PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 26819452-1 2016 IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. Ketoglutaric Acids 84-103 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 26819452-1 2016 IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. Ketoglutaric Acids 84-103 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 200-204 26819452-1 2016 IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. Ketoglutaric Acids 105-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 26819452-1 2016 IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. Ketoglutaric Acids 105-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 200-204 26188014-3 2016 IDH enzymes normally catalyze the decarboxylation of isocitrate to generate alpha-ketoglutarate (alphaKG), but recurrent mutations at Arg(132) of IDH1 and Arg(172) of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of alphaKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). Ketoglutaric Acids 76-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 146-150 27005468-1 2016 Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to alpha-ketoglutarate (alphaKG).IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Ketoglutaric Acids 101-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 27005468-1 2016 Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to alpha-ketoglutarate (alphaKG).IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Ketoglutaric Acids 101-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 131-135 27014635-3 2016 Wild-type IDH catalyzes the interconversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 61-80 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-13 27014635-3 2016 Wild-type IDH catalyzes the interconversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 82-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-13 26943899-0 2016 Registered report: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Ketoglutaric Acids 128-147 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 61-65 26943899-3 2016 This Registered Report describes the proposed replication plan of key experiments from "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate" by Ward and colleagues, published in Cancer Cell in 2010 (Ward et al., 2010). Ketoglutaric Acids 197-216 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 130-134 27292784-1 2016 Isocitrate dehydrogenase (IDH) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 81-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 27292784-1 2016 Isocitrate dehydrogenase (IDH) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 81-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 27292784-1 2016 Isocitrate dehydrogenase (IDH) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 102-110 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 27292784-1 2016 Isocitrate dehydrogenase (IDH) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 102-110 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 81-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 6-10 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 102-110 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 6-10 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 145-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 6-10 26960449-4 2016 While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (alpha-KG), IDH1 and IDH2 mutations convert alpha-KG to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 145-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 113-117 26686626-2 2015 The benefit of this regimen, known as PCV, was recently linked to IDH mutation that occurs frequently in glioma and produces D-2-hydroxyglutarate (D-2-HG), a competitive inhibitor of alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 183-202 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-69 26686626-2 2015 The benefit of this regimen, known as PCV, was recently linked to IDH mutation that occurs frequently in glioma and produces D-2-hydroxyglutarate (D-2-HG), a competitive inhibitor of alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 204-212 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 66-69 26961604-9 2016 Treatment with a cell-permeable alpha-ketoglutarate analogue recovered the effect of TBT, suggesting the involvement of NAD-IDH. Ketoglutaric Acids 32-51 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 124-127 26508549-3 2015 We have observed that alpha-mangostin competitively inhibits the binding of alpha-ketoglutarate (alpha-KG) to IDH1-R132H. Ketoglutaric Acids 76-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 110-115 26508549-3 2015 We have observed that alpha-mangostin competitively inhibits the binding of alpha-ketoglutarate (alpha-KG) to IDH1-R132H. Ketoglutaric Acids 97-105 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 110-115 26147657-1 2015 In recent years, frequent isocitrate dehydrogenase 1/2 (IDH1/IDH2) gene mutations were found in a variety of tumors, which specifically alter arginine residues of catalytic active site in IDH1/IDH2 and confer new enzymatic function of directly catalyzing alpha-ketoglutarate (alpha-KG) to R-2-hydroxyglutarate (2-HG). Ketoglutaric Acids 255-274 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 56-60 26363012-1 2015 Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. Ketoglutaric Acids 145-164 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 26363012-1 2015 Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. Ketoglutaric Acids 145-164 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 26363012-1 2015 Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. Ketoglutaric Acids 145-164 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 81-85 26381180-2 2015 Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). Ketoglutaric Acids 69-88 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-13 26381180-2 2015 Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). Ketoglutaric Acids 69-88 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 120-124 26381180-2 2015 Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). Ketoglutaric Acids 90-98 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 9-13 26381180-2 2015 Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). Ketoglutaric Acids 90-98 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 120-124 26381180-2 2015 Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). Ketoglutaric Acids 164-172 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 120-124 26147657-1 2015 In recent years, frequent isocitrate dehydrogenase 1/2 (IDH1/IDH2) gene mutations were found in a variety of tumors, which specifically alter arginine residues of catalytic active site in IDH1/IDH2 and confer new enzymatic function of directly catalyzing alpha-ketoglutarate (alpha-KG) to R-2-hydroxyglutarate (2-HG). Ketoglutaric Acids 255-274 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 188-192 26178471-2 2015 In cancer, mutant IDH1/2 reduces alpha-KG to D2-hydroxyglutarate (D2-HG) disrupting alpha-KG-dependent dioxygenases. Ketoglutaric Acids 33-41 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 18-22 25909344-9 2015 Incubation with an alpha-ketoglutarate analogue partially recovered TBT-induced mitochondrial dysfunction, supporting the involvement of NAD-IDH. Ketoglutaric Acids 19-38 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 141-144 26280302-2 2015 With losing the activity of wild-type IDH1, the R132H and R132C mutant proteins can reduce alpha-ketoglutaric acid (alpha-KG) to d-2-hydroxyglutaric acid (D2HG). Ketoglutaric Acids 91-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-42 26280302-2 2015 With losing the activity of wild-type IDH1, the R132H and R132C mutant proteins can reduce alpha-ketoglutaric acid (alpha-KG) to d-2-hydroxyglutaric acid (D2HG). Ketoglutaric Acids 116-124 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-42 26007236-1 2015 Mitochondrial NADPH-dependent isocitrate dehydrogenase, IDH2, and cytosolic IDH1, catalyze reductive carboxylation of 2-oxoglutarate. Ketoglutaric Acids 118-132 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-80 25853107-5 2015 RESULTS: We have found that IDH1, but not IDH1-R132H, can catalyze the conversion of isocitrate into alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 101-120 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 26590767-1 2015 Isocitrate dehydrogenase (IDH) catalyzes the conversion of isocitrate to alpha ketoglutarate. Ketoglutaric Acids 73-92 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 26590767-1 2015 Isocitrate dehydrogenase (IDH) catalyzes the conversion of isocitrate to alpha ketoglutarate. Ketoglutaric Acids 73-92 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 25648147-3 2015 FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of alpha-ketoglutarate and NADPH. Ketoglutaric Acids 75-94 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-18 26018518-1 2015 BACKGROUND: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield alpha-ketoglutarate (alpha-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Ketoglutaric Acids 106-125 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-36 26018518-1 2015 BACKGROUND: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield alpha-ketoglutarate (alpha-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Ketoglutaric Acids 106-125 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-41 26018518-1 2015 BACKGROUND: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield alpha-ketoglutarate (alpha-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Ketoglutaric Acids 127-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-36 26018518-1 2015 BACKGROUND: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield alpha-ketoglutarate (alpha-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Ketoglutaric Acids 127-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-41 26018518-2 2015 Dysfunctional IDH leads to reduced production of alpha-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. Ketoglutaric Acids 49-57 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-17 25862748-1 2015 