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ACAT-2
| Catalog | Product Name | EC No. | CAS No. | Source | Price |
|---|---|---|---|---|---|
| NATE-0798 | Acetyl-Coenzyme A acetyltransferase 2 from Human, Recombinant | E. coli | Inquiry |
Related Reading
The ACAT-2 (Acyl-CoA:Cholesterol Acyltransferase 2) enzyme plays a crucial role in cellular lipid metabolism and cholesterol regulation. The ACAT-2 is an integral membrane protein primarily found in the endoplasmic reticulum of cells and is a key player in cellular cholesterol homeostasis. This enzyme is responsible for catalyzing the esterification of cholesterol through the transfer of acyl chains derived from fatty acyl-CoA. By regulating cholesterol storage and transport, ACAT-2 ensures a delicate balance between intracellular cholesterol levels and its utilization.
Structure
- N-terminal domain
The N-terminal domain of ACAT-2 is located on the cytoplasmic side of the endoplasmic reticulum membrane. This domain contains the active site responsible for catalyzing the esterification reaction. It interacts with cholesterol molecules, accepts fatty acyl-CoA substrates, and transfers the acyl chain to cholesterol to form cholesteryl esters.
- C-terminal domain
The C-terminal structural domain of ACAT-2 is located on the luminal side of the endoplasmic reticulum membrane and enhances the structural stability of the enzyme and influences its activity. It spans the membrane and extends into the lumen of the endoplasmic reticulum. This domain is involved in protein-protein interactions and helps maintain the normal folding and stability of ACAT-2.
Functions
- Cholesterol Storage
ACAT-2 plays an important role in the storage of excess cholesterol as cholesteryl esters. Compared to free cholesterol, cholesteryl esters are less hydrophilic and more hydrophobic, making them suitable for storage in intracellular lipid droplets. This mechanism helps regulate intracellular cholesterol levels and prevents the accumulation of free cholesterol, which can be cytotoxic.
- Lipid Droplet Formation
ACAT-2 activity contributes to the formation and growth of lipid droplets. These lipid droplets store cholesterol esters, triglycerides, and other neutral lipids. By converting cholesterol to cholesteryl esters, ACAT-2 promotes the accumulation and packaging of lipids in lipid droplets, thereby facilitating lipid storage and metabolic processes.
Applications
- Drug Development
Understanding the structure and function of ACAT-2 will enable the design of specific inhibitors to modulate its activity. Novel therapeutic interventions targeting ACAT-2 hold promise for the treatment of atherosclerosis, familial hypercholesterolemia, and other diseases related to cholesterol metabolism.
- Biomarker discovery
ACAT-2 expression and activity levels may serve as important biomarkers for monitoring cholesterol-related diseases and evaluating the efficacy of therapies. Further studies are needed to elucidate its diagnostic use.
Clinical Significance
- Atherosclerosis: ACAT-2 has been linked to atherosclerosis, a progressive arterial disease characterized by the buildup of cholesterol-rich plaques. Strategies targeting ACAT-2 have shown promise in preventing plaque development and reducing the risk of cardiovascular events.
- Niemann-Pick Type C Disease: Dysfunction or mutations in ACAT-2 contribute to Niemann-Pick Type C Disease, a rare genetic disorder resulting in impaired cholesterol trafficking and accumulation within lysosomes. Inhibition of ACAT-2 activity might provide a potential therapeutic approach for this condition.
- Cancer: The dysregulation of lipid metabolism, including ACAT-2 expression, is observed in various cancers. ACAT-2 inhibition has demonstrated anti-tumor effects, suggesting its potential as a therapeutic target for cancer treatment.
Conclusion
ACAT-2 enzyme plays a key role in cellular cholesterol homeostasis and lipid metabolism. Elucidating the structure and function of ACAT-2 will not only deepen our understanding of cholesterol metabolism but also provide potential avenues for the development of novel therapeutic and diagnostic tools. Continued research on ACAT-2 will undoubtedly reveal new insights into its physiological and pathophysiological roles, further advancing our understanding of lipid-related diseases and therapeutic strategies.