Clinlab Navigator

Isocitrate Dehydrogenase Mutations

Isocitrate dehydrogenase (IDH) normally catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate. IDH1 is a cytosolic enzyme that results in production of NADPH. It should not be confused with IDH2 which is an isoenzyme in the citric acid cycle that reduces NAD rather than NADP.  Mutations in IDH1 and IDH2 occur in a number of cancer types including ~20% of acute myeloid leukemias (AML).  IDH mutants gain the novel capacity to reduce α-ketoglutarate to D-2-hydroxyglutarate. D-2-hydroxyglutarate is known as an oncometabolite and its accumulation competitively inhibits α-ketoglutarate dependent enzyme activities including methlycytosine hydroxylation by members of the TET gene family and histone lysine demethylases belonging to the JMJD family. Such metabolic derangement promotes genetic hypermethylation and in the case of AML, leads to arrested differentiation of myeloid progenitors. 

IDH mutations have been identified in over 70% of lower-grade (II/III) diffuse gliomas and secondary glioblastoma. Assessment of IDH mutation status in central nervous system tumors assists in tumor classification and provide prognostic information for patients with diffuse gliomas.

Point mutations and small insertion/deletion mutations in the IDH1 and IDH2 genes are detected by next generation sequencing. Enasidenib and Ivosidenib are inhibitors of isocitrate dehydrogenase–1.

Updated Articles

Antineutrophil…

Systemic necrotizing vasculitides are inflammatory diseases of blood vessels, which are difficult to distinguish from infectious, connective tissue, and degenerative diseases. Biopsies often reveal only nonspecific acute or chronic inflammation.…

New Articles

Selenium

Selenium is an essential element that is a cofactor for glutathione peroxidase (GSH-Px). The normal daily dietary intake of selenium is 0.01 to 0.04 parts per million (ppm), which is similar to the typical content of soil (0.05 ppm) and sea water…

Blog

Procalcitonin Has…

Procalcitonin (PCT) is the precursor peptide of calcitonin which under normal circumstances is secreted by thyroid C-cells in response to hypercalcemia. PCT is normally undetectable in serum (<0.05 ng/mL), but is produced in large quantities by many…