Cholesterol synthesis in mammals is primarily regulated through a feedback mechanism involving sterol regulatory element-binding proteins (SREBPs). These proteins act as transcription factors that control the genes responsible for cholesterol production and fatty acid synthesis.
The SREBP Regulation System
Here's a breakdown of how this system works:
- Inactive SREBPs: SREBPs are initially produced as inactive precursor proteins that are embedded in the membranes of the endoplasmic reticulum (ER).
- Cholesterol Levels: Intracellular cholesterol levels act as the key trigger for SREBP activation.
- Activation Process: When cholesterol levels are low, SREBP is transported from the ER to the Golgi apparatus.
- Proteolytic Cleavage: Once in the Golgi, SREBPs undergo two sequential cleavages by specific proteases.
- This process releases the active portion of the SREBP which can then translocate to the nucleus.
- Gene Transcription: The active SREBP fragment enters the nucleus and binds to specific DNA sequences called sterol regulatory elements (SREs).
- This binding initiates the transcription of genes involved in both cholesterol and fatty acid synthesis.
- Increased Synthesis: The result is the increased production of enzymes needed to synthesize cholesterol and fatty acids.
- Feedback Inhibition: As the levels of cholesterol and fatty acids rise, the SREBP activation process is suppressed which stops further synthesis. This completes the negative feedback loop.
Key Points Summarized in a Table:
| Feature | Description |
|---|---|
| Regulatory Protein | Sterol regulatory element-binding proteins (SREBPs) |
| Initial State of SREBPs | Inactive precursors bound to endoplasmic reticulum (ER) membranes |
| Trigger for Activation | Low intracellular cholesterol levels |
| Location of Activation | Golgi apparatus |
| Mechanism of Activation | Proteolytic cleavage of SREBPs |
| SREBP Action | Translocation to the nucleus, binding to sterol regulatory elements (SREs) |
| Gene Control | Increased transcription of genes for cholesterol and fatty acid synthesis |
| Feedback | Elevated cholesterol and fatty acid levels inhibit SREBP activation |
Essentially, the SREBP system acts like a thermostat, ensuring that cholesterol and fatty acid synthesis is ramped up when cellular levels are low and turned down when they are sufficient. This elegant system helps maintain cellular homeostasis.
