1036 CHAPTER TWENTY-SIX Lipids Step 1: Squalene undergoes enzymic oxidation to the 2, 3-epoxide. This reaction has been described earlier, in Section 16 14 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 T electrons of the neighboring double bond. A series of ring closures leads to the tetracyclic H >HO- 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. HO H Tetracyclic carbocation formed in step 2 -Cont 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 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website1036 CHAPTER TWENTY-SIX Lipids Squalene O2, NADH, enzyme Squalene 2,3-epoxide O Step 1: Squalene undergoes enzymic oxidation to the 2,3-epoxide. This reaction has been described earlier, in Section 16.14. 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 electrons of the neighboring double bond. A series of ring closures leads to the tetracyclic carbocation shown. 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. HO H Lanosterol H H O H H HO Tetracyclic carbocation formed in step 2 H H H H H 9 8 14 13 17 20 HO Tetracyclic carbocation H Squalene 2,3-epoxide —Cont. 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. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website