### SIRT5 Gene Overview

**Gene Symbol**: SIRT5  
**Location**: Chromosome 2q35  

**Function**: SIRT5 is a member of the sirtuin family of proteins, which are NAD+-dependent lysine deacylases and have been implicated in various cellular processes such as metabolism, DNA repair, and gene expression regulation. Unlike other sirtuins, SIRT5 primarily exhibits demalonylation, desuccinylation, and deglutarylation activities, playing a critical role in regulating protein function through the removal of specific acyl groups.

### 1. Associated Genes

While the summaries provided mention specific interactions, here are other genes associated with SIRT5 based on various studies:

- **SIRT1**: Another member of the sirtuin family that has overlapping functions related to metabolism and aging.
- **CPS1 (Carbamoyl-phosphate synthetase 1)**: Known to interact with SIRT5; SIRT5 desuccinylates CPS1, enhancing its activity.
- **SOD1 (Superoxide dismutase 1)**: Interaction with SIRT5 enables the activation of SOD1, which plays a role in detoxifying reactive oxygen species.
- **SHMT2 (Serine hydroxymethyltransferase 2)**: SIRT5 has been noted to activate this enzyme via desuccinylation, affecting one-carbon metabolism.
- **HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2)**: Another enzyme involved in ketogenesis that is modulated by SIRT5.

### 2. Aging and Age-Related Diseases

SIRT5 has garnered attention due to its potential role in aging and age-related diseases:

- **Metabolic Regulation**: Alterations in SIRT5 activity have been linked to metabolic disorders such as obesity and diabetes. As SIRT5 regulates multiple metabolic enzymes, its dysregulation may affect energy homeostasis.
- **Oxidative Stress**: The activation of SOD1 by SIRT5 promotes the detoxification of reactive oxygen species, which is crucial for mitigating oxidative stress associated with aging.
- **Neurodegenerative Diseases**: Investigational studies suggest that SIRT5 may have implications in neurodegenerative diseases by influencing mitochondrial function and reducing oxidative damage, both critical aspects in diseases such as Alzheimer's and Parkinson's.

### 3. Drug Interactions

While direct drug interactions with SIRT5 are not extensively documented, the following drug classes may impact SIRT5 activity, primarily through their effects on cellular metabolism and NAD+ levels:

- **NAD+ Precursors**: Compounds like nicotinamide riboside (NR) or nicotinic acid may influence SIRT5's activity indirectly by increasing NAD+ availability.
- **Sirtuin Activators**: Resveratrol and other polyphenolic compounds have been studied for their potential to activate sirtuins, including SIRT5.

Note: Specific drugs directly targeting SIRT5 have not been established, largely due to the complexity of sirtuin biology and the intricacies of available pharmacological agents.

### 4. Pathways and Biological Processes

SIRT5 is involved in various biological pathways and processes, including:

- **Urea Cycle**: SIRT5 plays a role in regulating ammonia detoxification through its action on CPS1.
- **Fatty Acid Metabolism**: It has been implicated in the modulation of metabolic processes associated with ketogenesis and fatty acid metabolism.
- **Oxidative Stress Response**: By activating SOD1 and other enzymes, SIRT5 plays a critical role in the response to oxidative stress and mitochondrial function.
- **Regulation of Protein Acylation**: By removing malonyl, succinyl, and glutaryl groups from lysine residues, SIRT5 impacts various metabolic and signaling pathways, influencing cellular metabolism and homeostasis.

In summary, SIRT5 is a multifunctional protein involved in critical metabolic processes, oxidative stress response, and has potential implications in aging and related diseases. Its interactions with other metabolic genes highlight its regulatory significance in maintaining cellular health.