desmosterol

Desmosterol is a sterol and a cholesterol biosynthetic intermediate. It is chemically described as cholesta-5,24-dien-3β-ol, featuring a double bond in the side chain at the 24 position. In humans, desmosterol is a substrate in the Bloch pathway of cholesterol synthesis, and it is converted to cholesterol by the enzyme desmosterol reductase (DHCR24). Some mammals use parallel biosynthetic routes, but all converge on cholesterol.

Biosynthesis and metabolism: Desmosterol forms during cholesterol production as an intermediate enclosed in the sterol synthesis sequence. The final step in the Bloch pathway reduces desmosterol to cholesterol, while DHCR24 activity regulates this flux. The Kandutsch-Russell pathway provides an alternative route to cholesterol with different intermediates, but desmosterol remains a key marker of the Bloch branch.

Biological role: Desmosterol is an endogenous component of cell membranes and lipoproteins, contributing to membrane properties and lipid raft organization. As a biosynthetic intermediate, its levels reflect the activity of cholesterol synthesis in tissues.

Clinical significance: Elevated desmosterol is a hallmark of desmosterolosis, a rare autosomal recessive disorder caused by DHCR24 deficiency, leading to increased desmosterol and often reduced cholesterol with multiple congenital anomalies. Desmosterol can serve as a biomarker of cholesterol biosynthesis flux and is used in diagnostic workups alongside other sterols. In contrast, Smith-Lemli-Opitz syndrome results from DHCR7 deficiency and is characterized by elevated 7-dehydrocholesterol and low cholesterol. Desmosterol measurement is typically performed by LC-MS/MS in metabolic testing. Diet contributes minimally to circulating desmosterol, which is mainly of endogenous origin.