Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, China
    Neuro Oncol 14:518-25. 2012
    ..Presence of an oligodendroglial component may therefore be a useful classification and stratification variable in therapeutic trials of GBMs...
  78. ncbi Determinants of cofactor specificity in isocitrate dehydrogenase: structure of an engineered NADP+ --> NAD+ specificity-reversal mutant
    J H Hurley
    Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0580, USA
    Biochemistry 35:5670-8. 1996
    ..1Ala/Tyr391Lys/Arg395Ser converts the cofactor specificity of Escherichia coli isocitrate dehydrogenase from a 7000-fold preference for NADP+ to a 200-fold preference for NAD+, with overall activity comparable ..
  79. pmc Mutant IDH1 confers an in vivo growth in a melanoma cell line with BRAF mutation
    Tatsuhiro Shibata
    Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
    Am J Pathol 178:1395-402. 2011
    ..Our analyses demonstrate that IDH1 mutation works with other oncogenic mutations and could contribute to the metastasis in melanoma...
  80. ncbi IDH1 mutations in grade II astrocytomas are associated with unfavorable progression-free survival and prolonged postrecurrence survival
    Niklas Thon
    Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany
    Cancer 118:452-60. 2012
    ..The favorable prognostic impact of mutations in the IDH1 gene is well documented for malignant gliomas; its influence on World Health Organization (WHO) grade II astrocytomas, however, is still under debate...
  81. ncbi Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes
    David Capper
    Department of Neuropathology, Ruprecht Karls Universitat Heidelberg, Heidelberg, Germany
    Am J Surg Pathol 34:1199-204. 2010
    ..As IDH mutations are not characteristic of grade IV primary glioblastomas, this antibody cannot differentiate primary glioblastoma from reactive gliosis. Thus, caution has to be taken and a combined panel with other markers is needed...
  82. ncbi The prognostic significance of IDH2 mutations in AML depends on the location of the mutation
    Claire L Green
    Department of Haematology, UCL Cancer Institute, London, United Kingdom
    Blood 118:409-12. 2011
    We have investigated the prognostic significance of isocitrate dehydrogenase 2 (IDH2) mutations in 1473 younger adult acute myeloid leukemia patients treated in 2 United Kingdom Medical Research Council trials...
  83. pmc Structural studies of Saccharomyces cerevesiae mitochondrial NADP-dependent isocitrate dehydrogenase in different enzymatic states reveal substantial conformational changes during the catalytic reaction
    Yingjie Peng
    State Key Laboratory of Molecular Biology and Research Center for Structural Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Protein Sci 17:1542-54. 2008
    ....
  84. ncbi Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes
    J H Hurley
    Department of Biochemistry and Biophysics, University of California, San Francisco 94143 0448
    Biochemistry 30:8671-8. 1991
    The structures of NADP+ and magnesium isocitrate bound to the NADP(+)-dependent isocitrate dehydrogenase of Escherichia coli have been determined and refined at 2.5-A resolution...
  85. ncbi Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite. Implications for cytotoxicity and alcohol-induced liver injury
    Jin Hyup Lee
    Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702 701, Korea
    J Biol Chem 278:51360-71. 2003
    ..and mitochondrial redox balance and oxidative damage is one of the primary functions of NADP+-dependent isocitrate dehydrogenase (ICDH) by supplying NADPH for antioxidant systems...
  86. pmc IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis
    Felicitas Thol
    Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl Neuberg Strasse 1, Hannover, Germany
    Haematologica 95:1668-74. 2010
    ..However, little is known about the incidence and prognostic impact of IDH1 and IDH2 mutations in myelodysplastic syndromes...
  87. pmc Identification and functional characterization of isocitrate dehydrogenase 1 (IDH1) mutations in thyroid cancer
    Avaniyapuram Kannan Murugan
    Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Biochem Biophys Res Commun 393:555-9. 2010
    Mutations in the genes for isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) have been recently identified in glioblastoma...
  88. ncbi IDH1 mutations in gliomas: when an enzyme loses its grip
    Christian Frezza
    Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK
    Cancer Cell 17:7-9. 2010
    The growing interest in cancer metabolism is best demonstrated by the rapid progress made in studying isocitrate dehydrogenase (IDH) mutations since their discovery just over a year ago. In a recent study published in Nature, Dang et al...
