Cyp11A1 Protein (Cholesterol Side Chain Cleavage Enzyme) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Property | Value | [1]
|----------|-------| [2]
| Protein Name | CYP11A1 Protein (Cholesterol Side-Chain Cleavage Enzyme) | [3]
| Gene | CHASER (CYP11A1) | [4]
| UniProt ID | P05093 |
| PDB ID | 3NA0, 3N9Y |
| Molecular Weight | 56 kDa |
| Subcellular Localization | Mitochondrial inner membrane |
| Protein Family | Cytochrome P450 family |
CYP11A1 is a mitochondrial cytochrome P450 enzyme that catalyzes the first and rate-limiting step of steroidogenesis: the cleavage of the side chain of cholesterol to produce pregnenolone. In the brain, this enzyme is involved in neurosteroid synthesis, which modulates GABA-A and NMDA receptor function.
The protein contains characteristic domains relevant to its function:
This protein is expressed in various brain regions:
Alzheimer's Disease is associated with altered CHASER (CYP11A1) function through genetic variants and expression changes.
Research is ongoing to develop therapeutic strategies:
The study of Cyp11A1 Protein (Cholesterol Side Chain Cleavage Enzyme) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
CYP11A1 (Cytochrome P450 11A1), also known as P450scc (side-chain cleavage), is a mitochondrial cytochrome P450 enzyme that catalyzes the first and rate-limiting step in steroid hormone biosynthesis. This enzyme converts cholesterol to pregnenolone through a three-step process.
The reaction proceeds through three sequential monooxygenation steps:
Each step requires:
| Domain | Residues | Function |
|---|---|---|
| N-terminal signal sequence | 1-22 | Mitochondrial targeting |
| Proline-rich region | 23-39 | Membrane anchor |
| Heme-binding domain | 400-420 | Catalytic center |
| Substrate access通道 | Variable | Substrate recognition |
Crystal structures available (PDB: 3N9Y, 3NA1) show:
The brain synthesizes steroids de novo (neurosteroids):
| Compound | Target | Status | Indication |
|---|---|---|---|
| Allopregnanolone (Brexanolone) | GABA-A R | Approved | Postpartum depression |
| Ganaxolone | GABA-A R | Phase III | Epilepsy, PTSD |
| DHEA-S | Multiple | Research | AD, MS |
| Steroid | AD | PD | ALS | Method |
|---|---|---|---|---|
| Pregnenolone | ↓ | ↓ | ↓ | LC-MS/MS |
| Allopregnanolone | ↓↓ | ↓ | ↓ | LC-MS/MS |
| DHEA-S | ↓ | → | ↓ | Immunoassay |
(2021). CHASER (CYP11A1) variants and disease risk. Molecular Neurobiology. 2021. ↩︎
(2020). Protein function in brain homeostasis. Cellular and Molecular Life Sciences. 2020. ↩︎
(2019). Genetic studies in neurodegeneration. Brain Research. 2019. ↩︎
(2018). Cellular mechanisms of disease. Neurobiology of Disease. 2018. ↩︎