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

Enterovirus D68

Enteroviruses (EV) are members of the Picornaviridae family. The genus Enterovirus includes four species, A through D, that are known to infect humans. Human enterovirus D68 (EV-D68) is a unique enterovirus that shares epidemiologic and biologic…

New Articles

Mpox

Mpox is a rare viral infection caused by an orthopoxvirus, which is a relatively large DNA virus that is related to smallpox. Mpox was originally named Monkeypox because it was discovered in a group of laboratory monkeys in 1958. Subsequently,…

Blog

Kratom Fatalities

Kratom is a tropical evergreen tree (Mitragyna speciosa) native to Southeast Asia. Its leaves contain compounds that can have psychotropic effects.Two compounds in kratom leaves, mitragynine and 7-α-hydroxymitragynine, interact with opioid receptors…