BACKGROUND: Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert alpha-ketoglutarate into 2-hydroxyglutarate (2HG). Ketoglutaric Acids 74-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-53 25853107-6 2015 In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2-hydroxyglutarate (R-2HG). Ketoglutaric Acids 89-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 25853107-6 2015 In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2-hydroxyglutarate (R-2HG). Ketoglutaric Acids 89-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 70-74 25471051-1 2015 Mutations in isocitrate dehydrogenase 1 (IDH1) have been found in the vast majority of low grade and progressive infiltrating gliomas and are characterized by the production of 2-hydroxyglutarate from alpha-ketoglutarate. Ketoglutaric Acids 201-220 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-39 25706986-2 2015 IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while mutant IDH1 catalyzes the conversion of alpha-ketoglutarate into 2-hydroxyglutarate. Ketoglutaric Acids 81-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 25706986-2 2015 IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while mutant IDH1 catalyzes the conversion of alpha-ketoglutarate into 2-hydroxyglutarate. Ketoglutaric Acids 81-100 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 114-118 25706986-2 2015 IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while mutant IDH1 catalyzes the conversion of alpha-ketoglutarate into 2-hydroxyglutarate. Ketoglutaric Acids 147-166 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 25706986-2 2015 IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate while mutant IDH1 catalyzes the conversion of alpha-ketoglutarate into 2-hydroxyglutarate. Ketoglutaric Acids 147-166 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 114-118 25471051-1 2015 Mutations in isocitrate dehydrogenase 1 (IDH1) have been found in the vast majority of low grade and progressive infiltrating gliomas and are characterized by the production of 2-hydroxyglutarate from alpha-ketoglutarate. Ketoglutaric Acids 201-220 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 41-45 25391653-1 2015 Cancer-associated point mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) confer a neomorphic enzymatic activity: the reduction of alpha-ketoglutarate to d-2-hydroxyglutaric acid, which is proposed to act as an oncogenic metabolite by inducing hypermethylation of histones and DNA. Ketoglutaric Acids 143-162 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 37-63 25391653-1 2015 Cancer-associated point mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) confer a neomorphic enzymatic activity: the reduction of alpha-ketoglutarate to d-2-hydroxyglutaric acid, which is proposed to act as an oncogenic metabolite by inducing hypermethylation of histones and DNA. Ketoglutaric Acids 143-162 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 71-75 25993236-7 2015 The normal IDH protein continues to produce alpha-ketoglutarate (alpha-KG) whereas the mutant IDH protein converts KG to the oncometabolite 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 44-63 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 11-14 25993236-7 2015 The normal IDH protein continues to produce alpha-ketoglutarate (alpha-KG) whereas the mutant IDH protein converts KG to the oncometabolite 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 44-63 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 94-97 25324168-4 2015 In contrast, mutated IDH1/2 proteins possess a neomorphic enzymatic function that changes alpha-KG into the oncometabolite, R(-)-2-hydroxyglutarate, resulting in genomic hypermethylation, histone methylation, genetic instability, and malignant transformation. Ketoglutaric Acids 90-98 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-27 25324168-3 2015 IDH1 and IDH2 catalyze the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in the cytosol and mitochondria, respectively. Ketoglutaric Acids 68-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 25324168-3 2015 IDH1 and IDH2 catalyze the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in the cytosol and mitochondria, respectively. Ketoglutaric Acids 89-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 24668804-10 2014 Kinetic analyses combined with microscale thermophoresis and surface plasmon resonance indicate that this reversible inhibitor binds to IDH1 R132H competitively with respect to alpha-ketoglutarate and uncompetitively with respect to NADPH. Ketoglutaric Acids 177-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 136-140 24980596-2 2014 The most frequent mutation, IDH1 R132H, is a gain-of-function mutation resulting in an enzyme-catalyzing conversion of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 119-138 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 24980596-7 2014 An IDH1 heterodimer between wild-type and R132H mutant is capable of catalyzing conversion of alpha-KG to 2-HG and isocitrate to alpha-KG. Ketoglutaric Acids 94-102 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 3-7 24980596-7 2014 An IDH1 heterodimer between wild-type and R132H mutant is capable of catalyzing conversion of alpha-KG to 2-HG and isocitrate to alpha-KG. Ketoglutaric Acids 129-137 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 3-7 24980596-11 2014 The enhanced apparent affinity for alpha-KG suggests R132H/WT heterodimeric IDH1 can produce 2-HG more efficiently at normal intracellular levels of alpha-KG (approximately 100 microM). Ketoglutaric Acids 35-43 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-80 24857658-2 2014 In contrast, hypoxia and other impairments of mitochondrial function induce an alternative pathway that produces citrate by reductively carboxylating alpha-ketoglutarate (AKG) via NADPH-dependent isocitrate dehydrogenase (IDH). Ketoglutaric Acids 150-169 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 222-225 24898068-5 2014 The IDH mutations are remarkably specific to arginine 132 (R132) in IDH1 and arginine 172 (R172) or arginine 140 (R140) in IDH2; IDH1/2 mutations are known to convert alpha-ketoglutarate to oncometabolite R(-)-2-hydroxyglutarate. Ketoglutaric Acids 167-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-7 24898068-5 2014 The IDH mutations are remarkably specific to arginine 132 (R132) in IDH1 and arginine 172 (R172) or arginine 140 (R140) in IDH2; IDH1/2 mutations are known to convert alpha-ketoglutarate to oncometabolite R(-)-2-hydroxyglutarate. Ketoglutaric Acids 167-186 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 129-133 25502799-2 2014 Mutation of the catalytic Arg132 residue of human IDH1 (HcIDH) eliminates the enzyme"s wild-type isocitrate oxidation activity, but confer the mutant an ability of reducing alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 173-192 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 50-54 25502799-2 2014 Mutation of the catalytic Arg132 residue of human IDH1 (HcIDH) eliminates the enzyme"s wild-type isocitrate oxidation activity, but confer the mutant an ability of reducing alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 194-202 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 50-54 24880135-5 2014 In their wild-type forms, IDH1 and IDH2 convert isocitrate and NADP(+) to alpha-ketoglutarate (alphaKG) and NADPH. Ketoglutaric Acids 74-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-30 25271760-2 2014 Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of alpha-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Ketoglutaric Acids 85-108 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 24549719-2 2014 Mutations of IDH1 and IDH2 lead to simultaneous loss and gain of activities in the production of alpha-ketoglutarate and 2-hydroxyglutarate, respectively. Ketoglutaric Acids 97-116 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 24590270-1 2014 Isocitrate dehydrogenase 1 (IDH1), which localizes to the cytosol and peroxisomes, catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and in parallel converts NADP(+) to NADPH. Ketoglutaric Acids 140-159 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 24590270-1 2014 Isocitrate dehydrogenase 1 (IDH1), which localizes to the cytosol and peroxisomes, catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and in parallel converts NADP(+) to NADPH. Ketoglutaric Acids 161-169 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 24590270-4 2014 Mutant IDH1 gains novel enzyme activity converting alpha-KG to D-2-hydroxyglutarate (2-HG) which acts as a competitive inhibitor of alpha-KG. Ketoglutaric Acids 51-59 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 24590270-4 2014 Mutant IDH1 gains novel enzyme activity converting alpha-KG to D-2-hydroxyglutarate (2-HG) which acts as a competitive inhibitor of alpha-KG. Ketoglutaric Acids 132-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-11 24590270-12 2014 Intriguingly, in gliomas with IDH1-R132H, glutamine and glutamate levels were significantly reduced which implies replenishment of alpha-KG by glutaminolysis. Ketoglutaric Acids 131-139 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 24675140-3 2014 Thus, the cell permeant ester dimethyl alpha-ketoglutarate (DMKG) increased the cytosolic concentration of alpha-ketoglutarate, which was converted into AcCoA through a pathway relying on either of the 2 isocitrate dehydrogenase isoforms (IDH1 or IDH2), as well as on ACLY (ATP citrate lyase). Ketoglutaric Acids 39-58 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 239-243 24529257-1 2014 BACKGROUND: IDH mutations frequently occur in diffuse gliomas and result in a neo-enzymatic activity that results in reduction of alpha-ketoglutarate to D-2-hydroxyglutarate. Ketoglutaric Acids 130-149 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-15 24529257-6 2014 Enzyme kinetics of mutant IDH protein correlated well with D-2-hydroxyglutarate production in cells with R132H exhibiting the highest and R132L the lowest KM for alpha-ketoglutarate. Ketoglutaric Acids 162-181 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 24531386-2 2014 The IDH1 mutations lead to a loss of its normal