Although cholesterol is probably best known by most people for its association with atherosclerosis and heart disease, it has many essential roles in the body. It is the precursor of a large number of equally important steroids that include the bile acids, adrenocortical hormones, sex hormones, vitamin D, and cardiac glycosides.
All steroids have a similar cyclic nucleus resembling phenanthrene (rings A, B, and C) to which a cyclopentane ring (D) is attached. The carbon positions on the steroid nucleus are numbered as shown in Figure 1. It is important to realize that in structural formulas of steroids, a simple hexagonal ring denotes a completely saturated six-carbon ring with all valences satisfied by hydrogen bonds unless shown otherwise; that is, it is not a benzene ring. All double bonds are shown as such. Methyl groups (shown as single bonds unattached at the farther [methyl] end) occur typically at positions 10 and 13 and constitute C atoms 19 and 18. A side chain at position 17 is usual (as in cholesterol). If the compound has one or more hydroxyl groups and no carbonyl or carboxyl groups, it is a sterol, and the name terminates in -ol.
Fig1. The steroid nucleus.
Because of Asymmetry in the Steroid Molecule, Many Stereoisomers Are Possible
Each of the six-carbon rings of the steroid nucleus is capable of existing in the three-dimensional conformation either of a “chair” or a “boat” (Figure 2). In naturally occurring steroids, virtually all the rings are in the “chair” form, which is the more stable conformation. With respect to each other, the rings can be either cis or trans (Figure 3). The junction between the A and B rings may be cis or trans in naturally occurring steroids. The junction between B and C is trans, as is usually the C/D junction. Bonds attaching substituent groups above the plane of the rings (β bonds) are shown with bold solid lines, whereas those bonds attaching groups below (α bonds) are indicated with broken lines. The A ring of a 5α steroid (ie, the hydrogen at position 5 is in the α configuration) is always trans to the B ring, whereas it is cis in a 5β steroid (ie, the hydrogen at position 5 is in the β configuration). The methyl groups attached to C10 and C13 are invariably in the β configuration.
Fig2. Conformations of stereoisomers of the steroid nucleus.
Fig3. Generalized steroid nucleus, showing (A) an all-trans configuration between adjacent rings and (B) a cis con figuration between rings A and B.
Cholesterol Is a Significant Constituent of Many Tissues
Cholesterol (Figure 4) is widely distributed in all cells of the body but particularly in nervous tissue. It is a major constituent of the plasma membrane and of plasma lipoproteins. It is often found as cholesteryl ester, where the hydroxyl group on position 3 is esterified with a long-chain fatty acid. It occurs in animals but not in plants or bacteria.
Fig4. Cholesterol.
Ergosterol Is a Precursor of Vitamin D
Ergosterol occurs in plants and yeast and is important as a dietary source of vitamin D (Figure 5). When irradiated with ultraviolet light in the skin, ring B is opened to form vitamin D2 in a process similar to the one that forms vitamin D3 from 7-dehydrocholesterol in the skin.
Fig5. Ergosterol.
Polyprenoids Share the Same Parent Compound as Cholesterol
Polyprenoids are not steroids but are related to them because they are synthesized, like cholesterol, from five-carbon isoprene units (Figure 6). They include ubi quinone, which participates in the respiratory chain in mitochondria, and dolichols, long-chain alcohols containing 15 to 23 isoprene units in animal cells (Figure 7), which take part in glycoprotein synthesis by transferring oligosaccharide residues to asparagine residues of the glycoprotein polypeptide chains as they are formed. Plant-derived polyprenoids include rubber, camphor, the fat-soluble vitamins A, D, E, and K, and β-carotene (provitamin A).
Fig6. Isoprene unit.
Fig7. Dolichol. Major dolichols in humans contain 19 or 20 isoprene units.
