Desmosterol and DHCR24: Unexpected new directions for a terminal step in cholesterol synthesis

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• 作者：Eser J. Zerenturk ; Laura J. Sharpe ; Elina Ikonen ; Andrew J. Brown
• 关键词：ACTH ; adrenocorticotropic hormone ; CAR ; constitutive androstane receptor ; DHCR24 ; 3尾-hydroxysterol 螖24-reductase ; DHCR7 ; 7-dehydrocholesterol reductase ; DWF1 ; dwarf 1 ; ER ; endoplasmic reticulum ; FAD ; flavin adenine dinucleotide ; HCV ; hepatitis C virus ; HDL ; high-density lipoprotein ; HMGCR ; 3-hydroxy-3-methylglutaryl-coenzyme A reductase ; LXR ; liver X receptor ; Mdm2 ; mouse double minute 2 homolog ; NF-Y ; nuclear factor Y ; PXR ; pregnane X receptor ; Scap ; SREBP-cleavage activating protein ; Seladin
• 刊名：Progress in Lipid Research
• 出版年：October, 2013
• 年：2013
• 卷：52
• 期：4
• 页码：666-680
• 全文大小：1385 K

文摘

3尾-Hydroxysterol 螖²⁴-reductase (DHCR24) catalyzes the conversion of desmosterol to cholesterol. This ultimate step of cholesterol biosynthesis appears to be remarkable in its diverse functions and the number of diseases it is implicated in from vascular disease to Hepatitis C virus (HCV) infection to cancer to Alzheimer鈥檚 disease. This review summarizes the present knowledge on the DHCR24 gene, sterol 螖²⁴-reductase protein and the regulation of both. In addition, the functions of desmosterol, DHCR24 and their roles in human diseases are discussed. It is apparent that DHCR24 exerts more complex effects than what would be expected based on the enzymatic activity of sterol 螖²⁴-reduction alone, such as its influence in modulating oxidative stress. Increasing information about DHCR24 membrane association, processing, enzymatic regulation and interaction partners will provide further fundamental insights into DHCR24 and its many and varied biological roles.