enzymatic activity and acquisition of neomorphic activity in production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2-HG), which finally cause alterations of multiple gene expression of tumorigenesis-associated alpha-KG-dependent enzymes. Ketoglutaric Acids 123-142 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-8 24077805-1 2013 Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate by the mutant enzyme. Ketoglutaric Acids 179-198 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-47 23801081-1 2013 Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to alpha-ketoglutarate (alpha-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Ketoglutaric Acids 63-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 23801081-1 2013 Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to alpha-ketoglutarate (alpha-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Ketoglutaric Acids 63-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 23801081-1 2013 Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to alpha-ketoglutarate (alpha-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Ketoglutaric Acids 84-92 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 23801081-1 2013 Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to alpha-ketoglutarate (alpha-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Ketoglutaric Acids 84-92 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 23801081-2 2013 Mutation of R132 of IDH1 abrogates generation of alpha-KG and leads to conversion of alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 49-57 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 23801081-2 2013 Mutation of R132 of IDH1 abrogates generation of alpha-KG and leads to conversion of alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 85-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 25485496-3 2014 Mutant IDH acts through a novel mechanism of oncogenesis, producing high levels of the metabolite 2-hydroxyglutarate, which interferes with the function of alpha-ketoglutarate-dependent enzymes that regulate diverse cellular processes including histone demethylation and DNA modification. Ketoglutaric Acids 156-175 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 23876293-5 2013 Cellular levels of citrate, alpha-ketoglutarate, malate and ATP were altered in patterns consistent with blockage at the mitochondrial IDH reactions. Ketoglutaric Acids 28-47 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 135-138 24077805-1 2013 Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate by the mutant enzyme. Ketoglutaric Acids 179-198 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 49-53 23731180-1 2013 The human, cytosolic enzyme isocitrate dehydrogenase 1 (IDH1) reversibly converts isocitrate to alpha-ketoglutarate (alphaKG). Ketoglutaric Acids 96-115 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 56-60 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. Ketoglutaric Acids 68-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. Ketoglutaric Acids 68-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. Ketoglutaric Acids 89-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. Ketoglutaric Acids 89-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. Ketoglutaric Acids 188-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-6 23847760-2 2013 IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. Ketoglutaric Acids 188-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 23541771-2 2013 Mutated IDH1 produces the oncometabolite 2-hydroxyglutarate rather than alpha-ketoglutarate or isocitrate. Ketoglutaric Acids 72-91 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 23795241-2 2013 Different from the wild-type enzyme, mutant IDH1 catalyzes the reduction of alpha-ketoglutaric acid to D-2-hydroxyglutaric acid. Ketoglutaric Acids 76-99 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 44-48 23634848-9 2013 Since TET proteins and many lysine demethylases require 2-oxoglutarate as a cofactor, aberrations in cofactor biochemical pathways, including mutations in isocitrate dehydrogenase (IDH), may affect levels of 5hmC and 5mC in certain types of tumors, either directly or indirectly. Ketoglutaric Acids 56-70 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 155-179 23504317-2 2013 In addition, reductive carboxylation of alpha-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. Ketoglutaric Acids 40-59 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 91-95 23634848-9 2013 Since TET proteins and many lysine demethylases require 2-oxoglutarate as a cofactor, aberrations in cofactor biochemical pathways, including mutations in isocitrate dehydrogenase (IDH), may affect levels of 5hmC and 5mC in certain types of tumors, either directly or indirectly. Ketoglutaric Acids 56-70 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 181-184 22442146-1 2012 Isocitrate dehydrogenase (IDH) is a reversible enzyme that catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (ICT) to alpha-ketoglutarate (alphaKG) and the NADPH/CO(2)-dependent reductive carboxylation of alphaKG to ICT. Ketoglutaric Acids 140-159 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 23630074-2 2013 IDH1 and IDH2 catalyze the interconversion of isocitrate and 2-oxoglutarate (2OG). Ketoglutaric Acids 61-75 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 23107437-9 2013 In addition, we examined the levels of alpha-ketoglutarate, a product of IDH1, and WA blocked its reduction upon TPA treatment. Ketoglutaric Acids 39-58 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 73-77 22391558-2 2013 The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of alpha-KG, linking 5mC oxidation to cancer development. Ketoglutaric Acids 199-207 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 118-122 23232569-2 2013 Mutant IDH enzyme loses its normal activity to convert isocitrate into alpha-ketoglutarate (alphaKG) and instead acquires the ability to reduce alphaKG to D-2-hydroxyglutarate. Ketoglutaric Acids 71-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 141-160 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-36 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 141-160 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-42 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 162-170 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-36 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 162-170 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-42 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 218-226 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-36 24077277-1 2013 Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to alpha-ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG to 2-hydroxyglutarate. Ketoglutaric Acids 218-226 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-42 23507484-3 2013 In addition, IDH1/2 mutations confer a gain-of-function, allowing the enzymes to process alpha-ketoglutarate to 2-hydroxyglutarate, which inhibits the TET proteins and ultimately induces the same hypermethylation phenotype. Ketoglutaric Acids 89-108 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-19 22533343-1 2012 Isocitrate dehydrogenase 1 (IDH1), a cytosolic enzyme that converts isocitrate to alpha-ketoglutarate, has been shown to be dysregulated during tumorigenesis. Ketoglutaric Acids 82-101 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 22533343-1 2012 Isocitrate dehydrogenase 1 (IDH1), a cytosolic enzyme that converts isocitrate to alpha-ketoglutarate, has been shown to be dysregulated during tumorigenesis. Ketoglutaric Acids 82-101 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 24019001-3 2013 Here we show, in this proof-of-concept study, that [1-(13)C] alpha-ketoglutarate can serve as a metabolic imaging agent for non-invasive, real-time, in vivo monitoring of mutant IDH1 activity, and can inform on IDH1 status. Ketoglutaric Acids 61-80 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 178-182 24019001-3 2013 Here we show, in this proof-of-concept study, that [1-(13)C] alpha-ketoglutarate can serve as a metabolic imaging agent for non-invasive, real-time, in vivo monitoring of mutant IDH1 activity, and can inform on IDH1 status. Ketoglutaric Acids 61-80 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 211-215 24019001-5 2013 In lysates and tumours that express wild-type IDH1, only hyperpolarized [1-(13)C] alpha-ketoglutarate can be detected. Ketoglutaric Acids 82-101 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 46-50 23071358-2 2012 Mutations targeting IDH1 and IDH2 result in simultaneous loss of their normal catalytic activity, the production of alpha-ketoglutarate (alpha-KG), and gain of a new function, the production of 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 116-135 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 22772731-2 2012 Loss of catalytic activity leading to a decrease in alpha-ketoglutarate (alphaKG) and gain of novel catalytic activity leading to production of D: -2-hydroxylglutarate (D: -2-HG) are both found in IDH1-mutated glioma cells. Ketoglutaric Acids 52-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 197-201 22442146-1 2012 Isocitrate dehydrogenase (IDH) is a reversible enzyme that catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (ICT) to alpha-ketoglutarate (alphaKG) and the NADPH/CO(2)-dependent reductive carboxylation of alphaKG to ICT. Ketoglutaric Acids 140-159 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 22397365-1 2012 BACKGROUND: Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes encode cytosolic and mitochondrial enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 166-185 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 46-50 22105553-3 2012 Mutations of IDH1 and IDH2 led to simultaneous loss and gain of activities in the production of alpha-ketoglutarate and 2-hydroxyglutarate, respectively. Ketoglutaric Acids 96-115 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 22147457-1 2011 The NADP+-dependent isocitrate dehydrogenases 1 and 2 (IDH1/2) catalyze the oxidative decarboxylation of isocitrate into alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 