7-Dehydrocholesterol

7-Dehydrocholesterol (7-DHC) is a precursor of cholesterol and vitamin D, and is converted to vitamin D₃ in the skin upon exposure to ultraviolet B (UVB) light^{[1, 2]}. 7-Dehydrocholesterol is a natural anti-ferroptotic metabolite that protects cells by preventing lipid peroxidation, a key process in ferroptosis^[3]. 7-Dehydrocholesterol accumulates in Smith-Lemli-Opitz syndrome (SLOS), a disease caused by mutations in the DHCR7 gene, characterized by low cholesterol levels in tissues and body fluids, microcephaly, intellectual disability, and distinctive physical features^{[4, 5]}. 7-Dehydrocholesterol can be converted to 7-ketocholesterol by human cytochrome P450 7A1 (CYP7A1)^[6].

References:
[1] Lehmann B, Genehr T, Knuschke P, et al. UVB-induced conversion of 7-dehydrocholesterol to 1α, 25-dihydroxyvitamin D3 in an in vitro human skin equivalent model[J]. Journal of investigative dermatology, 2001, 117(5): 1179-1185.
[2] Shin M H, Lee Y, Kim M K, et al. UV increases skin-derived 1α, 25-dihydroxyvitamin D3 production, leading to MMP-1 expression by altering the balance of vitamin D and cholesterol synthesis from 7-dehydrocholesterol[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2019, 195: 105449.
[3] Li Y, Ran Q, Duan Q, et al. 7-Dehydrocholesterol dictates ferroptosis sensitivity[J]. Nature, 2024, 626(7998): 411-418.
[4] Waterham H R, Wanders R J A. Biochemical and genetic aspects of 7-dehydrocholesterol reductase and Smith-Lemli-Opitz syndrome[J]. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 2000, 1529(1-3): 340-356.
[5] Bianconi S E, Cross J L, Wassif C A, et al. Pathogenesis, epidemiology, diagnosis and clinical aspects of Smith–Lemli–Opitz syndrome[J]. Expert opinion on orphan drugs, 2015, 3(3): 267-280.
[6] Shinkyo R, Xu L, Tallman K A, et al. Conversion of 7-dehydrocholesterol to 7-ketocholesterol is catalyzed by human cytochrome P450 7A1 and occurs by direct oxidation without an epoxide intermediate[J]. Journal of Biological Chemistry, 2011, 286(38): 33021-33028.

7-Dehydrocholesterol（7-DHC）是胆固醇和维生素D的前体，在皮肤暴露于紫外B（UVB）光时转化为维生素D₃^{[1, 2]}。7-Dehydrocholesterol是一种天然抗铁死亡代谢物，通过防止脂质过氧化来保护细胞，脂质过氧化是铁死亡的一个关键过程^[3]。7-Dehydrocholesterol在Smith-Lemli-Opitz综合征（SLOS）中积累，这是一种由DHCR7基因突变引起的疾病，其特征是体内组织和体液中的胆固醇水平降低，以及小头畸形、智力障碍和独特的畸形特征^{[4, 5]}。7-Dehydrocholesterol能够由人细胞色素P450 7A1（CYP7A1）催化转化为7-酮胆固醇（7-Ketocholesterol）^[6]。