7-Dehydrocholesterol (7-DHC)

7-Dehydrocholesterol (7-DHC) is a vital zoosterol that serves as the immediate precursor for both cholesterol and Vitamin D3 in vertebrates. Located primarily in the epidermal layers of the skin, 7-DHC absorbs UV-B radiation to undergo a non-enzymatic photochemical reaction, forming previtamin D3, which then thermally isomerizes into cholecalciferol (Vitamin D3) (PubChem CID 439533). In the internal metabolic pathway, the enzyme 7-dehydrocholesterol reductase (DHCR7) reduces the double bond at the 7-position of 7-DHC to produce cholesterol, a critical component of cell membranes and a precursor to steroid hormones. Clinically, 7-DHC is central to the pathology of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive disorder caused by mutations in the DHCR7 gene. In SLOS patients, the inability to convert 7-DHC to cholesterol leads to toxic accumulations of 7-DHC and its oxysterol derivatives, resulting in severe congenital malformations and intellectual disabilities (NIH GARD). While 7-DHC itself is not a classical therapeutic target like a receptor, its levels are pharmacologically influenced by certain drugs, such as Trazodone and Haloperidol, which can off-target inhibit DHCR7. Monitoring 7-DHC levels remains the gold standard for diagnosing distal cholesterol synthesis defects and managing Vitamin D homeostasis.

Other names

Provitamin D3Cholesta-5,7-dien-3β-ol7,8-didehydrocholesterol

Functions as a metabolic substrate converted into Vitamin D3 via UV-B radiation exposure or reduced to cholesterol by the enzyme 7-dehydrocholesterol reductase (DHCR7).