121-140 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 55-61 22343901-1 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 alpha-ketoglutarate. Ketoglutaric Acids 231-250 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-49 22343901-1 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 alpha-ketoglutarate. Ketoglutaric Acids 231-250 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 51-55 22675360-8 2012 Arg172 mutants of human IDH2-frequently found with similar mutants of cytosolic IDH1 in grade 2 and 3 gliomas, secondary glioblastomas, and acute myeloid leukemia-catalyze reductive carboxylation of 2-oxoglutarate and reduction to D-2-hydroxyglutarate, which strengthens the neoplastic phenotype by competitive inhibition of histone demethylation and 5-methylcytosine hydroxylation, leading to genome-wide histone and DNA methylation alternations. Ketoglutaric Acids 199-213 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 80-84 22002076-1 2011 PURPOSE OF REVIEW: Isocitrate dehydrogenases, IDH1 and IDH2, decarboxylate isocitrate to alpha-ketoglutarate (alpha-KG) and reduce NADP to NADPH. Ketoglutaric Acids 89-108 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 46-50 22002076-1 2011 PURPOSE OF REVIEW: Isocitrate dehydrogenases, IDH1 and IDH2, decarboxylate isocitrate to alpha-ketoglutarate (alpha-KG) and reduce NADP to NADPH. Ketoglutaric Acids 110-118 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 46-50 22147457-1 2011 The NADP+-dependent isocitrate dehydrogenases 1 and 2 (IDH1/2) catalyze the oxidative decarboxylation of isocitrate into alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 142-150 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 55-61 22101433-6 2011 This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived alpha-ketoglutarate for de novo lipogenesis. Ketoglutaric Acids 225-244 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 5-31 22101433-6 2011 This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived alpha-ketoglutarate for de novo lipogenesis. Ketoglutaric Acids 225-244 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 33-37 21885076-3 2011 IDH1 encodes the cytoplasmic NADP dependent isocitrate dehydrogenase1 that catalyzes the oxidative decarboxylation of isocitrate into alpha-ketoglutarate. Ketoglutaric Acids 134-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21889589-2 2011 Overexpression studies with IDH1(R132H) and IDH2(R172K) mutations demonstrated that the enzymes acquired a new function, converting 2-ketoglutarate (2-KG) to d-2-hydroxyglutarate (D-2-HG), in lieu of the normal IDH reaction which reversibly converts isocitrate to 2-KG. Ketoglutaric Acids 132-147 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 21690245-1 2011 BACKGROUND: Miscoding mutations of the TET2 gene, which encodes the alpha-ketoglutarate-dependent enzyme that catalyses the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, thus producing DNA demethylation, have been detected in 10-25% of acute myeloid leukaemias lacking IDH1/2 mutations. Ketoglutaric Acids 68-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 282-288 21939466-5 2011 Specifically, 2-hydroxyglutarate, the oncometabolite produced by mutant IDH1 and IDH2 proteins, has been shown to function as a competitive inhibitor of various alpha-ketoglutarate (alpha-KG)-dependent dioxygenases, including histone demethylases and members of the ten-eleven-translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. Ketoglutaric Acids 161-180 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 72-76 21885076-7 2011 IDH1/IDH2 mutation results in a new enzymatic activity transforming alpha-ketoglutarate into 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 68-87 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 22040412-1 2011 BACKGROUND: Site A132Arg mutations potentially impair the affinity of isocitrate dehydrogenase 1 (IDH1) for its substrate isocitrate (ICT), consequently reducing the production of alpha-ketoglutarate and leading to tumor growth through the induction of the hypoxia-inducible factor-1 (HIF-1) pathway. Ketoglutaric Acids 180-199 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 70-96 22040412-1 2011 BACKGROUND: Site A132Arg mutations potentially impair the affinity of isocitrate dehydrogenase 1 (IDH1) for its substrate isocitrate (ICT), consequently reducing the production of alpha-ketoglutarate and leading to tumor growth through the induction of the hypoxia-inducible factor-1 (HIF-1) pathway. Ketoglutaric Acids 180-199 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 98-102 21045145-1 2010 Mutation at the R132 residue of isocitrate dehydrogenase 1 (IDH1), frequently found in gliomas and acute myelogenous leukemia, creates a neoenzyme that produces 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 192-211 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-58 21641335-4 2011 IDH1 and IDH2 mutations lead to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2HG), respectively, and result in lowering NADPH levels even further. Ketoglutaric Acids 94-113 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21641335-4 2011 IDH1 and IDH2 mutations lead to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2HG), respectively, and result in lowering NADPH levels even further. Ketoglutaric Acids 115-123 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21251613-1 2011 IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2-HG), respectively. Ketoglutaric Acids 153-172 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 21625441-5 2011 IDH1 and IDH2 mutations cause both loss of normal enzyme function and gain-of-function, causing reduction of alpha-KG to D-2-hydroxyglutarate (D-2HG) which accumulates. Ketoglutaric Acids 109-117 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 20972461-3 2010 Soon, it became clear that the mutations identified impaired the ability of IDH1 and IDH2 to catalyze the conversion of isocitrate to alpha-ketoglutarate (alphaKG), whereas conferring a gain of a novel enzymatic activity leading to the reduction of alphaKG to the metabolite D2-hydroxyglutarate (D-2HG). Ketoglutaric Acids 134-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 76-80 21045145-1 2010 Mutation at the R132 residue of isocitrate dehydrogenase 1 (IDH1), frequently found in gliomas and acute myelogenous leukemia, creates a neoenzyme that produces 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 192-211 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 60-64 21045145-2 2010 We sought to therapeutically exploit this neoreaction in mutant IDH1 cells that require alpha-KG derived from glutamine. Ketoglutaric Acids 88-96 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 64-68 21045145-5 2010 Growth suppression of mutant IDH1 cells by BPTES was rescued by adding exogenous alpha-KG. Ketoglutaric Acids 81-89 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 29-33 20603105-1 2010 Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+to NADPH). Ketoglutaric Acids 112-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 20975740-3 2010 This mutation impairs the oxidative IDH activity of the enzyme, but renders a new reduction function of converting alpha-ketoglutarate (alphaKG) to 2-hydroxyglutarate. Ketoglutaric Acids 115-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 36-39 20692206-1 2010 The systematic sequencing of glioblastoma 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-KG). Ketoglutaric Acids 250-269 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 108-112 20692206-1 2010 The systematic sequencing of glioblastoma 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-KG). Ketoglutaric Acids 250-269 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 176-180 20692206-1 2010 The systematic sequencing of glioblastoma 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-KG). Ketoglutaric Acids 271-279 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 108-112 20692206-1 2010 The systematic sequencing of glioblastoma 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-KG). Ketoglutaric Acids 271-279 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 176-180 8608121-5 1996 Enzymatic conversion of the liberated isocitrate to alpha-ketoglutarate was achieved in solution as well as in wild-type and mutant isocitrate dehydrogenase (IDH) protein crystals. Ketoglutaric Acids 52-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-156 20510884-2 2010 Heterozygous mutations in the IDH1 occur in the majority of grade II and grade III gliomas and secondary glioblastomas and change the structure of the enzyme, which diminishes its ability to convert isocitrate (ICT) to alpha-ketoglutarate (alpha-KG) and provides it with a newly acquired ability to convert alpha-KG to R(-)-2-hydroxyglutarate [R(-)-2HG]. Ketoglutaric Acids 219-238 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 20510884-2 2010 Heterozygous mutations in the IDH1 occur in the majority of grade II and grade III gliomas and secondary glioblastomas and change the structure of the enzyme, which diminishes its ability to convert isocitrate (ICT) to alpha-ketoglutarate (alpha-KG) and provides it with a newly acquired ability to convert alpha-KG to R(-)-2-hydroxyglutarate [R(-)-2HG]. Ketoglutaric Acids 240-248 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 20510884-2 2010 Heterozygous mutations in the IDH1 occur in the majority of grade II and grade III gliomas and secondary glioblastomas and change the structure of the enzyme, which diminishes its ability to convert isocitrate (ICT) to alpha-ketoglutarate (alpha-KG) and provides it with a newly acquired ability to convert alpha-KG to R(-)-2-hydroxyglutarate [R(-)-2HG]. Ketoglutaric Acids 307-315 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 20127344-4 2010 Mutated IDH1 has a gain of function to produce 2-hydroxyglutarate by NADPH-dependent reduction of alpha-ketoglutarate, but it is unknown whether NADPH production in gliomas is affected by IDH1 mutations. Ketoglutaric Acids 98-117 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 8-12 20171147-0 2010 The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Ketoglutaric