  89. pmc Molecular classification of low-grade diffuse gliomas
    Young Ho Kim
    International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France
    Am J Pathol 177:2708-14. 2010
    ..8737). The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and 1p/19q loss has power similar to histological classification and avoids the ambiguity inherent to the diagnosis of oligoastrocytoma...
  90. ncbi Cellular defense against heat shock-induced oxidative damage by mitochondrial NADP+ -dependent isocitrate dehydrogenase
    Hyun Jeong Kim
    Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702 701, South Korea
    Free Radic Res 39:441-8. 2005
    ..Mitochondrial NADP+ -dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system...
  91. ncbi IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms
    A Pardanani
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Leukemia 24:1146-51. 2010
    Bone marrow DNA was screened for isocitrate dehydrogenase (IDH) mutations in 200 patients with chronic (n=166) or blast (n=34) phase myeloproliferative neoplasms (MPN)...
  92. ncbi Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells
    Kyu Ho Jung
    School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702 701, Korea
    Free Radic Res 45:431-8. 2011
    ..It has been shown previously that mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) plays an essential role in defense against oxidative stress by supplying NADPH for antioxidant ..
  93. ncbi LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations
    A Pardanani
    Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA
    Leukemia 24:1713-8. 2010
    ....
  94. ncbi Cancer-associated IDH mutations: biomarker and therapeutic opportunities
    K E Yen
    Molecular Oncology, Agios Pharmaceuticals, Cambridge, MA 02139, USA
    Oncogene 29:6409-17. 2010
    The discovery of somatic mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone event in cancer biology...
  95. ncbi Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism
    Ho Jin Koh
    Department of Genetic Engineering, Kyungpook National University, Daegu 702 701, Korea
    J Biol Chem 279:39968-74. 2004
    ..We have reported recently an important role for mitochondrial NADP(+)-dependent isocitrate dehydrogenase in cellular defense against oxidative damage by providing NADPH needed for the regeneration of reduced ..
  96. ncbi Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation
    Wen Chien Chou
    Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
    Blood 115:2749-54. 2010
    Mutations of nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase gene (IDH1) have been identified in patients with gliomas...
  97. pmc IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas
    Takuya Watanabe
    International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon, France
    Am J Pathol 174:1149-53. 2009
    IDH1 encodes isocitrate dehydrogenase 1, which participates in the citric acid cycle and was recently reported to be mutated in 12% of glioblastomas...
  98. ncbi Aluminum decreases the glutathione regeneration by the inhibition of NADP-isocitrate dehydrogenase in mitochondria
    Keiko Murakami
    Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi 480 1195, Japan
    J Cell Biochem 93:1267-71. 2004
    ..the regeneration of glutathione from the oxidized form, and the effect was due to the inhibition of NADP-isocitrate dehydrogenase the only enzyme supplying NADPH in mitochondria...
  99. pmc Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase
    Sarah M Brown
    Department of Molecular Microbiology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63104, USA
    Eukaryot Cell 9:971-80. 2010
    ..the roles of two sources of NADPH, glucose-6-phosphate dehydrogenase (Zwf1) and NADP(+)-dependent isocitrate dehydrogenase (Idp1), in production of NADPH and resistance to oxidative and nitrosative stress. Deletion of ZWF1 in C...
  100. ncbi Cytosolic NADP-dependent isocitrate dehydrogenase contributes to redox homeostasis and the regulation of pathogen responses in Arabidopsis leaves
    Amna Mhamdi
    Institut de Biologie des Plantes, Université de Paris Sud 11, 91405 Orsay Cedex, France
    Plant Cell Environ 33:1112-23. 2010
    Cytosolic NADP-dependent isocitrate dehydrogenase (cICDH) produces 2-oxoglutarate (2-OG) and NADPH, and is encoded by a single gene in Arabidopsis thaliana...
  101. ncbi Some novel features of IDH1-mutated acute myeloid leukemia revealed in Chinese patients
    Yiqun Zhang
    State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, PR China
    Leuk Res 35:1301-6. 2011
    Mutations of isocitrate dehydrogenase 1 (IDH1) have recently been reported in acute myeloid leukemia (AML). However, the characteristics of IDH1-mutated AML are still not known clearly...

