Microsomal enzymes of cholesterol biosynthesis from lanosterol

Synthesis of cholesterol from lanosterol. The DHCR24 (Δ24‐reductase) enzyme can reduce all the sterols shown on the left side. The key carbon atoms are numbered in the lanosterol structure (top), and all carbon atoms of cholesterol are numbered (bottom).

Cholesterol biosynthesis from 18μM [24-3H]-lanosterol was inhibited by 40μM lanosterol analogs.

Steroids, sterols, and many other natural products all derive from isoprenoid building blocks via two common biosynthetic pathways. The subsequent processing of the structural core yields specific products that possess diverse structures and biological activities.


Synthesis of cholesterol from lanosterol

Among the analogs studied, 27-nordihydrolanosterol was most active in depressing cholesterol biosynthesis from lanosterol.

The effects of oxygenated lanosterol derivatives (1-14) on cholesterol biosynthesis from [24-3H]-lanosterol were tested in 10000×g supernatant (S10) fraction of rat liver homogenate (RLH). Among the derivatives studied, 7-oxo-24, 25-dihydrolanosterol (11) was most active in depressing cholesterol biosynthesis from lanosterol. The inhibitory activities of these derivatives on cholesterol synthesis are discussed in relation to the position and stereochemistry of the oxygen group on the side chain and the sterol nucleus.