7Dehydrocholesterol

7-Dehydrocholesterol, commonly abbreviated as 7-DHC, is a sterol that serves as an intermediate in the biosynthesis of cholesterol. It is the immediate precursor to cholesterol in the Kandutsch-Russell branch of the mevalonate pathway and is converted to cholesterol by the enzyme 7-dehydrocholesterol reductase (DHCR7). In vertebrates, 7-DHC is produced in tissues that synthesize cholesterol, including the liver and peripheral tissues, and it can be found in trace amounts in plasma.

A key feature of 7-DHC is its role as the substrate for vitamin D3 production. In the skin, ultraviolet B (UVB) irradiation of 7-DHC leads to the formation of previtamin D3, which spontaneously isomerizes to vitamin D3 (cholecalciferol). This photochemical conversion makes 7-DHC a major endogenous source of vitamin D in humans, dependent on sun exposure.

Biological and clinical significance

Because 7-DHC is rapidly converted to cholesterol in healthy individuals, its steady-state levels are normally low. Defects in DHCR7, the enzyme that reduces 7-DHC to cholesterol, cause Smith-Lemli-Opitz syndrome (SLOS), a developmental disorder characterized by elevated 7-DHC and reduced cholesterol. The accumulation of 7-DHC and its oxidized derivatives is thought to contribute to the clinical features of SLOS.

Chemically, 7-DHC is highly reactive and prone to oxidative modification, producing a variety of oxysterols. These properties have implications for both physiology and pathophysiology, particularly in tissues exposed to light or oxidative stress.

See also: cholesterol biosynthesis, DHCR7, vitamin D, Smith-Lemli-Opitz syndrome.