Research Grants49

  1. Gene therapy to support cone metabolism in retinitis pigmentosa
    Constance L Cepko; Fiscal Year: 2013
    ..It is also produced by two cytosolic enzymes, malic enzyme and isocitrate dehydrogenase. If glucose is shuttled to the PPP, the glycolytic pathway would slow, which could lead to several ..
  2. REGULATION OF GLUTAMATE SYNTHESIS IN BACILLUS SUBTILIS
    ABRAHAM LINCOLN SONENSHEIN; Fiscal Year: 2011
    ..of the enzymes of the tricarboxylic acid branch of the Krebs cycle (citrate synthase, aconitase and isocitrate dehydrogenase) that produce a-ketoglutarate and the enzymes of nitrogen assimilation (glutamine synthetase, glutamate ..
  3. Genotype and Metabolic Phenotype in Glioblastoma
    Elizabeth A Maher; Fiscal Year: 2010
    ..intense glucose uptake on FDG-PET, abundant lactate production, and a defect in NADP+ - dependent isocitrate dehydrogenase - may be interconnected events due to a specific genetic mutation...
  4. Defining the role of mutant IDH in glioma initiation and maintenance
    Sheri L Holmen; Fiscal Year: 2013
    ..sequencing of grade IV glioblastoma multiforme (GBM) tumors identified a novel mutation in isocitrate dehydrogenase 1 (IDH1) in 12% of the samples analyzed...
  5. Molecular Mechanisms of IDH1-mediated Gliomagenesis
    Ingo K Mellinghoff; Fiscal Year: 2013
    ..of these tumors harbor an identical missense mutation in the catalytic pocket of the metabolic enzyme isocitrate dehydrogenase (IDH)...
  6. The Significance of Isocitrate Dehydrogenase Mutations in Gliomas
    CRAIG MICHAEL HORBINSKI; Fiscal Year: 2013
    ..by applicant): The goal of this research proposal is to determine the mechanism(s) by which mutant isocitrate dehydrogenase 1 (IDH1) causes brain tumors to be less aggressive...
  7. Antibiotic pressure and selection of TCA cycle mutants in Staphylococcus epidermi
    Paul D Fey; Fiscal Year: 2010
    ..these studies, allelic replacement gene knockouts of the TCA cycle enzymes aconitase (acnB) and isocitrate dehydrogenase (icdA) abrogated the killing effect of bactericidal antibiotics...
  8. Chemical Probes Targeting Gliomas with IDH Mutation
    Yongcheng Song; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Isocitrate dehydrogenase (IDH) is one of the key enzymes in the tricarboxylic acid cycle, catalyzing the conversion of isocitric acid to ?-ketoglutaric acid (?-KG) using NADP+...
  9. CYTOSOLIC SOURCES OF NADPH AS ANTIOXIDANTS
    Lee McAlister Henn; Fiscal Year: 2009
    Two cytosolic sources of NADPH, the hexose monophosphate pathway and cytosolic NADP+-specific isocitrate dehydrogenase (IDP2), have been found to be essential in preventing the accumulation of deleterious oxidative byproducts of ..
  10. MOLECULAR GENETICS OF ISOCITRATE DEHYDROGENASES
    Lee McAlister Henn; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Mitochondrial NAD+-specific isocitrate dehydrogenase (IDH) is sensitive to cellular energy levels due to allosteric regulation by adenine nucleotides and NADH...
  11. SPORE: Targeted Therapies for Glioma
    Tracy T Batchelor; Fiscal Year: 2013
    ..Malignant gliomas, including glioblastomas, may harbor gain-offunction mutations in isocitrate dehydrogenase 1 (IDHI) resulting in accumulation of 2-hydroxyglutarate (2- HG) promoting tumorigenesis...
  12. Mechanisms of Metabolic Gene Mutations in Cancer
    Yue Xiong; Fiscal Year: 2013
    ..human cancer, including fumarate hydratase (FH), succinate gehygrogenase (SDHB, SDHC, SDHD and SDH5), and isocitrate dehydrogenase-1 and -2 (IDH1, IDH2)...
  13. Defining the metabolic phenotype of low grade gliomas in vivo
    Elizabeth A Maher; Fiscal Year: 2013
    ..Recently mutations have been identified in two isoforms of isocitrate dehydrogenase (IDH1 in the cytosol or IDH2 in the mitochondria) in >70% of LGGs...
