Recombinant Mouse Lanosterol 14-alpha demethylase (Cyp51a1)
Description
Introduction to Recombinant Mouse Lanosterol 14-alpha Demethylase (Cyp51a1)
Recombinant Mouse Lanosterol 14-alpha demethylase, also known as Cyp51a1, is a cytochrome P450 enzyme that plays a crucial role in the biosynthesis of sterols. This enzyme is responsible for the demethylation of lanosterol, a key step in the production of cholesterol in mammals and ergosterol in fungi. The recombinant form of this enzyme is produced through genetic engineering techniques, allowing for its expression in various host systems for research and therapeutic applications.
Function and Mechanism
Cyp51a1 catalyzes the removal of the 14α-methyl group from lanosterol through a three-step monooxygenation process. Each step requires one molecule of diatomic oxygen and one molecule of NADPH (or another reducing equivalent). The process involves the conversion of the methyl group into a carboxyalcohol, then a carboxyaldehyde, which finally departs as formic acid, introducing a double bond to yield the demethylated product .
Role in Sterol Biosynthesis
In mammals, Cyp51a1 is essential for cholesterol biosynthesis, which is critical for maintaining cell membrane integrity and serving as a precursor for bile acids and steroid hormones . In fungi, this enzyme is vital for ergosterol production, which is necessary for fungal cell membrane stability and function .
Inhibition Studies
Several compounds have been studied for their ability to inhibit Cyp51a1. In mammals, inhibitors like azoles are primarily used as antifungal agents in fungi but have been explored for their effects on mammalian Cyp51a1 . Flavonoids, such as luteolin 7,3'-disulfate, have shown potential in inhibiting human Cyp51a1, suggesting their utility in cholesterol-lowering and anti-cancer therapies .
Recombinant Expression
Recombinant expression systems allow for the production of Cyp51a1 in controlled environments, facilitating detailed biochemical studies and drug development. Mouse Cyp51a1 has been expressed in various systems to study its enzymatic properties and interactions with inhibitors .
Key Features of Cyp51a1
| Feature | Description |
|---|---|
| Enzyme Type | Cytochrome P450 |
| Function | Demethylation of lanosterol |
| Role in Mammals | Cholesterol biosynthesis |
| Role in Fungi | Ergosterol biosynthesis |
| Inhibitors | Azoles, certain flavonoids |
Inhibitor Potency
| Inhibitor | Potency Against Cyp51a1 |
|---|---|
| Ketoconazole | High (94.6% inhibition at 5 μM) |
| Luteolin 7,3'-disulfate | Moderate (50.1% inhibition at 25 μM) |
References Wikidoc. Lanosterol 14 alpha-demethylase. PubMed. Lanosterol 14 alpha-demethylase (P45014DM). PubMed. Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3'-disulfate. DrugBank. Lanosterol 14-alpha demethylase. PMC. Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3'-disulfate. UniProt. Cyp51a1 - Lanosterol 14-alpha demethylase - Mus musculus (Mouse). Wikipedia. Lanosterol 14 alpha-demethylase. ASM Journals. Three-Dimensional Model of Lanosterol 14α-Demethylase from Cryptococcus neoformans.
Product Specs
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Target Background
- Global, sex-dependent transcriptional dysregulation due to blocked cholesterol synthesis in Cyp51 knockout mice. Sterol intermediates downstream of lanosterol may regulate hepatic RORC activity. PMID: 28098217
- CYP51 mediates T3 and FSH-induced follicular development. PMID: 28938463
- Cyp51 LKO model demonstrates that steatosis develops with dietary fats in the absence of dietary cholesterol and its synthesis, while cholesterol pathway blockage leads to NASH-like features. PMID: 25739789
- Germ cell-specific Cyp51 ablation does not affect testicular morphology, sperm production, or reproductive performance in males. PMID: 23509403
- Cyp51 knockout mice demonstrate the essentiality of Cyp51 for embryogenesis, serving as a potential model for human ABS syndrome. PMID: 21705796
- FSH utilizes CYP51 and the MAS pathway to initiate oocyte meiosis. PMID: 19433477
- CYP51 is localized in testis and ovary, with highest expression in Leydig cells and spermatid acrosomes. PMID: 11988326
- Ejaculate sperm synthesize meiosis-activating sterols via acrosomal lanosterol 14 alpha-demethylase. PMID: 14630712
- CYP51, involved in cholesterol biosynthesis, undergoes immediate early regulation, influencing cellular sterol profiles. PMID: 16123160
- In vivo modulation exists between cholesterol synthesis (via CYP51) and transport (via LDL receptor). PMID: 18520052
- Crem-dependent regulation of Cyp51 in the liver results in circadian gene expression. PMID: 18775413
- Lanosterol 14alpha-demethylase (LDM) is linked to mouse embryo implantation and is upregulated by estrogen. PMID: 19007561
