### IDH2 Gene Overview

**Gene Symbol**: IDH2  
**Function**: The IDH2 gene encodes the enzyme isocitrate dehydrogenase (NADP(+)), which catalyzes the oxidative decarboxylation of isocitrate to 2-oxoglutarate, an important step in cellular metabolism that contributes to the citric acid cycle (Krebs cycle). This enzyme is primarily located in the mitochondria and operates in the context of intermediary metabolism and energy production. It can also interact with the pyruvate dehydrogenase complex, indicating its role in linking various metabolic pathways.

### 1. Associated Genes

While IDH2 has specific functions, it may be associated with several other genes involved in similar metabolic pathways or regulatory networks. These may include:

- **IDH1**: A closely related gene that encodes for a cytosolic form of isocitrate dehydrogenase (NAD(+)). Mutations in IDH1 and IDH2 are commonly studied together due to their related catalytic functions and implications in cancer.
- **PDHA1**: Pyruvate dehydrogenase (E1 component) involved in converting pyruvate into acetyl-CoA, which is crucial for the citric acid cycle.
- **CS**: Citrate synthase, which catalyzes the conversion of acetyl-CoA and oxaloacetate to citrate, a precursor for isocitrate.

### 2. Aging and Age-Related Diseases

IDH2 has been implicated in various aspects of metabolism that may impact aging and age-related diseases:

- **Mitochondrial Function**: Dysregulation of mitochondrial enzymes, including IDH2, has been linked with aging, as mitochondrial dysfunction is a hallmark of age-related degenerative diseases. 
- **Cancer**: Mutations in IDH2 lead to the production of 2-hydroxyglutarate (2-HG), which is associated with a variety of cancers, particularly glioma and acute myeloid leukemia (AML). The accumulation of 2-HG may affect cellular processes and contribute to oncogenesis.
- **Metabolic Disorders**: Altered activity of IDH2 has been studied in the context of metabolic syndromes, which are more prevalent with age and are related to insulin resistance, obesity, and cardiovascular diseases.

### 3. Drug Interactions

Drugs or drug classes known to interact with pathways involving IDH2 include:

- **IDH Inhibitors**: Compounds like enasidenib (IDH2 inhibitor) are used in the treatment of acute myeloid leukemia with specific IDH2 mutations.
- **Metabolic Modulators**: Some investigational agents targeting metabolic pathways might indirectly influence IDH2 activity.
- **Antioxidants**: Since IDH2 functions in redox metabolism, agents that modulate oxidative stress (like certain antioxidants) may impact its activity.

### 4. Pathways and Biological Processes

IDH2 is involved in several critical biological processes and pathways, including:

- **Citric Acid Cycle (Krebs Cycle)**: Essential for aerobic respiration and energy metabolism.
- **NADP(+)/NADPH Regeneration**: Contributes to the cellular redox balance and biosynthetic reactions.
- **Metabolism of Amino Acids**: Particularly in the context of converting isocitrate to 2-oxoglutarate, impacting glutamate and gamma-aminobutyric acid (GABA) pathways.
- **TCA Cycle Regulation**: Plays a role in the regulation of key metabolic intermediates, influencing cellular signaling and energy status.

In summary, IDH2 is a crucial enzyme involved in metabolic processes within the mitochondria, with associations to cancer, aging, and various metabolic disorders. Its interactions with other genes and pathways highlight its importance in health and disease.