3β-hydroxysterol-Δ7-reductase (DHCR7)

3β-hydroxysterol-Δ7-reductase (DHCR7) is a membrane-bound oxidoreductase enzyme involved in cholesterol biosynthesis, specifically catalyzing the reduction of the Δ7 double bond of 7-dehydrocholesterol to produce cholesterol. The DHCR7 gene is located on human chromosome 11q12-q13 and mutations cause Smith-Lemli-Opitz syndrome (SLOS), a congenital disorder marked by severe developmental, neurobehavioral, and metabolic abnormalities due to low cholesterol and high 7-dehydrocholesterol. The enzyme and its deficiency play roles in normal development of neural and retinal tissues; loss of function leads to disrupted signaling, membrane composition, and potentially toxic accumulation of sterol precursors and oxysterol metabolites. Therapy for SLOS has centered around dietary cholesterol supplementation and, in experimental research, the use of antioxidants and receptor antagonists to modify downstream pathological effects.

Other names

Delta(7)-sterol reductase7-dehydrocholesterol reductaseDHCR7EC 1.3.1.21

Inhibition: Blocks the final reduction step in cholesterol biosynthesis, leading to accumulation of 7-dehydrocholesterol and deficiency in cholesterol. Supplementation: Dietary cholesterol normalizes metabolic defects and partially reverses symptoms in animal models and patients. Oxysterol modulation: Accumulation of oxysterol metabolites can alter signaling by glucocorticoid receptor and neurotrophin receptor pathways.