Inhibition of cholesterol biosynthesis by carbon monoxide: accumulation of lanosterol and 24,25-dihydrolanosterol

It has been shown (Wada et al., 1969) that CO inhibits the conversion of acyclic precursors into digitonin-precipitable sterols in lOOOOg supernatant fractions of rat liver homogenates. Although no direct experimental attempt was made to characterize the biosynthetic site of inhibition, this was attributed to an effect on the microsomal enzyme squalene 2,3oxidase. More recent work, however, has demon- strated that squalene 2,3-oxidase is not inhibited by CO (Yamamoto & Bloch, 1969). The present in- vestigation was undertaken to clarify this apparent contradiction by establishing the nature of the inter- mediates that accumulate during CO inhibition of cholesterol biosynthesis from selected precursors.