### ACACA Gene Overview

**Gene Symbol**: ACACA  
**Location**: Chromosome 17 (17p11.2)  
**Aliases**: ACC, ACC1, Acetyl-CoA carboxylase alpha  

**Function**:  
The ACACA gene encodes the enzyme Acetyl-CoA carboxylase alpha (ACC-alpha), which plays a crucial role in lipid metabolism by catalyzing the carboxylation of acetyl-CoA to produce malonyl-CoA. This reaction is the first and rate-limiting step in de novo fatty acid biosynthesis. Given its significant regulatory role, ACC-alpha is densely expressed in lipogenic tissues, such as liver and adipose tissue, and its activity is modulated by both transcriptional and post-translational mechanisms.

### 1. Associated Genes

The ACACA gene interacts with several other genes and pathways involved in lipid metabolism and energy homeostasis:

- **ACC-beta (ACACB)**: Another isoform of acetyl-CoA carboxylase, which is encoded by a distinct gene and is involved in similar metabolic pathways.
- **FASN (Fatty Acid Synthase)**: This gene encodes an enzyme that catalyzes the synthesis of fatty acids from acetyl-CoA and malonyl-CoA.
- **CPT1 (Carnitine Palmitoyltransferase 1)**: Plays a role in fatty acid oxidation, which counterbalances the fatty acid synthesis pathway.
- **SREBF1 (Sterol Regulatory Element Binding Transcription Factor 1)**: A transcription factor that regulates fat and cholesterol metabolism, influencing ACACA expression.

### 2. Aging and Age-Related Diseases

Research has indicated that dysregulation of ACACA may be linked to age-related metabolic disorders, including:

- **Obesity**: Changes in fatty acid synthesis and regulation of ACC are frequently observed in obese individuals.
- **Type 2 diabetes**: The role of malonyl-CoA in the regulation of glucose and lipid metabolism suggests that ACACA could influence insulin sensitivity and overall energy homeostasis.
- **Neurodegenerative diseases**: Impaired lipid metabolism, including fatty acid synthesis via ACC, has been associated with conditions like Alzheimer's disease.

### 3. Drug Interactions

Certain drugs and drug classes are known to modulate the activity of ACACA:

- **Fibrate drugs (e.g., Fenofibrate, Gemfibrozil)**: Primarily used to lower lipid levels, they may affect the transcriptional regulation of ACC genes.
- **Statins (HMG-CoA reductase inhibitors)**: While their primary action is on cholesterol synthesis, there may be downstream effects on lipid pathways involving ACACA.
- **Metformin**: Primarily used in diabetes management, it influences lipid metabolism and may indirectly affect ACC activity.

### 4. Pathways and Biological Processes

ACACA is involved in several critical metabolic and signaling pathways:

- **Fatty Acid Metabolism**: As the rate-limiting enzyme in de novo lipogenesis.
- **Insulin Signaling Pathway**: ACACA activity is modulated by insulin, influencing overall metabolic homeostasis.
- **AMPK Signaling Pathway**: AMPK activation leads to phosphorylation of ACC, which inhibits its activity and promotes fatty acid oxidation.
- **Citrate Metabolism**: The enzyme is regulated allosterically by citrate, which indicates cellular energy status and promotes fatty acid synthesis when energy is abundant.

### Summary

The ACACA gene is a key player in fatty acid metabolism, with significant implications for clinical conditions related to metabolism, obesity, and aging. Its interactions with other metabolic genes and pathways further underline its importance in cellular energy homeostasis and physical health. Understanding ACACA and its regulation could provide insights into potential therapeutic targets for managing metabolic diseases.