The biosynthetic pathway shown in Figure 26.10 was developed with the aid of isotopic labeling experiments. Which carbon atoms of cholesterol would you expect to be labeled when acetate enriched with 14C in its methyl group (14CH3COOH) is used as the carbon source?
FIGURE 26.10
The biosynthetic conversion of squalene to cholesterol proceeds through lanosterol. Lanosterol is formed by a cyclization reaction of squalene-2,3-epoxide.

Step 1: Squalene undergoes enzymic oxidation to the 2,3-epoxide. This reaction has been described earlier, in Section 16.14 Squalene O NADH, eny Squalene 2.3-epoxide Step 2: Cyclization of squalene 2.3-epoxide, shown in its coiled form, is triggered by ring opening of the epoxide. Cleavage of the carbon-oxygen bond is assisted by protonation of oxygen and by nucleophilic participation of the r electrons of the neighboring double bond. A series of ring closures leads to the tetracyclic carbocation shown. Squalene 2.3-epoxide Tetracyclic carbocation Step 3: Rearrangement of the tertiary carbocation formed by cyclization produces lanosterol. Two hydride shifts. from C-17 to C-20 and from C-13 to C-17, are accompanied by methyl shifts from C-14 to C-13 and from C-8 to C-14. A double bond is formed at C-8 by loss of the proton at C-9 0 HO Tetracyclic carbocation formed in step Lanosterol -Cont. Step 4: A series of enzyme-catalyzed reactions converts lanosterol to cholesterol. The three highlighted methyl groups in the structural formula of lanosterol are lost via separate multistep operations, the C-8 and C-24 double bonds are reduced, and a new double bond is introduced at C-5 HO many sinpe HO Lanosterol Cholesterol