  14. Role of IDH Mutations in Acute Myeloid Malignancies
    Craig B Thompson; Fiscal Year: 2013
    ..The discovery of recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) that result in a gain-of-function ability to produce the ..
  15. Role of IDH1 and IDH2 Mutations in Glioma Cellular Biology and Pathogenesis
    Hai Yan; Fiscal Year: 2013
    ..20,361 protein coding genes in 22 GBMs and identified frequent somatic mutations in NADP+dependent isocitrate dehydrogenase 1 (IDH1)...
  16. MR Investigation of IDH Mutation and Its Marker 2-HG in Brain Tumor Patients
    Hui Mao; Fiscal Year: 2013
    ..discovery of "onco-metabolite" 2-HG resulting from the heterozygous mutations in the active site of isocitrate dehydrogenase (IDH)1 and IDH2 in low-grade gliomas and secondary GBM links genetic alterations to the tumor metabolism...
  17. MR Imaging of IDH Mutational Status in Brain Tumors
    SABRINA MIRIAM RONEN; Fiscal Year: 2013
    ..spectroscopy (MRS)- based approach for noninvasive assessment of the mutational status and activity of isocitrate dehydrogenase (IDH) by detecting synthesis of the oncometabolite 2-hydroxyglutarate (2-HG), which is produced by mutant ..
  18. In vivo detection of 2-hydroxyglutarate in gliomas by spectroscopic MRI
    Changho Choi; Fiscal Year: 2012
    ..This metabolite accumulates only in gliomas that bear specific mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH), and the presence of these mutations in gliomas is strongly associated with low- grade ..
  19. HTS for inhibitors of IDH1m &synthetic-lethal in tumor cells producing 2HG
    Lenny Dang; Fiscal Year: 2012
    ..by applicant): The goal of this project is to identify and optimize inhibitors that are specific for the isocitrate dehydrogenase 1 (IDH1)...
  20. Novel Therapeutic Agents for Gliomas with IDH Mutations
    Takashi Tsukamoto; Fiscal Year: 2012
    ..that approximately 80% of grade II-III gliomas and secondary glioblasotomas harbor mutations in cytosolic isocitrate dehydrogenase 1 (IDH1)...
  21. Metabolic Reprogramming in Brain Tumors
    SABRINA MIRIAM RONEN; Fiscal Year: 2013
    ..applicant): The goal of this application is to test the hypothesis that the neomorphic activity of mutant isocitrate dehydrogenase (IDH) results not only in production of the oncometabolite 2-hydroxygluatarte (2-HG), but also in a wider ..
  22. Mammalian Heart Isocitrate Dehydrogenases
    ROBERTA COLMAN; Fiscal Year: 2004
    ..dehydrogenases, one mitochondrial and the other cytoplasmic, as well as an allosteric NAD-dependent isocitrate dehydrogenase located in the mitochondria...
  23. Hypoxia-induced Metabolic Changes in Cancer
    Gregory Stephanopoulos; Fiscal Year: 2013
    ..Our preliminary data indicate that Isocitrate Dehydrogenase 1, an enzyme mutated in gliomas and acute leukemias, is necessary for this phenomenon and that the ..
  24. INDUCTION OF AMINOLEVULINIC ACID SYNTHASE BY EXERCISE
    David Essig; Fiscal Year: 1993
    ..enzyme and mRNA content will be determined and compared to levels of cytochrome c, mitochondrial DNA, and isocitrate dehydrogenase. Rates of AS synthesis will also be correlated to mRNA contents at selected time points during induction ..
  25. ACTIVE AND ALLOSTERIC SITES ISOCITRATE DEHYDROGENASES
    ROBERTA COLMAN; Fiscal Year: 2000
    Mammalian tissues contain an NADP- and an NAD-specific isocitrate dehydrogenase which both catalyze a metal-dependent oxidative decarboxylation of isocitrate, but differ in their affinities for substrate, their mode of regulation and ..
  26. GLYOXYLATE SHUNT AND PARASITISM BY MYCOBACTERIUM SPP
    David Russell; Fiscal Year: 2004
    ..ICL competes with isocitrate dehydrogenase to divert the flux of carbon away from the TCA cycle and into this alternative pathway of carbon ..
