IDH2 Blocking Peptide

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in intermediary metabolism and energy production. This protein may tightly associate or interact with the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

IDH2: a mitochondrial oxidoreductase that catalyzes the third step of the citric acid cycle: the oxidative decarboxylation of isocitrate, consuming NADP(+), and producing alpha-ketoglutarate (alpha-KG) and CO2. Can also use oxalosuccinate as a substrate. Alpha-KG is an activator the dioxygenases that hydroxylate the transcription factor HIF and lead to its degradation by VHL. Since HIF turns on oncogenic pathways, IDH2 has apparent tumor suppressor activity. Homo-dimerization is required for activity. Each subunit binds 1 magnesium or manganese ion. May tightly associate or interact with the pyruvate dehydrogenase complex. A somatic mutation resulting in the R172K conversion results in a neomorphic enzyme activity that converts isocitrate to R(-)-2-hydroxyglutarate (2HG) occurs in a significant percentage of patients with cytogenetically normal acute myeloid leukemia (AML). Elevated levels of 2HG are also correlated with an elevated risk of malignant brain tumors.

Protein type: Other Amino Acids Metabolism - glutathione; Oxidoreductase; Carbohydrate Metabolism - citrate (TCA) cycle; Mitochondrial; EC 1.1.1.42

Chromosomal Location of Human Ortholog: 15q26.1

Cellular Component: mitochondrion; mitochondrial matrix; mitochondrial inner membrane

Molecular Function: magnesium ion binding; isocitrate dehydrogenase (NADP+) activity; NAD binding

Biological Process: isocitrate metabolic process; glyoxylate cycle; cellular metabolic process; tricarboxylic acid cycle; carbohydrate metabolic process; 2-oxoglutarate metabolic process

Disease: D-2-hydroxyglutaric Aciduria 2