Acids 109-128 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-46 20142433-8 2010 Recombinant IDH1 R132C and IDH2 R172K proteins catalyze the novel nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of alpha-ketoglutarate (alpha-KG) to 2-HG. Ketoglutaric Acids 141-160 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 20142433-8 2010 Recombinant IDH1 R132C and IDH2 R172K proteins catalyze the novel nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of alpha-ketoglutarate (alpha-KG) to 2-HG. Ketoglutaric Acids 162-170 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 19935646-2 2009 These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme"s ability to catalyse conversion of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 160-179 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 60-64 19935646-4 2009 Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Ketoglutaric Acids 134-153 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 36-40 19359588-3 2009 Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, alpha-ketoglutarate (alpha-KG), and increases the levels of hypoxia-inducible factor subunit HIF-1alpha, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by alpha-KG. Ketoglutaric Acids 92-111 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 8608121-5 1996 Enzymatic conversion of the liberated isocitrate to alpha-ketoglutarate was achieved in solution as well as in wild-type and mutant isocitrate dehydrogenase (IDH) protein crystals. Ketoglutaric Acids 52-71 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 158-161 34968705-4 2022 The results reveal that isocitrate is blocked from conversion to alpha-ketoglutarate and that acetyl-coenzyme A (CoA) accumulates, which is consistent with a reduction in oxygen consumption rate and inactivation of isocitrate dehydrogenase (IDH) activity. Ketoglutaric Acids 65-84 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 215-239 8369301-0 1993 Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate. Ketoglutaric Acids 43-62 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-37 8369301-1 1993 The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. Ketoglutaric Acids 71-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-45 8369301-1 1993 The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. Ketoglutaric Acids 71-90 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-50 32796956-5 2021 It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. Ketoglutaric Acids 50-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 22-26 33808599-4 2021 This is the case of IDH1/2 mutations generating the abnormal conversion of alpha-ketoglutarate (KG) to 2-hydroxyglutarate, an oncometabolite inhibiting KG-dependent enzymes, such as the TET family of genes (pivotal in characterizing leukemia cells either by mutations, e.g., TET2, or by altered expression, e.g., TET1/2/3). Ketoglutaric Acids 75-94 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-26 27655638-1 2016 Isocitrate dehydrogenase (IDH1) is an NADP-dependent enzyme that catalyzes the decarboxylation of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 112-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-30 34968705-4 2022 The results reveal that isocitrate is blocked from conversion to alpha-ketoglutarate and that acetyl-coenzyme A (CoA) accumulates, which is consistent with a reduction in oxygen consumption rate and inactivation of isocitrate dehydrogenase (IDH) activity. Ketoglutaric Acids 65-84 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 241-244 34725432-5 2021 The isocitrate-Mg2+ complex is the preferred wt IDH1 substrate; with R132H IDH1, separate and weaker binding of 2-oxoglutarate and Mg2+ is preferred. Ketoglutaric Acids 112-126 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 48-52 34854890-1 2021 Human isocitrate dehydrogenase (IDH) genes encode for the IDH1, 2 & 3 isoenzymes which catalyse the formation of 2-oxoglutarate from isocitrate and are essential for normal mammalian metabolism. Ketoglutaric Acids 113-127 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 6-30 34854890-1 2021 Human isocitrate dehydrogenase (IDH) genes encode for the IDH1, 2 & 3 isoenzymes which catalyse the formation of 2-oxoglutarate from isocitrate and are essential for normal mammalian metabolism. Ketoglutaric Acids 113-127 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 32-35 34854890-1 2021 Human isocitrate dehydrogenase (IDH) genes encode for the IDH1, 2 & 3 isoenzymes which catalyse the formation of 2-oxoglutarate from isocitrate and are essential for normal mammalian metabolism. Ketoglutaric Acids 113-127 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 58-62 34725432-1 2021 Cancer linked isocitrate dehydrogenase (IDH) 1 variants, notably R132H IDH1, manifest a "gain-of-function" to reduce 2-oxoglutarate to 2-hydroxyglutarate. Ketoglutaric Acids 117-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 71-75 34725432-5 2021 The isocitrate-Mg2+ complex is the preferred wt IDH1 substrate; with R132H IDH1, separate and weaker binding of 2-oxoglutarate and Mg2+ is preferred. Ketoglutaric Acids 112-126 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 75-79 34143606-1 2021 Isocitrate dehydrogenase 1 (IDH1) is a key metabolic enzyme for maintaining cytosolic levels of alpha-ketoglutarate (AKG) and preserving the redox environment of the cytosol. Ketoglutaric Acids 96-115 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 34321251-1 2021 Point mutations in isocitrate dehydrogenase 1 (IDH1) result in conversion of alpha-ketoglutarate to the oncometabolite, D-2-hydroxyglutarate (2-HG). Ketoglutaric Acids 77-96 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 19-45 34321251-1 2021 Point mutations in isocitrate dehydrogenase 1 (IDH1) result in conversion of alpha-ketoglutarate to the oncometabolite, D-2-hydroxyglutarate (2-HG). Ketoglutaric Acids 77-96 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-51 34095989-3 2021 IDH mutations induce a neomorphic enzyme that converts alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate, which leads to widespread effects on cellular epigenetics and metabolism. Ketoglutaric Acids 55-74 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 34356864-2 2021 IDH enzymes catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG), an intermediate in the citric acid cycle. Ketoglutaric Acids 53-72 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 34356864-2 2021 IDH enzymes catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG), an intermediate in the citric acid cycle. Ketoglutaric Acids 74-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 34143606-1 2021 Isocitrate dehydrogenase 1 (IDH1) is a key metabolic enzyme for maintaining cytosolic levels of alpha-ketoglutarate (AKG) and preserving the redox environment of the cytosol. Ketoglutaric Acids 96-115 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 35267433-2 2022 IDH-mutated genes encode for a neomorphic enzyme that converts alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG), which accumulates to high concentrations and alters cellular epigenetics and metabolism. Ketoglutaric Acids 63-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 34065652-1 2021 Isocitrate dehydrogenase (IDH1) catalyzes the reversible NADP+-dependent oxidation of isocitrate to alpha-ketoglutarate (alphaKG). Ketoglutaric Acids 100-119 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-30 33981605-1 2021 Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the interconversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 105-124 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 33367952-8 2021 This was concomitant with better prognosis indicating a differential metabolic reliance between these two subtypes, in which enhanced expression of IDH1 may replenish the alpha-ketoglutarate pool in cells with increased hBCATm expression. Ketoglutaric Acids 171-190 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 148-152 33981605-1 2021 Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the interconversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 105-124 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 33981605-1 2021 Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the interconversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 126-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-24 33981605-1 2021 Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the interconversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 126-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 26-29 33981605-2 2021 Mutations in IDH lead to loss of normal enzymatic activity and gain of neomorphic activity that irreversibly converts alpha-KG to 2-hydroxyglutarate (2-HG), which can competitively inhibit a-KG-dependent enzymes, subsequently induces cell metabolic reprograming, inhibits cell differentiation, and initiates cell tumorigenesis. Ketoglutaric Acids 118-126 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-16 33578097-12 2021 Ni(II) also significantly decreased the protein expression of IDH1 and the synthesis rate of NAPDH, which competitively inhibited alpha-ketoglutarate (alpha-KG) generation. Ketoglutaric Acids 130-149 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 62-66 33578097-12 2021 Ni(II) also significantly decreased the protein expression of IDH1 and the synthesis rate of NAPDH, which competitively inhibited alpha-ketoglutarate (alpha-KG) generation. Ketoglutaric Acids 151-159 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 62-66 32313423-5 2020 Conclusion: In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests. Ketoglutaric Acids 254-273 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-51 33713004-1 2021 BACKGROUND: Isocitrate dehydrogenase (IDH) is an important enzyme that oxidatively decarboxylates isocitrate to alpha-ketoglutarate, and three isoforms (IDH1-3) have been identified. Ketoglutaric Acids 112-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-36 33713004-1 2021 BACKGROUND: Isocitrate dehydrogenase (IDH) is an important enzyme that oxidatively decarboxylates isocitrate to