What is the Difference Between IDH1 and IDH2?
🆚 Go to Comparative Table 🆚IDH1 and IDH2 are both isocitrate dehydrogenase enzymes that play roles in cellular metabolism. They catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) and are involved in the citric acid (TCA) cycle for energy production. However, there are some differences between IDH1 and IDH2:
- Cellular Localization: IDH1 is located in the cytoplasm, while IDH2 is found in the mitochondria.
- Physiological Roles: Although both enzymes have similar functions in cellular metabolism, they have distinct physiological roles.
- Mutations: IDH1 and IDH2 mutations are often mutually exclusive and are typically heterozygous, meaning one allele is mutated while the other remains wild-type. These mutations are frequent in certain cancers, such as acute myeloid leukemia (AML), gliomas, and other solid tumors.
- Oncometabolite: Both IDH1 and IDH2 mutant enzymes gain neomorphic enzymatic activity, converting NADPH and α-KG to NADP+ and D-2HG, which acts as a weak competitive inhibitor of the TCA cycle.
- Prognostic Value: In AML, IDH1 and IDH2 mutations are associated with older age at presentation, diploid or intermediate-risk cytogenetics (i.e., trisomy 8), and a sustained platelet count at presentation. However, the prognostic relevance of IDH mutations in AML is controversial due to inconsistent findings in various patient series.
In summary, IDH1 and IDH2 enzymes share similar functions but have distinct physiological roles and cellular localizations. They are both involved in cellular metabolism and are frequent targets of mutations in certain cancers.
Comparative Table: IDH1 vs IDH2
IDH1 and IDH2 are isocitrate dehydrogenase enzymes that play crucial roles in cellular processes. They share many similarities but also have distinct differences. Here is a table comparing the differences between IDH1 and IDH2:
| Feature | IDH1 | IDH2 |
|---|---|---|
| Location | Cytosol and peroxisomes | Mitochondria |
| Substrate | NADP+ | NADP+ |
| Frequency of Mutations | IDH1 mutations are found in various cancers, including lower-grade gliomas, secondary glioblastomas, chondrosarcomas, and intrahepatic cholangiocarcinomas. | IDH2 mutations are found in acute myeloid leukemia, angioimmunoblastic T-cell lymphoma, and other myeloid malignancies. |
| Mutation Spectrum | The most frequent IDH1 mutation is the substitution of arginine 132. Less frequent mutations can be detected by DNA sequencing. | The most frequent IDH2 mutations are the substitutions of arginine 140 and arginine 172. |
IDH1 and IDH2 mutations result in the production of 2-hydroxyglutarate (2-HG), an oncometabolite that promotes leukemogenesis by blocking myeloid differentiation. Selective oral inhibitors of mutant IDH1 and IDH2 have been developed and are now under clinical investigation.