Molecular Mechanisms of Isocitrate Dehydrogenase 1 Mutants in Driving the Oncogenic Neomorphic Reaction
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چکیده
منابع مشابه
Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities.
Heterozygous mutations in catalytic arginine residues of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are common in glioma, acute myeloid leukemia, chondrosarcoma, cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma. The mutant enzymes acquire a neomorphic activity that converts α-ketoglutarate (α-KG) to D-2-hydroxyglutarate (D2HG), a rare metabolite. In cells and tissues expressing...
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NAD-dependent isocitrate dehydrogenase (IDH) is a TCA cycle enzyme that produces 2oxoglutarate, an organic acid required by the glutamine synthetase/glutamate synthase cycle to assimilate ammonium. Three Arabidopsis IDH mutants have been characterized, corresponding to an insertion into a different IDH gene (At5g03290, idhv; At4g35260, idhi; At2g17130, idhii). Analysis of IDH mRNA and protein s...
متن کاملAn investigation of imine formation in the isocitrate dehydrogenase reaction.
The occurrence of imine formation at the active site of acetoacetate decarboxylase and several aldolases prompted an attempt to demonstrate this mechanism in the formally similar isocitrate dehydrogenase reaction. Although treatment of isocitrate dehydrogenase with NaBH4 in the presence of cr-ketoglutarate resulted in inactivation of the enzyme, reduction in the presence of labeled a-ketoglutar...
متن کاملMolecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer.
IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-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. The mutant protein loses its n...
متن کاملThe equilibrium constant of the isocitrate dehydrogenase reaction.
1. The equilibrium constant for oxidative decarboxylation of isocitrate by NADP(+), catalysed by isocitrate dehydrogenase, was measured in solutions of various ionic strengths and at several temperatures. 2. Thermodynamic values for the reaction were obtained by extrapolation to zero ionic strength, and the heat of reaction was estimated. 3. The effect of Mg(2+) ion concentration on the equilib...
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ژورنال
عنوان ژورنال: The FASEB Journal
سال: 2019
ISSN: 0892-6638,1530-6860
DOI: 10.1096/fasebj.2019.33.1_supplement.633.23