alpha-ketoglutarate, and three isoforms (IDH1-3) have been identified. Ketoglutaric Acids 112-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 38-41 32880665-2 2020 We have explored how mutated isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate which in turn is converted to d-2-hydroxyglutatrate (d-2HG) as a preferred product instead of l-2-hydroxyglutatrate (l-2HG) according to quantum chemical calculations. Ketoglutaric Acids 117-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 29-53 32880665-2 2020 We have explored how mutated isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate which in turn is converted to d-2-hydroxyglutatrate (d-2HG) as a preferred product instead of l-2-hydroxyglutatrate (l-2HG) according to quantum chemical calculations. Ketoglutaric Acids 117-136 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 55-58 32727816-1 2020 Isocitrate dehydrogenase 1 (IDH1) encodes a protein which catalyses the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 115-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 32727816-1 2020 Isocitrate dehydrogenase 1 (IDH1) encodes a protein which catalyses the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 115-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 32955829-1 2020 The isocitrate dehydrogenases enzymes, IDH1 and IDH2, catalyze the conversion of isocitrate to alpha-ketoglutarate (alphaKG) in the cell cytoplasm and mitochondria, respectively, and contribute to generating the dihydronicotinamide-adenine dinucleotide phosphate (NADPH) as reductive potential in different cellular processes. Ketoglutaric Acids 95-114 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 39-43 32878781-2 2020 IDH1 mutants produce 2-hydroxyglutarate (2-HG), an oncometabolite, from alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 72-91 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32878781-2 2020 IDH1 mutants produce 2-hydroxyglutarate (2-HG), an oncometabolite, from alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 93-101 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32705169-7 2020 Furthermore, alpha-ketoglutarate (alpha-KG), which is the main product of IDH1-catalyzed reactions, was significantly decreased by IDH1 knockdown and upregulated by IDH1 overexpression. Ketoglutaric Acids 13-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 74-78 32705169-7 2020 Furthermore, alpha-ketoglutarate (alpha-KG), which is the main product of IDH1-catalyzed reactions, was significantly decreased by IDH1 knockdown and upregulated by IDH1 overexpression. Ketoglutaric Acids 13-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 131-135 32705169-7 2020 Furthermore, alpha-ketoglutarate (alpha-KG), which is the main product of IDH1-catalyzed reactions, was significantly decreased by IDH1 knockdown and upregulated by IDH1 overexpression. Ketoglutaric Acids 13-32 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 131-135 32705169-7 2020 Furthermore, alpha-ketoglutarate (alpha-KG), which is the main product of IDH1-catalyzed reactions, was significantly decreased by IDH1 knockdown and upregulated by IDH1 overexpression. Ketoglutaric Acids 34-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 74-78 32705169-7 2020 Furthermore, alpha-ketoglutarate (alpha-KG), which is the main product of IDH1-catalyzed reactions, was significantly decreased by IDH1 knockdown and upregulated by IDH1 overexpression. Ketoglutaric Acids 34-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 131-135 32705169-7 2020 Furthermore, alpha-ketoglutarate (alpha-KG), which is the main product of IDH1-catalyzed reactions, was significantly decreased by IDH1 knockdown and upregulated by IDH1 overexpression. Ketoglutaric Acids 34-42 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 131-135 32729927-1 2020 Isocitrate dehydrogenase 1 (IDH1) catalyzes the reversible NADP+-dependent conversion of isocitrate to alpha-ketoglutarate (alphaKG) to provide critical cytosolic substrates and drive NADPH-dependent reactions like lipid biosynthesis and glutathione regeneration. Ketoglutaric Acids 103-122 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 32729927-1 2020 Isocitrate dehydrogenase 1 (IDH1) catalyzes the reversible NADP+-dependent conversion of isocitrate to alpha-ketoglutarate (alphaKG) to provide critical cytosolic substrates and drive NADPH-dependent reactions like lipid biosynthesis and glutathione regeneration. Ketoglutaric Acids 103-122 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 32824685-4 2020 Indeed, some IDH1 point mutations induce widespread epigenetic alterations by means of a gain-of-function of the enzyme, which becomes able to produce the oncometabolite 2-hydroxyglutarate, with inhibitory activity on alpha-ketoglutarate-dependent enzymes, such as DNA and histone demethylases. Ketoglutaric Acids 218-237 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 13-17 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). Ketoglutaric Acids 80-94 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). Ketoglutaric Acids 80-94 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). Ketoglutaric Acids 308-322 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 32777735-3 2020 Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). Ketoglutaric Acids 308-322 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-38 32754276-2 2020 IDH1mut catalyzes the reduction of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG), an oncometabolite which drives tumorigenesis. Ketoglutaric Acids 35-54 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32754276-2 2020 IDH1mut catalyzes the reduction of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG), an oncometabolite which drives tumorigenesis. Ketoglutaric Acids 56-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 32150688-2 2020 TET is an alpha-ketoglutarate (alpha-KG)-dependent enzyme, and the production of alpha-KG is catalyzed by isocitrate dehydrogenase (IDH). Ketoglutaric Acids 10-29 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 106-130 32150688-2 2020 TET is an alpha-ketoglutarate (alpha-KG)-dependent enzyme, and the production of alpha-KG is catalyzed by isocitrate dehydrogenase (IDH). Ketoglutaric Acids 10-29 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-135 32150688-2 2020 TET is an alpha-ketoglutarate (alpha-KG)-dependent enzyme, and the production of alpha-KG is catalyzed by isocitrate dehydrogenase (IDH). Ketoglutaric Acids 31-39 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-135 32150688-2 2020 TET is an alpha-ketoglutarate (alpha-KG)-dependent enzyme, and the production of alpha-KG is catalyzed by isocitrate dehydrogenase (IDH). Ketoglutaric Acids 81-89 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 106-130 32150688-2 2020 TET is an alpha-ketoglutarate (alpha-KG)-dependent enzyme, and the production of alpha-KG is catalyzed by isocitrate dehydrogenase (IDH). Ketoglutaric Acids 81-89 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 132-135 32373065-11 2020 Additionally, IDH1 mutation reduced the levels of NADPH and alpha-KG. Ketoglutaric Acids 60-68 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-18 32825279-2 2020 IDH mutants confer a neomorphic enzyme activity that converts alpha-ketoglutarate to an oncometabolite D-2-hydroxyglutarate, which impacts cellular epigenetics and metabolism. Ketoglutaric Acids 62-81 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 31257503-2 2019 By catalyzing the reversible conversion between isocitrate and alpha-ketoglutarate (alpha-KG), IDH1 and 2 contribute to the central process of metabolism, including oxidative and reductive metabolism. Ketoglutaric Acids 63-82 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 95-105 31485826-2 2020 IDH enzyme normally catalyzes isocitrate to alpha-keto-glutarate (alpha-KG), but once the gene is mutated it produces an "oncometabolite", 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 44-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 31485826-2 2020 IDH enzyme normally catalyzes isocitrate to alpha-keto-glutarate (alpha-KG), but once the gene is mutated it produces an "oncometabolite", 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 66-74 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 31960518-5 2020 Specifically, the enzymes involved in the metabolism of glutamate, lactate, and enzymes involved in the conversion of alpha-ketoglutarate were increased in IDH1 mut gliomas. Ketoglutaric Acids 118-137 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 156-160 31475115-9 2019 Gain-of-function mutations in IDH1, such as c.394C>T/p.Arg132Cys, create a neo-activity of isocitrate dehydrogenase 1 converting alpha-ketoglutarate into the oncometabolite D-2-hydroxyglutarate, inhibiting alpha-ketoglutarate-dependent enzymes, such as histone and DNA demethylases. Ketoglutaric Acids 132-151 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 31475115-9 2019 Gain-of-function mutations in IDH1, such as c.394C>T/p.Arg132Cys, create a neo-activity of isocitrate dehydrogenase 1 converting alpha-ketoglutarate into the oncometabolite D-2-hydroxyglutarate, inhibiting alpha-ketoglutarate-dependent enzymes, such as histone and DNA demethylases. Ketoglutaric Acids 209-228 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 31257503-2 2019 By catalyzing the reversible conversion between isocitrate and alpha-ketoglutarate (alpha-KG), IDH1 and 2 contribute to the central process of metabolism, including oxidative and reductive metabolism. Ketoglutaric Acids 84-92 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 95-105 31257503-3 2019 IDH1 and 2 mutations result in the loss of normal catalytic function and acquire neomorphic activity, facilitating the conversion of alpha-KG into an oncometabolite, (R)-2-hydroxyglutarate, which can cause epigenetic modifications and tumorigenesis. Ketoglutaric Acids 133-141 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-10 31105869-1 2019 The family of isocitrate dehydrogenase (IDH) enzymes is vital for cellular metabolism, as IDH1 and IDH2 are required for the decarboxylation of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 158-177 