Structure of Cholesterol

STRUCTURE OF CHOLESTEROL

Cholesterol is a very hydrophobic compound. It consists of four fused hydrocarbon rings (A^-D) called the “steroid nucleus,” and it has an eight-carbon, branched hydrocarbon chain attached to carbon 17 of the D ring. Ring A has a hydroxyl group at carbon 3, and ring B has a double bond between carbon 5 and carbon 6 (Figure 18.2).

Figure 18.2 Structure of cholesterol and its ester.

A. Sterols

Steroids with eight to ten carbon atoms in the side chain at carbon 17 and a hydroxyl group at carbon 3 are classified as sterols. Cholesterol is the major sterol in animal tissues. It arises from de novo synthesis and absorption of dietary cholesterol. [Note: Intestinal uptake of cholesterol is mediated, at least in part, by the protein Niemann-Pick C1-like 1 protein (NPC1-L1), the target of the drug ezetimibe that reduces absorption of dietary cholesterol. Plant sterols (phytosterols), such as β-sitosterol, are poorly absorbed by humans (5% absorbed as compared to 40% for cholesterol). After entering the enterocytes, they are actively transported back into the intestinal lumen. Defects in the transporter result in the rare condition of sitosterolemia. Because some cholesterol is transported back as well, plant sterols reduce the absorption of dietary cholesterol. Daily ingestion of plant sterol esters supplied, for example, in spreads or juices, is one of a number of dietary strategies to reduce plasma cholesterol levels.]

B. Cholesteryl esters

Most plasma cholesterol is in an esterified form (with a fatty acid attached at carbon 3, as shown in Figure 18.2), which makes the structure even more hydrophobic than free (unesterified) cholesterol. Cholesteryl esters are not found in membranes and are normally present only in low levels in most cells. Because of their hydrophobicity, cholesterol and its esters must be transported in association with protein as a component of a lipoprotein particle or be solubilized by phospholipids and bile salts in the bile.