### IDH1 Gene Overview

#### General Information
- **Gene Symbol:** IDH1 (Isocitrate Dehydrogenase 1)
- **Location:** Chromosome 2q34
- **Function:** The IDH1 gene encodes an enzyme that catalyzes the oxidative decarboxylation of isocitrate to 2-oxoglutarate using NADP+ as an electron acceptor. It has crucial roles in cellular metabolism, particularly in the generation of NADPH, which is essential for various biosynthetic pathways and cellular antioxidant defenses.

### 1. Associated Genes
IDH1 has been primarily studied in connection with metabolic pathways and certain cancers, including:

- **IDH2:** A closely related gene that encodes an NAD(+)-dependent isocitrate dehydrogenase, primarily found in mitochondria. Mutations in both IDH1 and IDH2 have been implicated in gliomas and acute myeloid leukemia (AML).
- **NADP**-dependent enzymes: Other enzymes that rely on NADPH for their function, such as those involved in steroid biosynthesis and fatty acid synthesis.
- **Phytanoyl-CoA dioxygenase (Phyx):** An enzyme involved in phytanic acid metabolism that requires 2-oxoglutarate as a substrate.

### 2. Aging and Age-Related Diseases
- **Cancers:** Mutations in IDH1 are often associated with specific types of cancers, particularly gliomas and AML. The resulting neomorphic activity produces 2-hydroxyglutarate (2-HG), an oncometabolite that interferes with cellular metabolism and epigenetic regulation, potentially leading to malignancy.
- **Neurodegenerative disorders:** Inhibition of IDH1 has been explored in relation to neurodegenerative diseases, as altered metabolic profiles are often seen in aging-related pathologies.
- **Metabolic syndrome:** There is emerging evidence linking IDH1 activity and NADPH production to metabolic conditions that are prevalent with aging, such as obesity and insulin resistance.

### 3. Drug Interactions
- **IDH1 inhibitors:** Drugs like ivosidenib (AG-120), which specifically targets mutant IDH1, have been developed and approved for the treatment of specific leukemia types, highlighting the clinical importance of the IDH1 gene.
- **Metformin:** Research has indicated potential interactions of metformin with the metabolic pathways involving IDH1, particularly in the context of cancer metabolism.
- **Blood glucose regulators:** Some other diabetes medications may impact pathways influenced by IDH1 activity, as NADPH plays a role in cellular redox states and insulin signaling.

### 4. Pathways and Biological Processes
- **Citric Acid Cycle:** IDH1 plays a role in the citric acid cycle (Krebs cycle) by converting isocitrate to 2-oxoglutarate.
- **NADPH production:** The enzyme is pivotal in generating NADPH, which is crucial for reductive biosynthetic reactions and maintaining the cellular redox state.
- **Fatty acid metabolism:** Engagement in the beta-oxidation of fatty acids, especially involving peroxisomes.
- **Amino acid metabolism:** Participation in the metabolism of amino acids and their derivatives, impacting nitrogen metabolism across different tissues.
- **Cell signaling:** Emerging evidence suggests that IDH1 may have roles in signaling pathways related to oxidative stress and metabolism.

In summary, the IDH1 gene is crucial for metabolic processes and has significant clinical implications, especially in cancer biology. Understanding its interactions and pathways could aid in developing targeted therapies and managing age-related diseases.