26.11 Steroids Cholesterol verified until 1955. Steroids are characterized by the tetracyclic ring system shown in Figure 269a. As shown in Figure 269b, cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C-3, a double bond at C-5, methyl groups at C-10 and C-13, and a CgH17 side chain at C-17. Isoprene units may be discerned in var ious portions of the cholesterol molecule, but the overall correspondence with the iso- prene rule is far from perfect. Indeed, cholesterol has only 27 carbon atoms, three too few for it to be classed as a triterpene Animals accumulate cholesterol from their diet, but are also able to biosynthesize it from acetate. The pioneering work that identified the key intermediates in the com- plicated pathway of cholesterol biosynthesis was carried out by Konrad Bloch(Harvard) and Feodor Lynen(Munich), corecipients of the 1964 Nobel Prize for physiology or med- icine. An important discovery was that the triterpene squalene(see Figure 26.6) is an termediate in the formation of cholesterol from acetate. Thus, the early stages of cho lesterol biosynthesis are the same as those of terpene biosynthesis described in Sections 26.8-26.10. In fact, a significant fraction of our knowledge of terpene biosynthesis is a direct result of experiments carried out in the area of steroid biosynthesis How does the tetracyclic steroid cholesterol arise from the acyclic triterpene squa lene? Figure 26.10 outlines the stages involved. It has been shown that the first step is oxidation of squalene to the corresponding 2, 3-epoxide. Enzyme-catalyzed ring opening of this epoxide in step 2 is accompanied by a cyclization reaction, in which the electrons of four of the five double bonds of squalene 2, 3-epoxide are used to close the A, B, C, and d rings of the potential steroid skeleton. The carbocation that results from the cycliza- tion reaction of step 2 is then converted to a triterpene known as lanosterol by the Lanosterol is one component rearrangement shown in step 3. Step 4 of Figure 26.10 simply indicates the structural of lanolin, changes that remain to be accomplished in the transformation of lanosterol to cholesterol. substances that coats the FIGURE 26.9(a)The tetracyclic ring system cha The structure of cholesterol A unique numbering system used for steroids and is in dicated Back Forward Main MenuToc Study Guide ToC Student o MHHE Website26.11 Steroids: Cholesterol 1035 verified until 1955. Steroids are characterized by the tetracyclic ring system shown in Figure 26.9a. As shown in Figure 26.9b, cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C-3, a double bond at C-5, methyl groups at C-10 and C-13, and a C8H17 side chain at C-17. Isoprene units may be discerned in var￾ious portions of the cholesterol molecule, but the overall correspondence with the iso￾prene rule is far from perfect. Indeed, cholesterol has only 27 carbon atoms, three too few for it to be classed as a triterpene. Animals accumulate cholesterol from their diet, but are also able to biosynthesize it from acetate. The pioneering work that identified the key intermediates in the com￾plicated pathway of cholesterol biosynthesis was carried out by Konrad Bloch (Harvard) and Feodor Lynen (Munich), corecipients of the 1964 Nobel Prize for physiology or med￾icine. An important discovery was that the triterpene squalene (see Figure 26.6) is an intermediate in the formation of cholesterol from acetate. Thus, the early stages of cho￾lesterol biosynthesis are the same as those of terpene biosynthesis described in Sections 26.8–26.10. In fact, a significant fraction of our knowledge of terpene biosynthesis is a direct result of experiments carried out in the area of steroid biosynthesis. How does the tetracyclic steroid cholesterol arise from the acyclic triterpene squa￾lene? Figure 26.10 outlines the stages involved. It has been shown that the first step is oxidation of squalene to the corresponding 2,3-epoxide. Enzyme-catalyzed ring opening of this epoxide in step 2 is accompanied by a cyclization reaction, in which the electrons of four of the five double bonds of squalene 2,3-epoxide are used to close the A, B, C, and D rings of the potential steroid skeleton. The carbocation that results from the cycliza￾tion reaction of step 2 is then converted to a triterpene known as lanosterol by the rearrangement shown in step 3. Step 4 of Figure 26.10 simply indicates the structural changes that remain to be accomplished in the transformation of lanosterol to cholesterol. A B C D (a) (b) 1 H 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 HO CH3 CH3 H CH3 CH3 CH3 H (c) Lanosterol is one component of lanolin, a mixture of many substances that coats the wool of sheep. FIGURE 26.9 (a) The tetracyclic ring system char￾acteristic of steroids. The rings are designated A, B, C, and D as shown. (b) and (c) The structure of cholesterol. A unique numbering system is used for steroids and is in￾dicated in the structural formula. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website