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-38 31155409-1 2019 BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1/2 genes result in nicotinamide adenine dinucleotide phosphate-dependent reduction of alpha-ketoglutarate and formation of 2-hydroxyglutarate, which blocks normal cellular differentiation and promotes leukemogenesis. Ketoglutaric Acids 142-161 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 51-56 30862724-4 2019 Mechanistically, Y42 phosphorylation occurs in IDH1 monomers, which promotes dimer formation with enhanced substrate (isocitrate or alpha-ketoglutarate) binding, whereas Y42-phosphorylated dimers show attenuated disruption to monomers. Ketoglutaric Acids 132-151 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 47-51 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. Ketoglutaric Acids 238-257 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 25-51 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. Ketoglutaric Acids 238-257 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 53-57 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. Ketoglutaric Acids 259-267 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 25-51 31139406-1 2019 Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of alpha-ketoglutarate (alpha-KG) and NADPH. Ketoglutaric Acids 259-267 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 53-57 30575118-7 2019 This arises as a result of the conversion of alpha-ketoglutarate to R(-)-2-hydroxyglutarate by the IDH1 mutant and the resultant phosphorylation of nuclear factor kappa B. Knockdown of CX3CL1 decreased the migration of NK cells. Ketoglutaric Acids 45-64 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 99-103 31221981-5 2019 Furthermore, gain-of-function mutations in genes encoding metabolic enzymes, such as isocitrate dehydrogenases (IDH)1/2, drive tumor progression by producing an oncometabolite, D-2-hydroxyglutarate (D-2HG), which is a competitive inhibitor of alpha-ketoglutarate, O2-dependent dioxygenases such as Jumonji domain-containing histone demethylases, and DNA demethylases. Ketoglutaric Acids 243-262 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 85-119 31105869-1 2019 The family of isocitrate dehydrogenase (IDH) enzymes is vital for cellular metabolism, as IDH1 and IDH2 are required for the decarboxylation of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 158-177 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 40-43 31105869-1 2019 The family of isocitrate dehydrogenase (IDH) enzymes is vital for cellular metabolism, as IDH1 and IDH2 are required for the decarboxylation of isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 158-177 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 90-94 30573870-3 2019 IDH mutation has a remarkable neomorphic activity of converting alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG), which is now commonly referred to as an oncometabolite and biomarker for gliomas. Ketoglutaric Acids 64-83 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 30573870-3 2019 IDH mutation has a remarkable neomorphic activity of converting alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG), which is now commonly referred to as an oncometabolite and biomarker for gliomas. Ketoglutaric Acids 85-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-3 30857299-1 2019 Isocitrate dehydrogenases (IDH) 1 and 2 are key metabolic enzymes that generate reduced nicotinamide adenine dinucleotide phosphate (NADPH) to maintain a pool of reduced glutathione and peroxiredoxin, and produce alpha-ketoglutarate, a co-factor of numerous enzymes. Ketoglutaric Acids 213-232 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-39 31086759-9 2019 Almost unique amongst intracellular bacteria, MAP"s variant isocitrate dehydrogenase 1 (IDH1) enzyme, a type 2-oxoglutarate ferredoxin oxidoreductase, can use a host cell"s cytosolic alpha-ketoglutarate in its own Krebs or tricarboxylic acid cycle. Ketoglutaric Acids 183-202 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 88-92 31086759-10 2019 MAP"s ability to use a host cell"s alpha-ketoglutarate may explain the survival advantage of the cytosolic IDH1 enzyme mutation for patients with diffuse gliomas including glioblastoma, astrocytoma, and oligdendroglioma, a mutation that results in a reduced supply of cytosolic alpha-ketoglutarate. Ketoglutaric Acids 35-54 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 107-111 31086759-10 2019 MAP"s ability to use a host cell"s alpha-ketoglutarate may explain the survival advantage of the cytosolic IDH1 enzyme mutation for patients with diffuse gliomas including glioblastoma, astrocytoma, and oligdendroglioma, a mutation that results in a reduced supply of cytosolic alpha-ketoglutarate. Ketoglutaric Acids 278-297 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 107-111 29547090-3 2018 Mutant IDH produces 2-hydroxyglutarate from alpha-ketoglutarate, a key metabolite of the Krebs cycle. Ketoglutaric Acids 44-63 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 7-10 30381394-3 2018 Several studies have proposed that retention of this WT allele is protumorigenic by facilitating substrate channeling through a WT-mutant IDH1 heterodimer, with the WT subunit generating a local supply of alpha-ketoglutarate and NADPH that is then consumed by the mutant subunit to produce 2-HG. Ketoglutaric Acids 205-224 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 138-142 30003571-1 2018 AIMS: Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 90-109 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 6-32 30003571-1 2018 AIMS: Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 90-109 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 30506321-1 2018 Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 102-121 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 29847930-1 2018 Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG) in the tricarboxylic acid cycle. Ketoglutaric Acids 113-132 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-41 29847930-1 2018 Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG) in the tricarboxylic acid cycle. Ketoglutaric Acids 134-142 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-41 30405699-2 2018 This is exemplified by the isoforms of isocitrate dehydrogenase (IDH1/2), which metabolize isocitrate to alpha-Ketoglutarate (alpha-KG). Ketoglutaric Acids 105-124 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 65-71 30405699-2 2018 This is exemplified by the isoforms of isocitrate dehydrogenase (IDH1/2), which metabolize isocitrate to alpha-Ketoglutarate (alpha-KG). Ketoglutaric Acids 126-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 65-71 30405699-3 2018 Gain of function mutations in IDH1 or IDH2 result in reduced levels of alpha-KG as a result of increased formation of D-2-Hydroxyglutarate (2-HG). Ketoglutaric Acids 71-79 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-34 30249606-2 2018 Most tumor-relevant IDH1 mutations are deficient in the normal oxidization of isocitrate to alpha-ketoglutarate (alphaKG), but gain the neomorphic activity of reducing alphaKG to D-2-hydroxyglutarate (D2HG), which drives tumorigenesis. Ketoglutaric Acids 92-111 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 20-24 30134173-2 2018 Hallmarks of this metabolic rewiring are downregulation of alpha-ketoglutarate formation by isocitrate dehydrogenase (IDH) and accumulation of glutamine-derived succinate, which enhances the inflammatory response via the activity of succinate dehydrogenase (SDH). Ketoglutaric Acids 59-78 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 118-121 29733964-2 2018 Recently, IDH1/2 mutations have been identified in approximately 20% of CCAs which suggests an involvement of 2-oxoglutarate (2-OG) -dependent dioxygenases in oncogenesis. Ketoglutaric Acids 110-124 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-16 29733964-2 2018 Recently, IDH1/2 mutations have been identified in approximately 20% of CCAs which suggests an involvement of 2-oxoglutarate (2-OG) -dependent dioxygenases in oncogenesis. Ketoglutaric Acids 126-130 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 10-16 29723602-1 2018 Isocitrate dehydrogenases 1 and 2 (IDH1/2) are important metabolic enzymes that convert isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 102-121 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-41 29545476-1 2018 Mutant isocitrate dehydrogenase (IDH) 1/2 converts alpha-ketoglutarate (alpha-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit alpha-KG-dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. Ketoglutaric Acids 51-70 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 33-36 29545476-1 2018 Mutant isocitrate dehydrogenase (IDH) 1/2 converts alpha-ketoglutarate (alpha-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit alpha-KG-dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. Ketoglutaric Acids 72-80 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 33-36 30483760-1 2019 The mutation of isocitrate dehydrogenase (IDH)1 (R132H) and IDH2 (R172K) and the induction of hypoxia in various solid tumors results in alterations in metabolic profiles, including the production of the d- or l-forms of 2-hydroxyglutarate (2HG) from alpha-ketoglutarate in aerobic metabolism in the tricarboxylic acid (TCA) cycle. Ketoglutaric Acids 251-270 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 42-47 29439493-1 2018 Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the alpha-ketoglutarate (alpha-KG) to D-2 hydroxyglutarate (D-2HG) in a NADPH-consuming reaction. Ketoglutaric Acids 277-296 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-41 29439493-1 2018 Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the alpha-ketoglutarate (alpha-KG) to D-2 hydroxyglutarate (D-2HG) in a NADPH-consuming reaction. Ketoglutaric Acids 298-306 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-41 28827794-3 2017 In RNA-sequencing analyses searching for novel anti-oxidant genes downstream of DJ-1, a gene encoding NADP+-dependent isocitrate dehydrogenase (IDH), which converts isocitrate into alpha-ketoglutarate, was