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Luu, W., Hart-Smith, G., Sharpe, L. J., & Brown, A. J. (2015). The terminal enzymes of cholesterol synthesis, DHCR24 and DHCR7, interact physically and functionally. Journal of lipid research, 56(4), 888–897. Added by: Dr. Enrique Feoli (16/06/2020, 21:06) |
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| Resource type: Journal Article DOI: 10.1194/jlr.M056986 ID no. (ISBN etc.): 1539-7262 BibTeX citation key: Luu2015 View all bibliographic details  |
Categories: Mendeley, Mendeley Subcategories: Dermatologia Creators: Brown, Hart-Smith, Luu, Sharpe Collection: Journal of lipid research |
Views: 4/287
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| Abstract |
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Cholesterol is essential to human health, and its levels are tightly regulated by a balance of synthesis, uptake, and efflux. Cholesterol synthesis requires the actions of more than twenty enzymes to reach the final product, through two alternate pathways. Here we describe a physical and functional interaction between the two terminal enzymes. 24-Dehydrocholesterol reductase (DHCR24) and 7-dehydrocholesterol reductase (DHCR7) coimmunoprecipitate, and when the DHCR24 gene is knocked down by siRNA, DHCR7 activity is also ablated. Conversely, overexpression of DHCR24 enhances DHCR7 activity, but only when a functional form of DHCR24 is used. DHCR7 is important for both cholesterol and vitamin D synthesis, and we have identified a novel layer of regulation, whereby its activity is controlled by DHCR24. This suggests the existence of a cholesterol "metabolon", where enzymes from the same metabolic pathway interact with each other to provide a substrate channeling benefit. We predict that other enzymes in cholesterol synthesis may similarly interact, and this should be explored in future studies.
Added by: Dr. Enrique Feoli |