title: DHCR7: A vital enzyme switch between cholesterol and vitamin D production.
abstract: The conversion of 7-dehydrocholesterol to cholesterol, the final step of cholesterol synthesis in the Kandutsch-Russell pathway, is catalyzed by the enzyme 7-dehydrocholesterol reductase (DHCR7). Homozygous or compound heterozygous mutations in DHCR7 lead to the developmental disease Smith-Lemli-Opitz syndrome, which can also result in fetal mortality, highlighting the importance of this enzyme in human development and survival. Besides serving as a substrate for DHCR7, 7-dehydrocholesterol is also a precursor of vitamin D via the action of ultraviolet light on the skin. Thus, DHCR7 exerts complex biological effects, involved in both cholesterol and vitamin D production. Indeed, we argue that DHCR7 can act as a switch between cholesterol and vitamin D synthesis. This review summarizes current knowledge about the critical enzyme DHCR7, highlighting recent findings regarding its structure, transcriptional and post-transcriptional regulation, and its links to vitamin D synthesis. Greater understanding about DHCR7 function, regulation and its place within cellular metabolism will provide important insights into its biological roles.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia.
authors.forename: Anika V
authors.initials: AV
authors.lastname: Prabhu
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia.
authors.forename: Winnie
authors.initials: W
authors.lastname: Luu
authors.affiliation: National Center for Protein Sciences, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Dianfan
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sharpe
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia. Electronic address: aj.brown@unsw.edu.au.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003684:Dehydrocholesterols / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D006801:Humans; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D019082:Smith-Lemli-Opitz Syndrome / Q000378:metabolism / Q000473:pathology; D014807:Vitamin D / Q000378:metabolism*; D014981:Xenopus / Q000254:growth & development / Q000378:metabolism
chemical_list: D003684:Dehydrocholesterols; D014807:Vitamin D; D002784:Cholesterol; C016705:7-dehydrocholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase
keywords: 7-Dehydrocholesterol; 7-Dehydrocholesterol reductase; Cholesterol; Smith-Lemli-Opitz syndrome; Vitamin D(3)