detected. Ketoglutaric Acids 181-200 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 144-147 29312565-6 2017 Of particular significance, miR-144-5p exhibits a high positive correlation with oxoglutaric acid, isocitrate dehydrogenase (IDH) 1 and 2 that involved in the TCA cycle. Ketoglutaric Acids 81-97 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 99-137 29137396-3 2017 Our data demonstrated that IDH1 was downregulated by TGF-beta signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of alpha-ketoglutarate (alpha-KG) by accelerating glutamine metabolization. Ketoglutaric Acids 152-171 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 111-115 27856334-8 2017 We also observed an unusual lipogenic pathway in which carbon from glucose supplies mitochondrial production of alpha-ketoglutarate (AKG), which is then trafficked to the cytosol and used to supply reductive carboxylation by isocitrate dehydrogenase 1 (IDH1). Ketoglutaric Acids 112-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 225-251 27856334-8 2017 We also observed an unusual lipogenic pathway in which carbon from glucose supplies mitochondrial production of alpha-ketoglutarate (AKG), which is then trafficked to the cytosol and used to supply reductive carboxylation by isocitrate dehydrogenase 1 (IDH1). Ketoglutaric Acids 112-131 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 253-257 29458964-1 2018 Isocitrate dehydrogenases (IDH1/2) are frequently mutated in multiple types of human cancer, resulting in neomorphic enzymes that convert alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG). Ketoglutaric Acids 138-157 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-33 29382206-3 2018 Owing to a mutation in an important arginine residue in the catalytic pocket, mutant IDH1 catalyzes the production of 2-hydroxyglutarate (2-HG) instead of its wild type product alpha-ketoglutarate (alpha-KG), which is involved in multiple cellular pathways involving the hydroxylation of proteins, ribonucleic acid, and deoxyribose nucleic acid (DNA). Ketoglutaric Acids 177-196 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 85-89 29382206-3 2018 Owing to a mutation in an important arginine residue in the catalytic pocket, mutant IDH1 catalyzes the production of 2-hydroxyglutarate (2-HG) instead of its wild type product alpha-ketoglutarate (alpha-KG), which is involved in multiple cellular pathways involving the hydroxylation of proteins, ribonucleic acid, and deoxyribose nucleic acid (DNA). Ketoglutaric Acids 198-206 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 85-89 29773061-1 2018 Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate (alphaKG). Ketoglutaric Acids 122-141 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 35-39 28711227-3 2017 Gain-of-function mutations in IDH1/2 have been shown to stimulate production of the oncogenic metabolite R-2-hydroxyglutarate (R-2HG), which inhibits alpha-ketoglutarate (alphaKG)-dependent enzymes. Ketoglutaric Acids 150-169 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-36 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). Ketoglutaric Acids 155-174 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-47 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). Ketoglutaric Acids 155-174 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 49-53 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). Ketoglutaric Acids 176-184 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 21-47 28467784-1 2017 Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts alpha-ketoglutarate (alpha-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). Ketoglutaric Acids 176-184 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 49-53 28665599-2 2017 In particular, we focus our attention on the ability of the -CF3 group to participate in noncovalent interactions as Lewis acids, and we show the importance of this interaction in the inhibition mechanism of a NADP+-dependent isocitrate dehydrogenase (IDH) enzyme that converts isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 292-311 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 252-255 26970248-6 2016 RESULTS: The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2-hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20%, P = 0.024), which probably reflects an attempt to replenish alpha-ketoglutarate lost by conversion to 2HG. Ketoglutaric Acids 352-371 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 138-141 28653623-0 2017 Replication Study: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Ketoglutaric Acids 128-147 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 61-65 28653623-1 2017 In 2016, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fiehn et al., 2016), that described how we intended to replicate selected experiments from the paper "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate" (Ward et al., 2010). Ketoglutaric Acids 310-329 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 243-247 28319047-2 2017 LGG-associated IDH mutations confer gain-of-function activity by converting alpha-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Ketoglutaric Acids 76-95 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 15-18 27819678-10 2017 A gene co-expression network identified using TCGA prostate tumour RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. Ketoglutaric Acids 135-149 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 284-290 28705010-1 2017 Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG), producing NADPH in the process. Ketoglutaric Acids 115-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-25 28705010-1 2017 Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG), producing NADPH in the process. Ketoglutaric Acids 115-134 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-30 28705010-1 2017 Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG), producing NADPH in the process. Ketoglutaric Acids 136-144 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-25 28705010-1 2017 Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG), producing NADPH in the process. Ketoglutaric Acids 136-144 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 27-30 28564604-4 2017 On a molecular level, diminished IDH1 activity results in reduced alpha-ketoglutarate (alphaKG) and NADPH production, paralleled by deficient carbon flux from glucose or acetate into lipids, exhaustion of reduced glutathione, increased levels of reactive oxygen species (ROS), and enhanced histone methylation and differentiation marker expression. Ketoglutaric Acids 66-85 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 33-37 28330869-1 2017 Isocitrate dehydrogenase 1 (IDH1) catalyzes the reversible NADP+-dependent conversion of isocitrate (ICT) to alpha-ketoglutarate (alphaKG) in the cytosol and peroxisomes. Ketoglutaric Acids 109-128 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-26 28330869-1 2017 Isocitrate dehydrogenase 1 (IDH1) catalyzes the reversible NADP+-dependent conversion of isocitrate (ICT) to alpha-ketoglutarate (alphaKG) in the cytosol and peroxisomes. Ketoglutaric Acids 109-128 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 28-32 27721426-5 2017 Both IDH2 and IDH1 (localized in the cytoplasm) proteins catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 113-132 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-18 27721426-5 2017 Both IDH2 and IDH1 (localized in the cytoplasm) proteins catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 134-142 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 14-18 27624942-2 2016 IDH1/2 normally catalyse the oxidative decarboxylation of isocitrate into alpha-ketoglutarate (alphaKG). Ketoglutaric Acids 74-93 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 27621679-1 2016 Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to alpha-ketoglutarate. Ketoglutaric Acids 102-121 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 34-38 27430238-2 2016 IDH1 mutations lead to the formation of the oncometabolite 2-hydroxyglutarate (2-HG) from the reduction of alpha-ketoglutarate (alpha-KG), which in turn facilitates tumorigenesis by modifying DNA and histone methylation as well blocking differentiation processes. Ketoglutaric Acids 107-126 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 0-4 27466503-1 2016 The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 168-187 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-28 27466503-1 2016 The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 168-187 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-33 27466503-1 2016 The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 189-197 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 4-28 27466503-1 2016 The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to alpha-ketoglutarate (alpha-KG). Ketoglutaric Acids 189-197 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 30-33 27063596-1 2016 Canonical mutations in IDH1 and IDH2 produce high levels of the R-enantiomer of 2-hydroxyglutarate (R-2HG), which is a competitive inhibitor of alpha-ketoglutarate (alphaKG)-dependent enzymes and a putative oncometabolite. Ketoglutaric Acids 144-163 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 23-27 27194485-1 2016 Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led to reduced affinity of the respective enzymes for isocitrate and increased affinity for alpha-ketoglutarate (AKG) and NADPH. Ketoglutaric Acids 184-203 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 58-84 27194485-1 2016 Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led to reduced affinity of the respective enzymes for isocitrate and increased affinity for alpha-ketoglutarate (AKG) and NADPH. Ketoglutaric Acids 184-203 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 86-90 27355333-3 2016 The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Ketoglutaric Acids 109-128 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16 27355333-3 2016 The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of alpha-ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Ketoglutaric Acids 130-138 isocitrate dehydrogenase (NADP(+)) 1 Homo sapiens 12-16