regulation of cholesterol biosynthetic process

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of cholesterol. [GOC:go_curators]

Cholesterol biosynthesis is a tightly regulated process that involves multiple steps and intricate feedback mechanisms to maintain cholesterol homeostasis. The process starts with the condensation of acetyl-CoA, derived from glucose or fatty acid metabolism, into mevalonate. This key precursor undergoes several enzymatic reactions to produce squalene, a linear molecule. Squalene is then cyclized and modified to yield lanosterol, which is further processed through a series of 19 enzymatic steps to produce cholesterol.

The regulation of cholesterol biosynthesis occurs at multiple levels:

1. **Transcriptional Regulation:**
* **SREBPs (Sterol Regulatory Element Binding Proteins):** SREBPs are transcription factors that control the expression of genes involved in cholesterol biosynthesis. They are synthesized as inactive precursors bound to the endoplasmic reticulum (ER). When cellular cholesterol levels are low, SREBPs are escorted to the Golgi apparatus, where they are cleaved by proteases to release the active transcription factor. This active SREBP then translocates to the nucleus and binds to sterol regulatory elements (SREs) in the promoters of genes involved in cholesterol synthesis, like HMG-CoA reductase.

2. **Feedback Inhibition:**
* **HMG-CoA Reductase:** This enzyme, which catalyzes the rate-limiting step in cholesterol biosynthesis, is tightly regulated. Cholesterol, the end product of the pathway, acts as a negative feedback inhibitor of HMG-CoA reductase. High cholesterol levels suppress the enzyme's activity, while low cholesterol levels stimulate its activity.

3. **Post-translational Modifications:**
* **Phosphorylation:** HMG-CoA reductase is regulated by phosphorylation, a process that can either activate or inhibit the enzyme's activity.

4. **Protein Degradation:**
* **Proteasome Degradation:** HMG-CoA reductase is also subject to proteasome degradation, a process that removes damaged or misfolded proteins from the cell.

5. **Hormonal Regulation:**
* **Insulin:** Insulin increases the synthesis of cholesterol by stimulating the expression of genes involved in cholesterol biosynthesis.
* **Glucagon:** Glucagon has the opposite effect, decreasing cholesterol synthesis.

6. **Dietary Cholesterol:**
* The body can synthesize cholesterol, but dietary cholesterol also plays a significant role in regulating cellular cholesterol levels. When dietary cholesterol intake is high, the body reduces its own cholesterol synthesis to maintain homeostasis.

The intricate regulation of cholesterol biosynthesis ensures that the body maintains sufficient levels of this essential molecule for cell membranes, steroid hormone synthesis, and other vital functions while preventing the accumulation of excess cholesterol, which can lead to cardiovascular disease.'
"

Proteins (2)

Compounds (1)