文章基本信息

标题：The terminal enzymes of cholesterol synthesis, DHCR24 and DHCR7, interact physically and functionally
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作者：Winnie Luu ; Gene Hart-Smith ; Laura J. Sharpe 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2015
卷号：56
期号：4
页码：888-897
DOI：10.1194/jlr.M056986
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
关键词：24-dehydrocholesterol reductase ; 7-dehydrocholesterol reductase ; desmosterol ; 7-dehydrocholesterol