  27. COMPARTMENTALIZED ISOZYMES OF ISOCITRATE DEHYDROGENASE
    Lee McAlister Henn; Fiscal Year: 1990
    Considerable evidence suggests key metabolic functions for compartmentalized isozymes of isocitrate dehydrogenase in eurcaryotic cells: the mitochondrial NAD+-specific enzyme as the site for control of rates of aerobic metabolism and the ..
  28. STRUCTURE AND REGULATION OF A PROTEIN KINASE/PHOSPHATASE
    David LaPorte; Fiscal Year: 1992
    ..The phosphorylation of isocitrate dehydrogenase (IDH) of Escherichia coli is an example of this form of regulation...
  29. STRUCTURE AND REGULATION OF A PROTEIN KINASE/PHOSPHATASE
    David LaPorte; Fiscal Year: 1991
    ..For example, the glyoxylate bypass of Escherichia coli is controlled by the phosphorylation of isocitrate dehydrogenase (IDH), by regulation of the expression of the glyoxylate bypass operon and by allosteric mechanisms...
  30. Evolution of a Dehydrogenase in its Adaptive Landscape
    Antony Dean; Fiscal Year: 2009
    ..Phylogenetic analyses reveal that 3.5 billion years ago an ancient bacterial NAD-dependent isocitrate dehydrogenase evolved the ability to utilize NADP. In contrast, all known isopropylmalate dehydrogenases utilize NAD...
  31. The Role of OTX2 in Molecular Pathogenesis of Medulloblastoma
    Hai Yan; Fiscal Year: 2010
    ....
  32. Small Molecule X-Ray Diffraction Instrumentation
    Andrew Mesecar; Fiscal Year: 2002
    ..abstract_text> ..
  33. A Molecular Basis for Phytoestrogen Chemoprevention
    Andrew Mesecar; Fiscal Year: 2002
    ..aid in the design of new compounds that can serve as selective estrogen modulators (SERMs). ..
  34. Macromolecular X-ray Structure Facility Instrumentation
    Andrew Mesecar; Fiscal Year: 2003
    ....
  35. GENETIC AND BIOLOGIC STUDIES OF 1P AND 19Q IN GLIOMAS
    Robert Jenkins; Fiscal Year: 2001
    ..abstract_text> ..
  36. REGULATORY DOMAINS OF PROTEIN PHOSPHATASE-1
    PETER KENNELLY; Fiscal Year: 2004
    ..The realization of these aims will contribute to our long-term goal of mapping and modeling the molecular interplay of a complete signal transduction/regulatory network on a cellular scale. ..
  37. Lifespan Neuronal/Glial Metabolism During Hypoglycemia
    Dennis Turner; Fiscal Year: 2003
    ..These in vitro slice models of hypoglycemia will contribute greatly to the understanding of neuronal metabolism, and particularly the metabolic interactions between neurons and glia as a function of lifespan. ..
  38. Cellular Mechanisms of Preconditioning Neuroprotection
    BethAnn McLaughlin; Fiscal Year: 2009
    ..These studies will provide novel insight into endogenous molecular events that can be exploited to enhance neuronal survival. ..
  39. High Throughput Screen for JAK2V617F Mutant Selective Inhibitors
    Ross Levine; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  40. A Luciferase Fusion Protein Library to Identify & Monitor Ubiquitylation Targets
    William Kaelin; Fiscal Year: 2008
    ..Reisolation of HIF in aims 2 and 3 would constitute proof of concept with respect to the potential utility of this approach. ..
  41. Neuronal and Circuitry Mechanisms of Epileptogenesis in a Complex in Vitro Model
    Dennis Turner; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  42. Novel Organophosphorous Hydrolases for Decontamination
    Andrew Mesecar; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  43. Lifespan Metabolic Neuroprotection during Hypoglycemia
    Dennis Turner; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  44. 2006 Cancer Model Mechanisms
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  45. Real-Time Imaging of Hypoxia based on VHL Activity
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  46. Using Synthetic Lethality to Select Cancer Drug Targets
    William Kaelin; Fiscal Year: 2005
    ..Moreover, they may establish a new paradigm for the selection of anticancer drug targets based on inactivating mutations of TSG. ..
  47. Skin Manifestations of Tuberous Sclerosis
    Jack Arbiser; Fiscal Year: 2009
    ..Specific Aim 3. To determine whether dysregulation of p16ink4a and PTCH (patched) acts as a modifier of theTS phenotype in transgenic mice expressing dominant negative tuberin. ..